A 52-year-old woman with lupus nephritis (Class IV) achieved remission with mycophenolate and prednisone 18 months ago. She now presents with recurrent proteinuria (urine protein-to-creatinine ratio 2,800 mg/g, increased from 200 mg/g), stable creatinine 1.4 mg/dL, C3 68 mg/dL (decreased from 110 mg/dL), anti-dsDNA positive at high titer. She has been medication-compliant. Repeat kidney biopsy shows active proliferative lesions with no chronic changes. Evaluate the optimal therapeutic strategy.
Q2
A 25-year-old woman presents with acute kidney injury, hemoptysis, and dyspnea. Labs show: creatinine 4.2 mg/dL (baseline 0.8 mg/dL), urinalysis with RBC casts and 3+ protein. Chest X-ray shows bilateral infiltrates. Anti-GBM antibodies are positive at high titer, ANCA is negative, complement levels are normal. She is started on plasmapheresis and pulse steroids. Her creatinine continues to rise to 6.8 mg/dL after 5 days. Kidney biopsy shows 95% crescents. Evaluate the next management priority.
Q3
A 68-year-old man with CKD stage 4 (eGFR 24 mL/min/1.73m²) secondary to diabetic nephropathy presents for dialysis planning. He is asymptomatic, lives alone, works full-time, and wants to maintain independence. Labs show: creatinine 3.8 mg/dL, potassium 5.1 mEq/L, bicarbonate 20 mEq/L, albumin 3.6 g/dL, phosphorus 5.2 mg/dL. He has adequate health literacy and manual dexterity. Evaluate the optimal renal replacement strategy.
Q4
A 42-year-old African American man presents with progressive renal insufficiency over 6 months. He has hypertension and a family history of ESRD in his father at age 45. Labs show: creatinine 3.2 mg/dL, urinalysis with 2+ protein and no cells, urine protein-to-creatinine ratio 1,200 mg/g. Kidney biopsy shows segmental sclerosis affecting <50% of glomeruli with foot process effacement. Genetic testing reveals APOL1 high-risk genotype. What factor most significantly impacts prognosis?
Q5
A 58-year-old man with hepatitis C and cirrhosis presents with nephrotic-range proteinuria. Kidney biopsy shows subepithelial immune deposits on electron microscopy and granular IgG and C3 on immunofluorescence with capillary wall thickening. Serum cryoglobulins are negative. What is the underlying pathophysiologic mechanism?
Nephrology (CKD, glomerular diseases) US Medical PG Practice Questions and MCQs
Question 1: A 52-year-old woman with lupus nephritis (Class IV) achieved remission with mycophenolate and prednisone 18 months ago. She now presents with recurrent proteinuria (urine protein-to-creatinine ratio 2,800 mg/g, increased from 200 mg/g), stable creatinine 1.4 mg/dL, C3 68 mg/dL (decreased from 110 mg/dL), anti-dsDNA positive at high titer. She has been medication-compliant. Repeat kidney biopsy shows active proliferative lesions with no chronic changes. Evaluate the optimal therapeutic strategy.
A. Switch to rituximab as primary therapy (Correct Answer)
B. Repeat induction therapy with cyclophosphamide
C. Increase mycophenolate dose and continue current regimen
D. Switch mycophenolate to azathioprine for maintenance
E. Add hydroxychloroquine to current immunosuppression
Explanation: ***Switch to rituximab as primary therapy***
- In patients with **Class IV lupus nephritis** who experience a relapse while compliant with **mycophenolate mofetil (MMF)** maintenance, switching to **rituximab** or **cyclophosphamide** is indicated for repeat induction.
- **Rituximab** is a recommended alternative for **refractory or relapsing** proliferative lupus nephritis, especially when there is evidence of active disease (low C3, high anti-dsDNA) despite standard therapy.
*Increase mycophenolate dose and continue current regimen*
- Simply increasing the dose is unlikely to be sufficient for a patient who has developed **nephrotic-range proteinuria** and **active proliferative lesions** while already on MMF.
- Clinical guidelines suggest a **change in the class** of induction agent when a patient relapses on their current maintenance medication to regain disease control.
*Add hydroxychloroquine to current immunosuppression*
- **Hydroxychloroquine** should already be a background therapy for all SLE patients as it reduces flares and **kidney damage accrual**, but it is not sufficient as a primary rescue for an acute Class IV relapse.
- While essential for long-term management, it does not provide the **aggressive immunosuppression** required to treat active, biopsy-proven proliferative GN.
*Repeat induction therapy with cyclophosphamide*
- Although **cyclophosphamide** is a valid induction alternative, modern guidelines like **KDIGO** increasingly support **rituximab** or multi-target therapy for relapses occurring during MMF maintenance.
- In clinical practice, if a patient relapses on MMF, shifting to a different mechanism of action like **B-cell depletion** is an optimal strategy to achieve a new remission.
*Switch mycophenolate to azathioprine for maintenance*
- **Azathioprine** is generally considered less effective than MMF for maintaining remission in **proliferative lupus nephritis** and would be inappropriate during an active flare.
