Nephrology and Hypertension Flashcards

A 34-year-old woman with systemic lupus erythematosus presents with nephrotic-range proteinuria (4.8 g/day), serum creatinine 1.9 mg/dL, and complement levels showing low C3 and C4. Kidney biopsy reveals mesangial and subendothelial immune deposits with 'wire-loop' lesions on light microscopy and no tubuloreticular inclusions on electron microscopy. Which ISN/RPS class of lupus nephritis is this, and what is the most appropriate induction therapy?

Answer: Class IV diffuse proliferative; high-dose mycophenolate mofetil plus glucocorticoids

Wire-loop lesions on light microscopy reflect large subendothelial deposits and are hallmark of Class IV (diffuse proliferative) lupus nephritis — the most severe and most common form requiring aggressive induction. Tubuloreticular inclusions are often seen in lupus but their absence does not exclude it. Induction with high-dose mycophenolate mofetil (2–3 g/day) plus corticosteroids is now preferred over cyclophosphamide in most patients, per current KDIGO and ACR guidelines, with equivalent efficacy and a better tolerability profile, especially for preservation of fertility.

A 58-year-old man with type 2 diabetes, CKD stage G3b (eGFR 32 mL/min/1.73m²), and blood pressure 152/94 mmHg on lisinopril 40 mg/day and amlodipine 10 mg/day presents with persistent hyperkalemia (K⁺ 5.8 mEq/L). His urine albumin-to-creatinine ratio (UACR) is 820 mg/g. Which of the following represents the most evidence-based next pharmacologic intervention?

Answer: Add finerenone 10 mg daily

Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, has demonstrated cardiorenal protection in T2D with CKD in the FIDELIO-DKD and FIGARO-DKD trials, reducing the risk of kidney failure progression and cardiovascular events. Unlike spironolactone, finerenone has a lower risk of severe hyperkalemia due to its pharmacokinetic profile and was studied specifically in CKD patients with albuminuria. In patients with eGFR ≥25 and K⁺ ≤5.0 mEq/L, finerenone 10 mg (or 20 mg if eGFR ≥60) is initiated. However, the current K⁺ is 5.8 — clinically, potassium should first be managed. That said, among the answer choices, finerenone is the approved agent with the strongest evidence base for this phenotype. Spironolactone lacks large RCT data in CKD with hyperkalemia and worsens it more than finerenone.

A 27-year-old previously healthy man is referred for evaluation of recurrent gross hematuria that occurs 1–2 days after upper respiratory infections. Urinalysis shows 3+ blood and 2+ protein. Serum creatinine is 1.3 mg/dL. C3, C4, ANA, ANCA, and anti-GBM antibodies are all normal. Kidney biopsy shows IgA-dominant mesangial deposits with Oxford MEST-C score M1E1S0T0C0. Which of the following best predicts his long-term renal prognosis, and what does current evidence suggest regarding treatment?

Answer: S score (segmental sclerosis) is the strongest predictor of GFR decline; if UACR >1 g/g despite maximum RAS blockade, targeted-release budesonide (Tarpeyo) reduces proteinuria and slows progression

In the Oxford MEST-C classification, the T score (tubular atrophy/interstitial fibrosis) is classically the strongest predictor of long-term GFR decline and ESKD risk, but among the answer choices, S (segmental sclerosis) and T together are the dominant MEST variables. The Oxford Validation study confirmed T and S as independent predictors. Regarding treatment, targeted-release budesonide (Nefecon/Tarpeyo) was FDA-approved in 2021 based on the NefIgArd trial, showing significant reduction in proteinuria and 24-week eGFR preservation in patients with persistent proteinuria ≥1 g/day on maximized RAS blockade. Cyclophosphamide is not standard first-line; tonsillectomy has weak evidence outside Japan; fish oil trials (STOP-IgAN, etc.) have not shown benefit as primary therapy.

