Generate 150 high yeild mcqs for sple doctor of pharmacy regarding nephrology drugs , disease, uses, contraindications, adrs, in detail

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I now have sufficient textbook context from Brenner & Rector's The Kidney, Comprehensive Clinical Nephrology, National Kidney Foundation Primer, and Katzung's pharmacology. I'll now generate all 150 high-yield MCQs from my deep nephrology knowledge base, organized by topic.

150 High-Yield Nephrology MCQs for PharmD SPLE Examination

Topics covered: Nephrology drugs, diseases, mechanisms, uses, contraindications, ADRs

SECTION 1: ACUTE KIDNEY INJURY (AKI) — Q1–20

Q1. A 68-year-old man develops oliguria and rising creatinine 48 hours after receiving IV contrast for a CT scan. Which of the following best describes the mechanism of contrast-induced AKI?

A. Immune complex deposition in glomeruli B. Renal tubular obstruction by uric acid crystals C. Direct tubular toxicity combined with renal vasoconstriction D. Interstitial nephritis triggered by iodine allergy E. Retrograde pyelonephritis

Answer: C Contrast nephropathy results from a combination of direct tubular cytotoxicity and afferent arteriolar vasoconstriction causing medullary ischemia. N-acetylcysteine and IV hydration are preventive strategies.

Q2. Which diuretic is most appropriate for managing fluid overload in oliguric AKI when the patient is still making some urine?

A. Acetazolamide B. Spironolactone C. Furosemide D. Hydrochlorothiazide E. Torsemide oral

Answer: C Loop diuretics (furosemide, bumetanide, torsemide) are the agents of choice in AKI-related volume overload. High doses IV may be required due to impaired tubular secretion.

Q3. A patient with AKI develops serum K⁺ of 6.8 mEq/L with peaked T-waves on ECG. What is the FIRST medication to administer?

A. Sodium polystyrene sulfonate B. IV sodium bicarbonate C. IV 10% calcium gluconate D. Regular insulin + D50W E. IV furosemide

Answer: C Calcium gluconate is the first-line treatment for hyperkalemia with ECG changes. It acts within minutes to stabilize the cardiac membrane. It does NOT lower potassium but protects the heart while other agents act.

Q4. Which of the following medications is most commonly associated with causing pre-renal AKI due to reduced renal perfusion pressure?

A. Vancomycin B. NSAIDs C. Amphotericin B D. Aminoglycosides E. Cisplatin

Answer: B NSAIDs block prostaglandin-mediated afferent arteriolar dilation, which is particularly critical in states of reduced renal perfusion (CHF, dehydration, cirrhosis). This results in pre-renal or functional AKI.

Q5. A 72-year-old woman with CKD stage 3 is started on an NSAID for arthritis. Her creatinine rises from 1.8 to 3.2 mg/dL. What is the most likely mechanism?

A. Immune complex glomerulonephritis B. Inhibition of renal prostaglandins causing afferent arteriolar constriction C. Direct tubular necrosis D. Papillary necrosis from chronic use E. Allergic interstitial nephritis

Answer: B In CKD, renal perfusion increasingly depends on vasodilatory prostaglandins. NSAIDs block COX, eliminating this compensatory mechanism, leading to hemodynamically mediated AKI.

Q6. Which aminoglycoside has the LEAST nephrotoxic potential?

A. Gentamicin B. Tobramycin C. Amikacin D. Neomycin E. Streptomycin

Answer: E Streptomycin is the least nephrotoxic aminoglycoside. Neomycin is the most nephrotoxic. Gentamicin and tobramycin carry moderate nephrotoxicity risk; amikacin is slightly less nephrotoxic than gentamicin.

Q7. Aminoglycoside nephrotoxicity preferentially damages which part of the nephron?

A. Bowman's capsule podocytes B. Proximal convoluted tubule C. Loop of Henle ascending limb D. Distal convoluted tubule E. Collecting duct

Answer: B Aminoglycosides accumulate in the lysosomes of proximal tubular cells, causing tubular necrosis. Clinically this presents as non-oliguric AKI, cast-containing urine, and electrolyte wasting (Mg, K, Ca).

Q8. A patient develops AKI after starting amphotericin B deoxycholate. Which formulation significantly reduces nephrotoxicity while maintaining efficacy?

A. Amphotericin B oral suspension B. Liposomal amphotericin B (AmBisome) C. Nystatin IV D. Voriconazole IV E. Micafungin IV

Answer: B Liposomal amphotericin B (L-AmB) is dramatically less nephrotoxic than conventional amphotericin B because the liposomal packaging reduces uptake by renal tubular cells. It remains equally effective.

Q9. Which of the following best defines the RIFLE criteria for "Risk" of AKI?

A. Creatinine increase ×3 OR GFR decrease >75% B. Creatinine increase ×1.5 OR GFR decrease >25%, urine output <0.5 mL/kg/hr ×6h C. Creatinine increase ×2 OR GFR decrease >50% D. Any creatinine rise with oliguria >12 hours E. Need for renal replacement therapy

Answer: B RIFLE = Risk (Cr ×1.5 or GFR -25%; UO <0.5 mL/kg/hr ×6h), Injury (×2 or -50%; UO <0.5 ×12h), Failure (×3 or -75%; UO <0.3 ×24h or anuria ×12h), Loss (>4 weeks), ESRD (>3 months).

Q10. Cisplatin nephrotoxicity is best prevented by which of the following strategies?

A. Coadministration with probenecid B. Aggressive IV normal saline hydration before and after infusion C. Alkalinization of urine D. Coadministration with allopurinol E. Use of acetazolamide pre-treatment

Answer: B Vigorous saline hydration (1–2 L before and after cisplatin) remains the gold standard for preventing cisplatin nephrotoxicity. Amifostine is an adjunctive cytoprotective agent. Mannitol diuresis may also help.

Q11. A patient on long-term lithium therapy develops nephrogenic diabetes insipidus. What is the best pharmacologic treatment for lithium-induced NDI?

A. Desmopressin B. Furosemide + low-salt diet C. Amiloride D. Hydrochlorothiazide alone E. Indomethacin

Answer: C Amiloride blocks epithelial sodium channels (ENaC) in the collecting duct, the same channels through which lithium enters principal cells to inhibit aquaporin-2. It is the preferred treatment for lithium-induced NDI.

Q12. Which diuretic can paradoxically reduce urine output in nephrogenic DI by reducing free water delivery to the collecting duct?

A. Loop diuretics B. Thiazide diuretics C. Potassium-sparing diuretics D. Osmotic diuretics E. Carbonic anhydrase inhibitors

Answer: B Thiazides cause mild volume depletion, activating proximal tubule sodium and water reabsorption, thereby reducing water delivery to the ADH-resistant collecting duct. This reduces polyuria in both central and nephrogenic DI.

Q13. Which of the following is the most accurate early biomarker of AKI, rising within 2–4 hours of tubular injury?

A. Serum creatinine B. Blood urea nitrogen (BUN) C. NGAL (neutrophil gelatinase-associated lipocalin) D. Cystatin C E. Fractional excretion of sodium (FeNa)

Answer: C NGAL rises within 2–4 hours of AKI and is highly sensitive. Serum creatinine rises late (24–48 hours after significant GFR loss). Cystatin C is a better GFR marker than creatinine but is not an early injury biomarker.

Q14. What is the mechanism of N-acetylcysteine (NAC) in preventing contrast-induced AKI?

A. Acts as a direct vasodilator of afferent arterioles B. Chelates iodine contrast molecules in the tubules C. Antioxidant that scavenges reactive oxygen species D. Inhibits complement activation E. Competitively blocks renal organic ion transporters

Answer: C NAC is a free radical scavenger and antioxidant. It replenishes glutathione stores, reducing oxidative tubular injury from contrast media. Evidence is mixed for efficacy, but it is low-risk and inexpensive.

Q15. A patient with AKI has BUN of 95 mg/dL, creatinine of 7.2 mg/dL, and is becoming confused. What BUN:Cr ratio suggests pre-renal etiology?

A. 5:1 B. 10:1 C. Greater than 20:1 D. Equal to 15:1 E. Less than 10:1

Answer: C A BUN:Cr ratio >20:1 suggests pre-renal azotemia (increased urea reabsorption due to avid sodium and water reabsorption). Intrinsic renal disease gives a ratio of ~10–15:1.

Q16. A 55-year-old man on gentamicin develops AKI with urine sodium of 45 mEq/L and fractional excretion of sodium of 4%. What does this suggest?

A. Pre-renal AKI B. Intrinsic (tubular) AKI - ATN C. Post-renal obstruction D. Glomerulonephritis E. Hepatorenal syndrome

Answer: B FeNa >2% with tubular casts and high urine Na suggests tubular damage (ATN). Pre-renal AKI shows FeNa <1% with low urine Na (<20 mEq/L). Aminoglycosides cause direct proximal tubular injury.

Q17. Which of the following medications used in critically ill patients is most associated with acute tubular necrosis due to accumulation of its solvent?

A. IV lorazepam (propylene glycol-based formulation) B. IV furosemide C. IV vasopressin D. IV norepinephrine E. Oral mycophenolate mofetil

Answer: A High-dose IV lorazepam contains propylene glycol as a solvent. Prolonged use leads to propylene glycol toxicity, causing an osmol gap and AKI (primarily tubular toxicity). This is an SPLE-relevant pharmacist fact.

Q18. In hepatorenal syndrome (HRS) type 1, which is the preferred pharmacologic treatment to bridge to liver transplant?

A. Dopamine + furosemide B. Terlipressin + albumin C. Midodrine + albumin D. Norepinephrine alone E. Vasopressin + octreotide

Answer: B Terlipressin (a vasopressin analogue) combined with IV albumin is the preferred treatment for HRS-1 in many guidelines. It causes splanchnic vasoconstriction, improving renal perfusion. FDA approved terlipressin (Terlivaz) in 2022.

Q19. Which statement about renal replacement therapy (RRT) initiation in AKI is CORRECT?

A. Dialysis should start when BUN exceeds 50 mg/dL regardless of symptoms B. Emergent indications include refractory hyperkalemia, severe acidosis, uremic pericarditis, fluid overload C. Peritoneal dialysis is preferred over hemodialysis in all AKI patients D. Continuous RRT is always superior to intermittent hemodialysis in outcomes E. RRT is contraindicated if AKI is expected to be reversible

Answer: B "AEIOU" indications: Acidosis (pH <7.1), Electrolytes (K⁺ >6.5 resistant), Intoxication, Overload (refractory), Uremia (pericarditis, encephalopathy). These are emergent dialysis indications.

Q20. A patient with AKI secondary to rhabdomyolysis has myoglobinuria. Which urinary finding distinguishes myoglobinuria from hemoglobinuria on dipstick?

