3.12

Summary

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I. Major Nephrology Syndromes and Clinical Database

• The 10 Nephrology Syndromes include Acute Nephritic, Nephrotic, Isolated Urinary Abnormalities, AKI, CKD, UTI, Renal Tubular Defects, HTN, Obstruction, and Urolithiasis. [Clinical Database]
• The Acute Nephritic Syndrome is characterized by glomerular inflammation leading to hematuria, dysmorphic RBCs, HTN, and reduced GFR. [Nephritic Syndrome]
• The Nephrotic Syndrome is defined by massive proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia. [Nephrotic Syndrome]
• Functional vs. Structural AKI is distinguished by prerenal states (decreased perfusion) vs. intrinsic renal disease (structural damage). [AKI Classification]

II. Acute Kidney Injury (AKI): Etiology and Pathophysiology

• Acute Kidney Injury (AKI) is defined as an impairment of filtration and excretion occurring within 7 days, staged by SCr rise and oliguria duration. [Definition]

• Prerenal AKI is caused by reduced renal perfusion; common triggers include Heart Failure (low CO), Hepatic Failure (excess Nitric Oxide causing vasodilation), and Burn injuries (capillary leak). [Prerenal States]

• Dehydration vs. Hypovolemia in AKI: Dehydration is a total body water deficit, whereas Hypovolemia is a decrease in intravascular volume that directly reduces renal perfusion. [Prerenal States]

• Intrinsic AKI involves direct tissue damage, most commonly Acute Tubular Necrosis (ATN), with the S3 segment of the proximal tubule being the most vulnerable site. [Intrinsic Renal Disease]

• Fractional Excretion of Sodium (FENa) is typically &lt1% in prerenal states (conserving Na) and >1% in intrinsic AKI (tubular inability to reabsorb Na). [FENa]

• Postrenal AKI results from urinary tract obstruction such as BPH, urolithiasis, or malignancy. [Postrenal States]

• NSAIDs cause AKI by inhibiting prostaglandins, leading to afferent arteriolar vasoconstriction and reduced GFR. [Pathophysiology]

• ACEi and ARBs cause AKI by inhibiting Angiotensin II, leading to efferent arteriolar vasodilation and reduced glomerular pressure. [Pathophysiology]

• Endothelin-1 (ET-1) is noted as the most potent vasoconstrictor in the context of renal regulation. [Pathophysiology]

III. Glomerular Diseases and Histopathology

• IgA Nephropathy is the most common glomerulonephritis worldwide and in Southeast Asia, typically following a URI. [Glomerular Disease]
• Rapidly Progressive Glomerulonephritis (RPGN) is a clinical syndrome characterized by a rapid decline in GFR and the presence of crescents on renal biopsy. [Glomerular Disease]
• Alport’s Syndrome is a hereditary disease presenting with the triad of hematuria, neurosensory hearing loss, and ocular abnormalities. [Hereditary Disease]
• Diabetes Mellitus is the most common cause of nephrotic-range proteinuria and the leading cause of CKD in adults. [Diagnostic Evaluation]
• Multiple Myeloma in older patients with renal failure and proteinuria is suggested by the presence of Bence-Jones proteins on UPEP/SPEP. [Diagnostic Evaluation]

IV. Chronic Kidney Disease (CKD): Staging and Pathophysiology

• Chronic Kidney Disease (CKD) is defined by abnormal kidney function or progressive GFR decline for >3 months. [Definition]
• The Normal decline in GFR with age after the 3rd decade is approximately 1 mL/min per year. [Staging]
• Hyperfiltration and Hypertrophy are nonspecific mechanisms where remaining nephrons compensate for lost mass, eventually leading to overwork and failure. [Pathophysiology]
• Spot Protein-to-Creatinine Ratio (UACR) is more practical than 24-hr collection and is preferred for monitoring glomerular injury and therapy response. [Proteinuria]
• ACEi and ARBs are mainstay drugs in CKD for controlling intraglomerular HTN and proteinuria, but are contraindicated in AKI. [Management]

V. Electrolyte, Mineral, and Hematologic Complications

• Hyperkalemia in Diabetes/Obstruction is often caused by hyporeninemic hypoaldosteronism, appearing out of proportion to GFR decline. [Electrolytes]
• Hyperkalemia Emergency Management includes:
  1. Calcium gluconate (stabilizes myocardium);
  2. Insulin + Glucose (shifts K into cells);
  3. Inhaled Beta-agonists (shifts K into cells). [Management]
• Metabolic Acidosis in CKD is typically due to decreased Ammonia (NH3) production by diseased kidneys. [Acid-Base]
• Anemia in CKD is usually normocytic and normochromic, primarily caused by insufficient Erythropoietin (EPO) production; target Hb is 10-11.5 g/dL. [Anemia]
• Secondary Hyperparathyroidism in CKD is driven by phosphate retention, decreased calcitriol, and hypocalcemia. [Bone Disease]
• Osteitis Fibrosa Cystica results from high bone turnover due to hyperparathyroidism; advanced stages may show hemorrhagic cysts known as Brown Tumors. [Bone Disease]
• Calciphylaxis is a condition "almost exclusive" to advanced CKD, characterized by painful livedo reticularis and ischemic skin necrosis. [Bone Disease]
• Fibroblast Growth Factor-23 (FGF-23) is a phosphaturic hormone that acts as an independent risk factor for LVH and mortality in CKD. [Mineral Metabolism]
• Nephrogenic Systemic Fibrosis (NSF) is a skin condition unique to CKD patients exposed to Gadolinium-based MRI contrast. [Contrast Injury]

VI. Clinical Management and Dialysis

• Renal Replacement Therapy (RRT) indications in AKI follow the "AEIOU" mnemonic: Refractory **A**cidosis, **E**lectrolyte issues (K+), **I**ntoxications (Lithium, alcohols), Fluid **O**verload, and **U**remic symptoms. [RRT Indications]
• Uremic Pericarditis is an absolute indication for urgent dialysis initiation or intensification of dialysis prescription. [Management]
• Hypotension is the most common acute complication of hemodialysis, especially in diabetic patients. [Dialysis]
• Type A Dialyzer Reaction is an IgE-mediated hypersensitivity to ethylene oxide (occurs within minutes); Type B Reaction is complement/cytokine-mediated (nonspecific chest/back pain). [Dialysis]
• CAPD Peritonitis is most commonly caused by Coagulase-negative Staphylococcus (skin flora). [Peritoneal Dialysis]
• Arteriovenous (AV) Fistulas can lead to High-output Heart Failure due to blood shunting. [Complications]

VII. High-Yield Distinctions and Comparisons

• Prerenal vs. Intrinsic AKI: Prerenal has FENa <1% and high urine osmolarity; Intrinsic (ATN) has FENa >1% and "muddy brown" casts.
• Nephrotic vs. Nephritic Proteinuria: Nephrotic is massive (>3.5g/d) with no active sediment; Nephritic is often <3.5g/d and accompanied by dysmorphic RBCs/casts.
• Afferent vs. Efferent Arteriolar Drugs: NSAIDs vasoconstrict the afferent arteriole (bad in AKI); ACEi/ARBs vasodilate the efferent arteriole (bad in AKI, good in chronic proteinuria).
• Hepatitis B vs. Hepatitis C Renal Association: Hepatitis B is linked to Membranous Nephropathy (MN); Hepatitis C is linked to Membranoproliferative GN (MPGN).
• Calcium Gluconate vs. Insulin in Hyperkalemia: Calcium gluconate protects the heart but does not lower K+; Insulin/Glucose actually lowers serum K+.
• Dehydration vs. Hypovolemia: Dehydration is loss of total body water; Hypovolemia is loss of intravascular volume and is more likely to cause AKI.
• Type A vs. Type B Dialyzer Reactions: Type A is anaphylactic (IgE/Ethylene oxide); Type B is mild chest/back pain (Complement/Cytokines).
• Uremic vs. Spontaneous Tumor Lysis: Both cause AKI; Spontaneous TLS occurs due to overwhelming tumor burden, whereas standard TLS follows chemotherapy.
• Thiazide vs. Loop Diuretics in CKD: Thiazides lose efficacy as GFR drops below 30 (Stage 4-5); Loop diuretics are the preferred choice, though higher doses are required.
• 24-hour Protein vs. Spot UACR: 24-hour is gold standard but cumbersome; Spot Morning UACR is preferred for practicality and correlates well.
• Target Hb in General Population vs. CKD: Normal Hb is >12-13; CKD Hb target is restricted to 10-11.5 g/dL to avoid cardiovascular/clotting risks.
• Osteitis Fibrosa Cystica vs. Adynamic Bone Disease: Osteitis fibrosa cystica is "high turnover" (high PTH); Adynamic bone disease is "low turnover" (very low PTH).
• Contrast Nephropathy vs. NSF: Contrast Nephropathy is AKI from iodinated CT contrast; Nephrogenic Systemic Fibrosis (NSF) is skin induration from MR Gadolinium contrast.
• AKI (7 days) vs. CKD (3 months): AKI describes an acute, potentially reversible drop in function; CKD describes irreversible, structural, or functional decline over at least 90 days.
• Low BP Prognosis: In the general population, low BP is often good; in dialysis/ESRD patients, low BP (under 140) often carries a worse prognosis/higher mortality.

QA

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I. Major Nephrology Syndromes and Clinical Database

1. What is the primary finding in Acute Kidney Injury (AKI)? | Rapid rise in SCr/Urea
2. What is the GFR and duration criteria for Chronic Kidney Disease (CKD)? | GFR <60 for >3 months
3. What is the level of proteinuria defining Nephrotic Syndrome? | >3.5 g/day
4. What are the two primary findings in Nephritic Syndrome? | Hematuria and hypertension
5. What type of urinary sediment is characteristic of Acute Tubular Necrosis (ATN)? | Muddy brown casts
6. What type of urinary sediment is characteristic of Chronic Kidney Disease (CKD)? | Broad waxy casts
7. What are the urinary sediment findings (2) for Nephrotic Syndrome? | 1) Fatty casts
   2) Lipiduria
8. What are the urinary sediment findings (2) for Nephritic Syndrome? | 1) Dysmorphic RBCs
   2) RBC casts
9. What are the common symptoms (2) of Acute Kidney Injury (AKI)? | 1) Oliguria
   2) Uremia
10. What are the common symptoms (3) of Chronic Kidney Disease (CKD)? | 1) Uremia
    2) Anemia
    3) Bone disease
11. What is the hallmark symptom of Nephrotic Syndrome? | Massive Edema
12. List the symptoms (3) of Nephritic Syndrome. | 1) Hematuria
    2) HTN
    3) Edema
13. Enumerate the 10 Nephrology Syndromes. (10) | Acute Nephritic, Nephrotic, Isolated Urinary Abnormalities, AKI, CKD, UTI, Renal Tubular Defects, HTN, Obstruction, Urolithiasis.
14. What are the characteristics (4) of Acute Nephritic Syndrome? | 1) Hematuria
    2) Dysmorphic RBCs
    3) HTN
    4) Reduced GFR
15. What are the defining features (4) of Nephrotic Syndrome? | 1) Proteinuria >3.5g/d
    2) Hypoalbuminemia
    3) Edema
    4) Hyperlipidemia
16. How is Functional vs. Structural AKI distinguished? | Prerenal states vs. Intrinsic disease

II. Acute Kidney Injury (AKI): Etiology and Pathophysiology

17. What is the mechanism of Prerenal AKI? | Hypoperfusion (No damage)
18. What is the FENa in Prerenal AKI? | <1%
19. What type of urinary sediment is found in Prerenal AKI? | Bland or Normal
20. What is the mechanism of Intrinsic AKI? | Structural Damage (ATN)
21. What is the typical FENa in Intrinsic AKI? | >1% (often >2%)
22. What is the mechanism of Postrenal AKI? | Outflow Obstruction
23. What is the urinary sediment in Postrenal AKI? | Bland (unless infected)
24. How is the duration and staging of Acute Kidney Injury (AKI) defined? | Within 7 days
25. Prerenal AKI: What causes vasodilation in Hepatic Failure? | Excess Nitric Oxide
26. Prerenal AKI: What is the mechanism of low CO in Heart Failure? | Reduced renal perfusion
27. Prerenal AKI: What occurs in Burn injuries to cause AKI? | Capillary leak
28. Contrast Dehydration vs. Hypovolemia in the context of AKI. | Total water deficit vs. Intravascular volume decrease
29. What is the most common cause of Intrinsic AKI? | Acute Tubular Necrosis (ATN)
30. Which specific area is the most vulnerable site in ATN? | S3 segment of proximal tubule
31. Why is FENa &lt1% in prerenal states? | Body is conserving Sodium
32. Why is FENa >1% in intrinsic AKI? | Tubular inability to reabsorb Sodium
33. List causes (3) of Postrenal AKI. | 1) BPH
    2) Urolithiasis
    3) Malignancy
34. How do NSAIDs cause AKI? | Afferent arteriolar vasoconstriction
35. How do ACEi and ARBs cause AKI? | Efferent arteriolar vasodilation
36. What is the most potent vasoconstrictor in renal regulation? | Endothelin-1 (ET-1)

