Summary GNRS 610 / GNRS610: Understanding
Kidney Function Disorders A-Comprehensive Guide
4: Latest Fall 2025/26.
1. A patient with a history of hypertension and type 2 diabetes presents with a serum creatinine of
2.8 mg/dL, eGFR 24 mL/min/1.73 m², and urine albumin-to-creatinine ratio (UACR) of 850 mg/g.
Which of the following drug classes is most likely to slow progression to end-stage renal disease
when added to standard antihypertensive therapy?
A. Calcium channel blocker (dihydropyridine)
B. SGLT2 inhibitor
C. Loop diuretic
D. Alpha-1 blocker
Answer: B
Rationale: SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) reduce albuminuria, slow eGFR decline,
and decrease cardiovascular risk in CKD with albuminuria, independent of glycemic control. Calcium
channel blockers are antihypertensives but lack the renal protective benefits seen with SGLT2 inhibitors.
Loop diuretics are used for volume overload but do not slow progression. Alpha blockers are
second-line for hypertension and do not have renoprotective evidence.
2. In a clinical trial investigating a novel complement inhibitor for IgA nephropathy, researchers
observe a significant reduction in proteinuria but no change in eGFR decline over 2 years. Which
of the following best explains this discrepancy?
A. The drug only affects podocyte function without altering tubulointerstitial fibrosis.
B. Proteinuria reduction is a surrogate endpoint that does not always correlate with long-term renal survival.
C. The complement pathway is not involved in IgA nephropathy pathogenesis.
D. The trial was underpowered to detect eGFR changes despite a true benefit.
Answer: B
Rationale: Proteinuria is a well-established surrogate marker for CKD progression, but it does not
always predict eGFR decline in short-term trials due to variability and lag time. The dissociation may
reflect incomplete capture of long-term benefits. Option A is plausible but less specific; complement
inhibition does affect tubulointerstitial injury. Option C is false; complement activation is central to IgA
nephropathy. Option D is possible but not the best explanation given the observed data.
3. A researcher studying renal tubular acidosis (RTA) generates a mouse model with a knockout of
the Cl/HCO exchanger AE1 in the basolateral membrane of -intercalated cells. Which laboratory
abnormality would most likely be observed in these mice?
A. Hyperchloremic metabolic acidosis with normal anion gap
B. Hypokalemic metabolic alkalosis
Page 1
,C. Hyperkalemic metabolic acidosis with increased anion gap
D. Normal acid-base status with hypercalciuria
Answer: A
Rationale: AE1 (SLC4A1) is essential for bicarbonate reabsorption in the collecting duct. Its loss impairs
acid secretion, leading to distal (type 1) RTA, characterized by hyperchloremic metabolic acidosis with
normal anion gap. Option B describes Bartter/Gitelman-like syndromes. Option C describes type 4 RTA
(hypoaldosteronism). Option D is not typical of AE1 deficiency.
4. A 35-year-old female with a history of recurrent urinary tract infections and nephrolithiasis is
found to have a urine pH of 8.2, hypercalciuria, and hypocitraturia. Which of the following is the
most likely underlying diagnosis?
A. Primary hyperparathyroidism
B. Distal renal tubular acidosis (type 1)
C. Medullary sponge kidney
D. Cystinuria
Answer: B
Rationale: Distal RTA (type 1) impairs urinary acidification, leading to alkaline urine (pH >7.0),
hypercalciuria, hypocitraturia (due to proximal tubule citrate reabsorption), and calcium phosphate
stone formation. Primary hyperparathyroidism causes hypercalciuria but typically acidic urine.
Medullary sponge kidney can cause stones but not alkaline urine. Cystinuria causes cystine stones with
acidic urine.
5. A patient with chronic kidney disease stage 4 (eGFR 28 mL/min/1.73 m²) is started on
spironolactone for heart failure. After 2 weeks, serum potassium rises from 4.2 to 5.9 mEq/L.
Which of the following best explains the increased risk of hyperkalemia in this setting?