- Switching to a weaker maintenance agent when the patient is currently failing a stronger one with **active lesions** would lead to further renal deterioration.
Question 2: A 25-year-old woman presents with acute kidney injury, hemoptysis, and dyspnea. Labs show: creatinine 4.2 mg/dL (baseline 0.8 mg/dL), urinalysis with RBC casts and 3+ protein. Chest X-ray shows bilateral infiltrates. Anti-GBM antibodies are positive at high titer, ANCA is negative, complement levels are normal. She is started on plasmapheresis and pulse steroids. Her creatinine continues to rise to 6.8 mg/dL after 5 days. Kidney biopsy shows 95% crescents. Evaluate the next management priority.
A. Increase frequency of plasmapheresis sessions
B. Consider kidney transplantation after antibody clearance
C. Add cyclophosphamide to current regimen
D. Transition to rituximab-based therapy
E. Initiate urgent hemodialysis and continue immunosuppression (Correct Answer)
Explanation: ***Initiate urgent hemodialysis and continue immunosuppression***
- The patient has developed **end-stage renal disease (ESRD)** due to **Goodpasture syndrome**; with 95% crescents and failure to respond to initial therapy, **renal replacement therapy** is mandatory for survival.
- Immunosuppression and **plasmapheresis** must continue to treat the life-threatening **pulmonary hemorrhage** (hemoptysis) and clear **anti-GBM antibodies**, even if renal recovery is unlikely.
*Add cyclophosphamide to current regimen*
- While **cyclophosphamide** is part of the standard induction regimen, it is ineffective at reversing established **global glomerular sclerosis** or near-total **crescentic involvement**.
- The primary clinical urgency for a patient with a creatinine of 6.8 mg/dL and rising is managing **uremia** and fluid status via **hemodialysis**.
*Increase frequency of plasmapheresis sessions*
- Standard **plasmapheresis** is already being utilized to remove **anti-GBM antibodies**; increasing frequency will not salvage kidneys that demonstrate **95% crescents** on biopsy.
- This intervention focuses on managing the **pulmonary-renal syndrome's** lung involvement rather than addressing the immediate need for **renal replacement**.
*Consider kidney transplantation after antibody clearance*
- While transplantation is the long-term goal for **anti-GBM-induced ESRD**, it cannot be performed until the patient has been stable and **antibody-negative** for at least 6 months.
- It is not the immediate "next management priority" in the setting of **acute kidney injury** and rising creatinine.
*Transition to rituximab-based therapy*
- **Rituximab** is occasionally used in refractory cases or as an alternative to cyclophosphamide, but it does not resolve the mechanical failure of the **glomerular filtration** caused by diffuse crescents.
- Management must prioritize **hemodialysis** for metabolic stability over switching second-line **immunosuppressive agents**.
Question 3: A 68-year-old man with CKD stage 4 (eGFR 24 mL/min/1.73m²) secondary to diabetic nephropathy presents for dialysis planning. He is asymptomatic, lives alone, works full-time, and wants to maintain independence. Labs show: creatinine 3.8 mg/dL, potassium 5.1 mEq/L, bicarbonate 20 mEq/L, albumin 3.6 g/dL, phosphorus 5.2 mg/dL. He has adequate health literacy and manual dexterity. Evaluate the optimal renal replacement strategy.
A. Home hemodialysis with nocturnal sessions
B. Preemptive kidney transplantation evaluation (Correct Answer)
C. In-center hemodialysis three times weekly
D. Continue conservative management until symptomatic
E. Peritoneal dialysis with continuous cycling
Explanation: ***Preemptive kidney transplantation evaluation***
- **Preemptive kidney transplantation** is the **gold standard** renal replacement strategy as it is associated with the best long-term survival and quality of life outcomes.
- For patients with **CKD stage 4** (eGFR < 30 mL/min/1.73m²), referral for evaluation is recommended to allow for identification of donors before dialysis is even required.
*In-center hemodialysis three times weekly*
- This modality is highly restrictive, involving fixed schedules that often conflict with **full-time employment** and personal **independence**.
- It is generally reserved for patients who lack the manual dexterity or home environment required for **self-care therapies**.
*Home hemodialysis with nocturnal sessions*
- While it allows for more flexibility and a higher dose of dialysis, it typically requires a **care partner** to assist with needles and safety.
- Since the patient **lives alone**, the risks associated with solo home hemodialysis often make it a less suitable option than other home-based therapies.
*Peritoneal dialysis with continuous cycling*
- PD is an excellent home-based option that supports **independence** and work, but it is still a form of dialysis initiated once the patient reaches end-stage disease.
- **Preemptive transplantation** is superior to PD as it avoids the complications of dialysis entirely and offers better preservation of **cardiovascular health**.
*Continue conservative management until symptomatic*
- Waiting until the patient is **symptomatic** often leads to urgent, unplanned dialysis starts with catheters, which increases the risk of **infection and mortality**.