III. Glomerular Diseases and Histopathology

37. What are the key associations (3) for Minimal Change Disease (MCD)? | 1) Children
    2) NSAIDs
    3) Hodgkin
38. What is the biopsy clue for Minimal Change Disease (MCD)? | Normal light microscopy
39. What are the key associations (3) for FSGS? | 1) HIV
    2) Heroin
    3) Obesity
40. What is the biopsy clue for FSGS? | Segmental scarring
41. What is the specific histopathology of FSGS in HIV? | Collapsing variant
42. What are the key associations (2) for Membranous Nephropathy (MN)? | 1) Hepatitis B
    2) Solid tumors
43. What is the biopsy clue for Membranous Nephropathy (MN)? | Subepithelial spikes
44. What are the key associations (2) for MPGN? | 1) Hepatitis C
    2) Cryoglobulinemia
45. What is the biopsy clue for MPGN? | Tram-track double contour
46. What are the associations (2) for IgA Nephropathy? | 1) URI
    2) SEA populations
47. What is the clinical clue for IgA Nephropathy? | Hematuria within days of infection
48. What are the associations (2) for RPGN? | 1) Vasculitis
    2) Anti-GBM
49. What is the defining biopsy clue for RPGN? | Crescents
50. What is the most common glomerulonephritis worldwide? | IgA Nephropathy
51. What defines the clinical syndrome of RPGN? | Rapid decline in GFR
52. Enumerate the triad of Alport’s Syndrome. (3) | 1) Hematuria
    2) Neurosensory hearing loss
    3) Ocular abnormalities
53. What is the most common cause of CKD in adults? | Diabetes Mellitus
54. What is the most common cause of nephrotic-range proteinuria? | Diabetes Mellitus
55. What should be suspected in older patients with renal failure and Bence-Jones proteins? | Multiple Myeloma
56. What tests (2) are used to detect Multiple Myeloma proteins? | UPEP and SPEP

IV. Chronic Kidney Disease (CKD): Staging and Pathophysiology

57. What is the GFR for CKD Stage 1? | >90
58. What is the GFR for CKD Stage 2? | 60-89
59. What is the GFR for CKD Stage 3a? | 45-59
60. What is the GFR for CKD Stage 3b? | 30-44
61. What is the GFR for CKD Stage 4? | 15-29
62. What is the GFR for CKD Stage 5? | <15
63. What is the duration requirement to define Chronic Kidney Disease (CKD)? | >3 months
64. What is the normal decline in GFR per year after the 3rd decade? | 1 mL/min
65. What nonspecific mechanisms (2) lead to nephron overwork and failure in CKD? | Hyperfiltration and Hypertrophy
66. Why is Spot UACR preferred over 24-hr urine collection? | More practical
67. What drugs (2) are the mainstay for CKD intraglomerular HTN control? | ACEi and ARBs
68. When are ACEi and ARBs contraindicated? | Acute Kidney Injury (AKI)

V. Electrolyte, Mineral, and Hematologic Complications

69. What is the cause of Hyperkalemia in Diabetes/Obstruction? | Hyporeninemic hypoaldosteronism
70. What is the role of Calcium gluconate in hyperkalemia management? | Stabilizes myocardium
71. What is the role of Insulin + Glucose in hyperkalemia management? | Shifts K into cells
72. What is the role of Inhaled Beta-agonists in hyperkalemia management? | Shifts K into cells
73. What causes Metabolic Acidosis in CKD? | Decreased Ammonia (NH3) production
74. What is the primary cause of Anemia in CKD? | Insufficient Erythropoietin (EPO) production
75. What is the target Hb range for Anemia in CKD? | 10-11.5 g/dL
76. What drives Secondary Hyperparathyroidism in CKD? (3) | 1) Phosphate retention
    2) Decreased calcitriol
    3) Hypocalcemia
77. What condition is characterized by high bone turnover and Brown Tumors? | Osteitis Fibrosa Cystica
78. What condition in advanced CKD presents with painful livedo reticularis and skin necrosis? | Calciphylaxis
79. What hormone acts as an independent risk factor for LVH and mortality in CKD? | FGF-23
80. What skin condition is linked to Gadolinium exposure in CKD patients? | Nephrogenic Systemic Fibrosis (NSF)

VI. Clinical Management and Dialysis

81. Enumerate the AEIOU mnemonic for RRT indications in AKI. | 1) Acidosis
    2) Electrolytes
    3) Intoxications
    4) Overload
    5) Uremia
82. What is an absolute indication for urgent dialysis initiation? | Uremic Pericarditis
83. What is the most common acute complication of hemodialysis? | Hypotension
84. What is the cause of Type A Dialyzer Reaction? | IgE-mediated hypersensitivity (Ethylene oxide)
85. What is the cause of Type B Dialyzer Reaction? | Complement/cytokine-mediated
86. What is the most common cause of CAPD Peritonitis? | Coagulase-negative Staphylococcus
87. What cardiac complication can AV Fistulas cause? | High-output Heart Failure

VII. High-Yield Distinctions and Comparisons

88. Compare Prerenal vs. Intrinsic AKI in terms of FENa. | Prerenal <1%; Intrinsic >1%
89. Compare Nephrotic vs. Nephritic Proteinuria by amount. | Nephrotic >3.5g/d; Nephritic often <3.5g/d
90. Contrast the effects of NSAIDs vs. ACEi/ARBs on arterioles. | NSAIDs (Afferent vasoconstriction); ACEi/ARBs (Efferent vasodilation)
91. Contrast Hepatitis B vs. Hepatitis C renal associations. | Hepatitis B (Membranous); Hepatitis C (MPGN)
92. Contrast Calcium Gluconate vs. Insulin in hyperkalemia management. | Calcium (protects heart); Insulin (lowers Serum K+)
93. Contrast Dehydration vs. Hypovolemia by water/volume loss. | Dehydration (total water); Hypovolemia (intravascular volume)
94. Contrast Type A vs. Type B Dialyzer Reactions by speed/severity. | Type A (Anaphylactic/Minutes); Type B (Nonspecific/Mild)
95. Contrast Uremic vs. Spontaneous Tumor Lysis AKI triggers. | Spontaneous (tumor burden); Standard (chemotherapy)
96. Compare Thiazide vs. Loop Diuretics in late-stage CKD. | Thiazide (loses efficacy); Loop (preferred choice)
97. Contrast 24-hour Protein vs. Spot UACR for monitoring. | 24-hour (Gold standard); Spot (Practical/Preferred)
98. Contrast Target Hb in General Population vs. CKD. | General (>12-13); CKD (10-11.5)
99. Contrast Osteitis Fibrosa Cystica vs. Adynamic Bone Disease by PTH levels. | Osteitis (High PTH); Adynamic (Very Low PTH)
100. Contrast Contrast Nephropathy vs. NSF by contrast agent used. | Contrast Nephropathy (Iodinated); NSF (Gadolinium)
101. Contrast AKI vs. CKD by time definition. | AKI (7 days); CKD (3 months)
102. What is the Low BP Prognosis in dialysis/ESRD patients vs the general population? | Worse prognosis/Higher mortality (below 140)

3.13 - Tubulointerstitial from Harrisons

Summary

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GENERAL CLASSIFICATION OVERVIEW

COMPREHENSIVE FLASHCARD BULLET POINTS

I. ACUTE INTERSTITIAL NEPHRITIS (AIN) & ETIOLOGIES

• In the context of Acute Interstitial Nephritis (AIN), the disorder is far more often encountered today as an allergic reaction to a drug rather than a postinfectious complication.
• For Allergic Interstitial Nephritis, therapeutic agents associated with the condition include antibiotics (β-lactams, sulfonamides, quinolones), NSAIDs, diuretics, anticonvulsants, and proton pump inhibitors (PPIs).
• The Classic Presentation of Allergic AIN involves fever, rash, peripheral eosinophilia, and oliguric AKI occurring 7–10 days after starting methicillin or other β-lactams, though this is the exception, not the rule.
• In NSAID-induced AIN, fever, rash, and eosinophilia are rare, but acute kidney injury with heavy (nephrotic-range) proteinuria is common.
• A particularly severe and rapid-onset Acute Interstitial Nephritis (AIN) may occur specifically upon the reintroduction of rifampin after a drug-free period.
• For Diagnosis of AIN, peripheral blood eosinophilia is a supportive finding but is present in only a minority of patients.
• Within the Urinalysis of AIN, findings typically reveal pyuria with white blood cell casts and hematuria; however, urinary eosinophils are neither sensitive nor specific and are not recommended for testing.
• The primary treatment for Allergic Interstitial Nephritis is the discontinuation of the offending agent, which often leads to reversal of the injury.
• In Glucocorticoid Therapy for AIN, use is reserved for severe kidney injury where dialysis is imminent or if kidney function fails to improve after stopping the drug; delaying steroids once dialysis is indicated leads to worse outcomes.

II. AUTOIMMUNE & SYSTEMIC TUBULOINTERSTITIAL DISORDERS

• The Most Common Renal Manifestation of Sjögren's Syndrome is tubulointerstitial nephritis with a predominant lymphocytic infiltrate, which may cause distal RTA or nephrogenic diabetes insipidus.
• The hallmark feature of Tubulointerstitial Nephritis with Uveitis (TINU) is a painful anterior uveitis (bilateral, blurred vision, photophobia) accompanying a lymphocyte-predominant AIN.
• Tubulointerstitial Nephritis with Uveitis (TINU) occurs in females three times more often than males, has a median age of 15, and features sterile pyuria and Fanconi's syndrome features.
• In Systemic Lupus Erythematosus (SLE), tubulointerstitial inflammation usually accompanies class III or IV lupus nephritis, but may occasionally manifest alone with azotemia and Type IV RTA.
• Granulomatous Interstitial Nephritis biopsy reveals a chronic inflammatory infiltrate with granulomas and giant cells; it is often idiopathic or associated with sarcoidosis or tuberculosis.
• IgG4-Related Systemic Disease presents as AIN with a dense infiltrate of IgG4-expressing plasma cells and may involve "pseudotumors," autoimmune pancreatitis, or retroperitoneal fibrosis.
• In AIN associated with Immune Checkpoint Inhibitors, kidney impact occurs in 2-5% of cases, usually within 15 weeks of therapy; treatment involves corticosteroids and stopping inciting drugs like PPIs or NSAIDs.
• Infection-Associated AIN is most commonly seen in immunocompromised patients (e.g., kidney transplant recipients) due to reactivation of Polyomavirus BK.
• A significant increase in Acute TIN or TINU has been noted in Children following SARS-CoV-2 infection.

III. ACUTE OBSTRUCTIVE DISORDERS & CRYSTAL NEPHROPATHIES

• Acute Urate Nephropathy causes oliguric AKI due to intratubular obstruction by uric acid crystals, typically following Tumor Lysis Syndrome in lympho- or myeloproliferative disorders.
• The treatment for Acute Urate Nephropathy once oliguria develops usually requires emergent hemodialysis or Rasburicase (recombinant urate oxidase) to lower uric acid levels.
• Acute Phosphate Nephropathy is a serious complication of oral Phosphosoda used for colonoscopy preparation, resulting in calcium phosphate crystal deposition in those with hypovolemia.
• Light Chain Cast Nephropathy (Myeloma Kidney) occurs when filtered monoclonal Bence-Jones proteins form aggregates with Tamm-Horsfall protein in the distal tubule, causing obstruction and a giant cell reaction.
• A clinical clue for Light Chain Cast Nephropathy is a negative urinary dipstick (which detects albumin) but high total protein on a spot urine specimen (due to light chains).
• In Crystal-induced AKI from Drugs, medications like Acyclovir (needle-shaped crystals), Indinavir, or Sulfadiazine precipitate in tubules during hypovolemia; this is reversible with saline repletion.

IV. CHRONIC TUBULOINTERSTITIAL DISEASES (CIN)

• Reflux Nephropathy (formerly "Chronic Pyelonephritis") is the consequence of vesicoureteral reflux (VUR) in early childhood, leading to patchy interstitial scarring and secondary FSGS.
• The classic imaging finding for Reflux Nephropathy on ultrasound is small, asymmetric kidneys with irregular outlines and thinned cortices over clubbed calyces.
• In Sickle Cell Nephropathy, the most common early signs are polyuria (impaired concentrating ability) and Type IV RTA; papillary necrosis may present as gross hematuria.
• Analgesic Nephropathy results from long-term use of compound preparations (phenacetin, aspirin, caffeine) and is characterized by papillary necrosis and small, scarred kidneys with calcifications.
• Aristolochic Acid Nephropathy (AAN), which includes "Chinese Herbal Nephropathy" and "Balkan Endemic Nephropathy," is a CIN associated with a very high incidence of upper urinary tract urothelial cancers.
• Lithium-Associated Nephropathy most commonly presents as Nephrogenic Diabetes Insipidus (polyuria/polydipsia) due to ENaC-mediated entry into collecting duct cells and downregulation of aquaporin.
• On Lithium-Associated Nephropathy Biopsy, a highly characteristic finding is small cysts or dilation of the distal tubule and collecting duct.
• Calcineurin Inhibitor (CNI) Nephrotoxicity (Cyclosporine/Tacrolimus) shows a "striped" pattern of patchy interstitial fibrosis and tubular hyalinosis on biopsy.
• The Triad of "Saturnine Gout" consists of hypertension, hyperuricemia (due to lead-induced urate secretion failure), and impaired kidney function associated with Lead Nephropathy.
• In Hypercalcemic Nephropathy, the earliest lesion is a focal degeneration in the collecting ducts, and the most striking clinical defect is an inability to maximally concentrate urine.
• Hypokalemic Nephropathy (from chronic laxative abuse or vomiting) is characterized histologically by vacuolar degeneration of proximal and distal tubular cells.

