Nephrology and Hypertension Flashcards

A 58-year-old man with IgA nephropathy and a GFR of 32 mL/min/1.73m² is started on sparsentan (a dual endothelin/angiotensin receptor antagonist). Six weeks later, his serum potassium is 5.8 mEq/L and creatinine has risen 28% from baseline. His blood pressure is 118/74 mmHg. Which is the most appropriate next step?

Answer: Continue sparsentan, reduce dietary potassium, and recheck labs in 4 weeks

A creatinine rise of up to 30% with initiation of renin-angiotensin-aldosterone system (RAAS)-blocking agents is expected due to reduced intraglomerular pressure and is not an indication to discontinue therapy — it predicts long-term nephroprotection. Mild-to-moderate hyperkalemia (K+ <6.0 mEq/L) should be managed with dietary restriction and reassessment rather than drug discontinuation. Sparsentan received accelerated FDA approval for IgA nephropathy and provides dual proteinuria reduction; abandoning it prematurely forfeits proteinuria benefit. Sodium polystyrene sulfonate has a poor safety profile in CKD patients and is not first-line. Finerenone is indicated in diabetic kidney disease, not IgA nephropathy.

A 44-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) and a total kidney volume (TKV) of 2,100 mL (height-adjusted TKV class 1C) is on tolvaptan 60/30 mg daily. She develops serum ALT 6× the upper limit of normal and mild jaundice. Her creatinine is stable. What is the most appropriate management?

Answer: Permanently discontinue tolvaptan and do not rechallenge

Tolvaptan carries an FDA black-box warning for serious and potentially fatal hepatotoxicity. Drug-induced liver injury from tolvaptan is an idiosyncratic reaction, and clinical guidelines recommend permanent discontinuation when ALT exceeds 3× ULN with symptoms or 8× ULN without symptoms. Jaundice with ALT 6× ULN clearly meets criteria for permanent discontinuation. Rechallenge is explicitly contraindicated. Dose reduction does not mitigate idiosyncratic hepatotoxicity. Lanreotide may slow cyst growth but lacks the TKV-slowing efficacy of tolvaptan and would not substitute its mechanism; moreover, the scenario calls for managing the hepatotoxicity.

A 67-year-old man with stage 3b CKD (GFR 34), type 2 diabetes, and hypertension presents with resistant hypertension despite maximum-dose lisinopril, amlodipine, and chlorthalidone. His aldosterone-to-renin ratio (ARR) is 42 ng/dL per ng/mL/hr (>30 is positive screen). Adrenal CT shows bilateral adrenal hyperplasia. His serum potassium is 3.2 mEq/L. Which intervention is most appropriate before planning adrenal vein sampling (AVS)?

Answer: Replace potassium to ≥3.5 mEq/L, discontinue interfering medications, and then perform AVS

AVS is the definitive test to distinguish unilateral from bilateral primary aldosteronism (PA) and guides surgical versus medical management. However, hypokalemia itself suppresses aldosterone secretion and can produce false-negative AVS results; potassium must be repleted to ≥3.5 mEq/L before AVS. Additionally, interfering medications (mineralocorticoid receptor antagonists, beta-blockers, ACE inhibitors) must be discontinued or substituted with non-interfering agents (alpha-blockers, verapamil) before the test. Bilateral CT findings do not reliably distinguish bilateral hyperplasia from bilateral macro-adenomas or contralateral micro-adenomas — CT misclassifies lateralization in ~25% of cases. Bilateral adrenalectomy would be inappropriate without AVS confirmation of true bilateral disease. Glucocorticoid-remediable aldosteronism (GRA/FH-I) is suspected when PA begins before age 20 or has strong family history; it is not a first-line consideration here.

A 29-year-old woman is referred for evaluation of hematuria and proteinuria (protein:creatinine ratio 1.8 g/g) found incidentally. She is 14 weeks pregnant. Creatinine is 1.4 mg/dL (baseline unknown). Renal biopsy shows diffuse endocapillary proliferative glomerulonephritis with prominent subendothelial and mesangial deposits on electron microscopy; immunofluorescence reveals dominant C3 with trace IgG. Serum C3 is markedly low, C4 is normal. ADAMTS13 activity is normal. Which diagnosis best fits this presentation?