- Proactive planning and evaluation for **preemptive options** should begin when the eGFR falls below 30 mL/min/1.73m² to ensure a smooth transition.
Question 4: A 42-year-old African American man presents with progressive renal insufficiency over 6 months. He has hypertension and a family history of ESRD in his father at age 45. Labs show: creatinine 3.2 mg/dL, urinalysis with 2+ protein and no cells, urine protein-to-creatinine ratio 1,200 mg/g. Kidney biopsy shows segmental sclerosis affecting <50% of glomeruli with foot process effacement. Genetic testing reveals APOL1 high-risk genotype. What factor most significantly impacts prognosis?
A. Percentage of glomeruli with sclerosis
B. Family history of ESRD
C. Degree of proteinuria at presentation
D. Response to initial immunosuppressive therapy (Correct Answer)
E. Presence of APOL1 risk variants
Explanation: ***Response to initial immunosuppressive therapy***
- For patients with **Focal Segmental Glomerulosclerosis (FSGS)**, the achievement of complete or partial **remission of proteinuria** following therapy is the strongest predictor of long-term **kidney survival**.
- Patients who fail to respond to **corticosteroids** or other immunosuppressants have a significantly higher risk of progressing to **end-stage renal disease (ESRD)** regardless of other baseline factors.
*Degree of proteinuria at presentation*
- While **nephrotic-range proteinuria** is associated with poor outcomes, the initial amount is less predictive than how the protein levels **change in response** to treatment.
- Many patients with high baseline proteinuria can still have a good prognosis if they exhibit a **dramatic reduction** after starting therapy.
*Percentage of glomeruli with sclerosis*
- This histological finding confirms the diagnosis of **FSGS**, but the static percentage on a single biopsy does not accurately forecast the **rate of progression** as well as clinical response.
- **Segmental sclerosis** is a marker of past injury; it is the ongoing **podocyte damage** and treatment resistance that drive future prognosis.
*Presence of APOL1 risk variants*
- **APOL1 high-risk genotypes** increase the susceptibility to and severity of FSGS in populations of **African ancestry**, but they do not outweigh **clinical response** to therapy as a prognostic marker.
- Even in high-risk **APOL1** carriers, the clinical course is primarily determined by whether the disease remains **steroid-sensitive** or becomes resistant.
*Family history of ESRD*
- A positive family history indicates a high **genetic risk**, such as the **APOL1** variants mentioned, which alerts the clinician to a potentially aggressive course.
- However, family history is a non-modifiable background factor and does not provide the same dynamic **prognostic value** as the patient's actual **treatment outcomes**.
Question 5: A 58-year-old man with hepatitis C and cirrhosis presents with nephrotic-range proteinuria. Kidney biopsy shows subepithelial immune deposits on electron microscopy and granular IgG and C3 on immunofluorescence with capillary wall thickening. Serum cryoglobulins are negative. What is the underlying pathophysiologic mechanism?
A. In situ immune complex formation from planted antigens (Correct Answer)
B. Anti-glomerular basement membrane antibodies
C. Circulating immune complexes depositing in glomeruli
D. Deposition of light chain proteins
E. Direct viral cytopathic effect on podocytes
Explanation: ***In situ immune complex formation from planted antigens***
- The patient presents with **Membranous Nephropathy (MN)** secondary to Hepatitis C, characterized by **subepithelial deposits** and **capillary wall thickening**.
- MN is primarily caused by **in situ immune complex formation**, where antibodies react with antigens either native to the **podocyte** or extrinsic antigens that have become "planted" in the subepithelial space.
*Circulating immune complexes depositing in glomeruli*
- This mechanism is typical of **Membranoproliferative Glomerulonephritis (MPGN)** associated with cryoglobulinemia, where complexes deposit in the **subendothelial space**.
- In MN, the deposits are distinctly **subepithelial**, which generally results from localized formation rather than the filtration of large, pre-formed circulating complexes through the **Glomerular Basement Membrane**.
*Direct viral cytopathic effect on podocytes*
- Direct podocyte injury is the hallmark of **HIV-associated nephropathy (HIVAN)**, which typically presents as a collapsing variant of **FSGS**.
- Hepatitis C-related renal disease is mediated by the **immune system** (antibodies and complement) rather than direct viral invasion of the kidney tissue.
*Anti-glomerular basement membrane antibodies*
- These antibodies are specific to **Goodpasture Syndrome**, which presents with **Rapidly Progressive Glomerulonephritis** and linear IgG staining on immunofluorescence.
- This patient has **granular** staining and subepithelial deposits, which are inconsistent with the **linear** pattern seen in anti-GBM disease.
*Deposition of light chain proteins*
- Light chain deposition is seen in **AL Amyloidosis** or **Light Chain Deposition Disease**, often associated with plasma cell dyscrasias.
- These conditions show **Congo-Red positive** fibrils or non-granular linear deposition, which does not match the **granular IgG/C3** and discrete electron-dense deposits found here.