COMPARISON POINTS FOR EXAM DIFFERENTIATION

1. Beta-Lactam AIN vs. NSAID-induced AIN: Beta-lactam AIN typically presents with the systemic triad (fever, rash, eosinophilia) and mild proteinuria, while NSAID-induced AIN usually lacks systemic symptoms but presents with nephrotic-range proteinuria.
2. Acute TIN vs. Chronic TIN (Urinalysis): Acute TIN features an active sediment (leukocytes and WBC casts), whereas Chronic TIN usually presents with a bland sediment and features of tubular dysfunction (glycosuria, bicarbonaturia).
3. Type II RTA vs. Type IV RTA: Type II (Proximal) RTA is part of Fanconi's syndrome (bicarbonaturia); Type IV RTA features hyperkalemia and impaired ammoniagenesis and is common in SLE or Sickle Cell.
4. Light Chain Cast Nephropathy vs. Glomerular Amyloidosis: Myeloma Kidney (LCCN) presents with a negative dipstick but positive sulfosalicylic acid test for protein; Amyloidosis (glomerular) would be dipstick-positive for high albumin.
5. Acute Urate Nephropathy vs. Gouty Nephropathy (CIN): Acute Urate Nephropathy is a sudden tubular obstruction (Tumor Lysis); Gouty Nephropathy is a chronic medullary fibrosis due to monosodium urate deposits over years.
6. TINU vs. Sjögren's Syndrome: TINU is classically seen in adolescents with painful uveitis; Sjögren's is seen in middle-aged women with sicca symptoms (dry eyes/mouth) and anti-Ro/La antibodies.
7. Reflux Nephropathy Imaging vs. Analgesic Nephropathy Imaging: Reflux Nephropathy shows asymmetric scarring at the poles over clubbed calyces; Analgesic Nephropathy shows bilateral small kidneys with papillary calcifications ("ring sign").
8. Lead Nephropathy vs. Other CIN: Lead Nephropathy is uniquely associated with "Saturnine Gout" (hyperuricemia out of proportion to GFR) and exposure to moonshine or batteries.
9. Lithium Nehpropathy vs. CNI Nephrotoxicity: Lithium causes distal tubular/collecting duct cysts and diabetes insipidus; CNIs cause a "striped" fibrosis and arteriolar hyalinosis.
10. Urine Bence-Jones Protein vs. Albumin: Standard dipsticks ONLY detect Albumin; they will miss the light chains found in Multiple Myeloma.
11. Hypercalcemia vs. Hypokalemia (Pathology): Hypercalcemia causes nephrocalcinosis and collecting duct injury; Hypokalemia causes pathognomonic vacuolar degeneration of proximal tubules.
12. BK Virus vs. Bacterial Pyelonephritis: BK Virus causes Tubulointerstitial Nephritis (AKI) in transplant patients; Acute Bacterial Pyelonephritis rarely causes AKI unless it is bilateral or leads to sepsis.
13. Acyclovir vs. Indinavir Crystals: Acyclovir crystals are red-green birefringent needles; Indinavir crystals are rectangular plates or "fans."
14. Balkan Endemic vs. Chinese Herbal Nephropathy: Both are now Aristolochic Acid Nephropathy (AAN); the former is from grain contamination, the latter from slimming tea/weight-loss agents.
15. Steroid Use in Allergic AIN vs. Autoimmune AIN: In Allergic AIN, steroids are relative indications (if no recovery after stopping drug); in TINU or Sarcoidosis, steroids are absolute indications.

QA

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GENERAL CLASSIFICATION OVERVIEW

1. What is the primary target of injury in Acute Tubulointerstitial Nephritis? | Tubules and interstitium.
   Relative sparing of glomeruli and vessels.
2. What is the primary target of injury in Chronic Tubulointerstitial Nephritis? | Tubules and interstitium.
   Relative sparing of glomeruli and vessels.
3. Contrast the clinical presentation of Acute vs Chronic TIN. | Acute: Acute Kidney Injury.
   Chronic: Indolent; progressive azotemia.
4. What physical symptom may occur in Acute Tubulointerstitial Nephritis due to capsular distention? | Flank pain.
5. Describe the urinary sediment in Acute Tubulointerstitial Nephritis. | Active: leukocytes, WBC casts, hematuria.
6. Describe the urinary sediment in Chronic Tubulointerstitial Nephritis. | Bland or modest proteinuria.
   Usually less than 2 grams per day.
7. What are the hallmark pathologic findings in Acute Tubulointerstitial Nephritis? | Edema and aggressive inflammatory infiltrates.
8. What are the hallmark pathologic findings in Chronic Tubulointerstitial Nephritis? | Interstitial fibrosis and tubular atrophy.
9. Describe the kidney size in Acute Tubulointerstitial Nephritis imaging. | Normal size or enlarged.
10. Describe the kidney size and appearance in Chronic Tubulointerstitial Nephritis imaging. | Small/shrunken; cortical scarring.
11. What happens to corticomedullary differentiation in Chronic Tubulointerstitial Nephritis? | Loss of differentiation.

I. ACUTE INTERSTITIAL NEPHRITIS (AIN) & ETIOLOGIES

12. What is the most common cause of Acute Interstitial Nephritis (AIN) today? | Allergic reaction to a drug.
13. Enumerate therapeutic agent classes associated with Allergic Interstitial Nephritis. (6) | 1) Antibiotics
    2) NSAIDs
    3) Diuretics
    4) Anticonvulsants
    5) Proton pump inhibitors
    6) Rifampin
14. What are the Classic Triad symptoms of Allergic AIN? | Fever, Rash, and Eosinophilia.
15. How long after starting methicillin does the classic AIN presentation usually occur? | 7 to 10 days.
16. How does the presentation of NSAID-induced AIN differ from the classic presentation? | Fever, rash, eosinophilia are rare.
17. What level of proteinuria is common in NSAID-induced AIN? | Heavy (nephrotic-range) proteinuria.
18. Which drug causes severe AIN specifically upon reintroduction after a drug-free period? | Rifampin.
19. Is peripheral eosinophilia required for a diagnosis of AIN? | No.
    Present in only a minority of patients.
20. What specific urinary cast is found in Acute Interstitial Nephritis? | White blood cell casts.
21. Are urinary eosinophils recommended for testing AIN? | No.
    Neither sensitive nor specific.
22. What is the primary treatment for Allergic Interstitial Nephritis? | Discontinuation of offending agent.
23. When is Glucocorticoid Therapy reserved for use in AIN? | Severe kidney injury/imminent dialysis.
24. What is the consequence of delaying steroids in AIN once dialysis is indicated? | Worse outcomes.

II. AUTOIMMUNE & SYSTEMIC TUBULOINTERSTITIAL DISORDERS

25. What is the most common renal manifestation of Sjögren's Syndrome? | Tubulointerstitial nephritis.
26. What type of infiltrate is predominant in Sjögren's Syndrome AIN? | Lymphocytic infiltrate.
27. List two tubular functions impaired by Sjögren's Syndrome. | Distal RTA; nephrogenic diabetes insipidus.
28. What is the hallmark feature of Tubulointerstitial Nephritis with Uveitis (TINU)? | Painful anterior uveitis.
29. Describe the uveitis in TINU syndrome. | Bilateral; blurred vision; photophobia.
30. What is the median age and gender predilection for TINU? | Median age 15; females (3:1).
31. What urinary finding and syndrome are associated with TINU? | Sterile pyuria; Fanconi's syndrome.
32. In Systemic Lupus Erythematosus, which RTA type is commonly seen with tubulointerstitial inflammation? | Type IV RTA.
33. What characterizes a biopsy of Granulomatous Interstitial Nephritis? | Granulomas and giant cells.
34. List two systemic diseases associated with Granulomatous Interstitial Nephritis. | Sarcoidosis or tuberculosis.
35. What is the pathognomonic biopsy finding in IgG4-Related Systemic Disease? | IgG4-expressing plasma cells.
36. List three systemic involvements of IgG4-Related Systemic Disease. | Pseudotumors; autoimmune pancreatitis; retroperitoneal fibrosis.
37. What is the incidence and timing of AIN in Immune Checkpoint Inhibitor therapy? | 2-5%; usually within 15 weeks.
38. What is the most common cause of Infection-Associated AIN in transplant recipients? | Polyomavirus BK reactivation.
39. Which recent viral infection is linked to an increase in Acute TIN or TINU in children? | SARS-CoV-2.

III. ACUTE OBSTRUCTIVE DISORDERS & CRYSTAL NEPHROPATHIES

40. What is the mechanism of AKI in Acute Urate Nephropathy? | Intratubular obstruction by crystals.
41. Acute Urate Nephropathy typically follows which oncologic complication? | Tumor Lysis Syndrome.
42. Enumerate treatments (2) for Acute Urate Nephropathy once oliguria develops. | Hemodialysis or Rasburicase.
43. What is the cause of Acute Phosphate Nephropathy? | Oral Phosphosoda for colonoscopy.
44. Name the two proteins that aggregate to cause Light Chain Cast Nephropathy. | Bence-Jones protein and Tamm-Horsfall protein.
45. Where in the nephron does the obstruction occur in Myeloma Kidney? | Distal tubule.
46. Contrast dipstick vs spot urine protein in Light Chain Cast Nephropathy. | Dipstick-negative; high total spot protein.
47. Why is the urinary dipstick negative in Multiple Myeloma? | It detects albumin, not light chains.
48. What is the appearance of Acyclovir crystals? | Needle-shaped crystals.
49. What physical state precipitates Crystal-induced AKI from Indinavir or Sulfadiazine? | Hypovolemia.
50. How is Drug-induced crystal AKI reversed? | Saline repletion.

IV. CHRONIC TUBULOINTERSTITIAL DISEASES (CIN)

51. What is the cause of Reflux Nephropathy? | Vesicoureteral reflux (VUR) in childhood.
52. Reflux nephropathy leads to which secondary glomerular lesion? | Secondary FSGS.
53. Describe the ultrasound findings (3) for Reflux Nephropathy. | 1) Small asymmetric kidneys
    2) Thinned cortices
    3) Clubbed calyces.
54. What are the common early signs of Sickle Cell Nephropathy? | Polyuria and Type IV RTA.
55. How does Papillary Necrosis manifest clinically in Sickle Cell patients? | Gross hematuria.
56. What compound agents cause Analgesic Nephropathy? | Phenacetin, aspirin, and caffeine.
57. What imaging findings (2) characterize Analgesic Nephropathy? | Papillary necrosis and calcifications.
58. What cancer is highly associated with Aristolochic Acid Nephropathy (AAN)? | Upper urinary tract urothelial cancer.
59. Name two historical names for Aristolochic Acid Nephropathy. | Chinese Herbal and Balkan Endemic Nephropathy.
60. What clinical condition is caused by Lithium-Associated Nephropathy? | Nephrogenic Diabetes Insipidus.
61. What is the mechanism of Lithium entry into collecting duct cells? | ENaC-mediated entry.
62. What is the characteristic biopsy finding for Lithium toxicity? | Small cysts or distal tubular dilation.
63. Describe the biopsy pattern in Calcineurin Inhibitor Nephrotoxicity. | "Striped" pattern of interstitial fibrosis.
64. Enumerate the triad of Saturnine Gout. | 1) Hypertension
    2) Hyperuricemia
    3) Impaired kidney function.
65. What causes the hyperuricemia in Lead Nephropathy? | Failure of lead-induced urate secretion.
66. Where is the earliest lesion in Hypercalcemic Nephropathy? | Collecting ducts.
67. What is the most striking clinical defect in Hypercalcemia? | Inability to maximally concentrate urine.
68. What histological finding is pathognomonic for Hypokalemic Nephropathy? | Vacuolar degeneration.