A. Dipstick positive for blood but microscopy shows no RBCs (both) B. Dipstick negative in myoglobinuria C. Only hemoglobinuria causes red-brown urine D. Myoglobinuria shows large numbers of RBC casts E. Both cause negative dipstick results

Answer: A Both myoglobin and hemoglobin test positive on urine dipstick "blood" (heme-positive) but microscopically show no red blood cells. Clinical context differentiates: rhabdomyolysis has elevated CK, hemolysis has elevated LDH and indirect bilirubin.

SECTION 2: CHRONIC KIDNEY DISEASE (CKD) — Q21–50

Q21. According to KDIGO guidelines, CKD Stage G3a is defined by which GFR range?

A. GFR 60–89 mL/min/1.73m² B. GFR 45–59 mL/min/1.73m² C. GFR 30–44 mL/min/1.73m² D. GFR 15–29 mL/min/1.73m² E. GFR <15 mL/min/1.73m²

Answer: B KDIGO stages: G1 ≥90, G2 60–89, G3a 45–59, G3b 30–44, G4 15–29, G5 <15 mL/min/1.73m². All require concurrent evidence of kidney damage (proteinuria, imaging, biopsy) persisting >3 months.

Q22. Which of the following best describes the "intact nephron hypothesis" in CKD progression?

A. Damaged nephrons are replaced by functional new nephrons B. Surviving nephrons undergo hypertrophy and hyperfiltration to compensate C. CKD progression is halted by compensatory tubular regeneration D. The glomerulus remains intact even as tubules are destroyed E. Damaged nephrons excrete more toxins per unit than normal nephrons

Answer: B Bricker's intact nephron hypothesis: remaining nephrons undergo compensatory hypertrophy and hyperfiltration, which partially maintains overall GFR but ultimately causes progressive glomerulosclerosis and accelerates CKD.

Q23. Which drug class is first-line for slowing CKD progression in diabetic nephropathy?

A. Calcium channel blockers B. Beta-blockers C. ACE inhibitors or ARBs D. Alpha-1 blockers E. Thiazide diuretics

Answer: C ACEi/ARBs reduce intraglomerular pressure by blocking angiotensin II-mediated efferent arteriolar constriction, lowering proteinuria and slowing GFR decline independent of BP lowering.

Q24. A CKD patient on an ACE inhibitor develops progressive hyperkalemia and a rise in creatinine of 30% above baseline after drug initiation. What is the appropriate action?

A. Immediately stop the ACEi B. Add sodium polystyrene sulfonate and continue ACEi C. A creatinine rise up to 30% and mild hyperkalemia are acceptable; optimize diet and continue D. Switch to a calcium channel blocker E. Add a loop diuretic and monitor closely while switching medications

Answer: C A creatinine rise of up to 30–35% within the first 2 months of RAAS blockade is acceptable and does not require stopping the drug. Greater rises or persistent hyperkalemia (>5.5 mEq/L) require dose reduction or discontinuation.

Q25. SGLT2 inhibitors have nephroprotective effects in CKD. What is their primary renal mechanism beyond glucose lowering?

A. Inhibition of mesangial cell proliferation B. Reduction of tubuloglomerular feedback-mediated glomerular hypertension C. Direct inhibition of the RAAS system D. Reduction of renal fibrosis via TGF-β blockade E. Blocking proximal tubule glucose reabsorption causing glycosuria only

Answer: B SGLT2 inhibitors increase sodium delivery to the macula densa, restoring tubuloglomerular feedback (TGF), causing afferent arteriolar constriction and reducing intraglomerular pressure/hyperfiltration. This is independent of glucose lowering.

Q26. Which SGLT2 inhibitor has shown significant reduction in CKD progression and cardiovascular death in the DAPA-CKD and CREDENCE trials?

A. Dapagliflozin (DAPA-CKD) and Canagliflozin (CREDENCE) B. Empagliflozin only C. Ertugliflozin only D. All SGLT2 inhibitors equally E. None have proven renal outcomes benefit

Answer: A CREDENCE (canagliflozin) and DAPA-CKD (dapagliflozin) showed ~40% relative risk reduction in composite kidney endpoints. EMPA-KIDNEY (empagliflozin) also showed benefit. These are class effects.

Q27. Which of the following is a contraindication to SGLT2 inhibitors?

A. CKD stage G3a (GFR 45–59) B. Type 2 diabetes with microalbuminuria C. Recurrent urinary tract infections AND eGFR <20 mL/min/1.73m² (for glucose lowering) D. Hypertension without diabetes E. CKD with proteinuria >300 mg/day

Answer: C SGLT2 inhibitors are not effective as glucose-lowering agents when eGFR <30 but retain kidney/CV protection down to eGFR ≥20 in some indications. Genital mycotic infections are common ADRs; UTIs are a relative concern.

Q28. Which mineral bone disorder complication is MOST common in advanced CKD?

A. Hypercalcemia and hyperphosphatemia B. Hypocalcemia, hyperphosphatemia, and secondary hyperparathyroidism C. Primary hyperparathyroidism D. Osteoporosis from vitamin D excess E. Adynamic bone disease from excess parathyroid hormone

Answer: B CKD-MBD: reduced 1,25-dihydroxyvitamin D → hypocalcemia; reduced GFR → hyperphosphatemia; FGF-23 rises early; secondary hyperparathyroidism develops to maintain calcium homeostasis.

Q29. Which form of vitamin D is used to treat secondary hyperparathyroidism in CKD patients who cannot activate vitamin D in the kidney?

A. Cholecalciferol (vitamin D3) B. Ergocalciferol (vitamin D2) C. Calcitriol (1,25-dihydroxyvitamin D) D. 25-hydroxyvitamin D E. Dihydrotachysterol

Answer: C Since CKD impairs 1-alpha-hydroxylase in the kidney, the final activation step to calcitriol is impaired. Therefore, active forms - calcitriol or synthetic analogues (paricalcitol, doxercalciferol) - must be given directly.

Q30. Cinacalcet works by what mechanism to treat secondary hyperparathyroidism in CKD?

A. Binds and activates vitamin D receptors in the parathyroid gland B. Chelates phosphate in the GI tract C. Allosteric activator of the calcium-sensing receptor (CaSR) in parathyroid cells D. Competitive inhibitor of PTH release from parathyroid cells E. Directly binds PTH and prevents its action at the kidney

Answer: C Cinacalcet is a calcimimetic - it sensitizes the CaSR on parathyroid cells to calcium, causing reduced PTH secretion. It lowers PTH, calcium, and phosphorus simultaneously. Side effects include nausea, hypocalcemia.

Q31. Which phosphate binder is contraindicated in patients with hypercalcemia?

A. Sevelamer hydrochloride B. Lanthanum carbonate C. Calcium carbonate D. Sucroferric oxyhydroxide E. Ferric citrate

Answer: C Calcium-based phosphate binders (calcium carbonate, calcium acetate) can worsen hypercalcemia and are associated with vascular calcification in CKD/ESRD. Non-calcium binders (sevelamer, lanthanum, iron-based) are preferred when calcium is elevated.

Q32. Sevelamer carbonate (vs. sevelamer HCl) has which additional benefit in CKD patients?

A. More potent phosphate binding B. Reduces LDL cholesterol by binding bile acids C. Corrects metabolic acidosis rather than worsening it D. Has fewer GI side effects E. Both B and C

Answer: E Sevelamer in all forms binds bile acids, lowering LDL. Sevelamer carbonate provides a bicarbonate ion upon absorption, helping correct metabolic acidosis, unlike sevelamer HCl which can worsen acidosis by releasing HCl.

Q33. What is the target hemoglobin range recommended for ESA (erythropoiesis-stimulating agent) therapy in CKD patients on dialysis?

A. 8–9 g/dL B. 10–11.5 g/dL C. 12–13 g/dL D. 13–14 g/dL E. >14 g/dL

Answer: B KDIGO recommends a target Hgb of 10–11.5 g/dL in CKD patients on ESAs. Targeting >13 g/dL (CHOIR, TREAT, CREATE trials) increased cardiovascular events, stroke, and thrombosis risk.

Q34. Which serious ADR is associated with supratherapeutic use of erythropoietin-stimulating agents (EPO)?

A. Hemolytic anemia B. Pure red cell aplasia (PRCA) C. Aplastic anemia D. Megaloblastic anemia E. Sickle cell crisis

Answer: B Pure red cell aplasia is a rare but serious complication of ESA therapy (especially subcutaneous epoetin alfa) due to development of neutralizing anti-EPO antibodies that cross-react with endogenous EPO.

Q35. A dialysis patient with functional iron deficiency (normal ferritin but low transferrin saturation <20%) should receive:

A. Oral ferrous sulfate B. IV iron supplementation C. Folic acid and B12 D. Darbepoietin alfa dose increase E. Red blood cell transfusion

Answer: B Oral iron is poorly absorbed and often inadequate in dialysis patients. IV iron (ferric carboxymaltose, iron sucrose, ferumoxytol, low-molecular-weight iron dextran) effectively replenishes iron stores. Target: ferritin 200–500 ng/mL, TSAT >20%.

Q36. Which of the following is the mechanism of metabolic acidosis in CKD?

A. Increased production of lactic acid B. Reduced GFR leads to retention of organic acid anions and impaired ammonia excretion C. Loss of bicarbonate through the damaged tubules D. Excess mineralocorticoid activity causing proton retention E. Increased carbonic anhydrase activity

Answer: B In CKD, the kidneys fail to excrete the daily ~1 mEq/kg acid load due to reduced ammoniagenesis and reduced nephron mass. Retained anions (sulfate, phosphate, urate) contribute to anion-gap acidosis. Bicarbonate supplementation is used when HCO₃⁻ <22 mEq/L.

Q37. Which antihypertensive drug combination is CONTRAINDICATED in CKD patients due to increased risk of hyperkalemia and AKI (per VA NEPHRON-D and ONTARGET trials)?

A. ACEi + calcium channel blocker B. ACEi + ARB (dual RAAS blockade) C. ARB + beta-blocker D. Thiazide + loop diuretic E. ACEi + aldosterone antagonist

Answer: B Dual RAAS blockade (ACEi + ARB) markedly increases risk of hyperkalemia, AKI, and hypotension without additional cardioprotective benefit (ONTARGET, VA NEPHRON-D). Contraindicated in CKD. Direct renin inhibitors (aliskiren) are also contraindicated with ACEi/ARB.

Q38. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is FDA-approved for which CKD indication?

A. CKD in Type 1 diabetes B. CKD with proteinuria in Type 2 diabetes, to reduce renal and cardiovascular events C. CKD Stage 5 on hemodialysis D. Polycystic kidney disease E. Nephrotic syndrome with minimal change disease

Answer: B Finerenone (FDA 2021) is approved for CKD with albuminuria in T2DM. The FIDELIO-DKD and FIGARO-DKD trials showed reduced kidney failure progression and cardiovascular events. Less hyperkalemia risk than steroidal MRAs.

Q39. Which is the preferred diuretic class in CKD stages G1–G3 for hypertension management when diuresis is needed?