Answer: C3 glomerulopathy (C3 glomerulonephritis)

C3 glomerulopathy (C3G) is defined by dominant C3 staining (≥2 orders of magnitude greater than any immunoglobulin) on immunofluorescence with electron-dense deposits (subendothelial, mesangial, and/or subepithelial) and low complement C3 due to alternative pathway dysregulation — exactly the pattern here. The normal C4 excludes classical pathway activation, arguing against lupus nephritis (which typically activates C1q→C4→C3 with low both C3 and C4) and hepatitis C–associated MPGN (which tends toward classical/lectin pathway). Post-infectious GN typically has dominant C3 but resolves within weeks of infection; no antecedent infection is described, and the degree of proteinuria is atypical. IgA staining would be expected in IgA nephropathy. Lupus nephritis class III would show IgG-dominant or 'full house' immunofluorescence with low C4.

A 72-year-old man with a 3-year history of multiple myeloma (IgG kappa, on lenalidomide maintenance) develops slowly progressive renal failure over 6 months, now at GFR 19 mL/min/1.73m². Urinalysis shows no hematuria, no casts, and trace proteinuria on dipstick. 24-hour urine protein is 4.2 g, but urine protein electrophoresis reveals the protein is 92% Bence-Jones protein (free kappa light chains) with minimal albumin. Renal biopsy shows Congo red–negative amorphous eosinophilic material filling tubular lumens with giant cell reaction. Which condition is most likely?

Answer: Light chain cast nephropathy (myeloma kidney)

Light chain cast nephropathy (myeloma kidney) is characterized by intratubular precipitation of monoclonal free light chains with uromodulin (Tamm-Horsfall protein), forming obstructing casts with a surrounding giant cell inflammatory reaction. On biopsy, casts appear amorphous and eosinophilic, and are Congo red–negative (distinguishing from amyloid). The trace dipstick proteinuria with large 24-hour protein confirms the protein is primarily light chains (not detected by albumin-based dipstick). AL amyloidosis is Congo red–positive and typically shows glomerular involvement with nephrotic-range albumin. LCDD shows linear light chain deposits along tubular and glomerular basement membranes (PAS-positive nodular glomerulosclerosis), not intraluminal casts. PGNMID presents with glomerulonephritis and would show intraglomerular deposits on immunofluorescence.

A 51-year-old woman with scleroderma presents to the emergency department with sudden-onset severe headache and blood pressure of 218/126 mmHg. Her creatinine has risen from 0.9 to 3.1 mg/dL over the past week. Peripheral blood smear shows schistocytes; platelet count is 58,000/μL; LDH is elevated; ADAMTS13 activity is 62% (normal >67%). Urinalysis shows 2+ protein and RBC casts. She is currently on glucocorticoids (prednisone 30 mg/day) started 2 weeks ago for inflammatory arthritis. Which is the most critical immediate intervention?

Answer: Start captopril (short-acting ACE inhibitor) urgently and taper glucocorticoids

This presentation is scleroderma renal crisis (SRC), a hypertensive emergency driven by RAAS-mediated renal ischemia and intimal hyperplasia in small renal arteries. Glucocorticoid use (particularly doses >15 mg prednisone/day) is the strongest known precipitant of SRC. The microangiopathic hemolytic anemia (MAHA) and thrombocytopenia are secondary to severe hypertension-induced endothelial injury, not primary TTP (ADAMTS13 activity >10% excludes TTP). The cornerstone of SRC management is aggressive, prompt ACE inhibitor therapy — captopril is preferred for its short duration of action and titratability. ACE inhibitors have been shown to improve renal outcomes even if dialysis is required acutely. Glucocorticoids must be tapered as quickly as the inflammatory indication allows. Plasma exchange and eculizumab are not indicated here; emergent dialysis addresses uremia but does not treat the underlying vasospastic mechanism.