V. COMPARISON POINTS FOR EXAM DIFFERENTIATION

69. Compare Beta-Lactam vs NSAID AIN regarding systemic symptoms. | Beta-Lactam: Common (triad).
    NSAID: Rare.
70. Compare Beta-Lactam vs NSAID AIN regarding protein levels. | Beta-Lactam: Mild proteinuria.
    NSAID: Nephrotic-range proteinuria.
71. Compare Acute vs Chronic TIN sediment. | Acute: Active (leukocytes/casts).
    Chronic: Bland.
72. What are the signs of tubular dysfunction in Chronic TIN sediment? | Glycosuria and bicarbonaturia.
73. Contrast Type II vs Type IV RTA features. | Type II: Bicarbonaturia (Fanconi).
    Type IV: Hyperkalemia.
74. Which condition presents with a positive Sulfosalicylic acid test but negative dipstick? | Light Chain Cast Nephropathy.
75. Contrast Amyloidosis vs Myeloma Kidney on dipstick. | Amyloidosis: Dipstick positive (albumin).
    LCCN: Dipstick negative.
76. Contrast Acute Urate vs Gouty Nephropathy mechanism. | Acute: Tubular obstruction.
    Gouty: Chronic medullary fibrosis.
77. Contrast TINU vs Sjögren's Syndrome demographics. | TINU: Adolescents.
    Sjögren's: Middle-aged women.
78. What antibodies characterize Sjögren's Syndrome? | Anti-Ro and Anti-La antibodies.
79. Contrast Reflux vs Analgesic Nephropathy scarring. | Reflux: Asymmetric polar scarring.
    Analgesic: Bilateral small kidneys.
80. What is the "ring sign" on imaging indicative of? | Analgesic Nephropathy (papillary calcifications).
81. Which CIN is associated with exposure to Moonshine or batteries? | Lead Nephropathy.
82. Contrast Lithium vs CNI biopsy features. | Lithium: Distal cysts.
    CNI: Striped fibrosis.
83. Does a standard dipstick detect Bence-Jones proteins? | No.
    Detects Albumin only.
84. Contrast Hypercalcemia vs Hypokalemia pathology. | Hypercalcemia: Nephrocalcinosis.
    Hypokalemia: Vacuolar degeneration.
85. Contrast BK Virus vs Bacterial Pyelonephritis in AKI. | BK Virus: Causes AKI.
    Bacteria: Rarely causes AKI unless sepsis.
86. What is the birefringence of Acyclovir crystals? | Red-green birefringent.
87. Describe Indinavir crystals shape. | Rectangular plates or "fans."
88. What is the common cause of Balkan Endemic Nephropathy? | Aristolochic Acid (grain contamination).
89. Contrast Allergic vs Autoimmune AIN steroid indication. | Allergic: Relative indication.
    Autoimmune: Absolute indication.
90. Which RTA is associated with Sickle Cell or SLE? | Type IV RTA.
91. What is the primary cause of Chinese Herbal Nephropathy? | Aristolochic Acid (slimming tea/weight-loss).
92. Define Fanconi's Syndrome in the context of TINU. | Proximal tubular dysfunction.
93. In CNI Nephrotoxicity, what vascular change is seen beside fibrosis? | Arteriolar hyalinosis.
94. When does Hyperuricemia occur in Lead Nephropathy? | Out of proportion to GFR.
95. What drug class is associated with Acute Phosphate Nephropathy? | Oral Phosphosoda.
96. Describe the location of Medullary Fibrosis in Chronic Gout. | Medullary interstitium.
97. What defines Active Sediment? | Presence of WBCs, RBCs, and casts.
98. What denotes Indolent Progression in Chronic TIN? | Slow, asymptomatic decline in GFR.
99. What inflammatory cell is hallmark of Sjögren's renal biopsy? | Lymphocytes.
100. What is Rasburicase? | Recombinant urate oxidase.
101. What is the hallmark of Sarcoidosis on kidney biopsy? | Granulomatous Interstitial Nephritis.
102. Where does Vesicoureteral Reflux typically cause scarring? | Renal poles.
103. What causes Clubbed Calyces in chronic injury? | Chronic reflux and scarring.
104. Which condition is associated with Autoimmune Pancreatitis? | IgG4-Related Systemic Disease.
105. What is the classic timeline for Checkpoint Inhibitor AIN? | 15 weeks after therapy start.
106. Is Acyclovir AKI reversible? | Yes, with saline repletion.
107. Which drug reacts to reintroduction with rapid AKI? | Rifampin.
108. Compare AIN vs CIN kidney size on ultrasound. | AIN: Large/Normal.
     CIN: Small/Shrunken.
109. What clinical sign suggests TINU in an adolescent? | Painful uveitis + kidney injury.
110. What RTA causes Bicarbonaturia? | Type II RTA.

3.14 - Dialysis and Transplantation

Summary

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• In Acute Therapies for kidney failure, Continuous Renal Replacement Therapy (CRRT) is performed continuously, while PIRRT/SLED is performed over 6–12 hours. [Context: Kidney Failure RRT]
• Intermittent Hemodialysis (IHD) typically lasts 3–4 hours per session and is the standard for chronic maintenance. [Context: Kidney Failure RRT]
• Peritoneal Dialysis in Acute Care is rarely used in developed countries due to lower clearance efficiency and higher infection risks compared to HD. [Context: Kidney Failure RRT]
• Normal Kidney Functions include waste removal, electrolyte balance, fluid regulation, acid-base control, and hormonal production (EPO and Vit D). [Context: Renal Physiology]
• Metabolic Acidosis in moderately advanced CKD (Stage 3A) starts as non-ionic gap metabolic acidosis and progresses to ionic gap metabolic acidosis as the disease advances. [Context: CKD Clinical Features]
• Erythropoietin (EPO) is secreted by peritubular capillaries of the proximal tubular cells; deficiency in advanced CKD leads to anemia. [Context: Renal Physiology]
• Vitamin D Activation is a kidney function where Vitamin D2 is converted to D3 (the active form). [Context: Renal Physiology]
• Renal Replacement Therapy (RRT) is indicated when GFR falls to <10-15 ml/min and the patient becomes symptomatically uremic. [Context: RRT Indications]

• Hemodialysis (HD) only addresses the waste removal function of the kidney, which is why patients may still have hormonal or bone complications. [Context: HD Mechanism]
• Diffusion is the movement of solutes from high to lower concentration across a semipermeable membrane; it is the primary mechanism for urea and creatinine removal. [Context: HD Principles]
• Convection occurs when a pressure gradient forces water across a membrane, dragging dissolved solutes along with it (solvent drag). [Context: HD Principles]
• Ultrafiltration (UF) is the process of fluid removal achieved through negative hydrostatic pressure on the dialysate side. [Context: HD Principles]
• Urea (60 Da) is a small molecule that undergoes substantial clearance during HD, whereas Creatinine (113 Da) is larger and cleared less efficiently. [Context: HD Principles]
• Dialysate Potassium usually ranges from 0–4 mmol/L; using very low levels carries the risk of arrhythmia and sudden death. [Context: HD Components]
• Dialysate Sodium is typically 135–140 mmol/L; "Sodium modeling" (starting high at 145-155) helps prevent hypotension but may increase thirst and weight gain. [Context: HD Components]
• Water Treatment for dialysate involves filtration, softening, deionization, and reverse osmosis to remove contaminants from the ~120L of water used per session. [Context: HD Components]
• Criteria for Initiating Maintenance Dialysis includes uremic symptoms (nausea, encephalopathy), refractory hyperkalemia, persistent fluid overload, or GFR <10 mL/min per 1.73 m². [Context: HD Indications]
• Refractory Pulmonary Edema is an absolute indication for dialysis when the patient does not respond to diuretics. [Context: HD Indications]

• Arteriovenous (AV) Fistula is the "lifeline" and preferred access due to having the lowest infection risk and highest long-term patency. [Context: HD Access]
• Arterialization refers to the process where an AV fistula causes a vein to increase in diameter and pressure, allowing the use of large 15-16 gauge needles. [Context: HD Access]
• Arteriovenous (AV) Graft uses prosthetic material (PTFE) between an artery and vein; its main complication is thrombosis due to intimal hyperplasia. [Context: HD Access]
• Tunneled Hemodialysis Catheters are preferred in the Internal Jugular vein and are tunneled under skin to reduce bacterial translocation. [Context: HD Access]
• Subclavian Catheters should be avoided to prevent subclavian stenosis, which can prohibit future permanent access in that arm. [Context: HD Access]

• Intradialytic Hypotension (IDH) is defined as a decrease in SBP $\ge$ 20 mmHg or MAP drop $\ge$ 10 mmHg during dialysis. [Context: HD Complications]
• Risk Factors for IDH include elderly age, DM neuropathy, heart failure, sepsis, and high ultrafiltration (UF) rates (>10-13 ml/kg/hr). [Context: IDH Risk]
• Post-prandial Hypotension occurs because eating during dialysis causes splanchnic vasodilation, reducing systemic vascular resistance. [Context: IDH Risk]
• IDH Management includes stopping ultrafiltration, placing the patient in Trendelenburg position, and giving a 100-200 ml NSS bolus. [Context: IDH Management]
• Midodrine is an alpha-1 agonist that can be given before dialysis to prevent hypotension by increasing systemic vascular resistance. [Context: IDH Prevention]
• Disequilibrium Syndrome (DDS) is a neurologic syndrome caused by rapid osmotic shifts leading to cerebral edema, typically during the first dialysis when BUN is very high (>100). [Context: HD Complications]
• DDS Pathophysiology involves dialysis removing urea rapidly from blood, creating an osmotic gradient that pulls water into the brain because urea crosses the blood-brain barrier slowly. [Context: HD Complications]
• Mannitol can be used in patients at high risk for DDS to raise plasma osmolality and pull water out of the brain. [Context: DDS Management]
• B2-microglobulin Amyloidosis is a long-term complication (>5-7 years) where MHC Class 1 components deposit in tissues, classically presenting as Carpal Tunnel Syndrome. [Context: HD Chronic Complications]
• Dialyzer Reaction Type A is an IgE-mediated hypersensitivity to ethylene oxide (sterilization) occurring within the first few minutes, potentially leading to anaphylaxis. [Context: HD Complications]
• Dialyzer Reaction Type B involves complement activation, causing nonspecific chest or back pain several minutes into dialysis. [Context: HD Complications]

• Peritoneal Dialysis (PD) is the preferred modality for patients with severe heart failure due to better fluid control and hemodynamic stability. [Context: PD Indications]
• Continuous Ambulatory Peritoneal Dialysis (CAPD) involves manual exchanges (3-5 per day) and requires no machine. [Context: PD Types]
• Automated Peritoneal Dialysis (APD) uses a machine called a cycler, usually performed overnight. [Context: PD Types]
• Peritonitis is the most common PD complication, diagnosed by cloudy dialysate, abdominal pain, fever, and dialysate WBC >100/uL with >50% PMNs. [Context: PD Complications]
• Metabolic Complications of PD include hyperglycemia and weight gain due to absorption of the glucose used in the dialysate. [Context: PD Complications]
• Encapsulating Peritoneal Sclerosis is a rare but severe long-term PD complication where the peritoneal membrane becomes fibrosed. [Context: PD Complications]
• PD Diet is generally more liberal regarding potassium and phosphorus compared to HD because the dialysis is continuous. [Context: PD vs. HD]
• PD Contraindications include absolute (Loss of membrane function, extensive adhesions) and relative (Recurrent abdominal infections, large hernias, severe malnutrition). [Context: PD Contraindications]

• Kidney Transplantation is the treatment of choice for ESKD, providing the best survival and Quality of Life. [Context: Transplant Overview]
• ABO Incompatibility results in hyperacute rejection within minutes to hours because ABO antigens are expressed on the vascular endothelium of kidney grafts. [Context: Transplant Typing]
• HLA Matching focusing on A, B, and DR loci is key to long-term allograft survival and reducing rejection risk. [Context: Transplant Typing]
• HLA Class I (A, B, C) is found on all nucleated cells and presents to CD8+ T cells; it is critical in acute rejection. [Context: Transplant Immunology]
• HLA Class II (DR, DQ, DP) is found on APCs and presents to CD4+ T cells; mismatch often contributes to chronic rejection. [Context: Transplant Immunology]
• Panel Reactive Antibody (PRA) measures the percentage of the general donor population a recipient is sensitized against; a high PRA makes finding a donor difficult. [Context: Transplant Typing]
• Crossmatch Test is positive if recipient antibodies exist against donor lymphocytes; a positive result is a contraindication to transplantation with that donor. [Context: Transplant Typing]

• Hyperacute Rejection occurs within minutes on the operating table due to preformed antibodies activation of complement. [Context: Rejection Types]
• Acute T-cell-mediated Rejection features tubulitis and interstitial infiltrates on histology and is treated with high-dose steroids (Methylprednisolone). [Context: Rejection Management]
• Antibody-mediated Rejection (AMR) features C4d deposition in peritubular capillaries and donor-specific antibodies (DSA). [Context: Rejection Types]
• Tacrolimus is a Calcineurin Inhibitor (CNI) used for maintenance; common side effects include nephrotoxicity, hair loss, and Post-Transplant Diabetes (NODAT). [Context: Immunosuppression]
• mTOR Inhibitors (Sirolimus/Everolimus) are used in patients with a history of malignancy but are avoided in the immediate post-op period due to poor wound healing. [Context: Immunosuppression]
• Azathioprine can cause severe myelosuppression in patients with TPMT deficiency and should not be used with Allopurinol. [Context: Immunosuppression]
• Belatacept is a monthly IV infusion that blocks CD28 costimulation; it has a higher risk of acute rejection but better long-term survival compared to CNIs. [Context: Immunosuppression]

• Cardiovascular Events are the leading cause of death (29%) in kidney transplant recipients. [Context: Transplant Complications]
• Cytomegalovirus (CMV) risk is highest in a seronegative recipient receiving a seropositive donor kidney; managed with Valganciclovir. [Context: Transplant Infection]
• BK Virus Nephropathy is caused by reactivation of the virus under immunosuppression and presents as progressive graft loss; managed by reducing immunosuppression. [Context: Transplant Infection]
• Pneumocystis jirovecii prophylaxis is classically provided by low-dose TMP-SMX daily for 6 months post-transplant. [Context: Transplant Infection]
• Post-transplant lymphoproliferative disease (PTLD) is often associated with the Epstein-Barr virus (EBV) and carries a poor prognosis. [Context: Transplant Complications]
• Skin and Lip Cancers are 100x more common in transplant recipients; lifelong UV protection and surveillance are required. [Context: Transplant Complications]

