Nephrology and Hypertension Flashcards

A 34-year-old woman with lupus nephritis (class IV) is maintained on mycophenolate mofetil and hydroxychloroquine. She presents with a creatinine rise from 0.9 to 2.1 mg/dL over 6 weeks, new proteinuria of 3.8 g/day, and a urine sediment showing RBC casts. Repeat renal biopsy shows class IV-S (A/C) disease with 40% tubular atrophy and interstitial fibrosis. Which of the following is the most appropriate next step?

Answer: Initiate voclosporin in addition to mycophenolate and low-dose corticosteroids

Voclosporin (a next-generation calcineurin inhibitor) combined with mycophenolate mofetil and low-dose corticosteroids is now FDA-approved for active lupus nephritis and has shown superior complete renal response rates in the AURORA trial. This patient has active disease (RBC casts, rising creatinine, heavy proteinuria) despite maintenance MMF, justifying escalation. The significant chronic damage (40% tubular atrophy/interstitial fibrosis) on biopsy argues against aggressive cyclophosphamide, which would not reverse established fibrosis and carries greater toxicity. Belimumab is approved as add-on therapy but has less evidence for acute flare with active sediment.

A 58-year-old man with resistant hypertension on maximum doses of amlodipine, lisinopril, and chlorthalidone has a blood pressure of 168/102 mmHg. Plasma aldosterone concentration (PAC) is 22 ng/dL and plasma renin activity (PRA) is 0.4 ng/mL/hr. He is started on spironolactone 25 mg daily with good BP control. Three months later his serum potassium is 6.1 mEq/L and creatinine has risen from 1.1 to 1.7 mg/dL. Which of the following is the MOST appropriate next step?

Answer: Perform adrenal vein sampling to guide unilateral adrenalectomy

This patient has biochemical primary hyperaldosteronism (PAC/PRA ratio >20 with PAC >15 ng/dL). After confirming primary aldosteronism, adrenal vein sampling (AVS) is the gold-standard procedure to distinguish unilateral from bilateral disease. Unilateral disease (adenoma) is curable with laparoscopic adrenalectomy, which would eliminate the need for lifelong mineralocorticoid antagonist therapy and its attendant side effects (hyperkalemia, rising creatinine from reduced GFR). Switching to amiloride or reducing spironolactone simply manages the drug toxicity without addressing the underlying surgically correctable cause. Discontinuing the ACE inhibitor worsens long-term cardiovascular and renal outcomes without solving the primary problem.

A 45-year-old man with type 2 diabetes, hypertension, and CKD stage G3b A3 (eGFR 38 mL/min, urine ACR 920 mg/g) is on maximum-dose lisinopril 40 mg daily. His BP is 138/88 mmHg and HbA1c is 7.1%. He asks about adding a second agent for kidney protection. Which combination provides the STRONGEST evidence for additive cardiorenal protection in this specific scenario?

Answer: Add finerenone

Finerenone, a non-steroidal selective mineralocorticoid receptor antagonist, demonstrated significant reductions in both the composite kidney endpoint (40% eGFR decline, ESKD, renal death) and cardiovascular events in the FIDELIO-DKD and FIGARO-DKD trials when added to maximum-tolerated RAS blockade in patients with diabetic kidney disease and significant albuminuria. Its selectivity for the MR results in less hyperkalemia and gynecomastia than spironolactone. Dual RAS blockade (ACEi + ARB) is contraindicated given the ONTARGET trial showing increased AKI, hyperkalemia, and hypotension without cardiovascular benefit. Spironolactone has no dedicated outcome trial data in DKD at scale and carries higher hyperkalemia risk at eGFR <45.