A. Spironolactone B. Thiazide diuretics (chlorthalidone or HCTZ) C. Acetazolamide D. Loop diuretics E. Mannitol

Answer: B Thiazides are effective antihypertensives in CKD stages 1–3 (GFR >30). At GFR <30, thiazides lose efficacy and loop diuretics become necessary for fluid management, though thiazides retain some antihypertensive effect.

Q40. A CKD patient develops worsening leg edema and dyspnea. Which combination of diuretics provides synergistic "sequential nephron blockade"?

A. Two loop diuretics together B. Loop diuretic + thiazide/thiazide-like diuretic (metolazone) C. Spironolactone + eplerenone D. Furosemide + mannitol E. Torsemide + acetazolamide

Answer: B Metolazone (or HCTZ) blocks the distal tubule, preventing sodium reabsorption that "escapes" loop diuretic action. This synergistic combination is highly effective for diuretic-resistant edema. Monitor for severe electrolyte disturbances.

Q41. Which statement about metformin use in CKD is CORRECT per current FDA labeling (2016 update)?

A. Metformin is absolutely contraindicated in all CKD patients B. Metformin is contraindicated when eGFR <30 mL/min/1.73m²; initiate cautiously if eGFR 30–45 C. Metformin can be used safely at all CKD stages with dose reduction D. Metformin risk is only related to GI side effects in CKD E. Metformin is safe in dialysis patients

Answer: B Metformin is contraindicated in eGFR <30 due to lactic acidosis risk (impaired renal clearance of metformin and lactate). Use with caution if eGFR 30–45, and re-check eGFR frequently. Avoid in eGFR <30.

Q42. Which antimicrobial requires a dose reduction of approximately 50% when eGFR falls below 30 mL/min because it is renally cleared as active drug?

A. Azithromycin B. Moxifloxacin C. Ciprofloxacin D. Clindamycin E. Rifampin

Answer: C Ciprofloxacin is primarily renally excreted (50–70%). Dose reduction is needed with GFR <30. Moxifloxacin is hepatically metabolized and does not require dose adjustment in renal impairment.

Q43. Which drug used for hyperphosphatemia is associated with iron deficiency due to binding dietary iron?

A. Sevelamer carbonate B. Lanthanum carbonate C. Calcium acetate D. Ferric citrate is the reverse (provides iron) E. Sucroferric oxyhydroxide

Answer: A Sevelamer can reduce absorption of various nutrients. Ferric citrate (Auryxia) and sucroferric oxyhydroxide (Velphoro) actually provide or contain iron and can improve iron status while binding phosphate.

Q44. What is the target BP in CKD patients with proteinuria >500 mg/day, according to KDIGO 2021 guidelines?

A. <140/90 mmHg B. <130/80 mmHg C. <120/80 mmHg D. <150/90 mmHg E. <125/75 mmHg

Answer: B KDIGO 2021 recommends BP <120 mmHg systolic (using standardized office measurement) in CKD based on SPRINT trial data. Many clinicians target <130/80 as a practical goal, particularly for proteinuric CKD. Know both targets.

Q45. Patiromer (Veltassa) and sodium zirconium cyclosilicate (Lokelma) are novel treatments for which electrolyte disorder in CKD?

A. Hypokalemia B. Hyperphosphatemia C. Hyperkalemia D. Hyponatremia E. Hypomagnesemia

Answer: C Both are potassium binders approved for chronic hyperkalemia management. Patiromer (cation exchanger) exchanges calcium for potassium in the GI tract. SZC (zirconium silicate) is a highly selective potassium-trapping ion exchanger.

Q46. Sodium polystyrene sulfonate (Kayexalate) is associated with which rare but serious GI complication?

A. Paralytic ileus B. Intestinal necrosis (particularly when given with sorbitol) C. GI hemorrhage from direct erosion D. Mesenteric ischemia E. Appendicitis

Answer: B Kayexalate (particularly in sorbitol suspension) is associated with intestinal necrosis, especially in post-operative patients or those with ileus. This has led to FDA warnings and growing preference for newer K⁺ binders.

Q47. Which of the following statements about bicarbonate supplementation in CKD is CORRECT?

A. Bicarbonate supplementation has no benefit in slowing CKD progression B. Maintaining serum bicarbonate >22 mEq/L may slow CKD progression and reduce protein catabolism C. IV bicarbonate is required for CKD acidosis D. Bicarbonate supplementation worsens hypertension in all cases E. Acidosis in CKD should never be treated pharmacologically

Answer: B Several trials (de Brito-Ashurst, Mahajan) demonstrated that correcting metabolic acidosis with oral sodium bicarbonate slows CKD progression, reduces protein catabolism, and may improve bone density. KDIGO recommends treating when HCO₃⁻ <22 mEq/L.

Q48. Which GFR formula is recommended by KDIGO for routine clinical use?

A. Cockcroft-Gault (CG) B. MDRD-4 variable equation C. CKD-EPI creatinine equation D. Schwartz formula E. Jelliffe formula

Answer: C CKD-EPI creatinine is recommended for most adults. CKD-EPI creatinine-cystatin C is more accurate. Schwartz is for pediatric patients. Cockcroft-Gault is used for drug dosing calculations by pharmacists.

Q49. In a CKD patient with severe hyperkalemia (K⁺ = 6.5) resistant to medical management, which type of dialysis removes potassium most efficiently?

A. Peritoneal dialysis (PD) B. Continuous renal replacement therapy (CRRT) C. Intermittent hemodialysis (IHD) D. Both IHD and CRRT equally E. Plasmapheresis

Answer: C IHD removes potassium most rapidly (in 3–4 hours), making it the preferred modality for acute, life-threatening hyperkalemia. CRRT removes potassium slowly but continuously. PD is least efficient for acute K⁺ removal.

Q50. Allopurinol in CKD patients with hyperuricemia and gout requires dose adjustment because:

A. Allopurinol worsens CKD progression directly B. Its active metabolite oxypurinol is renally cleared and accumulates in CKD C. Allopurinol is nephrotoxic at standard doses D. CKD reduces allopurinol absorption E. Allopurinol interacts with erythropoietin

Answer: B Oxypurinol (active metabolite) accumulates in CKD. Dose should be reduced based on GFR. Febuxostat is an alternative with less renal dose adjustment needed, but requires caution in cardiovascular disease.

SECTION 3: GLOMERULAR DISEASES — Q51–75

Q51. A 4-year-old boy presents with periorbital edema, heavy proteinuria (>40 mg/m²/hr), hypoalbuminemia, and hyperlipidemia. Urine shows no hematuria. The MOST likely diagnosis is:

A. IgA nephropathy B. Focal segmental glomerulosclerosis (FSGS) C. Minimal change disease (MCD) D. Membranous nephropathy E. Lupus nephritis

Answer: C Nephrotic syndrome in children is MCD in ~90% of cases. It is steroid-responsive, shows no hematuria, and electron microscopy reveals podocyte foot process effacement with no immune deposits.

Q52. First-line treatment for minimal change disease in adults is:

A. Mycophenolate mofetil B. Cyclophosphamide C. High-dose oral prednisone (1 mg/kg/day up to 80 mg) D. Tacrolimus E. Rituximab

Answer: C Prednisone 1 mg/kg/day (max 80 mg) for 8–16 weeks is first-line for MCD. Adults respond more slowly than children. Rituximab is used for steroid-dependent/frequently relapsing MCD.

Q53. A patient with nephrotic syndrome has the following findings: subepithelial immune deposits ("spike and dome" pattern), positive PLA2R antibodies. What is the most likely diagnosis?

A. FSGS B. Minimal change disease C. Membranous nephropathy (primary) D. Membranoproliferative GN E. IgA nephropathy

Answer: C Primary membranous nephropathy is associated with anti-PLA2R (phospholipase A2 receptor) antibodies in ~70–80% of cases. Subepithelial deposits create the "spike and dome" appearance on silver stain.

Q54. Which treatment regimen is used for primary membranous nephropathy in patients at high risk of progression (high anti-PLA2R titers, declining GFR, nephrotic-range proteinuria)?

A. Prednisone monotherapy B. Modified Ponticelli regimen (alternating months of methylprednisolone + chlorambucil or cyclophosphamide) C. Mycophenolate alone D. Tacrolimus monotherapy E. ACEi/ARB alone

Answer: B The Ponticelli regimen alternates IV methylprednisolone + oral corticosteroids with chlorambucil (or cyclophosphamide) for 6 months. Rituximab is increasingly first-line based on the MENTOR and STARMEN trials.

Q55. What is the most common primary cause of nephrotic syndrome in ADULTS in the United States?

A. Minimal change disease B. Membranous nephropathy C. Focal segmental glomerulosclerosis (FSGS) D. Membranoproliferative GN E. IgA nephropathy

Answer: C FSGS is now the most common primary nephrotic syndrome in adults in the US. Membranous nephropathy is second. MCD is the most common in children.

Q56. A patient with FSGS fails steroids. Which is the most appropriate second-line immunosuppressive agent?

A. Cyclophosphamide B. Azathioprine C. Calcineurin inhibitors (cyclosporine or tacrolimus) D. Mycophenolate mofetil alone E. Chlorambucil

Answer: C Calcineurin inhibitors (cyclosporine, tacrolimus) are the most evidence-supported second-line agents for steroid-resistant FSGS. They work by stabilizing the actin cytoskeleton of podocytes in addition to immunosuppression.

Q57. IgA nephropathy is MOST commonly diagnosed in which demographic?

A. Elderly women with diabetes B. African American adults over 50 C. Asian young adult males D. Children under 5 years of age E. Post-menopausal women with hypertension

Answer: C IgA nephropathy (Berger's disease) is the most common primary GN worldwide. It affects predominantly young Asian and Caucasian males (2:1 male predominance). Classic presentation: gross hematuria with upper respiratory infections ("synpharyngitic hematuria").

Q58. Sparsentan is a novel dual-receptor antagonist approved for IgA nephropathy. What receptors does it antagonize?

A. Angiotensin II receptor type 1 AND endothelin type A receptor B. Aldosterone receptor AND angiotensin receptor C. Endothelin A AND endothelin B receptors D. Bradykinin receptor AND complement C5 receptor E. FcRn receptor AND TNF receptor

Answer: A Sparsentan (FDA approved 2023) is a dual AT1/ETA antagonist. It reduces intraglomerular pressure (AT1 blockade) and reduces mesangial cell proliferation/fibrosis (ETA blockade), significantly reducing proteinuria in IgA nephropathy.

Q59. Which treatment for IgA nephropathy was FDA-approved based on the NefIgArd trial?

A. Budesonide targeted-release capsules (Nefecon/Tarpeyo) B. Rituximab C. Mycophenolate mofetil D. Belimumab E. Voclosporin

Answer: A Budesonide (Tarpeyo/Nefecon) is a targeted-release oral corticosteroid that releases in the ileum, suppressing mucosal IgA production with reduced systemic side effects. FDA accelerated approval 2021, full approval 2023.

Q60. In lupus nephritis class IV (diffuse proliferative), what is the induction regimen of choice?

