Renal Pathology and Biopsy Interpretation — Advanced

This question tests recognition of the appropriate timing to change modality. The best answer is to transition to intermittent haemodialysis when the patient is haemodynamically stable with minimal vasopressor support (option 3). Continuing CRRT unnecessarily prolongs intensive use of resources; peritoneal dialysis is not the usual next step in this setting. Stopping dialysis immediately is unsafe because the patient remains oliguric and may still require solute/volume control. Increasing CRRT dose has not been shown to accelerate renal recovery. Therefore transitioning to intermittent haemodialysis as haemodynamics permit is the correct action.

Correct answer: B. Focal glomerular diseases (for example FSGS) can be missed if sampling is small because only a subset of glomeruli are involved. Most textbooks and pathology guidance state that ~10 glomeruli is a practical minimum for reasonable sensitivity; 20 or more is ideal. A sample with only 6 glomeruli risks false-negative results for focal lesions. Option A is incorrect because 6 glomeruli are insufficient to exclude focal pathology confidently. Option C is incorrect: electron microscopy provides ultrastructural detail but cannot compensate fully for insufficient numbers of glomeruli when lesions are segmental/focal. Option D is incorrect because 30 glomeruli is not a universal requirement for routine native biopsies (it may be desirable in research or lupus categorisation but is not a standard minimum). Option E is incorrect because immunofluorescence positivity does not negate the importance of glomerular sampling for assessing the distribution and chronicity of disease.

Correct answer: C. Linear IgG staining of the GBM on immunofluorescence is characteristic of anti-GBM disease (Goodpasture's), which often presents with rapidly progressive glomerulonephritis with crescents. Option A (immune complex GN) typically shows granular (‘lumpy-bumpy’) immune complex deposition rather than smooth linear staining. Option B (pauci-immune ANCA-associated GN) is defined by little or no immune deposition on IF (pauci-immune), not linear IgG. Option D (membranous nephropathy) classically shows granular subepithelial immune deposits with a granular IF pattern. Option E (IgA nephropathy) shows dominant/codominant mesangial IgA deposition, not diffuse linear GBM IgG.

Diffuse foot-process effacement with otherwise normal light microscopy and no immune-complex deposits is classic for minimal change disease in the appropriate nephrotic clinical context. Primary FSGS can also show foot-process effacement, but would be supported by segmental sclerosis on light microscopy. Membranous nephropathy has subepithelial immune deposits, diabetic nephropathy has mesangial expansion/GBM thickening, amyloidosis has Congo-red-positive fibrils, and IgA nephropathy has mesangial immune deposits.

Correct answer: D. Pauci-immune crescentic GN most often reflects ANCA-associated vasculitis; this is a rapidly progressive condition where early high‑dose corticosteroids (often IV methylprednisolone followed by oral prednisolone) are started promptly while diagnostic serology (ANCA) is obtained and decisions about additional induction therapy (cyclophosphamide or rituximab) are made. Option A is unsafe—delaying steroids pending serology risks further irreversible renal injury. Option B is inadequate for rapidly progressive GN. Option C (plasma exchange as sole therapy) is not routinely the correct initial sole therapy for ANCA-associated GN; plasma exchange may be considered in specific scenarios (e.g. concomitant severe pulmonary haemorrhage or certain severe presentations) but steroids and induction immunosuppression are the first steps. Option E (repeat biopsy) is unnecessary and delays urgent treatment.

Correct answer: E. Acute T-cell–mediated rejection is defined histologically by dense interstitial mononuclear (mostly T cell) infiltrates accompanied by tubulitis—lymphocytes infiltrating and damaging tubular epithelium. Option A (diffuse C4d in peritubular capillaries) is a marker suggestive of antibody-mediated rejection. Option B (granular immune complex deposition) suggests immune-complex glomerulonephritis, not acute cellular rejection. Option C (TMA) can be seen in many contexts, including antibody-mediated rejection or drug toxicity, but is not the defining feature of acute cellular rejection. Option D indicates acute pyelonephritis or severe infection rather than rejection. The Banff classification uses the degree of interstitial inflammation and tubulitis to grade cellular rejection.

Correct answer: B. Extensive chronic changes—high proportion of interstitial fibrosis/tubular atrophy and global glomerulosclerosis—predict poor potential for recovery with immunosuppression; risks of aggressive immunosuppression often outweigh benefits. Management should focus on supportive measures (blood pressure and proteinuria control with RAAS blockade, salt restriction, diuretics as needed, and preparation for renal replacement therapy if progressive). Option A is incorrect because substantial chronic irreversible damage reduces likelihood of benefit from aggressive immunosuppression. Option C (plasmapheresis) is not standard for primary membranous nephropathy without specific indications (e.g. severe anti-GBM disease or refractory cases). Option D (calcineurin inhibitors) carry nephrotoxicity risk and are unlikely to reverse established fibrosis. Option E (repeat biopsy) is unnecessary and would delay appropriate supportive care.

Correct answer: D. If fresh/frozen tissue for direct immunofluorescence is not available because the specimen was fixed in formalin, paraffin immunofluorescence or immunohistochemistry after protease (pronase) antigen retrieval can often recover masked immune deposits, including mesangial IgA. This approach avoids re-biopsy. Option A is incorrect because a negative IF in a specimen fixed incorrectly may be a false negative. Option B (serum IgA) is neither sensitive nor specific for tissue deposition and cannot replace tissue diagnosis. Option C (empiric treatment) without confirmation may subject the patient to unnecessary risks. Option E (EM only) will not reliably demonstrate IgA immune complexes—EM can show electron-dense deposits but without immunostaining it may not distinguish IgA deposits definitively.

Correct answer: B. MIDD (often light-chain deposition disease) characteristically shows linear, nodular, or diffuse deposition along the glomerular and tubular basement membranes with restriction to a single light chain (kappa or lambda) and a single heavy-chain isotype—evidence of monoclonality. Option A (secondary membranous) shows granular subepithelial deposits and is typically polyclonal. Option C (amyloidosis) shows Congo red–positive deposits and nonbranching fibrils on EM rather than linear monoclonal staining along basement membranes. Option D (IgA nephropathy) shows mesangial-dominant IgA deposition. Option E (post-infectious GN) shows granular 'lumpy-bumpy' deposits and hypocomplementaemia, not monoclonal linear TBM/GBM staining.

Correct answer: D. Significant haematuria with hypotension after renal biopsy suggests active bleeding; immediate resuscitation, correction/cessation of anticoagulation, blood crossmatch and urgent imaging (contrast CT angiography) to localise bleeding with a view to urgent angioembolisation are appropriate. Option A is unsafe because delay risks ongoing haemodynamic compromise. Option B (start antibiotics) is not the immediate priority for an acute bleed. Option C (tranexamic acid and discharge) is inappropriate in a haemodynamically unstable patient—the antifibrinolytic alone is insufficient and discharge would be unsafe. Option E (elective imaging next week) dangerously delays urgent intervention.