A. Reduced distal sodium delivery due to decreased GFR
B. Impaired aldosterone synthesis from renal disease
C. Increased potassium intake from dietary sources
D. Competition between spironolactone and potassium for tubular secretion
Answer: A
Rationale: In CKD, reduced GFR decreases distal sodium delivery, limiting the Na z/K z exchange in the
collecting duct. Spironolactone blocks aldosterone receptors, further impairing potassium secretion. The
combination of low distal flow and aldosterone antagonism markedly increases hyperkalemia risk.
Aldosterone synthesis is often preserved or elevated in CKD. Dietary intake is not the primary
mechanism. Spironolactone does not compete for secretion; it blocks the receptor.
6. In a patient with acute kidney injury (AKI) following cardiac surgery, urine sediment shows
muddy brown granular casts and renal tubular epithelial cells. Fractional excretion of sodium
(FENa) is 1.2%. Which of the following is the most likely cause?
A. Prerenal azotemia due to hypoperfusion
B. Acute tubular necrosis (ATN)
C. Acute interstitial nephritis (AIN)
D. Postrenal obstruction
Page 2
,Answer: B
Rationale: Muddy brown granular casts and renal tubular epithelial cells are classic for ATN. FENa
<1% is typical of prerenal causes, but in ATN, FENa can be low (<1%) in early or non-oliguric cases,
especially with contrast or pigment nephropathy. Prerenal azotemia would not show granular casts. AIN
typically has white blood cell casts and eosinophiluria. Postrenal obstruction shows normal sediment or
hematuria.
7. A 28-year-old male presents with acute flank pain and hematuria. CT reveals a 5 mm
radiolucent stone in the left ureter. Urine pH is 6.0. Which of the following is the most likely stone
composition?
A. Calcium oxalate
B. Calcium phosphate
C. Uric acid
D. Cystine
Answer: C
Rationale: Radiolucent stones on CT are typically uric acid stones. Urine pH 6.0 is within the range
where uric acid can precipitate (pH <5.5 increases risk, but pH 6.0 is borderline). Calcium oxalate and
phosphate stones are radiopaque. Cystine stones are faintly radiopaque but often visible; they form in
acidic urine (pH <7.0) but are less common.
8. A patient with autosomal dominant polycystic kidney disease (ADPKD) has a rapid eGFR
decline of 8 mL/min/year. Which of the following therapies is most likely to slow disease
progression?
A. High-dose angiotensin-converting enzyme inhibitor (ACEi)
B. Tolvaptan, a vasopressin V2 receptor antagonist
C. Sodium bicarbonate supplementation
D. Low-protein diet (0.6 g/kg/day)
Answer: B
Rationale: Tolvaptan has been shown to slow eGFR decline and reduce kidney growth in ADPKD by
inhibiting cAMP-mediated cyst expansion. ACEi are used for hypertension but do not specifically target
cyst growth. Sodium bicarbonate corrects metabolic acidosis but does not alter cyst progression.
Low-protein diet has limited evidence in ADPKD.
9. A 45-year-old female with lupus nephritis class IV (diffuse proliferative) is treated with
mycophenolate mofetil and corticosteroids. After 6 months, proteinuria decreases from 3.5 g/day to
0.8 g/day, but serum creatinine remains stable at 1.2 mg/dL. Which of the following best describes
this outcome?
A. Complete renal remission
B. Partial renal remission
C. Treatment failure
D. Relapse of disease
Answer: B
Page 3
, Rationale: Partial remission in lupus nephritis is defined as a "e50% reduction in proteinuria to subnephrotic levels (<3.5
g/day) with stable or improved renal function. Complete remission requires proteinuria <0.5 g/day and normal renal
function. Since proteinuria is still >0.5 g/day, it is not complete. Treatment failure would show no improvement. Relapse
implies worsening after improvement.
10. A patient on hemodialysis develops symptomatic hypotension during a session. Which of the
following interventions is most likely to improve intradialytic hemodynamic stability without
compromising solute clearance?
