Nephrology Comprehensive Exam – KDIGO
2026 / ABIM–ESENeph Blueprint – 2026/2027
Edition – 120 Comprehensive Questions with
Verified Answers with detailed rationales | with
complete solutions.
SECTION 1: GLOMERULAR DISEASES (Questions 1-
20)
1. A 34-year-old woman presents with nephrotic syndrome. Renal
biopsy reveals immunoglobulin A (IgA) deposits. According to the
KDIGO 2026 guidelines, which of the following is the preferred
initial therapy for a patient with IgA nephropathy and persistent
proteinuria >1 g/day despite maximal supportive care?
A) High-dose corticosteroids alone
B) Mycophenolate mofetil
C) Targeted-release budesonide (Nefecon)
D) Cyclophosphamide
Answer: C) Targeted-release budesonide (Nefecon)
Rationale: KDIGO 2026 guidelines recommend targeted-release budesonide
(Nefecon) as a first-line agent for IgA nephropathy with persistent
proteinuria, based on evidence of reduced proteinuria and slowed eGFR
decline. The MEST-C score is used to guide therapy intensity, with
sparsentan as an alternative option.
Source: ESENeph Blueprint, iatroX
2. A 28-year-old patient with systemic lupus erythematosus (SLE)
develops nephrotic-range proteinuria and active urinary sediment.
,Renal biopsy shows Class IV lupus nephritis. According to KDIGO,
which induction regimen is recommended?
A) Mycophenolate mofetil (MMF) plus steroids
B) Cyclophosphamide plus steroids
C) Belimumab added to standard therapy
D) Both A and B are acceptable options
Answer: D) Both A and B are acceptable options
Rationale: For Class III/IV lupus nephritis, KDIGO recommends either MMF or
intravenous cyclophosphamide as induction therapy, combined with
corticosteroids. Belimumab and voclosporin are adjunctive options for
patients who do not respond to initial therapy.
Source: ESENeph Blueprint, iatroX
3. Which of the following is a characteristic feature of ANCA-
associated vasculitis (AAV) on renal biopsy?
A) Granulomatous inflammation with necrotizing vasculitis
B) Pauci-immune crescentic glomerulonephritis
C) Immune complex deposition in the mesangium
D) Diffuse membranoproliferative pattern
Answer: B) Pauci-immune crescentic glomerulonephritis
Rationale: Pauci-immune crescentic GN (with few or no immune deposits) is
the hallmark of renal involvement in ANCA-associated vasculitis. Treatment
options include cyclophosphamide or rituximab for induction, with avacopan
as an adjunctive therapy for severe disease.
Source: ESENeph Blueprint, iatroX
4. A 45-year-old patient with membranous nephropathy has not
responded to conservative therapy. Anti-PLA2R antibody titers are
elevated. What is the recommended first-line immunosuppressive
therapy?
,A) Corticosteroids alone
B) Cyclophosphamide plus corticosteroids (Ponticelli regimen)
C) Rituximab
D) Tacrolimus
Answer: C) Rituximab
Rationale: Rituximab is now considered first-line therapy for high-risk
membranous nephropathy, especially with elevated anti-PLA2R antibodies.
The Ponticelli regimen (cyclophosphamide + corticosteroids) is an
alternative. KDIGO recommends a risk-stratified approach based on antibody
titers and proteinuria.
Source: ESENeph Blueprint, iatroX
5. A 32-year-old man presents with microscopic hematuria,
proteinuria, and a family history of end-stage kidney disease. Renal
biopsy shows thinning of the glomerular basement membrane. What
is the most likely diagnosis, and what additional testing is
indicated?
A) Thin basement membrane nephropathy; no further testing needed
B) IgA nephropathy; serum IgA levels
C) Alport syndrome; genetic testing for COL4A5, COL4A3, COL4A4
D) Focal segmental glomerulosclerosis; genetic testing for APOL1
Answer: C) Alport syndrome; genetic testing for COL4A5, COL4A3,
COL4A4
Rationale: Alport syndrome is an inherited basement membrane disorder
caused by mutations in COL4A5 (X-linked), COL4A3, or COL4A4 (autosomal
recessive). Thin basement membrane nephropathy is a benign condition with
normal renal function and no hearing/eye findings.
Source: ESENeph Blueprint, iatroX
6. A patient with C3 glomerulopathy (C3G) is being evaluated. Which
medication has shown promise in this condition?
, A) Eculizumab
B) Iptacopan
C) Mycophenolate mofetil
D) Both A and B
Answer: D) Both A and B
Rationale: C3 glomerulopathy is a complement-mediated disease.
Eculizumab (anti-C5) and iptacopan (factor B inhibitor) have shown efficacy
in clinical trials. Management also includes control of proteinuria and blood
pressure.
Source: ESENeph Blueprint, iatroX
7. A patient with FSGS (focal segmental glomerulosclerosis) is being
started on therapy. Which of the following is a key prognostic
factor?
A) Level of proteinuria
B) eGFR at presentation
C) Presence of collapsing variant
D) All of the above
Answer: D) All of the above
Rationale: Key prognostic factors in FSGS include the degree of proteinuria,
eGFR at presentation, and the presence of specific variants such as
collapsing FSGS (which has a poorer prognosis). Genetic testing for APOL1
may be indicated in high-risk populations.
Source: ESENeph Blueprint, iatroX
8. In a patient with diabetic kidney disease, which medication class
has been shown to reduce the risk of kidney disease progression
and cardiovascular events?
