Glomerular And Tubulointerstitial Disease - USMLE Step 2

1. This patient's condition results from a genetic defect affecting the synthesis of which of the following proteins?
   Answer: Type IV collagen The triad of renal disease (hematuria progressing to renal failure), sensorineural hearing loss, and ocular abnormalities (though not present here) is characteristic of Alport syndrome. This is an inherited disorder caused by mutations in the genes encoding for the alpha chains of type IV collagen, a crucial structural component of the glomerular basement membrane, cochlea, and lens of the eye.
2. A renal biopsy is performed. In light of his resistance to steroid therapy, which of the following is the most likely diagnosis?
   Answer: Focal segmental glomerulosclerosis While minimal change disease is the most common cause of nephrotic syndrome in children and is typically steroid-responsive, a lack of response to an adequate course of corticosteroids should raise suspicion for focal segmental glomerulosclerosis (FSGS). FSGS is the most common cause of steroid-resistant nephrotic syndrome in children and often progresses to end-stage renal disease.
3. Which of the following serologic tests would be most specific for diagnosing this patient's condition?
   Answer: Anti-glomerular basement membrane (anti-GBM) antibody The combination of rapidly progressive glomerulonephritis (hematuria, RBC casts, acute renal failure) and pulmonary hemorrhage (hemoptysis, alveolar infiltrates) constitutes a pulmonary-renal syndrome. In a young man, the most likely diagnosis is Goodpasture syndrome, which is caused by autoantibodies directed against the alpha-3 chain of type IV collagen in the glomerular and alveolar basement membranes. The most specific diagnostic test is an assay for anti-GBM antibodies.
4. The renal pathology in this patient is most likely caused by which of the following mechanisms?
   Answer: Deposition of immune complexes in the glomeruli Lupus nephritis is a major cause of morbidity in patients with SLE and is caused by the deposition of circulating anti-dsDNA-containing immune complexes within the glomeruli. This deposition triggers inflammation and complement activation (evidenced by low C3/C4), leading to glomerular damage, which can manifest as either a nephritic or nephrotic syndrome, as seen in this patient.
5. A renal biopsy in this patient is most likely to show which of the following on light microscopy?
   Answer: Sclerosis and hyalinosis in some, but not all, glomeruli This patient's demographics (African American), clinical presentation of nephrotic syndrome, hypertension, and microscopic hematuria are most consistent with focal segmental glomerulosclerosis (FSGS). Light microscopy in FSGS characteristically shows sclerosis (scarring) and hyalinosis (deposition of glassy material) in only a portion (segmental) of some (focal) glomeruli.
6. Which urinalysis finding would most strongly suggest acute tubular necrosis (ATN) rather than acute interstitial nephritis (AIN) as the cause of her kidney injury?
   Answer: Muddy brown granular casts This patient has multiple risk factors for acute tubular necrosis (ATN), including hypotension (ischemia) and potential exposure to nephrotoxins. The hallmark urinalysis finding in ATN is muddy brown granular casts, which are formed from sloughed, dead tubular epithelial cells. White blood cell casts and eosinophils would suggest acute interstitial nephritis (AIN), while red blood cell casts would indicate glomerulonephritis.
7. Which of the following is the most likely diagnosis?
   Answer: Poststreptococcal glomerulonephritis This patient presents with a classic acute nephritic syndrome (hypertension, hematuria with RBC casts, edema) following a streptococcal skin infection (impetigo). The latency period of 2-4 weeks and the finding of low serum C3 are highly characteristic of poststreptococcal glomerulonephritis (PSGN).
8. Which of the following findings on urinalysis is the most specific indicator of glomerular disease?
   Answer: Red blood cell casts Red blood cell (RBC) casts are pathognomonic for glomerulonephritis. They are formed when RBCs that have leaked from damaged glomeruli become trapped within the tubular lumen in a protein matrix. While proteinuria and microscopic hematuria are common in glomerular disease, they are not specific and can be seen in many other renal and urologic conditions. Leukocyte esterase indicates pyuria, typically from infection or inflammation (like AIN).
9. Which of the following is the most common cause of primary nephrotic syndrome in this patient's demographic?
   Answer: Membranous nephropathy Membranous nephropathy is the most common cause of primary (idiopathic) nephrotic syndrome in non-diabetic Caucasian adults. While FSGS is also a major cause of nephrotic syndrome in adults, it is more common in individuals of African descent. Minimal change disease is the most common cause in children, and IgA nephropathy typically presents with hematuria (nephritic syndrome).
10. A renal biopsy in this patient would most likely reveal which of the following findings?
    Answer: Noncaseating granulomatous interstitial nephritis This patient's presentation with bilateral hilar adenopathy, hypercalcemia, and renal dysfunction is highly suggestive of sarcoidosis. The most common renal manifestation of sarcoidosis is granulomatous interstitial nephritis, which is characterized by noncaseating granulomas in the renal interstitium on biopsy. Hypercalcemia can also contribute to the renal dysfunction.