• Hemodialysis uses a machine and blood pump with high flows, risking hypotension, whereas Peritoneal Dialysis uses gravity/osmosis and is hemodynamically gentler.
• AV Fistula is a direct connection of native artery and vein (longest patency), whereas AV Graft uses synthetic tubing (higher thrombosis risk).
• Dialyzer Reaction Type A is an anaphylactic IgE reaction (immediate), whereas Type B is complement-mediated and manifests as chest/back pain (delayed).
• Disequilibrium Syndrome results from rapid urea removal (osmotic shift to brain), whereas IDH results from rapid fluid/water removal (intravascular depletion).
• Diffusion is solute-specific movement down a gradient, whereas Convection is non-selective "solvent drag" where water movement pulls all solutes.
• Hyperacute Rejection (minutes) is due to pre-existing antibodies (Type II hypersensitivity), while Acute Rejection (weeks) is usually T-cell mediated (Type IV hypersensitivity).
• HLA Class I antigens (A, B) activate CD8+ T cells (Cytotoxic), while HLA Class II (DR) antigens activate CD4+ T cells (Helper).
• Crossmatch identifies antibodies against a specific donor, whereas PRA identifies antibodies against the general population.
• Basiliximab is a non-depleting IL-2 blocker (prophylactic only), while Antithymocyte Globulin (ATG) is a depleting agent that wipes out T cells.
• Cyclosporine side effects include hirsutism and gingival hyperplasia, whereas Tacrolimus leads to hair loss and a higher incidence of NODAT.
• High-flux dialyzers have larger pores and can remove $\beta_2$-microglobulin, while Low-flux dialyzers cannot.
• CAPD is a manual PD exchange done by the patient at home, while APD uses an automated machine (cycler) usually at night.
• Midodrine is used to treat/prevent hypotension (alpha-1 agonist), while Mannitol is used to prevent DDS by maintaining plasma osmolality.
• Absolute Contraindication for PD includes loss of membrane function or adhesions, whereas Relative Contraindication includes hernias or malnutrition.
• Urea is the marker molecule for HD efficiency (60 Da), while $\beta_2$-microglobulin is the marker for middle-molecule (amyloid) clearance.

QA

text

1. What is the pathogenesis of End-Stage Kidney Disease (ESKD)? | Progressive loss of nephron function
   Most commonly due to chronic conditions.
2. What are the two leading causes of Kidney Failure? (2) | 1) Diabetes Mellitus (45%)
   2) Hypertension (30%)
3. Besides Diabetes and Hypertension, name three other causes of Kidney Failure. (3) | 1) Glomerulonephritis
   2) Polycystic kidney disease
   3) Obstructive uropathy
4. At what GFR level is Renal Replacement Therapy (RRT) typically indicated? | <10–15 mL/min
   When accompanied by symptomatic uremia or refractory complications.
5. In Acute Therapies for kidney failure, how is Continuous Renal Replacement Therapy (CRRT) performed? | Continuously
6. How long is a session of PIRRT/SLED in acute kidney failure therapy? | 6–12 hours
7. What is the standard duration for a session of Intermittent Hemodialysis (IHD)? | 3–4 hours
   Used for chronic maintenance.
8. Why is Peritoneal Dialysis rarely used in acute care in developed countries? | Lower clearance efficiency
   Also carries higher infection risks compared to Hemodialysis.
9. Enumerate the five primary functions of Normal Kidneys. (5) | 1) Waste removal
   2) Electrolyte balance
   3) Fluid regulation
   4) Acid-base control
   5) Hormonal production
10. Describe the progression of Metabolic Acidosis in CKD Stage 3A. | Non-ionic gap to ionic gap
    Starts as non-ionic and progresses as the disease advances.
11. Which cells secrete Erythropoietin (EPO)? | Peritubular capillaries
    Located in the proximal tubular cells.
12. What clinical condition results from Erythropoietin (EPO) deficiency in advanced CKD? | Anemia
13. Describe the process of Vitamin D Activation in the kidney. | Conversion of D2 to D3
    D3 is the active form of Vitamin D.
14. When should Renal Replacement Therapy (RRT) be initiated based on symptoms? | Symptomatic uremia
    Usually when GFR falls to <10-15 ml/min.
15. What are the Absolute Indications (AEIOU) for initiating dialysis? (5) | 1) Acidosis
    2) Electrolytes
    3) Intoxications
    4) Overload
    5) Uremia
16. In the AEIOU criteria for dialysis, what defines Acidosis? | Refractory pH <7.1
17. In the AEIOU criteria for dialysis, what defines Electrolyte imbalance? | K >6.5 or ECG changes
18. Name two common types of Intoxications that serve as absolute indications for dialysis. (2) | 1) Lithium
    2) Ethylene glycol
19. In the AEIOU criteria for dialysis, what defines Overload? | Refractory pulmonary edema
20. Enumerate the three primary mechanisms of Dialysis. (3) | 1) Diffusion
    2) Convection
    3) Ultrafiltration
21. What are the three key components of a Hemodialysis Blood Delivery System? (3) | 1) Dialyzer
    2) Dialysate
    3) Blood delivery system
22. Which kidney function is exclusively addressed by Hemodialysis (HD)? | Waste removal
    Patients may still have hormonal or bone complications.
23. Define Diffusion in the context of Hemodialysis. | Solute movement by concentration
    Movement from high to lower concentration across a semipermeable membrane.
24. Which two substances are primarily removed via Diffusion during dialysis? | Urea and Creatinine
25. Define Convection in the context of Hemodialysis. | Solvent drag
    Pressure gradient forces water across a membrane, dragging dissolved solutes.
26. Define Ultrafiltration (UF) in the context of Hemodialysis. | Fluid removal
    Achieved through negative hydrostatic pressure on the dialysate side.
27. Compare the clearance efficiency of Urea (60 Da) vs. Creatinine (113 Da) in HD. | Urea is cleared more efficiently
    Urea is smaller; Creatinine is larger and cleared less efficiently.
28. What is the typical Dialysate Potassium range and the risk of using very low levels? | 0–4 mmol/L
    Risk of arrhythmia and sudden death.
29. What is Sodium Modeling in Dialysate and why is it used? | Starting sodium at 145-155
    Helps prevent hypotension but may increase thirst/weight gain.
30. What is the typical concentration of Dialysate Sodium? | 135–140 mmol/L
31. Enumerate the processes involved in Water Treatment for dialysate. (4) | 1) Filtration
    2) Softening
    3) Deionization
    4) Reverse osmosis
32. Approximately how many liters of water are used per Hemodialysis session? | 120 Liters
33. What are the uremic symptoms considered Criteria for Initiating Maintenance Dialysis? | Nausea and Encephalopathy
34. Name three refractory conditions that act as Criteria for Maintenance Dialysis. (3) | 1) Hyperkalemia
    2) Fluid overload
    3) GFR <10 mL/min
35. When is Pulmonary Edema considered an absolute indication for dialysis? | Refractory to diuretics
36. What is the preferred vascular access for Hemodialysis? | Arteriovenous (AV) Fistula
    Brescia-Cimino is the common type.
37. What is the secondary vascular access choice for Hemodialysis? | Arteriovenous (AV) Graft
    Made of synthetic material.
38. What is used as tertiary/temporary access for Hemodialysis? | Central Venous Catheters
    Can be tunneled or untunneled.
39. Why is an Arteriovenous (AV) Fistula considered the "lifeline" of the patient? | Lowest infection risk
    Also provides the highest long-term patency.
40. Define Arterialization in the context of an AV Fistula. | Vein increases in diameter/pressure
    Allows the use of large 15-16 gauge needles.
41. What material is used in an AV Graft and what is its main complication? | PTFE (Prosthetic material)
    Thrombosis due to intimal hyperplasia.
42. Where is a Tunneled Hemodialysis Catheter preferably placed? | Internal Jugular vein
    Tunneled under skin to reduce bacterial translocation.
43. Why should Subclavian Catheters be avoided in dialysis patients? | Prevent subclavian stenosis
    Stenosis can prohibit future permanent access in that arm.
44. What is the most common acute complication of Hemodialysis? | Intradialytic Hypotension (IDH)
45. What is the defining criteria for Intradialytic Hypotension (IDH)? | SBP reduction ≥ 20 mmHg
    Or a MAP drop ≥ 10 mmHg during dialysis.
46. Enumerate 4 risk factors for Intradialytic Hypotension (IDH). (4) | 1) Elderly age
    2) DM neuropathy
    3) Heart failure/Sepsis
    4) High UF rates (>10-13 ml/kg/hr)
47. Why does eating cause Post-prandial Hypotension during dialysis? | Splanchnic vasodilation
    Reduces systemic vascular resistance.
48. What are the immediate management steps for IDH? (3) | 1) Stop ultrafiltration
    2) Trendelenburg position
    3) 100-200 ml NSS bolus
49. What is the mechanism and use of Midodrine in dialysis patients? | Alpha-1 agonist
    Given before HD to prevent hypotension by increasing SVR.
50. What is Disequilibrium Syndrome (DDS) and when does it occur? | Neurologic syndrome
    Occurs during first dialysis when BUN is very high (>100).
51. Describe the pathophysiology of Disequilibrium Syndrome (DDS). | Rapid urea removal
    Creates osmotic gradient pulling water into brain; urea crosses BBB slowly.
52. How is Mannitol used in patients at risk for DDS? | Raises plasma osmolality
    Pulls water out of the brain.
53. What is the cause and presentation of $\beta_2$-microglobulin Amyloidosis? | MHC Class 1 deposition
    Classically presents as Carpal Tunnel Syndrome (>5-7 years).
54. Describe Dialyzer Reaction Type A. | IgE-mediated hypersensitivity
    Reaction to ethylene oxide; occurs within minutes; possible anaphylaxis.
55. Describe Dialyzer Reaction Type B. | Complement activation
    Causes nonspecific chest or back pain several minutes into dialysis.
56. What acts as the semi-permeable membrane in Peritoneal Dialysis (PD)? | Peritoneal membrane
57. Compare CAPD vs. APD in Peritoneal Dialysis. | CAPD is manual
    APD uses an automated cycler (usually overnight).
58. What is the primary Osmotic Agent used in PD? | Glucose / Dextrose
    Pulls water from capillaries.
59. What are the diagnostic criteria for Peritonitis in PD? (3) | 1) Cloudy dialysate/Abdominal pain
    2) WBC >100/uL
    3) >50% PMNs
60. Which modality is preferred for patients with Severe Heart Failure and why? | Peritoneal Dialysis
    Better fluid control and hemodynamic stability.
61. What are the metabolic complications of Peritoneal Dialysis? (2) | Hyperglycemia and weight gain
    Due to absorption of glucose from the dialysate.
62. What is Encapsulating Peritoneal Sclerosis? | Rare fibrotic complication
    Peritoneal membrane becomes fibrosed over the long-term.
63. How does the PD Diet differ from the HD diet? | More liberal
    Regarding potassium and phosphorus because PD is continuous.
64. Enumerate absolute contraindications for Peritoneal Dialysis. (2) | 1) Loss of membrane function
    2) Extensive adhesions
65. Enumerate relative contraindications for Peritoneal Dialysis. (3) | 1) Recurrent abdominal infections
    2) Large hernias
    3) Severe malnutrition
66. What is the treatment of choice for ESKD and why? | Kidney Transplantation
    Best survival and quality of life.
67. What is the consequence of ABO Incompatibility in transplantation? | Hyperacute rejection
    Antigens are expressed on the vascular endothelium of the graft.
68. Which three loci are summarized in HLA Matching? | A, B, and DR
    Key to long-term allograft survival.
69. Where is HLA Class I (A, B, C) found and what does it present to? | All nucleated cells
    Presents to CD8+ T cells; critical in acute rejection.
70. Where is HLA Class II (DR, DQ, DP) found and what does it present to? | APCs
    Presents to CD4+ T cells; contributes to chronic rejection.
71. What does Panel Reactive Antibody (PRA) measure? | Percent sensitization
    The percentage of the general population the recipient has antibodies against.
72. What is a Crossmatch Test and what does a positive result indicate? | Recipient serum + Donor lymphocytes
    Positive means contraindication to transplant with that specific donor.
73. Describe the timing and cause of Hyperacute Rejection. | Minutes
    Preformed antibodies (ABO/Anti-HLA) activate complement.
74. Describe the timing and clinical features of Acute Rejection. | Weeks to months
    T-cell (Cellular) or B-cell (Humoral) mediated.
75. Describe the timing and clinical features of Chronic Rejection. | Years
    Gradual decline in GFR; Fibrosis/Intimal hyperplasia.
76. Enumerate two Induction Drugs used in transplant. (2) | 1) ATG (Thymocyte globulin)
    2) Basiliximab (IL-2 blocker)
77. Enumerate the three standard Maintenance Drugs in transplant. (3) | 1) CNIs (Tacro/Cyclo)
    2) Mycophenolate (MMF)
    3) Prednisone
78. What is the histological feature and treatment for Acute T-cell-mediated Rejection? | Tubulitis/interstitial infiltrates
    Treated with high-dose Methylprednisolone.
79. What characterizes Antibody-mediated Rejection (AMR) on biopsy? | C4d deposition
    Found in peritubular capillaries along with donor-specific antibodies (DSA).
80. What are the side effects of Tacrolimus? (3) | 1) Nephrotoxicity
    2) Hair loss
    3) Diabetes (NODAT)
81. Why are mTOR Inhibitors (Sirolimus) avoided in the immediate post-op period? | Poor wound healing
    Though useful for patients with a history of malignancy.
82. Azathioprine can cause severe myelosuppression in patients with which deficiency? | TPMT deficiency
    Should not be used with Allopurinol.
83. What is the mechanism and benefit of Belatacept? | Blocks CD28 costimulation
    Higher acute rejection risk but better long-term survival than CNIs.
84. What types of Infections occur in the 0–1 month post-transplant period? | Surgical-related
    Includes wound infections and UTIs.
85. What types of Infections occur in the 1–6 month post-transplant period? | Opportunistic
    Includes CMV, BK virus, and P. jirovecii.
86. What is the leading cause of death in Kidney Transplant recipients? | Cardiovascular Events (29%)
87. How is Cytomegalovirus (CMV) managed in high-risk recipients? | Valganciclovir
    Risk highest in D+/R- patients.
88. What is the management for BK Virus Nephropathy? | Reducing immunosuppression
    Presents as progressive graft loss.
89. How is Pneumocystis jirovecii prevented post-transplant? | Low-dose TMP-SMX
    Given daily for 6 months.
90. Which virus is associated with PTLD? | Epstein-Barr virus (EBV)
    Post-transplant lymphoproliferative disease.
91. How much more common are Skin and Lip Cancers in transplant recipients? | 100x more common
    Requires lifelong UV protection.
92. Compare Hemodialysis vs. Peritoneal Dialysis mechanisms and hemodynamics. | HD: Machine/Pump (Hypotension risk)
    PD: Gravity/Osmosis (Hemodynamically gentler).
93. Compare the construction of AV Fistula vs. AV Graft. | Fistula: Native artery/vein connection
    Graft: Synthetic tubing.
94. Differentiate Dialyzer Reaction Type A vs. Type B in timing and mechanism. | Type A: Immediate (Anaphylactic IgE)
    Type B: Delayed (Complement chest/back pain).
95. Compare the causes of DDS vs. IDH. | DDS: Rapid urea removal
    IDH: Rapid fluid/water removal.
96. Compare Diffusion vs. Convection solute specificity. | Diffusion: Solute-specific gradient
    Convection: Non-selective "solvent drag".
97. Compare hypersensitivity types for Hyperacute vs. Acute Rejection. | Hyperacute: Type II (Preformed antibodies)
    Acute: Type IV (T-cell mediated).
98. Compare the T-cell activation targets for HLA Class I vs. Class II. | Class I (A, B): CD8+ T cells
    Class II (DR): CD4+ T cells.
99. Compare Crossmatch vs. PRA testing targets. | Crossmatch: Specific donor
    PRA: General population.
100. Compare Basiliximab vs. ATG mechanisms. | Basiliximab: Non-depleting IL-2 blocker
     ATG: Depleting agent wipes out T cells.
101. Compare side effects of Cyclosporine vs. Tacrolimus. | Cyclo: Hirsutism/Gingival hyperplasia
     Tacro: Hair loss/NODAT.
102. Compare High-flux vs. Low-flux dialyzers regarding $\beta_2$-microglobulin. | High-flux: Removes $\beta_2$-microglobulin
     Low-flux: Cannot remove it.
103. Compare the use of Midodrine vs. Mannitol in HD. | Midodrine: Treats/prevents hypotension
     Mannitol: Prevents DDS.
104. Compare the Marker Molecules for HD efficiency vs. middle-molecule clearance. | Efficiency: Urea (60 Da)
     Middle-molecule: $\beta_2$-microglobulin.