A. High-dose prednisone alone B. Mycophenolate mofetil + low-dose prednisone OR cyclophosphamide (NIH protocol) + high-dose prednisone C. Tacrolimus + prednisone D. Rituximab alone E. Azathioprine + prednisone

Answer: B Both MMF (2–3 g/day) + prednisone and cyclophosphamide (IV monthly for 6 months - NIH protocol) are acceptable for induction in class III/IV LN. MMF has similar efficacy with better tolerability. Voclosporin + MMF + prednisone (AURORA trial) is a newer option.

Q61. What is the most common cause of nephrotic syndrome in HIV-positive patients?

A. Membranous nephropathy B. HIV-associated nephropathy (HIVAN) - collapsing FSGS C. IgA nephropathy D. Membranoproliferative GN E. Minimal change disease

Answer: B HIVAN causes a collapsing variant of FSGS with podocyte injury, and is most common in patients of African descent with uncontrolled HIV. Highly active antiretroviral therapy (HAART) is the primary treatment.

Q62. A patient develops a positive ANCA (PR3-ANCA) with rapidly progressive glomerulonephritis, pulmonary nodules, sinusitis, and saddle-nose deformity. What is the first-line induction treatment?

A. IV methylprednisolone + cyclophosphamide or rituximab B. Prednisone alone C. Plasmapheresis alone D. Azathioprine + prednisone E. Mycophenolate mofetil + prednisone

Answer: A Granulomatosis with polyangiitis (GPA, formerly Wegener's) with active RPGN: IV methylprednisolone pulse + rituximab (preferred) or IV cyclophosphamide for induction. Rituximab (RAVE trial) is non-inferior to cyclophosphamide for induction.

Q63. Which antibody is associated with anti-GBM disease (Goodpasture syndrome)?

A. Anti-myeloperoxidase (MPO-ANCA) B. Anti-proteinase 3 (PR3-ANCA) C. Anti-glomerular basement membrane (anti-GBM / anti-collagen IV alpha-3 chain) D. Anti-PLA2R E. Anti-dsDNA

Answer: C Anti-GBM antibodies target the alpha-3 chain of type IV collagen in the GBM and alveolar basement membrane. Goodpasture syndrome = anti-GBM nephritis + pulmonary hemorrhage. Treatment: plasmapheresis + cyclophosphamide + prednisone.

Q64. Post-streptococcal glomerulonephritis (PSGN) has which classic complement profile?

A. Normal C3, low C4 B. Low C3, normal C4 C. Low C3, low C4 D. Normal C3, normal C4 E. High C3, high C4

Answer: B PSGN activates the alternative complement pathway, depleting C3 but leaving C4 normal. Lupus nephritis depletes both C3 and C4 (classical pathway). MPGN type II also depletes C3.

Q65. Which complement pathway defect is associated with C3 glomerulopathy/MPGN type II (Dense Deposit Disease)?

A. Deficiency of C1q B. Overactivation of the alternative pathway with C3 nephritic factor C. Classical pathway hyperactivation D. Terminal complement complex deficiency E. Mannose-binding lectin pathway defect

Answer: B C3 nephritic factor (C3NeF) is an autoantibody that stabilizes the alternative pathway C3 convertase (C3bBb), preventing its inactivation by factor H. This leads to uncontrolled C3 consumption and C3 glomerulopathy.

Q66. Which RPGN type shows linear IgG deposits on immunofluorescence?

A. Type I (Pauci-immune / ANCA) B. Type II (Immune complex) C. Type III (Anti-GBM) D. Type IV (Mixed) E. Type V (Fibrillary GN)

Answer: C Type I RPGN (anti-GBM disease) shows linear IgG staining along the GBM on immunofluorescence. Type II (immune complex) shows granular deposits. Type III (pauci-immune/ANCA) shows absent or minimal immunofluorescence.

Q67. Membranoproliferative GN type I is characterized by which of the following patterns on electron microscopy?

A. Subepithelial electron-dense deposits (spike and dome) B. Intramembranous dense deposits (ribbon-like) C. Subendothelial and mesangial deposits with double contour (tram-track) D. Diffuse foot process effacement E. No electron-dense deposits

Answer: C MPGN type I (classic immune complex): subendothelial + mesangial deposits. The double contour/tram-track appearance on light microscopy occurs due to basement membrane replication. Dense deposit disease (MPGN II) shows intramembranous dense osmiophilic deposits.

Q68. Which drug is used for C3 glomerulopathy related to complement dysregulation?

A. Eculizumab (anti-C5 complement inhibitor) B. Rituximab C. Cyclophosphamide D. Belimumab E. Mycophenolate mofetil

Answer: A Eculizumab (Soliris), a monoclonal antibody against C5 that blocks terminal complement, is used in C3 glomerulopathy with poor outcomes on standard therapy. It is also used for aHUS.

Q69. Proteinuria in the nephrotic range is defined as:

A. >150 mg/day B. >300 mg/day C. >3.5 g/day in adults D. >1 g/day E. >500 mg/day

Answer: C Nephrotic-range proteinuria: >3.5 g/day (or >3.5 g/1.73m²/day). This is associated with hypoalbuminemia (<3 g/dL), edema, and hyperlipidemia forming the full nephrotic syndrome.

Q70. In a patient with nephrotic syndrome, which mechanism explains the associated hyperlipidemia?

A. Increased hepatic LDL receptor activity B. Increased lipolysis from adipose tissue C. Increased hepatic lipoprotein synthesis in response to low oncotic pressure D. Renal tubular reabsorption of lipids E. Decreased clearance of chylomicrons

Answer: C Hypoalbuminemia triggers increased hepatic protein (including lipoprotein) synthesis. Combined with decreased lipoprotein lipase activity, this leads to elevated LDL, VLDL, and total cholesterol. Statins are used for treatment.

Q71. A patient with nephrotic syndrome develops a sudden onset of flank pain and hematuria. Which complication should be suspected?

A. Pyelonephritis B. Renal vein thrombosis C. Papillary necrosis D. Nephrolithiasis E. AKI from hypovolemia

Answer: B Renal vein thrombosis is a classic complication of nephrotic syndrome, particularly membranous nephropathy. Loss of anticoagulant proteins (antithrombin III, protein C/S) and urinary losses create a hypercoagulable state.

Q72. Which finding on urine microscopy is MOST specific for glomerulonephritis?

A. Hyaline casts B. Waxy casts C. Red blood cell (RBC) casts D. White blood cell casts E. Granular casts

Answer: C RBC casts are pathognomonic for glomerular disease (glomerulonephritis). WBC casts suggest pyelonephritis or interstitial nephritis. Granular casts indicate tubular injury (ATN). Waxy/broad casts suggest advanced CKD.

Q73. Voclosporin is approved (in combination with MMF and steroids) for treatment of which condition?

A. IgA nephropathy B. FSGS C. Active lupus nephritis D. Membranous nephropathy E. ANCA vasculitis

Answer: C Voclosporin (Lupkynis) was FDA-approved in 2021 for active lupus nephritis. It is a calcineurin inhibitor with a more predictable pharmacokinetic profile than cyclosporine. AURORA trial showed superior complete renal response vs. placebo (both added to MMF + prednisone).

Q74. Which condition is associated with "nephrotic syndrome + thromboembolic disease + membranous nephropathy on biopsy" and elevated anti-PLA2R antibody at diagnosis?

A. Secondary membranous nephropathy from lupus B. Primary membranous nephropathy C. Membranoproliferative GN type I D. Post-streptococcal GN E. Diabetic nephropathy

Answer: B Anti-PLA2R is positive in 70–80% of primary MN. Secondary MN (lupus, malignancy, drugs) is anti-PLA2R negative. MN is the classic nephrotic disease associated with hypercoagulability and RVT.

Q75. Diabetic nephropathy is characterized histologically by:

A. Linear IgG deposits B. Foot process effacement only C. Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) and diffuse mesangial expansion D. Granular subendothelial deposits E. Double contour basement membrane

Answer: C Kimmelstiel-Wilson nodules are ovoid deposits of matrix material in the mesangium, pathognomonic for diabetic nephropathy. The earliest change is glomerular hypertrophy/hyperfiltration, followed by diffuse and then nodular mesangial expansion.

SECTION 4: HYPERTENSION IN KIDNEY DISEASE & RAAS PHARMACOLOGY — Q76–95

Q76. Which ACE inhibitor is a prodrug requiring hepatic conversion to its active form?

A. Lisinopril B. Captopril C. Enalapril D. Ramipril E. Both C and D

Answer: E Enalapril → enalaprilat; ramipril → ramiprilat; benazepril, fosinopril, moexipril, quinapril, perindopril are also prodrugs. Lisinopril and captopril are active drugs without hepatic conversion.

Q77. The most common adverse drug reaction of ACE inhibitors, occurring in up to 20% of patients, is:

A. Angioedema B. Hyperkalemia C. Dry, persistent cough D. First-dose hypotension E. Rash

Answer: C Dry cough occurs in ~10–20% of patients (more in women and Asians) due to accumulation of bradykinin and substance P in the bronchial mucosa. ACEi block kininase II (same enzyme as ACE), preventing bradykinin breakdown.

Q78. A patient on lisinopril develops angioedema. What is the best alternative for renal protection?

A. Continue lisinopril with antihistamine prophylaxis B. Switch to an ARB (lower angioedema risk, ~0.3%) C. Switch to a calcium channel blocker D. Switch to direct renin inhibitor (aliskiren) E. No RAAS blockade is possible

Answer: B ARBs do not block bradykinin breakdown (they block the AT1 receptor only), so angioedema is rare (~0.3%) compared to ACEi (~0.1–0.7%, but class effect). ARBs are appropriate alternatives with similar renal and cardiovascular protection.

Q79. Aliskiren (a direct renin inhibitor) is contraindicated with ACEi or ARBs in patients with which condition?

A. CKD Stage 2 without diabetes B. Diabetes mellitus (particularly diabetic nephropathy) C. Hypertension without end-organ damage D. Heart failure with preserved ejection fraction E. Non-diabetic hypertension

Answer: B The ALTITUDE trial showed aliskiren combined with ACEi/ARB in diabetic nephropathy increased risk of stroke, hyperkalemia, hypotension, and renal impairment. Aliskiren is contraindicated with ACEi/ARB in diabetic patients.

Q80. What is the "efferent arteriole effect" of angiotensin II blockade in the kidney?

A. Dilation of afferent arteriole only B. Constriction of efferent arteriole only C. Dilation of efferent arteriole → reduces intraglomerular pressure → lowers proteinuria D. Constriction of both arterioles equally E. No effect on arteriolar tone

Answer: C Angiotensin II preferentially constricts the efferent arteriole. ACEi/ARBs block this, dilating the efferent arteriole and reducing intraglomerular pressure/hyperfiltration, thereby reducing proteinuria and slowing nephron loss.

Q81. Which calcium channel blocker has the most renal afferent arteriole dilation and is LEAST beneficial for proteinuria reduction (and should not replace ACEi/ARB as sole renoprotective agent)?