A 72-year-old woman is admitted with confusion and fatigue. Labs: Na 118 mEq/L, K 3.8 mEq/L, BUN 8 mg/dL, creatinine 0.7 mg/dL, serum osmolality 248 mOsm/kg, urine osmolality 520 mOsm/kg, urine Na 68 mEq/L. She takes escitalopram and hydrochlorothiazide. Thyroid and cortisol are normal. She has no edema and appears euvolemic. Which feature would MOST reliably distinguish SIADH from the cerebral salt-wasting syndrome (CSWS) as the etiology?

Answer: Clinical assessment of extracellular fluid (ECF) volume status

The definitive distinguishing feature between SIADH and CSWS is extracellular fluid (ECF) volume status: SIADH is characterized by normal-to-expanded ECF (euvolemic or mildly hypervolemic), whereas CSWS is a salt-wasting nephropathy leading to true hypovolemia with volume depletion. Both conditions share elevated urine sodium (>40 mEq/L), urine osmolality > serum osmolality, and even low serum uric acid (both cause fractional uric acid excretion >12%). In CSWS, fluid restriction (SIADH treatment) worsens the condition, while volume and sodium replacement is correct. In practice, CVP measurement or careful clinical volume assessment (orthostatic BP, skin turgor, mucous membranes, weight trend) is the key differentiator. This distinction is critical because CSWS commonly occurs after subarachnoid hemorrhage.

A 29-year-old man is referred for evaluation of hematuria and proteinuria (1.2 g/day). He has a family history of end-stage renal disease in his maternal grandfather and sensorineural hearing loss diagnosed at age 12. Renal biopsy electron microscopy shows thinning and splitting of the glomerular basement membrane (GBM) with a characteristic 'basket-weave' pattern. Genetic testing confirms a heterozygous pathogenic variant in COL4A5. Which statement about his prognosis and management is MOST accurate?

Answer: ACE inhibitor therapy initiated before proteinuria exceeds 0.5 g/day has been shown to delay ESKD by approximately 13 years in retrospective studies

COL4A5 mutations cause X-linked Alport syndrome (XLAS). Males with XLAS are hemizygous and almost invariably progress to ESKD, typically by age 20-30 without treatment. Retrospective data from the European Alport Registry (Gross et al.) demonstrated that ACE inhibitor therapy started at the stage of microhematuria alone (before proteinuria develops) delayed ESKD by approximately 13 years compared to treatment started at the proteinuria stage, and by about 13 years compared to no treatment. This supports early nephroprotective intervention. Males with COL4A5 mutations are NOT mild carriers — that term applies to heterozygous females, who have variable expression. The basket-weave GBM is the EM hallmark of Alport syndrome regardless of inheritance pattern.

A 55-year-old woman with a history of Sjögren's syndrome presents with progressive fatigue and muscle weakness. Labs: Na 138, K 2.8, Cl 115, HCO3 10 mEq/L, pH 7.28, pCO2 22 mmHg. Urine pH is 6.5. Urine anion gap is +18. Serum anion gap is 13. She is not taking any medications. Which of the following best explains the pathophysiology of her acid-base disorder?

Answer: Impaired ammonium excretion due to defective alpha-intercalated cell H+-ATPase in the collecting duct

This patient has a normal anion gap (hyperchloremic) metabolic acidosis with a positive urine anion gap (+18, indicating impaired ammonium excretion) and an inappropriately alkaline urine pH of 6.5 despite systemic acidosis — the hallmarks of distal (Type 1) renal tubular acidosis (RTA). Sjögren's syndrome classically causes Type 1 dRTA through autoimmune-mediated destruction or dysfunction of the alpha-intercalated cell H+-ATPase in the collecting duct, impairing proton secretion. The kidney cannot acidify urine below pH 5.5 even in the face of systemic acidemia. Proximal (Type 2) RTA would show a negative urine anion gap (intact ammonium excretion), bicarbonaturia when plasma HCO3 is above threshold, and urine pH appropriately <5.5 once HCO3 falls below the reabsorptive threshold. Type 4 RTA (aldosterone resistance) presents with hyperkalemia, not hypokalemia.