3.15 - Glomerular Dx

Summary

GLOMERULAR DISEASES: PATHOGENESIS, PROGRESSION, AND DIAGNOSTIC APPROACH

ACUTE NEPHRITIC SYNDROMES

NEPHROTIC SYNDROMES

SPECIAL GLOMERULAR ENTITIES

DETAILED SYNDROME SPECIFICS (FLASHCARDS)

• The nephrotic syndrome is clinically defined by proteinuria >3.5 g/24 h, hypoalbuminemia <3 g/dL, edema, hyperlipidemia, and lipiduria.
• The acute nephritic syndrome features include hematuria, red blood cell casts, hypertension, and mild to moderate proteinuria (<3 g/24 h).
• In IgA Nephropathy, the "synpharyngitic" presentation refers to gross hematuria occurring simultaneously with or within 1-2 days of a respiratory infection (unlike PSGN which has a latent period).
• For Lupus Nephritis Class IV, the standard of care to balance efficacy and safety involves induction with high-dose steroids plus either mycophenolate mofetil (MMF) or cyclophosphamide.
• In Minimal Change Disease, the proteinuria is considered "selective," meaning it consists primarily of albumin rather than higher-molecular-weight proteins.
• The most common risk factor for FSGS in African Americans is the presence of high-risk APOL1 gene polymorphisms.
• The PLA2R antibody is highly specific for primary membranous nephropathy and can be used to monitor treatment response and predict relapse.
• In Alport's Syndrome, the characteristic electron microscopy finding is a "basket-weave" appearance of the basement membrane due to irregular thinning and thickening (splitting).
• The treatment for TTP involves emergent large-volume plasma exchange (plasmapheresis) to remove antibodies and provide functional ADAMTS13.
• In Diabetic Nephropathy, retinopathy is present in over 90% of Type 1 DM patients with nephropathy, making its absence a reason to consider alternative diagnoses.
• For Anti-GBM disease, serum testing must specifically target the α3 NC1 domain of collagen IV to avoid false positives from non-nephritic antibodies.
• In C3 Glomerulopathy, the "C3 Nephritic Factor" is an autoantibody that stabilizes C3 convertase, leading to continuous complement consumption.

COMPARISONS FOR EXAM DIFFERENTIATION

• PSGN vs. IgA Nephropathy: PSGN has a latent period of 1-3 weeks after infection and low C3 levels; IgA Nephropathy is "synpharyngitic" (occurs with the infection) and has normal C3 levels.
• MCD vs. FSGS: MCD shows normal glomeruli on light microscopy and is highly steroid-responsive; FSGS shows segmental scars and is often steroid-resistant.
• Linear vs. Granular IF: Linear IgG staining is pathognomonic for Anti-GBM disease; Granular ("lumpy-bumpy") staining indicates immune-complex diseases like Lupus, PSGN, or Membranous GN.
• GPA vs. MPA: Granulomatosis with Polyangiitis (GPA) features granulomatous inflammation and PR3-ANCA; Microscopic Polyangiitis (MPA) lacks granulomas and features MPO-ANCA.
• Hump vs. Ribbon vs. Spike: Subepithelial "humps" = PSGN; Intramembranous "ribbons" = Dense Deposit Disease; Subepithelial "spikes" = Membranous GN.
• Selective vs. Non-selective Proteinuria: Selective (Albumin only) is characteristic of Minimal Change Disease; Non-selective (Albumin + Globulins) is seen in most other Nephrotic syndromes.
• TTP vs. HUS: TTP is defined by ADAMTS13 deficiency and prominent neurologic symptoms; HUS is defined by Shiga-toxin or complement dysregulation and prominent AKI.
• AL vs. AA Amyloidosis: AL is derived from Ig light chains (plasma cell dyscrasias); AA is derived from Serum Amyloid A (chronic inflammation).
• Alport vs. Thin Basement Membrane: Alport features split/thickened GBM, deafness, and renal failure; TBMD features diffuse thinning only and a benign course.
• Primary vs. Secondary FSGS: Primary FSGS presents with sudden, massive nephrotic syndrome; Secondary FSGS (e.g., from obesity or reduced mass) presents with gradual, sub-nephrotic proteinuria and less hypoalbuminemia.
• C3 vs. C4 Levels: Low C3 with normal C4 suggests alternative pathway activation (e.g., PSGN, DDD); Low C3 and Low C4 suggest classical pathway activation (e.g., Lupus Nephritis).
• Kidney Size: Small kidneys suggest chronic disease; however, Diabetic Nephropathy, Amyloidosis, and HIVAN often present with normal or enlarged kidneys despite advanced failure.
• PLA2R vs. THSD7A: PLA2R is the antigen in 70-80% of primary Membranous GN; THSD7A is a rarer antigen (1-5%) sometimes associated with underlying malignancy.
• Subendothelial vs. Subepithelial Deposits: Subendothelial (and mesangial) deposits usually cause a Nephritic/inflammatory response; Subepithelial deposits (outside the GBM) usually cause a Nephrotic response with podocyte injury.
• Class IV-S vs. Class IV-G Lupus: Class IV-S (Segmental) traditionally carries a worse prognosis than Class IV-G (Global) in Lupus Nephritis.