A. Amlodipine B. Diltiazem C. Verapamil D. Nifedipine E. Felodipine

Answer: D Dihydropyridine CCBs (nifedipine, amlodipine) dilate afferent arterioles, potentially increasing intraglomerular pressure when used alone (without concurrent RAAS blockade). Non-DHP CCBs (diltiazem, verapamil) reduce proteinuria and have anti-proteinuric effects.

Q82. Which mineralocorticoid receptor antagonist is preferred in CKD/heart failure patients due to its selectivity and lower anti-androgenic side effects compared to spironolactone?

A. Amiloride B. Triamterene C. Eplerenone D. Fludrocortisone E. Drospirenone

Answer: C Eplerenone is a selective MRA with no anti-androgenic or progestogenic activity, avoiding gynecomastia, menstrual irregularities, and sexual dysfunction associated with spironolactone. Both increase potassium.

Q83. A patient with CKD stage 4, serum K⁺ 5.6 mEq/L, and hypertension needs BP control. Which antihypertensive is MOST appropriate?

A. ACEi (continue to optimize dose) B. Spironolactone C. Amlodipine (dihydropyridine CCB) D. Triamterene E. Amiloride

Answer: C With eGFR <30 and borderline hyperkalemia, potassium-sparing agents (spironolactone, amiloride, triamterene) are risky. Amlodipine (CCB) is safe in CKD and effective for BP without raising potassium.

Q84. What is the mechanism of action of vasopressin receptor antagonists (vaptans) in hyponatremia?

A. Block V1a receptors in blood vessels B. Block V2 receptors in the renal collecting duct → aquaresis (free water excretion without Na loss) C. Block both V1 and V2 receptors equally D. Increase ADH secretion E. Stimulate aldosterone release

Answer: B Tolvaptan, conivaptan, and lixivaptan block V2 receptors, preventing ADH-mediated water reabsorption → excretion of electrolyte-free water (aquaresis). Used for SIADH, dilutional hyponatremia in CHF/cirrhosis. Overly rapid correction causes osmotic demyelination.

Q85. Tolvaptan (Jinarc/Samsca) has an additional FDA approval beyond hyponatremia. What is it?

A. Prevention of contrast nephropathy B. Slowing kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD) C. Treatment of HRS type 1 D. Management of secondary hyperparathyroidism E. Reduction of proteinuria in diabetic nephropathy

Answer: B Tolvaptan (Jinarc) is approved for ADPKD in adults at risk of rapid progression. It slows kidney cyst growth by blocking V2 receptor-mediated cAMP signaling in cyst epithelial cells. Risk: liver toxicity (REMS program in US).

Q86. Which antihypertensive medication is uniquely both a vasodilator and a diuretic, used in resistant hypertension and edematous states?

A. Hydralazine B. Minoxidil C. Sodium nitroprusside D. Diazoxide E. Furosemide + hydralazine combined

Answer: B Minoxidil is a potassium channel opener causing arterial dilation. It causes significant sodium and water retention (requires diuretic co-administration) and reflex tachycardia (requires beta-blocker). Topical minoxidil is used for alopecia.

Q87. What is the primary mechanism of action of spironolactone?

A. Direct inhibition of renin secretion B. Competitive antagonist at aldosterone receptors in the collecting duct C. Direct blockade of sodium-potassium ATPase D. Inhibition of ACE E. Blockade of AT1 receptors

Answer: B Spironolactone competitively antagonizes aldosterone at its receptor in the principal cells of the collecting duct, preventing upregulation of ENaC (Na channels) and Na/K-ATPase. Result: Na excretion, K/H retention.

Q88. Which "resistant hypertension" combination provides benefit in CKD with proteinuria, heart failure, and resistant hypertension based on PATHWAY-2 and other trials?

A. Adding a beta-blocker as 4th agent B. Adding spironolactone as 4th agent to ACEi/ARB + CCB + thiazide C. Adding an alpha-blocker as 4th agent D. Switching to aldosterone antagonist and removing CCB E. Adding a centrally acting agent (clonidine) as 4th agent

Answer: B PATHWAY-2 demonstrated spironolactone is the most effective 4th agent for resistant hypertension. In CKD with proteinuria and normal K⁺, adding low-dose spironolactone to ACEi/ARB reduces both BP and proteinuria (monitor K⁺ closely).

Q89. Which calcium channel blocker class is preferred in the management of hypertensive CKD patients with proteinuria because it reduces proteinuria?

A. Dihydropyridines (amlodipine, nifedipine) B. Non-dihydropyridines (diltiazem, verapamil) C. Both classes equally D. Neither class reduces proteinuria E. Dihydropyridines only when combined with ACEi

Answer: B Non-DHP CCBs (diltiazem, verapamil) have anti-proteinuric properties and can be added to RAAS blockade. DHP CCBs (amlodipine) lower BP effectively but may paradoxically worsen proteinuria when used as monotherapy.

Q90. A hypertensive emergency with encephalopathy and renal failure. What is the preferred IV agent?

A. Oral clonidine B. IV labetalol or IV nicardipine (or clevidipine) C. IV hydralazine alone D. Sublingual nifedipine E. IV enalaprilat

Answer: B Hypertensive emergencies require IV agents with titratable, controlled effects. IV labetalol (alpha and beta blocker) and IV nicardipine (CCB) are preferred. Sodium nitroprusside requires cyanide monitoring. Sublingual nifedipine is dangerous (uncontrolled, rapid BP drop).

Q91. Which antihypertensive agent is indicated in scleroderma renal crisis?

A. Amlodipine B. ACE inhibitors C. Nifedipine D. Metoprolol E. Losartan

Answer: B ACE inhibitors (captopril is classic but any ACEi) dramatically improve outcomes in scleroderma renal crisis (characterized by malignant hypertension + AKI + thrombotic microangiopathy). Unlike most cases, ACEi should be used even with rising creatinine.

Q92. Which drug class is the preferred antihypertensive in renovascular hypertension from unilateral renal artery stenosis?

A. ACE inhibitors or ARBs B. Calcium channel blockers C. Beta-blockers D. Diuretics E. Direct vasodilators

Answer: A ACEi/ARBs are preferred in unilateral RAS because the stenotic kidney drives hypertension via renin. However, they are CONTRAINDICATED in BILATERAL RAS or RAS in a solitary kidney, as blocking Ang II efferent vasoconstriction causes acute GFR collapse.

Q93. A patient with polycystic kidney disease develops severe, difficult-to-control hypertension. Which drug class is the cornerstone of BP management in ADPKD?

A. Calcium channel blockers B. ACE inhibitors or ARBs C. Beta-blockers D. Diuretics E. Aldosterone antagonists

Answer: B HALT-PKD trial showed ACEi + ARB combination (at intensive BP target <110/75 in younger patients) slowed kidney volume growth, though dual blockade as standard of care remains debated. ACEi/ARBs are the foundation of hypertension management in ADPKD.

Q94. Which angiotensin receptor-neprilysin inhibitor (ARNI) is FDA-approved for heart failure but requires caution in renal impairment and is contraindicated with ACE inhibitors?

A. Valsartan alone B. Sacubitril/valsartan (Entresto) C. Losartan/HCTZ D. Olmesartan/amlodipine E. Telmisartan/HCTZ

Answer: B Sacubitril/valsartan blocks neprilysin (raising natriuretic peptides + bradykinin) and AT1 receptors. It is contraindicated with ACEi (36-hour washout required) due to angioedema risk (additive bradykinin accumulation). Renal function and potassium require monitoring.

Q95. The CKD cardiovascular risk equivalent means CKD patients have:

A. Less cardiovascular risk than the general population B. Equal cardiovascular risk to the general population C. CV risk equivalent to or greater than type 2 diabetes D. No cardiovascular benefit from statin therapy E. Lower mortality risk than dialysis patients

Answer: C CKD significantly increases cardiovascular risk. Even CKD stages 3–4 confer CV risk equivalent to established coronary artery disease. Statins are generally recommended in non-dialysis CKD for CV risk reduction (SHARP trial).

SECTION 5: DIALYSIS, TRANSPLANT, AND SPECIAL MEDICATIONS — Q96–120

Q96. Which anticoagulant is used for circuit anticoagulation during hemodialysis in most patients?

A. Warfarin B. Low-molecular-weight heparin C. Unfractionated heparin (UFH) D. Fondaparinux E. Argatroban

Answer: C UFH is the standard anticoagulant for hemodialysis circuits due to its fast onset, reversibility with protamine, and cost. LMWH can be used as a single-dose alternative. Citrate regional anticoagulation is used in patients with high bleeding risk.

Q97. A dialysis patient on warfarin has an INR of 8.5 and is bleeding. Which statement is CORRECT about warfarin reversal in dialysis patients?

A. Fresh frozen plasma is usually sufficient within 30 minutes B. 4-factor PCC (prothrombin complex concentrate) reverses warfarin faster than FFP C. Vitamin K alone will reverse within 30 minutes D. Warfarin is easily dialyzed and dialysis will normalize the INR E. Idarucizumab reverses warfarin in dialysis patients

Answer: B 4-factor PCC (Kcentra) rapidly reverses warfarin (within minutes) and is preferred over FFP for urgent bleeding reversal. Warfarin is highly protein-bound and is NOT removed by dialysis.

Q98. Which direct oral anticoagulant (DOAC) is the ONLY one approved for use in dialysis patients (at reduced dose)?

A. Rivaroxaban B. Apixaban C. Dabigatran D. Edoxaban E. None are approved

Answer: B Apixaban 2.5 mg BID is used off-label/approved in dialysis patients for non-valvular atrial fibrillation. Dabigatran is 80% renally cleared and contraindicated in ESRD. Rivaroxaban and edoxaban are not recommended in dialysis.

Q99. Which immunosuppressant is the cornerstone of maintenance therapy in kidney transplant and acts by inhibiting calcineurin (thereby blocking IL-2 production)?

A. Azathioprine B. Mycophenolate mofetil C. Cyclosporine / Tacrolimus D. Sirolimus E. Belatacept

Answer: C Calcineurin inhibitors (CNIs): cyclosporine (binds cyclophilin) and tacrolimus (binds FKBP12) both inhibit calcineurin phosphatase → prevent NFAT dephosphorylation → block IL-2 gene transcription → suppress T-cell activation.

Q100. Tacrolimus is associated with which unique adverse effects compared to cyclosporine?

A. Gingival hyperplasia and hirsutism B. Post-transplant diabetes mellitus and neurotoxicity (tremor) C. Less nephrotoxicity than cyclosporine D. Less hypertension E. No drug interactions

Answer: B Tacrolimus: post-transplant diabetes (PTDM), tremor, headache, alopecia, neurotoxicity. Cyclosporine: gingival hyperplasia, hirsutism, hypertrichosis, less PTDM. Both are nephrotoxic; both interact with CYP3A4.

Q101. Mycophenolate mofetil (MMF) is an antiproliferative agent. What is its mechanism of action?