A. Increase dialysate sodium concentration to 145 mEq/L
B. Reduce ultrafiltration rate by 50%
C. Switch from bicarbonate to acetate dialysate
D. Administer intravenous midodrine prior to dialysis
Answer: A
Rationale: Increasing dialysate sodium helps maintain plasma osmolality and supports refilling from the
interstitium, improving hemodynamic stability. Reducing ultrafiltration rate may help but compromises
fluid removal. Acetate dialysate is vasodilatory and worsens hypotension. Midodrine is used but is not a
dialysate adjustment; it has side effects and is not first-line.
11. A research study investigates the effect of a novel SGLT2 inhibitor on renal oxygenation in a
rat model of diabetic nephropathy. Using BOLD-MRI, they measure cortical and medullary R2*
values. Which of the following findings would best indicate improved renal oxygenation in the
treated group compared to controls?
A. Increased cortical R2* and decreased medullary R2*
B. Decreased cortical R2* and decreased medullary R2*
C. Increased cortical R2* and increased medullary R2*
D. Decreased cortical R2* and decreased medullary R2*
Answer: B
Rationale: R2* is inversely related to oxygenation; lower R2* indicates higher oxygen tension. Improved
oxygenation would reduce R2* in both cortex and medulla. Option A suggests worsening in cortex and
improvement in medulla, which is inconsistent. Options C and D have incorrect combinations.
12. In a patient with autosomal dominant polycystic kidney disease (ADPKD) who has a rapid
decline in eGFR, which of the following molecular mechanisms is most directly implicated in the
acceleration of cyst growth and fibrosis?
A. Loss of function of polycystin-1 leading to increased mTOR signaling
B. Gain-of-function mutation in PKD2 resulting in constitutive calcium influx
C. Overexpression of epidermal growth factor receptor (EGFR) in tubular epithelium
D. Inhibition of the Wnt/-catenin pathway in collecting duct cells
Answer: A
Rationale: ADPKD is caused by loss-of-function mutations in PKD1 or PKD2, leading to reduced
polycystin complex, which normally inhibits mTOR. Loss of inhibition increases mTOR activity, driving
cyst growth. Option B is incorrect because PKD2 mutations are loss-of-function. EGFR overexpression
is secondary, not primary. Wnt/-catenin is often activated, not inhibited.
Page 4
Kidney Function Disorders A-Comprehensive Guide
4: Latest Fall 2025/26.
1. A patient with a history of hypertension and type 2 diabetes presents with a serum creatinine of
2.8 mg/dL, eGFR 24 mL/min/1.73 m², and urine albumin-to-creatinine ratio (UACR) of 850 mg/g.
Which of the following drug classes is most likely to slow progression to end-stage renal disease
when added to standard antihypertensive therapy?
A. Calcium channel blocker (dihydropyridine)
B. SGLT2 inhibitor
C. Loop diuretic
D. Alpha-1 blocker
Answer: B
Rationale: SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) reduce albuminuria, slow eGFR decline,
and decrease cardiovascular risk in CKD with albuminuria, independent of glycemic control. Calcium
channel blockers are antihypertensives but lack the renal protective benefits seen with SGLT2 inhibitors.
Loop diuretics are used for volume overload but do not slow progression. Alpha blockers are
second-line for hypertension and do not have renoprotective evidence.
2. In a clinical trial investigating a novel complement inhibitor for IgA nephropathy, researchers
observe a significant reduction in proteinuria but no change in eGFR decline over 2 years. Which
of the following best explains this discrepancy?
A. The drug only affects podocyte function without altering tubulointerstitial fibrosis.
B. Proteinuria reduction is a surrogate endpoint that does not always correlate with long-term renal survival.
C. The complement pathway is not involved in IgA nephropathy pathogenesis.
D. The trial was underpowered to detect eGFR changes despite a true benefit.
Answer: B
Rationale: Proteinuria is a well-established surrogate marker for CKD progression, but it does not
always predict eGFR decline in short-term trials due to variability and lag time. The dissociation may
reflect incomplete capture of long-term benefits. Option A is plausible but less specific; complement
inhibition does affect tubulointerstitial injury. Option C is false; complement activation is central to IgA
nephropathy. Option D is possible but not the best explanation given the observed data.