11. A kidney biopsy is performed. Immunofluorescence microscopy is most likely to show which of the following patterns?
    Answer: Pauci-immune pattern This patient's presentation of rapidly progressive glomerulonephritis, pulmonary symptoms (hemoptysis), and a positive c-ANCA (anti-PR3) is classic for granulomatosis with polyangiitis, an ANCA-associated vasculitis. The characteristic finding on renal biopsy for ANCA-associated vasculitides is a pauci-immune glomerulonephritis, meaning there is little to no deposition of immunoglobulin or complement on immunofluorescence microscopy.
12. What is the most likely diagnosis?
    Answer: Acute interstitial nephritis The classic triad of fever, rash, and eosinophilia combined with acute kidney injury after exposure to a new medication (penicillins, PPIs, NSAIDs) is highly suggestive of drug-induced acute interstitial nephritis (AIN). The urinalysis finding of sterile pyuria with white blood cell casts is a key feature that distinguishes AIN from other causes of AKI like acute tubular necrosis (which would show muddy brown casts).
13. Which of the following is the most likely finding on electron microscopy?
    Answer: Subepithelial immune complex deposits This patient presents with nephrotic syndrome. In an adult, primary (idiopathic) membranous nephropathy is a common cause, but it can also be secondary to conditions like hepatitis B, malignancy, or SLE. The pathognomonic finding on electron microscopy for membranous nephropathy is the presence of dense immune complex deposits in the subepithelial space, which correspond to the 'spike and dome' appearance seen on silver stain.
14. The development of this patient's renal disease is primarily initiated by which of the following pathophysiologic changes?
    Answer: Glomerular hyperfiltration and increased glomerular capillary pressure The earliest pathophysiologic change in diabetic nephropathy is glomerular hyperfiltration, driven by increased glomerular capillary hydrostatic pressure. This initial insult leads to a cascade of events over years, including thickening of the glomerular basement membrane, mesangial expansion, and ultimately glomerulosclerosis, culminating in the proteinuria and decline in GFR seen in this patient.
15. What is the most likely diagnosis?
    Answer: IgA nephropathy Recurrent episodes of gross hematuria that occur concurrently with or within a few days of an upper respiratory tract infection (synpharyngitic hematuria) in a young adult is the classic presentation of IgA nephropathy (Berger disease). This contrasts with poststreptococcal glomerulonephritis, which has a latent period of 1-3 weeks after the infection.
16. A renal biopsy in this patient would most likely show which finding on light microscopy?
    Answer: Glomeruli with a 'tram-track' appearance of the basement membrane This patient's photosensitive rash, mixed nephritic-nephrotic presentation, and persistently low complement levels are highly suggestive of systemic lupus erythematosus with lupus nephritis. Lupus nephritis commonly presents as membranoproliferative glomerulonephritis (MPGN) pattern, either as a primary MPGN pattern or as part of diffuse proliferative lupus nephritis. The characteristic finding of MPGN on light microscopy is thickening of the glomerular basement membrane and mesangial hypercellularity, which creates a 'tram-track' or double-contour appearance on silver or PAS stains.
17. What is the most likely diagnosis for his kidney disease?
    Answer: Collapsing focal segmental glomerulosclerosis HIV-associated nephropathy (HIVAN) is a classic complication of advanced HIV infection, particularly in patients of African descent. The characteristic pathology is a collapsing variant of focal segmental glomerulosclerosis (FSGS). Clinically, it presents with a rapid decline in renal function and heavy nephrotic-range proteinuria, as seen in this patient.
18. Which of the following best describes this patient's clinical syndrome?
    Answer: Nephritic-nephrotic syndrome This patient exhibits features of both nephritic and nephrotic syndromes. The presence of hematuria with red blood cell casts, hypertension, and azotemia are characteristic of a nephritic process. However, the proteinuria is in the nephrotic range (>3.5 g/day). This combination is termed a nephritic-nephrotic syndrome (or mixed nephritic-nephrotic picture) and is often seen in conditions like membranoproliferative glomerulonephritis and diffuse proliferative lupus nephritis.
19. A renal biopsy is performed. Staining the tissue with Congo red and viewing it under polarized light would most likely reveal which finding?
    Answer: Apple-green birefringence This patient's history of a chronic inflammatory disease (rheumatoid arthritis) and presentation with severe nephrotic syndrome and enlarged kidneys is highly suspicious for secondary (AA) amyloidosis. The diagnosis of amyloidosis is confirmed by a tissue biopsy (often of abdominal fat pad or kidney) that demonstrates amorphous eosinophilic deposits which exhibit apple-green birefringence when stained with Congo red and viewed under polarized light.
20. What is the most likely diagnosis?
    Answer: Minimal change disease This patient's presentation of sudden-onset edema, massive proteinuria, and bland urinary sediment in a young child is classic for minimal change disease (MCD). MCD is the most common cause of nephrotic syndrome in children. The diagnosis is often made clinically, and treatment with corticosteroids is typically initiated without a biopsy.

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