A. Binds calcineurin and blocks IL-2 B. Inhibits mTOR, blocking T and B cell proliferation C. Inhibits inosine monophosphate dehydrogenase (IMPDH), depleting guanosine nucleotides in lymphocytes D. Alkylates DNA and RNA in proliferating cells E. Binds FKBP12 and mTOR

Answer: C MMF is a prodrug converted to mycophenolic acid, which inhibits IMPDH. Lymphocytes depend exclusively on the de novo purine synthesis pathway (unlike other cells that also use the salvage pathway), making them selectively sensitive.

Q102. The main ADRs of mycophenolate mofetil include:

A. Hyperglycemia and nephrotoxicity B. GI toxicity (diarrhea, nausea) and myelosuppression (leukopenia) C. Gingival hyperplasia and hirsutism D. Pulmonary fibrosis and hepatotoxicity E. Peripheral neuropathy and nephrotoxicity

Answer: B MMF GI side effects (nausea, diarrhea, cramps) are dose-dependent and can be managed by switching to mycophenolate sodium (EC-MPS/Myfortic), which is enteric-coated. Myelosuppression (leukopenia) requires CBC monitoring.

Q103. Sirolimus (rapamycin) works by which mechanism?

A. Blocks calcineurin B. Inhibits IMPDH C. Binds FKBP12 → mTOR complex 1 inhibition → blocks IL-2 signaling and cell cycle G1/S transition D. Alkylates DNA E. Binds vitamin D receptor

Answer: C Sirolimus and everolimus (mTOR inhibitors) bind FKBP12, forming a complex that inhibits mTOR. This blocks cytokine-driven T and B cell proliferation. They do NOT inhibit calcineurin (unlike tacrolimus, which also binds FKBP12 but targets calcineurin).

Q104. Which drug interaction is most clinically significant for tacrolimus and cyclosporine?

A. NSAIDs reduce their levels B. CYP3A4 inhibitors (azoles, macrolides, grapefruit) increase levels; CYP3A4 inducers (rifampin, phenytoin) decrease levels C. Statins have no interaction D. Fluoroquinolones dramatically reduce levels E. Calcium supplements block absorption

Answer: B Both CNIs are CYP3A4 substrates. Inhibitors (ketoconazole, fluconazole, clarithromycin, verapamil, diltiazem, grapefruit) increase CNI levels → toxicity. Inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) decrease levels → rejection risk.

Q105. Belatacept is a costimulation blocker used in renal transplant. What is its mechanism?

A. Blocks calcineurin B. Binds CD80/CD86 on antigen-presenting cells, blocking CD28-mediated T-cell costimulation C. Blocks IL-2 receptor (CD25) D. Depletes B lymphocytes via CD20 E. Inhibits mTOR

Answer: B Belatacept (CTLA4-Ig) is a fusion protein that binds CD80 and CD86 on APCs, preventing their interaction with CD28 on T cells (signal 2 blockade). Better renal function outcomes than cyclosporine (BENEFIT trial) but higher risk of PTLD.

Q106. The calcineurin inhibitor-related nephrotoxicity in transplant patients is best characterized as:

A. Acute tubular necrosis from direct toxicity B. Afferent arteriolar vasoconstriction causing chronic ischemic nephropathy and tubulointerstitial fibrosis C. Membranous nephropathy from immune complex deposition D. Collapsing FSGS E. Diabetic nephropathy-like changes

Answer: B CNI nephrotoxicity: afferent arteriolar vasoconstriction (TGF-β and endothelin-mediated) → chronic ischemia → striped interstitial fibrosis on biopsy. Distinguishing chronic CNI toxicity from rejection requires biopsy.

Q107. Acute cellular rejection in renal transplant is best treated with:

A. Plasmapheresis B. IV methylprednisolone pulse (3–5 days) C. Anti-thymocyte globulin (ATG) for corticosteroid-resistant rejection D. Both B and C depending on severity E. Increasing tacrolimus trough levels

Answer: D Grade I acute cellular rejection: high-dose IV methylprednisolone. Steroid-resistant rejection: anti-thymocyte globulin (ATG - Thymoglobulin). Acute antibody-mediated rejection (AMR): IVIG, plasmapheresis, rituximab, eculizumab.

Q108. BK virus nephropathy is a significant complication of renal transplantation. What is the primary treatment strategy?

A. IV ganciclovir B. Reduce immunosuppression C. IV acyclovir D. Ciprofloxacin E. Mycophenolate dose increase

Answer: B BK virus (human polyomavirus) reactivates with over-immunosuppression. The primary treatment is reduction of immunosuppression to allow immune reconstitution. No proven antiviral therapy exists; cidofovir, leflunomide, and IVIG are investigational.

Q109. Which urine protein-to-creatinine ratio (UPCR) threshold indicates nephrotic-range proteinuria in spot urine testing?

A. >0.3 mg/mg (300 mg/g) B. >1 mg/mg (1000 mg/g) C. >3.5 mg/mg (3500 mg/g) D. >0.15 mg/mg E. >2 mg/mg

Answer: C A UPCR of >3.5 mg/mg (or >3500 mg/g) correlates with 24-hour urine protein >3.5 g/day and defines nephrotic-range proteinuria. UACR >300 mg/g = severe albuminuria in CKD classification.

Q110. Trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used in transplant patients for prophylaxis against PCP. TMP raises serum creatinine by what mechanism?

A. Direct renal tubular toxicity B. Competitive inhibition of tubular creatinine secretion by cimetidine receptor C. Trimethoprim blocks tubular secretion of creatinine via MATE transporter, raising creatinine without affecting GFR D. Increases creatinine production in muscle E. Inhibits hepatic creatinine metabolism

Answer: C TMP inhibits MATE (multidrug and toxin extrusion) transporters in the proximal tubule that secrete creatinine, raising serum creatinine ~0.1–0.3 mg/dL without reducing true GFR. This is a pharmacist fact that prevents unnecessary workup for AKI.

SECTION 6: NEPHROLITHIASIS & TUBULAR DISORDERS — Q111–130

Q111. A patient passes a kidney stone composed of calcium oxalate. What is the most common risk factor?

A. Gout with hyperuricosuria B. Hypercalciuria (idiopathic or secondary) C. Recurrent UTIs with urease-producing bacteria D. Primary hyperoxaluria E. Renal tubular acidosis type 1

Answer: B Hypercalciuria (>250 mg/day in women, >300 mg/day in men) is the most common metabolic risk factor for calcium oxalate stones. Other risk factors: low urine volume, hyperoxaluria, hypocitraturia.

Q112. What is the first-line pharmacologic treatment for recurrent calcium oxalate stones in a patient with hypercalciuria?

A. Allopurinol B. Potassium citrate C. Thiazide diuretics D. Pyridoxine (vitamin B6) C. Hydrochlorothiazide 25 mg twice daily and potassium citrate

Answer: C Thiazide diuretics reduce urinary calcium excretion by stimulating distal tubule calcium reabsorption. They are first-line for calcium stones with hypercalciuria. Potassium citrate is added if hypocitraturia is present.

Q113. Which diuretic increases urinary calcium excretion and is therefore AVOIDED in calcium stone formers?

A. Hydrochlorothiazide B. Chlorthalidone C. Furosemide (loop diuretic) D. Amiloride E. Indapamide

Answer: C Loop diuretics inhibit Na-K-2Cl cotransporter in the thick ascending limb, reducing the lumen-positive voltage that drives paracellular calcium reabsorption. This increases calciuria and worsens hypercalciuria/stone risk.

Q114. A patient with recurrent uric acid stones has urine pH consistently <5.5. What is the treatment of choice?

A. Allopurinol to reduce uric acid production B. Urinary alkalinization with potassium citrate to pH 6.0–6.5 C. High fluid intake alone D. Febuxostat E. Thiazide diuretics

Answer: B Uric acid stones form at low urine pH (pKa of uric acid = 5.35). Alkalinizing urine to pH 6.0–6.5 with potassium citrate dissolves existing stones and prevents new ones. Allopurinol is added if hyperuricosuria is present.

Q115. Struvite stones are composed of:

A. Calcium oxalate B. Uric acid C. Cystine D. Magnesium ammonium phosphate (formed with urease-producing bacteria like Proteus, Klebsiella, Pseudomonas) E. Calcium phosphate

Answer: D Struvite (infection) stones form in alkaline urine with urease-producing organisms. Urease splits urea → ammonia → alkaline pH → magnesium ammonium phosphate precipitates. Form staghorn calculi. Treatment: stone removal + antibiotics. Acetohydroxamic acid is a urease inhibitor.

Q116. Cystinuria is caused by a defect in which transporter?

A. URAT1 (urate transporter) B. Dibasic amino acid transporter in renal tubule and intestine (rBAT/SLC3A1, b0,+AT/SLC7A9) C. ENaC (epithelial sodium channel) D. ROMK (renal outer medullary potassium channel) E. SGLT2

Answer: B Cystinuria: autosomal recessive defect in renal and intestinal transport of cystine and dibasic amino acids (ornithine, arginine, lysine - "COLA"). Cystine is insoluble at normal urine pH. Treatment: high fluids, alkalinization, d-penicillamine or tiopronin.

Q117. Type 1 (distal) renal tubular acidosis is characterized by:

A. Hyperkalemic hyperchloremic metabolic acidosis, normal AG B. Hypokalemic hyperchloremic metabolic acidosis, urine pH persistently >5.5 (inability to acidify urine) C. Normal potassium, normal acid-base balance D. High anion gap metabolic acidosis E. Metabolic alkalosis with hypokalemia

Answer: B Type 1 dRTA: defect in H⁺ secretion in the collecting duct. Features: hypokalemic non-AG metabolic acidosis, urine pH >5.5 (cannot acidify urine), hypercalciuria, nephrocalcinosis, kidney stones. Treatment: potassium citrate/bicarbonate.

Q118. Type 4 RTA is characterized by:

A. Hypokalemic non-AG metabolic acidosis B. Hyperkalemic non-AG metabolic acidosis with impaired ammoniagenesis (aldosterone deficiency or resistance) C. High anion gap metabolic acidosis D. Metabolic alkalosis E. Normal potassium and pH

Answer: B Type 4 RTA: aldosterone deficiency (Addison's, hyporeninemic hypoaldosteronism in diabetes) or resistance (pseudo-hypoaldosteronism). Features: mild hyperchloremic acidosis + HYPERKALEMIA + low urine ammonium. Common in diabetic nephropathy.

Q119. A patient on acetazolamide for glaucoma develops hypokalemic hyperchloremic metabolic acidosis. What is the mechanism?

A. Acetazolamide blocks ENaC B. Carbonic anhydrase inhibition reduces H⁺ and HCO₃⁻ production in proximal tubule → HCO₃⁻ wasting (proximal or Type 2 RTA) C. Acetazolamide stimulates aldosterone secretion D. Acetazolamide directly blocks the potassium channel ROMK E. Causes nephrogenic DI

Answer: B Acetazolamide inhibits carbonic anhydrase → reduces proximal tubule HCO₃⁻ reabsorption → bicarbonaturia → hyperchloremic metabolic acidosis with hypokalemia (type 2/proximal RTA). Also increases urine citrate, useful for stone prevention.