QA

text

1. What represents an arteriolar portal system in Glomerular Architecture? | Glomerular capillary tuft
2. What are the components of the Filtration Barrier? (3) | Fenestrated endothelial, GBM, Podocytes
3. What is the daily average albumin excretion in Normal Proteinuria? | 8-10 mg
4. What is the best histologic correlate for kidney failure in Glomerulonephritis? | Tubulointerstitial nephritis and fibrosis
5. What is the primary source of myofibroblasts in Renal Fibrosis? | Resident fibroblast proliferation (50%)
6. What urine sediment finding strongly suggests Glomerulonephritis? | RBC casts/Dysmorphic RBCs
7. What is the definition of microalbuminuria in Diabetic Nephropathy? | 30-300 mg/24 h
8. What is the definition of frank proteinuria in Diabetic Nephropathy? | >300 mg/24 h
9. What is the pathogenesis of Poststreptococcal Glomerulonephritis (PSGN)? | SPEB and NAPlr antigens
10. What is the latent period for PSGN after skin infection? | 2-6 weeks
11. What are the clinical manifestations of PSGN? (3) | 1) Edema
    2) HTN
    3) Smoky urine
12. What is the characteristic finding on electron microscopy for PSGN? | Subepithelial "Humps"
13. What complement levels are seen in PSGN? | Low C3 and CH50
14. What is the treatment for PSGN? | Supportive care
15. What is the pathogenesis of SBE-Associated GN? | Circulating immune complexes
16. What is the gross kidney appearance in SBE-Associated GN? | Flea-bitten appearance
17. What lab markers are often positive in SBE-Associated GN? (2) | Rheumatoid Factor; ANCA
18. What is the treatment course for SBE-Associated GN? | 4-6 weeks antibiotics
19. What is the most aggressive class of Lupus Nephritis? | Class IV (Diffuse)
20. What describes Class V Lupus Nephritis? | Membranous
21. What is the most common manifestation of Lupus Nephritis? | Proteinuria
22. What is the induction treatment for aggressive Lupus Nephritis? | Steroids + Cyclophosphamide/MMF
23. What is the autoantibody target in Anti-GBM (Goodpasture)? | α3 NC1 domain (Type IV Collagen)
24. What are the dual components of Goodpasture Syndrome? | Hemoptysis and GN
25. What is the characteristic Immunofluorescence finding in Anti-GBM disease? | Linear IgG
26. What is the light microscopy finding in Anti-GBM disease? | Crescentic GN
27. What is the triple therapy for Anti-GBM disease? | Plasmapheresis, Prednisone, Cyclophosphamide
28. What is the most common glomerulonephritis worldwide? | IgA Nephropathy (Berger’s)
29. What type of IgA is deficient in IgA Nephropathy? | Galactose-deficient IgA1
30. What is the classic presentation of IgA Nephropathy? | Synpharyngitic hematuria
31. What is the pathognomonic biopsy finding in IgA Nephropathy? | Mesangial IgA/C3
32. What is the primary treatment for IgA Nephropathy? | ACEi or ARB
33. What is the difference between GPA and MPA targets in ANCA Vasculitis? | PR3-ANCA (GPA); MPO-ANCA (MPA)
34. What characterizes the pathology of ANCA Vasculitis? | Pauci-immune (no staining)
35. What is the induction for severe ANCA Vasculitis? | Steroids + Cyclophosphamide/Rituximab
36. What is the pathogenetic hallmark of Minimal Change Disease (MCD)? | Podocyte foot process effacement
37. What is the most common cause of nephrotic syndrome in children? | Minimal Change Disease
38. What secondary factors cause Minimal Change Disease? (2) | NSAIDs; Hodgkin’s Lymphoma
39. What is the treatment response for Minimal Change Disease? | Highly steroid responsive
40. What is the high-risk gene for FSGS in African Americans? | APOL1 alleles
41. What is the most common primary GN cause of ESKD in the US? | FSGS
42. What variant of FSGS is associated with HIV or COVID? | Collapsing variant
43. What is the pathology finding for FSGS on light microscopy? | Segmental scarring
44. What is the specific antibody for primary Membranous GN (MGN)? | Anti-PLA2R antibodies
45. What is the classic Silver stain finding in Membranous GN? | "Spikes"
46. Which nephrotic disease has the highest incidence of renal vein thrombosis? | Membranous GN
47. What is the pathology of Membranous GN? | Thickened GBM
48. What is the most common cause of ESKD overall? | Diabetic Nephropathy
49. What are the pathognomonic nodules in Diabetic Nephropathy? | Kimmelstiel-Wilson nodules
50. What starts the injury in Diabetic Nephropathy? | Hyperfiltration
51. What defines C3 Glomerulopathy? | C3 accumulation (no Ig)
52. What is the characteristic EM finding in Dense Deposit Disease? | "Ribbons"
53. What creates the "tram-tracking" appearance in MPGN pattern? | Mesangial interposition
54. What constitutes the deposits in AL Amyloidosis? | Monoclonial light chains (lambda)
55. What is the stain finding for AL Amyloidosis? | Congo Red (apple-green)
56. What enzyme is deficient in Fabry's Disease? | Alpha-galactosidase A
57. What are the podocyte vacuoles in Fabry's Disease called? | Zebra bodies
58. What is the common mutation in Alport's Syndrome? | X-linked COL4A5
59. What are the triad features of Alport's Syndrome? | GN, deafness, ocular defects
60. What is the alternate name for Thin Basement Membrane Disease? | Benign familial hematuria
61. What are the bone features of Nail-Patella Syndrome? | Absent patellae, iliac horns
62. Why is the renal medulla injured in Sickle Cell Disease? | Hypoxic/Hypertonic environment
63. What is the hallmark pathology of HIV-associated nephropathy? | Collapsing variant (FSGS)
64. What is the ultrasound finding in HIVAN? | Large, echogenic kidneys
65. What deficiency causes TTP? | ADAMTS13
66. What is the common trigger for HUS? | Shiga-toxin (E. coli O157:H7)
67. What are the five criteria defining Nephrotic Syndrome? | Proteinuria (>3.5g), Hypoalbuminemia, Edema, Hyperlipidemia, Lipiduria
68. What are the clinical features of Acute Nephritic Syndrome? (4) | Hematuria, RBC casts, HTN, mild proteinuria
69. Contrast IgA Nephropathy vs. PSGN onset. | IgA: 1-2 days (Synpharyngitic)
    PSGN: 1-3 weeks (Latent)
70. What defines "selective" proteinuria in Minimal Change Disease? | Primarily albumin
71. What EM finding is specific for Alport's Syndrome? | "Basket-weave" GBM
72. What is the emergent treatment for TTP? | Large-volume plasmapheresis
73. What finding in Diabetic Nephropathy is present in 90% of Type 1 patients? | Retinopathy
74. What domain must be tested to confirm Anti-GBM disease? | α3 NC1 domain
75. What autoantibody stabilizes C3 convertase in C3 Glomerulopathy? | C3 Nephritic Factor
76. Compare PSGN vs. IgA Nephropathy complement levels. | PSGN: Low C3
    IgA: Normal C3
77. Compare MCD vs. FSGS light microscopy. | MCD: Normal glomeruli
    FSGS: Segmental scars
78. What is the significance of Linear IgG staining? | Pathognomonic for Anti-GBM
79. What IF staining pattern is seen in Lupus and PSGN? | Granular ("lumpy-bumpy")
80. Compare GPA vs. MPA inflammation. | GPA: Granulomatous
    MPA: No granulomas
81. What diagnosis is associated with subepithelial "humps"? | PSGN
82. What diagnosis is associated with intramembranous "ribbons"? | Dense Deposit Disease
83. What diagnosis is associated with subepithelial "spikes"? | Membranous GN
84. Compare TTP vs. HUS symptoms. | TTP: Neurologic symptoms
    HUS: Acute Kidney Injury
85. What is the source of AA Amyloidosis? | Serum Amyloid A (inflammation)
86. Compare Alport vs. TBMD prognosis. | Alport: Renal failure/deafness
    TBMD: Benign course
87. How does Primary vs. Secondary FSGS present? | Primary: Sudden/Massive proteinuria
    Secondary: Gradual/Sub-nephrotic
88. What complement pattern suggests Classical Pathway activation (e.g. Lupus)? | Low C3 and Low C4
89. What complement pattern suggests Alternative Pathway activation (e.g. PSGN)? | Low C3; Normal C4
90. Which chronic kidney diseases present with normal/large kidneys? (3) | DM, Amyloid, HIVAN
91. What is the rare antigen in Membranous GN linked to cancer? | THSD7A
92. Contrast Subendothelial vs. Subepithelial response. | Subendothelial: Nephritic
    Subepithelial: Nephrotic
93. Compare Class IV-S vs. Class IV-G Lupus prognosis. | Class IV-S (Segmental) is worse
94. What is the primary drug for Minimal Change Disease? | Prednisone
95. What treatment is used for Membranous GN? | Rituximab or Cyclophosphamide
96. What is the target NC1 domain in Anti-GBM disease? | Collagen IV
97. What defines Selective Proteinuria in MCD? | Albumin only
98. What defines Non-selective Proteinuria? | Albumin and Globulins
99. What are the components of AL Amyloid sheets? | Beta-pleated sheets
100. What is the major mutation in Nail-Patella Syndrome? | LMX1B
101. What is the treatment for IgA Nephropathy to reduce protein? | ACEi/ARB or Sparsentan
102. What characterizes Pauci-immune GN staining? | No immune staining (IF)

3.16

Summary

QA

3.16

Summary generated direct from harrison chapter

Inherited Diseases Associated with a Cystic Phenotype Comparison Table

General Concepts and Pathogenesis

• The Polycystic Kidney Diseases (PKD) are a group of genetically heterogeneous disorders and represent a leading cause of kidney failure.
• Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common life-threatening monogenic disease, affecting 12 million people worldwide.
• Autosomal Recessive Polycystic Kidney Disease (ARPKD) is rarer than the dominant form and primarily affects the pediatric population.
• Ciliopathies is the collective term for a wide spectrum of diseases, including PKD, that underlie defects in the structure or function of the primary cilia.
• The Primary Cilium is a hair-like structure on the apical membrane of tubular epithelial cells connected to the basal body through the transition zone.
• Polycystin-1 (PC1), encoded by PKD1, is a large 11-transmembrane protein that functions like a G protein–coupled receptor (GPCR).
• Polycystin-2 (PC2), encoded by PKD2, is a calcium-permeable six-transmembrane protein belonging to the TRP cation channel family.
• The PC1/PC2 Protein Complex serves as a mechanosensor or chemical sensor on the primary cilium, regulating calcium and G-protein signaling.
• High levels of cAMP in ADPKD kidneys promote protein kinase A activity, leading to cyst growth via cell proliferation and fluid secretion through chloride and aquaporin channels.
• The "Second Hit" Mutation hypothesis in ADPKD suggests that while every cell carries a germline mutant allele, cysts only develop from cells that receive a somatic mutation in the "normal" allele.

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• ADPKD Genetics involve PKD1 (85% of cases, more severe) on chromosome 16p13 and PKD2 (15% of cases, milder) on chromosome 4q21-q23. *
• ADPKD Renal Manifestations are characterized by progressive bilateral formation of renal cysts that can increase kidney weight up to 20 times the normal weight.
• ADPKD Pain is a frequent symptom (~60% of patients) and may result from cyst infection, hemorrhage, or nephrolithiasis.
• Gross Hematuria in ADPKD resulting from cyst rupture occurs in ~40% of patients and may coexist with flank pain if the cyst connects to the collecting system.
• Infection is the second most common cause of death for patients with ADPKD, often manifesting as infected cysts or acute pyelonephritis due to gram-negative bacteria.
• Nephrolithiasis in ADPKD occurs in ~20% of patients; notably, more than half of these stones are composed of Uric Acid, unlike the general population.
• Cardiovascular Complications are the major cause of mortality in patients with ADPKD.
• Hypertension in ADPKD is common and typically occurs before any reduction in GFR; it is a significant risk factor for both CV disease and kidney progression.
• Polycystic Liver Disease is the most common extrarenal complication of ADPKD, occurring almost exclusively in women, particularly those with multiple pregnancies.
• Intracranial Aneurysm (ICA) occurs four to five times more frequently in ADPKD patients than the general population, with family history being a major risk factor for rupture.
• ADPKD Vascular Abnormalities include mitral valve prolapse (up to 30%), tricuspid valve prolapse, and diffuse arterial dolichoectasias.
• ADPKD Diagnosis Criteria (Ultrasound) for at-risk subjects:
  1. Ages 15–29: At least two renal cysts (unilateral or bilateral).
  2. Ages 30–59: At least two cysts in each kidney.
  3. Ages ≥60: At least four cysts in each kidney. *
• Disease Exclusion in ADPKD for subjects aged 30–59 is defined as the absence of at least two cysts in each kidney (0% false-negative rate).
• MRI (T2-weighted) with gadolinium is more sensitive than ultrasound for ADPKD, capable of detecting cysts only 2–3 mm in diameter.
• ADPKD Blood Pressure Management recommends a target of 140/90 mmHg, though rigorous control to 110 mmHg systolic may slow cyst growth but increase risk of renal blood flow reduction.
• Cyst Infection Treatment in ADPKD requires lipid-soluble antibiotics like trimethoprim-sulfamethoxazole or quinolones to penetrate cyst walls, often for 4–6 weeks.
• Tolvaptan is an FDA-approved V2 receptor (V2R) antagonist that inhibits cAMP pathways to slow the decline of renal function in patients at risk of rapidly progressing ADPKD.
• Somatostatin Analogues (e.g., octreotide) reduce renal cAMP levels and have been shown to slow the decline of renal function in ADPKD trials.

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

• ARPKD Ecology results from mutations in a single gene, PKHD1, which encodes Fibrocystin/Polyductin (FPC).
• Neonatal ARPKD often presents with greatly enlarged echogenic kidneys and reduced fetal urine production, leading to Oligohydramnios and pulmonary hypoplasia. *
• ARPKD Mortality is high, with about 30% of neonates dying shortly after birth due to respiratory insufficiency; 60% of total mortality occurs within the first month.
• Caroli Disease is a hallmark of ARPKD liver disease and involves the dilatation of intrahepatic bile ducts. *
• Congenital Hepatic Fibrosis (CHF) in ARPKD can lead to portal hypertension, hepatosplenomegaly, and variceal bleeding.
• ARPKD Diagnosis (Ultrasound) typically reveals large, echogenic kidneys with poor corticomedullary differentiation.
• ARPKD Hypertension is systemic and common in all patients, even those with normal renal function.

Other Inherited Cystic Diseases

• Tuberous Sclerosis (TS) renal findings most commonly include Angiomyolipomas (often bilateral/multiple and prone to bleeding if >4 cm).
• TSC2 Gene is adjacent to PKD1; deletions can lead to a contiguous gene syndrome with features of both ADPKD and TS.
• Von Hippel-Lindau (VHL) Disease is an autosomal dominant cancer syndrome where kidney manifestations include multiple bilateral cysts and a high risk of Renal Cell Carcinoma (RCC).
• Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is characterized by progressive kidney failure, a benign urine sediment, and kidneys that are usually small and fibrotic rather than enlarged.
• ADTKD-UMOD (MCKD II) is frequently associated with Hyperuricemia and Gout in early adulthood. *
• ADTKD-MUC1 (MCKD I) patients typically do not have elevated uric acid levels.
• Nephronophthisis (NPHP) is the most common inherited childhood form of kidney failure requiring replacement therapy.
• NPHP Presentation includes small fibrotic kidneys, medullary cysts, and a lack of significant proteinuria or active urine sediment.
• Senior-Loken Syndrome is defined as the clinical combination of NPHP and Retinitis Pigmentosa.
• Bardet-Biedl Syndrome (BBS) features truncal obesity, polydactyly, retinal dystrophy, and NPHP-like kidney phenotype.
• Medullary Sponge Kidney (MSK) is usually a sporadic (not inherited) benign condition characterized by cystic dilatation of the collecting ducts, often appearing incidentally on imaging.
• MSK Complications include an increased frequency of Calcium Phosphate/Oxalate stones and recurrent UTIs.
• CAKUT (Congenital Abnormalities of the Kidney and Urinary Tract) accounts for more than one-third of end-stage kidney disease in children.