3. A researcher studying renal tubular acidosis (RTA) generates a mouse model with a knockout of
the Cl/HCO exchanger AE1 in the basolateral membrane of -intercalated cells. Which laboratory
abnormality would most likely be observed in these mice?
A. Hyperchloremic metabolic acidosis with normal anion gap
B. Hypokalemic metabolic alkalosis
Page 1
,C. Hyperkalemic metabolic acidosis with increased anion gap
D. Normal acid-base status with hypercalciuria
Answer: A
Rationale: AE1 (SLC4A1) is essential for bicarbonate reabsorption in the collecting duct. Its loss impairs
acid secretion, leading to distal (type 1) RTA, characterized by hyperchloremic metabolic acidosis with
normal anion gap. Option B describes Bartter/Gitelman-like syndromes. Option C describes type 4 RTA
(hypoaldosteronism). Option D is not typical of AE1 deficiency.
4. A 35-year-old female with a history of recurrent urinary tract infections and nephrolithiasis is
found to have a urine pH of 8.2, hypercalciuria, and hypocitraturia. Which of the following is the
most likely underlying diagnosis?
A. Primary hyperparathyroidism
B. Distal renal tubular acidosis (type 1)
C. Medullary sponge kidney
D. Cystinuria
Answer: B
Rationale: Distal RTA (type 1) impairs urinary acidification, leading to alkaline urine (pH >7.0),
hypercalciuria, hypocitraturia (due to proximal tubule citrate reabsorption), and calcium phosphate
stone formation. Primary hyperparathyroidism causes hypercalciuria but typically acidic urine.
Medullary sponge kidney can cause stones but not alkaline urine. Cystinuria causes cystine stones with
acidic urine.
5. A patient with chronic kidney disease stage 4 (eGFR 28 mL/min/1.73 m²) is started on
spironolactone for heart failure. After 2 weeks, serum potassium rises from 4.2 to 5.9 mEq/L.
Which of the following best explains the increased risk of hyperkalemia in this setting?
A. Reduced distal sodium delivery due to decreased GFR
B. Impaired aldosterone synthesis from renal disease
C. Increased potassium intake from dietary sources
D. Competition between spironolactone and potassium for tubular secretion
Answer: A
Rationale: In CKD, reduced GFR decreases distal sodium delivery, limiting the Na z/K z exchange in the
collecting duct. Spironolactone blocks aldosterone receptors, further impairing potassium secretion. The
combination of low distal flow and aldosterone antagonism markedly increases hyperkalemia risk.
Aldosterone synthesis is often preserved or elevated in CKD. Dietary intake is not the primary
mechanism. Spironolactone does not compete for secretion; it blocks the receptor.
6. In a patient with acute kidney injury (AKI) following cardiac surgery, urine sediment shows
muddy brown granular casts and renal tubular epithelial cells. Fractional excretion of sodium
(FENa) is 1.2%. Which of the following is the most likely cause?
A. Prerenal azotemia due to hypoperfusion
B. Acute tubular necrosis (ATN)
C. Acute interstitial nephritis (AIN)
D. Postrenal obstruction
Page 2
,Answer: B
Rationale: Muddy brown granular casts and renal tubular epithelial cells are classic for ATN. FENa
<1% is typical of prerenal causes, but in ATN, FENa can be low (<1%) in early or non-oliguric cases,
especially with contrast or pigment nephropathy. Prerenal azotemia would not show granular casts. AIN
typically has white blood cell casts and eosinophiluria. Postrenal obstruction shows normal sediment or
hematuria.
7. A 28-year-old male presents with acute flank pain and hematuria. CT reveals a 5 mm
radiolucent stone in the left ureter. Urine pH is 6.0. Which of the following is the most likely stone
composition?
A. Calcium oxalate
B. Calcium phosphate
C. Uric acid
D. Cystine
Answer: C
Rationale: Radiolucent stones on CT are typically uric acid stones. Urine pH 6.0 is within the range
where uric acid can precipitate (pH <5.5 increases risk, but pH 6.0 is borderline). Calcium oxalate and
phosphate stones are radiopaque. Cystine stones are faintly radiopaque but often visible; they form in
acidic urine (pH <7.0) but are less common.