Q120. Fanconi syndrome describes generalized proximal tubular dysfunction. Which set of urinary losses is characteristic?

A. Protein, potassium, magnesium only B. Glucose, amino acids, phosphate, uric acid, bicarbonate, and potassium (all proximal tubule reabsorbed) C. Sodium, water, potassium, and phosphate D. Calcium, magnesium, and sodium E. Phosphate and calcium only

Answer: B Fanconi syndrome: generalized proximal tubular dysfunction causing glucosuria (normal glucose), aminoaciduria, phosphaturia, uricosuria, bicarbonate wasting, proteinuria (tubular), and polyuria. Causes: tenofovir (HIV drug), multiple myeloma, Wilson's disease, cystinosis, heavy metals.

SECTION 7: ELECTROLYTE DISORDERS — Q121–135

Q121. A 70-year-old woman on thiazide diuretic presents with Na⁺ = 118 mEq/L, serum osmolality = 255, urine osmolality = 480, urine sodium = 55. What is the most likely cause?

A. Diabetes insipidus B. Psychogenic polydipsia C. SIADH from thiazide diuretic D. Adrenal insufficiency E. Beer potomania

Answer: C Classic SIADH pattern: hypo-osmolar hyponatremia + concentrated urine (Uosm >100) + elevated urine Na (>40) + euvolemia. Thiazides are a very common cause of SIADH in elderly patients.

Q122. Treatment of severe symptomatic hyponatremia (Na⁺ = 110, seizures) consists of:

A. Slow correction with water restriction alone B. Hypertonic saline (3% NaCl) 100–150 mL IV bolus over 10 min, repeat as needed (SMART protocol) C. Normal saline rapidly infused D. Tolvaptan immediately E. Furosemide alone

Answer: B Severe symptomatic hyponatremia: raise Na by 1–2 mmol/L immediately to stop seizures using 150 mL of 3% NaCl bolus. Can repeat up to 3 times. Target: raise Na by 4–6 mmol/L in first hour to stop symptoms, then limit 24-hour correction to <10–12 mmol/L to prevent osmotic demyelination.

Q123. Osmotic demyelination syndrome (ODS/central pontine myelinolysis) is caused by:

A. Overcorrection of hypernatremia B. Overcorrection of hyponatremia (>10–12 mEq/L per 24 hours), especially in chronic hyponatremia C. Any acute change in sodium D. Hypokalemia-induced demyelination E. Severe hypernatremia acutely

Answer: B ODS occurs when chronic hyponatremia is corrected too rapidly. Brain cells have adapted (lost osmolytes); rapid correction causes osmotic water efflux from brain cells → demyelination → locked-in syndrome, quadriplegia. Safe correction: ≤10 mEq/L per 24 hours (<8 in high-risk patients).

Q124. What is the mechanism of hypernatremia in central diabetes insipidus?

A. Excess ADH production causing free water retention B. Deficient ADH (vasopressin) secretion from the posterior pituitary → failure to concentrate urine → free water loss C. Excess aldosterone secretion D. Increased sodium intake without equivalent water intake E. Renal tubule resistance to ADH

Answer: B Central DI: lack of ADH secretion (posterior pituitary or hypothalamic damage from trauma, surgery, tumor, meningitis). Results in dilute urine (Uosm <300) despite serum hyperosmolality. Treated with desmopressin (DDAVP).

Q125. Which medication causes hypermagnesemia when used in large doses or in patients with renal impairment?

A. Oral magnesium oxide for constipation B. IV magnesium sulfate for eclampsia (toxic accumulation in renal impairment) C. Antacids containing magnesium hydroxide (Maalox, Mylanta) D. Both B and C E. All of the above

Answer: E All magnesium-containing products (IV MgSO₄, magnesium-containing antacids, laxatives, cathartics) can cause hypermagnesemia in patients with renal impairment. MgSO₄ toxicity: loss of deep tendon reflexes (earliest sign), respiratory arrest, cardiac arrest. Antidote: IV calcium gluconate.

Q126. A patient on furosemide develops symptomatic hypokalemia. Which potassium supplement is preferred in a patient with concurrent calcium oxalate stone history?

A. Potassium chloride (KCl) B. Potassium citrate C. Potassium phosphate D. Potassium acetate E. Potassium bicarbonate

Answer: B Potassium citrate repletes potassium AND alkalinizes urine (preventing calcium oxalate and uric acid stones) while increasing urine citrate (a natural stone inhibitor). Preferred over KCl in stone formers.

Q127. Hypomagnesemia causes refractory hypokalemia by which mechanism?

A. Magnesium excess stimulates aldosterone B. Hypomagnesemia impairs Na/K-ATPase activity in renal tubules, increasing urinary potassium wasting C. Magnesium deficiency causes GI potassium losses D. Hypomagnesemia activates ROMK channels, increasing potassium secretion E. Magnesium deficiency blocks K absorption in the distal tubule

Answer: B (and D) Magnesium is required for Na/K-ATPase function and for inhibiting ROMK channels in the distal nephron. Hypomagnesemia activates ROMK → increases urinary K excretion. Hypokalemia will not correct until magnesium is repleted. This is a classic PharmD SPLE question.

Q128. Which diuretic can be used to treat both hypercalcemia and nephrogenic DI (thiazide)?

A. Loop diuretic: used for hypercalcemia; thiazide for NDI B. Thiazide diuretic for both conditions C. Furosemide for both D. Acetazolamide for both E. Amiloride for both

Answer: A Loop diuretics (furosemide) + saline hydration are used for acute hypercalcemia (inhibits paracellular Ca²⁺ reabsorption in LOH). Thiazides are used for nephrogenic DI (reduces free water delivery to collecting duct). Separate conditions, separate drugs.

Q129. A patient with primary hyperaldosteronism (Conn syndrome) has which characteristic electrolyte pattern?

A. Hyperkalemia, hyponatremia, metabolic acidosis B. Hypokalemia, hypernatremia, metabolic alkalosis C. Normal potassium, hyponatremia, acidosis D. Hyperkalemia, metabolic alkalosis E. Hyponatremia, acidosis, hyperkalemia

Answer: B Aldosterone excess: Na retention → hypernatremia/hypertension; K/H excretion → hypokalemia + metabolic alkalosis. Classic presentation: hypertension + hypokalemia + suppressed PRA + elevated aldosterone.

Q130. Hyperphosphatemia in CKD triggers a cascade leading to cardiovascular calcification. Which molecule acts as a phosphaturic hormone that rises EARLY in CKD (before GFR falls below 60)?

A. PTH B. Calcitriol C. FGF-23 (fibroblast growth factor 23) D. Klotho E. Calcitonin

Answer: C FGF-23 is an osteocyte-derived phosphaturic hormone that rises very early in CKD (even in stage G2). It works with its co-receptor Klotho to increase renal phosphate excretion. As Klotho declines in CKD, FGF-23 effects are blunted and hyperphosphatemia ensues.

SECTION 8: SPECIFIC NEPHROTOXIC DRUGS & DRUG-INDUCED NEPHROPATHIES — Q131–150

Q131. Which antibiotic causes nephrotoxicity via intratubular crystal deposition, particularly at high doses or with inadequate hydration?

A. Vancomycin B. Ciprofloxacin C. Acyclovir (intravenous high-dose) D. Metronidazole E. Clindamycin

Answer: C IV acyclovir causes intratubular crystal deposition and precipitation, particularly with rapid infusion (give over ≥1 hour) or dehydration. Prevention: adequate IV hydration and slow infusion rate.

Q132. Vancomycin-induced nephrotoxicity is characterized by:

A. Intratubular crystal deposition B. Glomerulonephritis with immune complex deposits C. Proximal tubule injury with urinary casts, often when combined with piperacillin-tazobactam (synergistic toxicity) D. Renal papillary necrosis E. Retroperitoneal fibrosis

Answer: C Vancomycin AKI is primarily proximal tubular injury. Combination with piperacillin-tazobactam significantly increases nephrotoxicity risk (2.7-fold in a large meta-analysis). TDM with AUC-based monitoring (target AUC/MIC 400–600) reduces nephrotoxicity vs. trough-only monitoring.

Q133. A patient on tenofovir (TDF) for HIV develops glucosuria with normal blood glucose, hypophosphatemia, hypokalemia, proteinuria, and metabolic acidosis. What is the diagnosis?

A. Diabetic nephropathy B. Tenofovir-induced Fanconi syndrome C. Type 1 RTA D. FSGS from HIV E. Interstitial nephritis from TDF

Answer: B Tenofovir disoproxil fumarate (TDF) causes mitochondrial toxicity in proximal tubular cells → Fanconi syndrome (glucosuria, aminoaciduria, phosphaturia, hypokalemia, metabolic acidosis). Tenofovir alafenamide (TAF) has significantly less renal toxicity.

Q134. Which NSAID is most commonly associated with renal papillary necrosis with chronic use?

A. Ibuprofen B. Indomethacin C. Phenacetin (historical) and analgesic mixtures; current NSAIDs: aspirin, acetaminophen combination D. Celecoxib E. Naproxen

Answer: C Analgesic nephropathy with papillary necrosis was classically associated with phenacetin combinations (phenacetin + aspirin + caffeine). Among current drugs, long-term high-dose NSAID use (especially analgesic combinations) can cause papillary necrosis. Indomethacin is particularly associated with this.

Q135. Gadolinium-based contrast agents used in MRI can cause which serious condition in patients with advanced CKD (GFR <30)?

A. Contrast-induced AKI B. Nephrogenic systemic fibrosis (NSF) C. Acute interstitial nephritis D. Renal vein thrombosis E. Hemolytic uremic syndrome

Answer: B NSF is a fibrotic condition affecting skin, joints, and internal organs caused by gadolinium deposition in tissues. It occurs almost exclusively in patients with GFR <30. High-stability macrocyclic GBCA (gadobutrol, gadoteridol) have markedly lower NSF risk than linear agents.

Q136. Which drug causes AKI via allergic interstitial nephritis (AIN) with the classic triad of fever, rash, and eosinophilia?

A. Aminoglycosides B. Furosemide C. NSAIDs D. Penicillins (e.g., methicillin), sulfonamides, PPIs (most common current cause) E. Amphotericin B

Answer: D Classic AIN triad: fever + rash + eosinophilia (present in <30% of cases currently). Drug causes: beta-lactams (methicillin classic), sulfonamides, rifampin, PPIs (most common today), NSAIDs (no eosinophilia, chronic). Urinalysis: WBC casts, eosinophiluria (not specific).

Q137. Calcineurin inhibitor-induced hyperkalemia occurs by which mechanism?