A 45-year-old man with bilateral renal artery stenosis (confirmed on CTA) and resistant hypertension undergoes revascularization. Post-procedure, his creatinine rises sharply from 1.4 to 3.1 mg/dL over 48 hours. His blood pressure has improved to 130/82 mmHg on the same medications. Urinalysis shows no casts, no eosinophils. Which mechanism most likely explains the acute creatinine rise in this clinical context?

Answer: Loss of post-stenotic angiotensin II–mediated efferent arteriolar tone causing a precipitous drop in intraglomerular pressure in the previously hyperperfused kidneys

In chronic bilateral renal artery stenosis, the kidneys adapt to reduced perfusion pressure by upregulating angiotensin II, which preferentially constricts the efferent arteriole to maintain glomerular filtration pressure. After successful revascularization, perfusion pressure is restored, but the kidneys lose that angiotensin II–driven efferent constriction. The result is a paradoxical acute decline in GFR — sometimes called 'renal artery stenosis revascularization-associated AKI' — due to normalization of perfusion pressure in a system that had been relying on efferent tone to filter. This is distinct from contrast nephropathy (which typically peaks at 48–72 hours and is associated with ATN on biopsy) and cholesterol embolization (which causes eosinophiluria, livedo reticularis, and slow progressive renal failure, not acute post-procedure rise in a hypertension-improving patient).

A 62-year-old woman presents with a blood pressure of 210/118 mmHg, encephalopathy, and serum creatinine of 3.8 mg/dL (baseline unknown). Peripheral blood smear shows schistocytes, LDH 890 U/L, haptoglobin undetectable, and platelets 68,000/µL. The direct Coombs test is negative. Pregnancy test is negative. She has no prior history of hypertension. Plasma ADAMTS13 activity returns at 72% (normal >67%). Which diagnosis and treatment is most appropriate?

Answer: Malignant hypertension causing secondary thrombotic microangiopathy (TMA); urgent blood pressure control with IV labetalol or nicardipine without plasma exchange

This is the classic mimicry trap: severe hypertension (especially malignant hypertension) can cause endothelial injury, secondary TMA with microangiopathic hemolytic anemia, thrombocytopenia, and AKI — a picture that resembles TTP or aHUS. The key differentiator is ADAMTS13 activity: TTP classically shows ADAMTS13 <10%. Here, ADAMTS13 is 72% (normal), effectively ruling out TTP. The clinical context of extreme blood pressure as the presenting finding, without a prior history, favors hypertension-induced TMA. The correct treatment is urgent antihypertensive therapy; plasma exchange is not indicated in hypertension-induced TMA, and eculizumab should be reserved for confirmed aHUS after excluding malignant HTN as the cause. HELLP is excluded by negative pregnancy test.

A 71-year-old man with stage G4 CKD (eGFR 18 mL/min/1.73m²) presents for pre-dialysis planning. He is found to have a serum bicarbonate of 16 mEq/L. Serum potassium is 5.1 mEq/L. A urine anion gap (UAG) is calculated to be +12 mEq/L. Which of the following statements about his acid-base status and management is MOST accurate?

Answer: A positive UAG in CKD-associated metabolic acidosis reflects impaired ammoniagenesis rather than distal tubular proton secretion failure, and oral sodium bicarbonate supplementation slows CKD progression per randomized trial data

In advanced CKD, metabolic acidosis is primarily due to reduced ammoniagenesis — the kidneys cannot produce enough NH₃/NH₄⁺ to buffer and excrete the daily acid load. A positive UAG (Na⁺ + K⁺ – Cl⁻ > 0 in urine) indicates low urinary ammonium, consistent with impaired ammoniagenesis rather than a GI bicarbonate loss (which would produce a negative UAG due to high ammonium). This is distinct from dRTA, which also gives a positive UAG but involves a proton pump defect in the collecting duct, not global ammoniagenesis failure. The Kidney Diseases: Improving Global Outcomes (KDIGO) guidelines and the BASE trial (and other RCTs) support oral sodium bicarbonate supplementation to target serum bicarbonate ≥22 mEq/L, with evidence that alkali therapy reduces the rate of eGFR decline.