High-Yield Comparisons for Exams

1. In ADPKD, the kidneys are markedly enlarged, whereas in ADTKD or NPHP, the kidneys are typically small and fibrotic.
2. PKD1 mutations cause more severe ADPKD with earlier onset of ESRD (~54 years) compared to the milder PKD2 (~74 years).
3. Uric Acid Stones are the predominant stone type in ADPKD, whereas the general population more commonly forms Calcium Oxalate stones.
4. ADTKD-UMOD presents with early-onset gout/hyperuricemia, while ADTKD-MUC1 has a similar renal course but lacks the gout/uric acid finding.
5. Liver Cysts are common in ADPKD but do not usually result in liver failure; conversely, ARPKD liver involvement involves CHF and biliary dysgenesis that can lead to portal hypertension.
6. ICA Screening is specifically indicated for ADPKD patients with a positive family history of aneurysms, not for everyone with ADPKD.
7. ADPKD Infections are often gram-negative; lipid-soluble antibiotics are required to penetrate the cysts.
8. Potter Sequence (oligohydramnios, pulmonary hypoplasia, limb deformities) is a classic presentation of ARPKD in utero/neonatally.
9. Angiomyolipomas are the "most common" renal finding in Tuberous Sclerosis, distinguishing it from ADPKD where simple cysts predominate.
10. VHL is strongly associated with Renal Cell Carcinoma (RCC), necessitating annual CT/MRI screening.
11. NPHP often presents with salt-wasting and polyuria in children, whereas ADPKD is usually asymptomatic until adulthood.
12. MSK shows a "medullary blush" on IVP (historically) due to dilated collecting ducts, unlike the discrete "grape-like" cysts of ADPKD.
13. Tolvaptan is used for ADPKD, while Everolimus (mTOR inhibitor) is specifically approved for TS-associated kidney tumors.
14. NPHP and ARPKD are Both Autosomal Recessive, but NPHP kidneys are usually small while ARPKD kidneys are massively enlarged.
15. If a patient has ADPKD Symptoms + Subarachnoid Hemorrhage, always check for Intracranial Aneurysm.
16. ADPKD protein PC1 acts as a GPCR-like receptor, while PC2 acts as a calcium-permeable TRP channel.
17. Proteinuria is generally mild or absent in most hereditary cystic diseases; if nephrotic-range proteinuria is present, consider secondary glomerulosclerosis.
18. ARPKD cysts are derived from the collecting ducts, whereas ADPKD cysts can derive from any part of the nephron.
19. Renal Stones in MSK are treated the same as stones in the general population, but patients may have reduced concentrating ability.
20. ADPLD (Autosomal Dominant Polycystic Liver Disease) caused by PRKCSH/SEC63 does not typically progress to renal failure, unlike the liver cysts seen in ADPKD.

QA

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1. ADPKD: What is the mode of inheritance? | Autosomal Dominant
2. ADPKD: Describe the primary renal abnormalities. | Bilaterally enlarged kidneys;
   cortical and medullary cysts
3. ADPKD: Name three unique clinical features. | Liver/pancreas cysts,
   hypertension,
   subarachnoid hemorrhage
4. ADPKD: Which key genes are involved? | PKD1, PKD2
5. ADPKD-like: What is the mode of inheritance? | Autosomal Dominant
6. ADPKD-like: Describe the primary renal phenotype compared to classic ADPKD. | Normal to smaller kidneys;
   fewer cysts
7. ADPKD-like: What is the unique clinical feature regarding the liver? | Variable liver cysts
8. ADPKD-like: Which key genes are associated with this phenotype? | GANAB, DNAJB11
9. ARPKD: What is the mode of inheritance? | Autosomal Recessive
10. ARPKD: Where in the nephron do the cysts primarily form? | Distal and collecting ducts
11. ARPKD: Name three unique clinical features. (3) | 1) Oligohydramnios
    2) Ascending cholangitis
    3) Liver fibrosis
12. ARPKD: Which key gene is mutated? | PKHD1
13. ADTKD: What is the mode of inheritance? | Autosomal Dominant
14. ADTKD: Describe the primary renal abnormalities. | Small fibrotic kidneys;
    medullary cysts
15. ADTKD: What is a classic unique clinical feature in adults? | Gout
16. ADTKD: List the key genes involved. (4) | UMOD, MUC1, REN, HNF1B
17. NPHP: What is the mode of inheritance? | Autosomal Recessive
18. NPHP: Describe the morphology of the kidneys and location of cysts. | Small fibrotic kidneys;
    medullary cysts
19. NPHP: List three systemic clinical features often seen in syndromes. (3) | 1) Growth retardation
    2) Anemia
    3) Ocular/liver/cerebellar signs
20. NPHP: Which genes are involved in this disorder? | NPHP1 through NPHP20
21. Tuberous Sclerosis: What is the mode of inheritance? | Autosomal Dominant
22. Tuberous Sclerosis: What is the most common renal finding? | Angiomyolipomas
23. Tuberous Sclerosis: List three clinical features besides renal cysts. (3) | 1) Angiomyolipomas
    2) RCC
    3) Facial angiofibromas
24. Tuberous Sclerosis: Which two genes are mutated? | TSC1, TSC2
25. Von Hippel-Lindau: What is the mode of inheritance? | Autosomal Dominant
26. Von Hippel-Lindau: What are the primary manifestations in the kidney? | Cysts and RCC
27. Von Hippel-Lindau: List three unique clinical features of the syndrome. (3) | 1) Renal cell carcinoma
    2) Pheochromocytoma
    3) Retinal angiomas
28. Von Hippel-Lindau: Which gene is responsible? | VHL
29. General Pathogenesis: Collectively, what is the term for disorders caused by primary cilia defects? | Ciliopathies
30. General Pathogenesis: What is the most common life-threatening monogenic kidney disease? | ADPKD
31. General Pathogenesis: Which population is primarily affected by ARPKD? | Pediatric population
32. General Pathogenesis: Where is the Primary Cilium located on the epithelial cell? | Apical membrane
33. General Pathogenesis: Describe the structure of Polycystin-1 (PC1). | 11-transmembrane protein;
    GPCR-like function
34. General Pathogenesis: Describe the structure of Polycystin-2 (PC2). | 6-transmembrane protein;
    TRP cation channel
35. General Pathogenesis: What is the function of the PC1/PC2 protein complex? | Mechanosensor/Chemical sensor
36. General Pathogenesis: In ADPKD, elevated levels of what intracellular molecule promote cyst growth? | cAMP
37. General Pathogenesis: cAMP promotes cyst growth via which two cellular processes? | Cell proliferation;
    fluid secretion
38. General Pathogenesis: What hypothesis explains why only some cells in ADPKD develop into cysts? | "Second Hit" Mutation
39. ADPKD Genetics: Which gene mutation is responsible for 85% of cases and a more severe phenotype? | PKD1
40. ADPKD Genetics: On which chromosomes are PKD1 and PKD2 located, respectively? | 16p13 and 4q21-q23
41. ADPKD Clinical: How much can the kidney weight increase relative to normal in ADPKD? | Up to 20 times
42. ADPKD Symptoms: Name three causes of flank pain in these patients. (3) | 1) Cyst infection
    2) Hemorrhage
    3) Nephrolithiasis
43. ADPKD Symptoms: What percentage of patients experience gross hematuria? | ~40%
44. ADPKD Mortality: What is the second most common cause of death in ADPKD? | Infection
45. ADPKD Infection: Which class of bacteria typically causes cyst infections? | Gram-negative bacteria
46. ADPKD Stones: More than half of the kidney stones in ADPKD are composed of what? | Uric Acid
47. ADPKD Mortality: What is the leading cause of mortality in ADPKD patients? | Cardiovascular Complications
48. ADPKD Hypertension: When does hypertension typically manifest relative to GFR decline? | Before GFR reduction
49. ADPKD Extrarenal: What is the most common extrarenal manifestation? | Polycystic Liver Disease
50. ADPKD Liver Disease: Which demographic is most affected by severe polycystic liver disease? | Women;
    multiple pregnancies
51. ADPKD Vascular: How much more frequent are Intracranial Aneurysms (ICA) in ADPKD than the general population? | 4 to 5 times
52. ADPKD Vascular: What is the most common cardiac valvular abnormality? | Mitral valve prolapse
53. ADPKD Diagnosis: For ages 15-29, what is the ultrasound criteria for diagnosis? | ≥2 renal cysts
    (unilateral or bilateral)
54. ADPKD Diagnosis: For ages 30-59, what is the ultrasound criteria for diagnosis? | ≥2 cysts
    in each kidney
55. ADPKD Diagnosis: For ages ≥60, how many cysts are required for diagnosis? | ≥4 cysts in each kidney
56. ADPKD MRI: What is the minimum cyst size detectable by T2-weighted MRI? | 2–3 mm
57. ADPKD Management: What is the standard target blood pressure? | 140/90 mmHg
58. ADPKD Management: What is the antibiotic requirement for cyst infections? | Lipid-soluble antibiotics
    (e.g., fluoroquinolones)
59. ADPKD Tolvaptan: What is the mechanism of Tolvaptan? | V2 receptor antagonist
60. ADPKD Somatostatin: How do somatostatin analogues like octreotide affect renal cAMP? | Reduce cAMP levels
61. ARPKD Ecology: What protein is encoded by the PKHD1 gene? | Fibrocystin/Polyductin (FPC)
62. Neonatal ARPKD: Describe the ultrasound appearance of the kidneys. | Enlarged and echogenic
63. ARPKD Neonatal: What is the primary cause of death in neonatal ARPKD? | Respiratory insufficiency
    (Pulmonary hypoplasia)
64. ARPKD Liver: What is the specific term for the liver disease involving bile duct dilatation? | Caroli Disease
65. ARPKD Liver: Portal hypertension in ARPKD is a consequence of which condition? | Congenital Hepatic Fibrosis
66. ARPKD Ultrasound: What characteristic features are seen in kidney ultrasound? | Poor corticomedullary differentiation
67. ARPKD Hypertension: How common is hypertension in ARPKD patients with normal renal function? | Common/systemic
68. Tuberous Sclerosis: At what size does a renal angiomyolipoma become high-risk for bleeding? | >4 cm
69. TSC2/PKD1: What happens if the adjacent TSC2 and PKD1 genes are both deleted? | Contiguous gene syndrome
70. VHL Disease: What annual screening is required due to the high risk of RCC? | Annual CT/MRI
71. ADTKD: What is the primary urinary sediment finding? | Benign sediment
72. ADTKD-UMOD: What metabolic abnormality is specific to this mutation? | Hyperuricemia and Gout
73. ADTKD-MUC1: How does it differ from ADTKD-UMOD regarding serum uric acid? | Lacks elevated uric acid
74. Nephronophthisis (NPHP): What is its clinical significance in the pediatric population? | Most common inherited ESKD
75. NPHP Presentation: Describe the kidney size and presence of proteinuria. | Small kidneys;
    absent proteinuria
76. Senior-Loken Syndrome: What is the clinical combination? | NPHP and retinitis pigmentosa
77. Bardet-Biedl Syndrome: List four classic clinical features. (4) | Obesity, polydactyly,
    retinal dystrophy, NPHP
78. Medullary Sponge Kidney: Is this condition typically inherited? | Sporadic (not inherited)
79. Medullary Sponge Kidney: Where does cystic dilatation occur? | Collecting ducts
80. Medullary Sponge Kidney: List two common complications. (2) | Calcium stones,
    recurrent UTIs
81. CAKUT: What percentage of ESKD in children is due to CAKUT? | More than one-third
82. Comparison: Contrast kidney size in ADPKD vs. NPHP. | ADPKD enlarged;
    NPHP small
83. Comparison: Compare the age of ESKD onset for PKD1 vs. PKD2. | PKD1 ~54 years;
    PKD2 ~74 years
84. Comparison: What is the predominant stone type in ADPKD vs. the general population? | Uric acid;
    general: Calcium oxalate
85. Comparison: Contrast liver involvement in ADPKD vs. ARPKD. | ADPKD: Cysts;
    ARPKD: Fibrosis/Portal HTN
86. Comparison: When is ICA screening indicated in ADPKD? | Positive family history
87. Comparison: What triad defines Potter Sequence? (3) | Oligohydramnios,
    pulmonary hypoplasia,
    limb deformities
88. Comparison: What differentiates Tuberous Sclerosis renal imaging from ADPKD? | Angiomyolipomas (hyperechoic/fatty)
89. Comparison: Which cystic disease is most strongly associated with malignancy (RCC)? | VHL
90. Comparison: Contrast the childhood symptoms of NPHP and ADPKD. | NPHP: salt-wasting/polyuria;
    ADPKD: asymptomatic
91. Comparison: What is the classic radiologic finding for Medullary Sponge Kidney? | Medullary blush
92. Comparison: Compare the utility of Tolvaptan and Everolimus. | Tolvaptan: ADPKD;
    Everolimus: TS tumors
93. Comparison: Which two cystic diseases are autosomal recessive? | NPHP and ARPKD
94. Comparison: What should be suspected in an ADPKD patient with sudden headache/collapse? | Subarachnoid hemorrhage (ICA)
95. Comparison: If a cystic kidney patient has nephrotic-range proteinuria, what is likely present? | Secondary glomerulosclerosis
96. Comparison: Contrast the cyst origin in ADPKD vs. ARPKD. | ADPKD: ANY part;
    ARPKD: collecting ducts
97. Comparison: What is the renal concentration ability in Medullary Sponge Kidney? | Reduced
98. Comparison: How does ADPLD differ from ADPKD regarding renal failure? | ADPLD: no renal failure
99. ADPKD Antibiotics: Give two examples of lipid-soluble drugs for cyst penetration. | Trimethoprim-sulfamethoxazole;
    quinolones
100. ADTKD Genes: Which mutation causes the syndrome formerly called MCKD II? | UMOD
101. ADPKD Hematuria: How does flank pain relate to gross hematuria timing? | Often coexist
     (if cyst connects to system)
102. General Pathogenesis: Where is the transition zone located? | Apical membrane/Basal body
103. ADPKD Exclusion: What finding excludes ADPKD in an at-risk subject aged 30-59? | <2 cysts in each kidney