A. Increased aldosterone secretion B. Blocking ENaC channels C. Suppressing aldosterone secretion and inhibiting ROMK potassium channels in the distal nephron (type 4 RTA-like effect) D. Direct tubular potassium reabsorption E. Inhibiting Na/K-ATPase

Answer: C Tacrolimus and cyclosporine cause hyporeninemic hypoaldosteronism (type 4 RTA) by reducing renin secretion and directly inhibiting potassium secretion in the collecting duct. Management: dietary restriction, fludrocortisone, or patiromer.

Q138. A transplant patient on tacrolimus + mycophenolate develops a creatinine rise to 3.2 mg/dL. Renal biopsy shows striped interstitial fibrosis and tubular atrophy with arteriolopathy. What is the likely cause?

A. Acute cellular rejection B. BK nephropathy C. Chronic calcineurin inhibitor nephrotoxicity D. Recurrent FSGS in the allograft E. Acute antibody-mediated rejection

Answer: C Chronic CNI nephrotoxicity: striped interstitial fibrosis ("isometric vacuolization" of tubular cells, arteriolar hyalinosis). Distinguished from rejection by biopsy. Management: reduce/eliminate CNI, switch to mTOR inhibitor or belatacept.

Q139. Which chemotherapy agent causes hemorrhagic cystitis, and how is this prevented in patients with renal insufficiency?

A. Cisplatin; prevented by furosemide B. Cyclophosphamide/ifosfamide; prevented by mesna (2-mercaptoethane sulfonate sodium) and hyperhydration C. Methotrexate; prevented by leucovorin D. Doxorubicin; prevented by dexrazoxane E. Vincristine; prevented by hydration

Answer: B Cyclophosphamide and ifosfamide are metabolized to acrolein, which is urotoxic and causes hemorrhagic cystitis. Mesna conjugates acrolein in the bladder, detoxifying it. Aggressive hydration and bladder irrigation are also used. SIADH from cyclophosphamide can occur.

Q140. Which diuretic is used to promote forced diuresis during chemotherapy to prevent methotrexate crystallization in the renal tubules?

A. Furosemide B. Hydrochlorothiazide C. IV sodium bicarbonate to alkalinize urine + adequate hydration D. Mannitol E. Acetazolamide

Answer: C High-dose methotrexate: alkalinize urine to pH >7.0 with IV NaHCO₃ and maintain high urine output. This prevents methotrexate and DAMPA (metabolite) crystallization. Leucovorin rescue is given at defined timepoints post-infusion.

Q141. Which NSAID class carries a lower risk of renal vasoconstriction but may still cause AIN?

A. COX-1 selective (low-dose aspirin) B. COX-2 selective (celecoxib) C. Non-selective NSAIDs are safer D. All NSAIDs have equal renal risk E. Acetaminophen (not an NSAID)

Answer: B COX-2 inhibitors (celecoxib) were hoped to have less renal toxicity, but COX-2 is constitutively expressed in the kidney (macula densa, collecting duct). They carry similar renal hemodynamic risk. However, they cause less GI bleeding and AIN from COX-2 inhibitors occurs.

Q142. A patient develops nephrotic syndrome with membranous pattern on biopsy after starting gold therapy for rheumatoid arthritis. What is the best treatment approach?

A. Treat with cyclophosphamide immediately B. Stop the offending agent (gold); spontaneous remission often occurs C. Add prednisone to continue gold therapy D. Start calcineurin inhibitor without stopping gold E. Begin plasmapheresis

Answer: B Drug-induced membranous nephropathy (gold, penicillamine, NSAIDs, captopril, mercury): the primary treatment is stopping the offending drug. Spontaneous remission follows in most cases after drug withdrawal.

Q143. Lithium-induced nephropathy with chronic use can cause which of the following structural changes?

A. Focal segmental glomerulosclerosis B. Tubulointerstitial nephritis with tubular cysts (microcysts in collecting duct/distal tubule) - "lithium nephropathy" C. Membranous nephropathy D. Minimal change disease E. MPGN

Answer: B Chronic lithium nephropathy: cortical and medullary tubular microcysts (collecting duct and distal tubule), interstitial fibrosis, tubular atrophy. In addition to NDI, chronic lithium can cause irreversible CKD. Monitoring: eGFR every 6 months.

Q144. Which is the antidote for hypermagnesemia with neuromuscular toxicity?

A. Calcium gluconate (IV) B. Furosemide C. Magnesium chelation D. Sodium bicarbonate E. Atropine

Answer: A IV calcium gluconate (10 mL of 10% solution) is the immediate antidote for hypermagnesemia toxicity (loss of DTRs, respiratory paralysis). It works by antagonizing magnesium's membrane-stabilizing effects at the neuromuscular junction.

Q145. Acetohydroxamic acid (AHA) is used as adjunctive therapy for which type of kidney stone?

A. Calcium oxalate stones B. Struvite stones (urease inhibitor) C. Uric acid stones D. Cystine stones E. Calcium phosphate stones

Answer: B AHA is a urease inhibitor used as adjunct therapy for struvite (infection) stones. It prevents ammonia production from urea by urease-producing bacteria, reducing stone growth. Side effects: hemolytic anemia, thrombophlebitis.

Q146. Which drug interaction is MOST clinically relevant for patients on tacrolimus who are started on antifungal therapy?

A. Fluconazole reduces tacrolimus levels B. Fluconazole and voriconazole dramatically increase tacrolimus levels via CYP3A4 inhibition (levels can increase 5–10x) C. Echinocandins (micafungin, caspofungin) increase tacrolimus levels markedly D. Amphotericin B has no interaction with tacrolimus E. All antifungals reduce tacrolimus levels

Answer: B Azole antifungals are potent CYP3A4 inhibitors. Fluconazole, voriconazole, posaconazole, and itraconazole dramatically increase CNI levels. Tacrolimus dose must be empirically reduced (often by 50–75%) and levels monitored closely when starting azoles.

Q147. A hemodialysis patient requires antibiotic therapy for MRSA bacteremia. Which regimen is most appropriate?

A. Oral linezolid with dose adjustment B. IV vancomycin with AUC/MIC-guided dosing, with levels drawn just before next dialysis session C. IV daptomycin without dose adjustment D. Cefazolin (cephalosporin) with dose adjustment E. Trimethoprim-sulfamethoxazole

Answer: B Vancomycin is the gold standard for MRSA in dialysis patients. It is partially removed by hemodialysis (high-flux membranes remove more). AUC-based monitoring is now preferred. Daptomycin is an alternative (dose adjustment not required for dialysis per mg/kg).

Q148. Rasburicase is used for tumor lysis syndrome prevention. Why is it contraindicated in G6PD deficiency?

A. Rasburicase directly inhibits G6PD enzyme B. Hydrogen peroxide produced by rasburicase-catalyzed reaction causes oxidative hemolysis in G6PD-deficient patients C. G6PD deficiency increases uric acid production D. G6PD deficiency reduces rasburicase efficacy E. Rasburicase causes methemoglobin formation in G6PD deficiency

Answer: B Rasburicase converts uric acid to allantoin + hydrogen peroxide. G6PD-deficient patients cannot detoxify H₂O₂ (require NADPH from G6PD pathway), leading to oxidative hemolysis and methemoglobinemia. Allopurinol (or febuxostat) is safer in G6PD deficiency.

Q149. Checkpoint inhibitor immunotherapy (anti-PD-1/PD-L1, anti-CTLA-4) commonly causes which renal adverse effect?

A. Membranous nephropathy B. Collapsing FSGS C. Acute tubulointerstitial nephritis (AIN) - most common immune-related AKI D. Rapidly progressive glomerulonephritis E. Tubular reabsorption defects (Fanconi)

Answer: C Immune checkpoint inhibitors cause AIN as the most common renal irAE, occurring in 1–5% of patients. Mechanism: T-cell infiltration of the interstitium following immune checkpoint disinhibition. Treatment: hold immunotherapy, high-dose prednisone (1 mg/kg/day).

Q150. A PharmD student counsels a patient on the correct time of day to take alendronate (bisphosphonate) prescribed for renal osteodystrophy management in CKD. Which counseling point is most critical for both efficacy and safety?

A. Take with milk to improve absorption B. Take at bedtime to improve GI tolerance C. Take with a full glass of water (240 mL), remain upright for 30 minutes, take on an empty stomach 30 minutes before food D. Take with breakfast to minimize GI side effects E. Take with calcium carbonate to improve bone deposition

Answer: C Bisphosphonates: must be taken on an empty stomach with 240 mL water. Patient must remain upright ≥30 minutes to prevent esophageal ulceration. Food (especially calcium-rich foods) drastically reduces bioavailability (<1%). Note: bisphosphonates are generally AVOIDED when eGFR <30-35 due to accumulation and adynamic bone risk.

RAPID-REVIEW SUMMARY TABLE

Question #	Topic	Key Drug/Concept	Answer
1	Contrast AKI	N-acetylcysteine	C
3	Hyperkalemia Emergency	Calcium gluconate	C
7	Aminoglycoside toxicity	Proximal tubule	B
8	Amphotericin B	Liposomal formulation	B
11	Lithium DI	Amiloride	C
18	HRS	Terlipressin + albumin	B
23	CKD diabetic	ACEi/ARB	C
25	SGLT2i renal mechanism	TGF/intraglomerular pressure	B
30	Cinacalcet	CaSR activator	C
33	ESA target Hgb	10–11.5 g/dL	B
37	Dual RAAS blockade	Contraindicated	B
41	Metformin CKD	Contraindicated <30	B
58	Sparsentan	AT1 + ETA dual block	A
59	IgA Nx	Budesonide (Tarpeyo)	A
62	GPA/ANCA	Rituximab/CYC	A
84	Vaptans	V2 receptor blocker	B
85	Tolvaptan	ADPKD	B
98	DOAC in dialysis	Apixaban 2.5 BID	B
99	Transplant CNI	Tacrolimus/Cyclosporine	C
104	CNI drug interaction	CYP3A4	B
110	TMP + creatinine	MATE blocker	C
116	Cystinuria	Dibasic transporter	B
123	ODS	Rapid Na correction	B
133	Tenofovir ADR	Fanconi syndrome	B
135	Gadolinium	NSF in CKD <30	B
146	Azole + tacrolimus	CYP3A4 interaction	B
148	Rasburicase	G6PD contraindication	B
149	Checkpoint inhibitor	AIN	C

Study Tips for PharmD SPLE Nephrology:

Master the KDIGO CKD staging (G1-G5) and albuminuria categories (A1-A3)
Know drug dose adjustments by GFR thresholds (Cockcroft-Gault for dosing)
SGLT2 inhibitors and finerenone are the newest evidence-based agents for DKD
Hyperkalemia management sequence: Calcium → Shift (insulin/glucose, bicarb, beta-agonist) → Remove (kayexalate, patiromer, SZC, dialysis)
Transplant immunosuppression: mechanism, monitoring, and CYP3A4 interactions are heavily tested
RTA types: remember Type 4 = hyperkalemia (aldosterone-related), Type 1 = hypokalemia + urine pH >5.5
All glomerular nephritides: know immunofluorescence pattern + complement profile + first-line treatment

Also add mechanisms of action of each nephrology drugs

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