8. A patient with autosomal dominant polycystic kidney disease (ADPKD) has a rapid eGFR
decline of 8 mL/min/year. Which of the following therapies is most likely to slow disease
progression?
A. High-dose angiotensin-converting enzyme inhibitor (ACEi)
B. Tolvaptan, a vasopressin V2 receptor antagonist
C. Sodium bicarbonate supplementation
D. Low-protein diet (0.6 g/kg/day)
Answer: B
Rationale: Tolvaptan has been shown to slow eGFR decline and reduce kidney growth in ADPKD by
inhibiting cAMP-mediated cyst expansion. ACEi are used for hypertension but do not specifically target
cyst growth. Sodium bicarbonate corrects metabolic acidosis but does not alter cyst progression.
Low-protein diet has limited evidence in ADPKD.
9. A 45-year-old female with lupus nephritis class IV (diffuse proliferative) is treated with
mycophenolate mofetil and corticosteroids. After 6 months, proteinuria decreases from 3.5 g/day to
0.8 g/day, but serum creatinine remains stable at 1.2 mg/dL. Which of the following best describes
this outcome?
A. Complete renal remission
B. Partial renal remission
C. Treatment failure
D. Relapse of disease
Answer: B
Page 3
, Rationale: Partial remission in lupus nephritis is defined as a "e50% reduction in proteinuria to subnephrotic levels (<3.5
g/day) with stable or improved renal function. Complete remission requires proteinuria <0.5 g/day and normal renal
function. Since proteinuria is still >0.5 g/day, it is not complete. Treatment failure would show no improvement. Relapse
implies worsening after improvement.
10. A patient on hemodialysis develops symptomatic hypotension during a session. Which of the
following interventions is most likely to improve intradialytic hemodynamic stability without
compromising solute clearance?
A. Increase dialysate sodium concentration to 145 mEq/L
B. Reduce ultrafiltration rate by 50%
C. Switch from bicarbonate to acetate dialysate
D. Administer intravenous midodrine prior to dialysis
Answer: A
Rationale: Increasing dialysate sodium helps maintain plasma osmolality and supports refilling from the
interstitium, improving hemodynamic stability. Reducing ultrafiltration rate may help but compromises
fluid removal. Acetate dialysate is vasodilatory and worsens hypotension. Midodrine is used but is not a
dialysate adjustment; it has side effects and is not first-line.
11. A research study investigates the effect of a novel SGLT2 inhibitor on renal oxygenation in a
rat model of diabetic nephropathy. Using BOLD-MRI, they measure cortical and medullary R2*
values. Which of the following findings would best indicate improved renal oxygenation in the
treated group compared to controls?
A. Increased cortical R2* and decreased medullary R2*
B. Decreased cortical R2* and decreased medullary R2*
C. Increased cortical R2* and increased medullary R2*
D. Decreased cortical R2* and decreased medullary R2*
Answer: B
Rationale: R2* is inversely related to oxygenation; lower R2* indicates higher oxygen tension. Improved
oxygenation would reduce R2* in both cortex and medulla. Option A suggests worsening in cortex and
improvement in medulla, which is inconsistent. Options C and D have incorrect combinations.
12. In a patient with autosomal dominant polycystic kidney disease (ADPKD) who has a rapid
decline in eGFR, which of the following molecular mechanisms is most directly implicated in the
acceleration of cyst growth and fibrosis?
A. Loss of function of polycystin-1 leading to increased mTOR signaling
B. Gain-of-function mutation in PKD2 resulting in constitutive calcium influx
C. Overexpression of epidermal growth factor receptor (EGFR) in tubular epithelium
D. Inhibition of the Wnt/-catenin pathway in collecting duct cells
Answer: A
Rationale: ADPKD is caused by loss-of-function mutations in PKD1 or PKD2, leading to reduced
polycystin complex, which normally inhibits mTOR. Loss of inhibition increases mTOR activity, driving
cyst growth. Option B is incorrect because PKD2 mutations are loss-of-function. EGFR overexpression
is secondary, not primary. Wnt/-catenin is often activated, not inhibited.
Page 4