A) ACE inhibitors or ARBs
B) SGLT2 inhibitors
2026 / ABIM–ESENeph Blueprint – 2026/2027
Edition – 120 Comprehensive Questions with
Verified Answers with detailed rationales | with
complete solutions.
SECTION 1: GLOMERULAR DISEASES (Questions 1-
20)
1. A 34-year-old woman presents with nephrotic syndrome. Renal
biopsy reveals immunoglobulin A (IgA) deposits. According to the
KDIGO 2026 guidelines, which of the following is the preferred
initial therapy for a patient with IgA nephropathy and persistent
proteinuria >1 g/day despite maximal supportive care?
A) High-dose corticosteroids alone
B) Mycophenolate mofetil
C) Targeted-release budesonide (Nefecon)
D) Cyclophosphamide
Answer: C) Targeted-release budesonide (Nefecon)
Rationale: KDIGO 2026 guidelines recommend targeted-release budesonide
(Nefecon) as a first-line agent for IgA nephropathy with persistent
proteinuria, based on evidence of reduced proteinuria and slowed eGFR
decline. The MEST-C score is used to guide therapy intensity, with
sparsentan as an alternative option.
Source: ESENeph Blueprint, iatroX
2. A 28-year-old patient with systemic lupus erythematosus (SLE)
develops nephrotic-range proteinuria and active urinary sediment.
,Renal biopsy shows Class IV lupus nephritis. According to KDIGO,
which induction regimen is recommended?
A) Mycophenolate mofetil (MMF) plus steroids
B) Cyclophosphamide plus steroids
C) Belimumab added to standard therapy
D) Both A and B are acceptable options
Answer: D) Both A and B are acceptable options
Rationale: For Class III/IV lupus nephritis, KDIGO recommends either MMF or
intravenous cyclophosphamide as induction therapy, combined with
corticosteroids. Belimumab and voclosporin are adjunctive options for
patients who do not respond to initial therapy.
Source: ESENeph Blueprint, iatroX
3. Which of the following is a characteristic feature of ANCA-
associated vasculitis (AAV) on renal biopsy?
A) Granulomatous inflammation with necrotizing vasculitis
B) Pauci-immune crescentic glomerulonephritis
C) Immune complex deposition in the mesangium
D) Diffuse membranoproliferative pattern
Answer: B) Pauci-immune crescentic glomerulonephritis
Rationale: Pauci-immune crescentic GN (with few or no immune deposits) is
the hallmark of renal involvement in ANCA-associated vasculitis. Treatment
options include cyclophosphamide or rituximab for induction, with avacopan
as an adjunctive therapy for severe disease.
Source: ESENeph Blueprint, iatroX
4. A 45-year-old patient with membranous nephropathy has not
responded to conservative therapy. Anti-PLA2R antibody titers are
elevated. What is the recommended first-line immunosuppressive
therapy?
,A) Corticosteroids alone
B) Cyclophosphamide plus corticosteroids (Ponticelli regimen)
C) Rituximab
D) Tacrolimus
Answer: C) Rituximab
Rationale: Rituximab is now considered first-line therapy for high-risk
membranous nephropathy, especially with elevated anti-PLA2R antibodies.
The Ponticelli regimen (cyclophosphamide + corticosteroids) is an
alternative. KDIGO recommends a risk-stratified approach based on antibody
titers and proteinuria.
Source: ESENeph Blueprint, iatroX
5. A 32-year-old man presents with microscopic hematuria,
proteinuria, and a family history of end-stage kidney disease. Renal
biopsy shows thinning of the glomerular basement membrane. What
is the most likely diagnosis, and what additional testing is
indicated?
A) Thin basement membrane nephropathy; no further testing needed
B) IgA nephropathy; serum IgA levels
C) Alport syndrome; genetic testing for COL4A5, COL4A3, COL4A4
D) Focal segmental glomerulosclerosis; genetic testing for APOL1
Answer: C) Alport syndrome; genetic testing for COL4A5, COL4A3,
COL4A4
Rationale: Alport syndrome is an inherited basement membrane disorder
caused by mutations in COL4A5 (X-linked), COL4A3, or COL4A4 (autosomal
recessive). Thin basement membrane nephropathy is a benign condition with
normal renal function and no hearing/eye findings.
Source: ESENeph Blueprint, iatroX
6. A patient with C3 glomerulopathy (C3G) is being evaluated. Which
medication has shown promise in this condition?
, A) Eculizumab
B) Iptacopan
C) Mycophenolate mofetil
D) Both A and B
Answer: D) Both A and B
Rationale: C3 glomerulopathy is a complement-mediated disease.
Eculizumab (anti-C5) and iptacopan (factor B inhibitor) have shown efficacy
in clinical trials. Management also includes control of proteinuria and blood
pressure.
Source: ESENeph Blueprint, iatroX
7. A patient with FSGS (focal segmental glomerulosclerosis) is being
started on therapy. Which of the following is a key prognostic
factor?
A) Level of proteinuria
B) eGFR at presentation
C) Presence of collapsing variant
D) All of the above
Answer: D) All of the above
Rationale: Key prognostic factors in FSGS include the degree of proteinuria,
eGFR at presentation, and the presence of specific variants such as
collapsing FSGS (which has a poorer prognosis). Genetic testing for APOL1
may be indicated in high-risk populations.
Source: ESENeph Blueprint, iatroX
8. In a patient with diabetic kidney disease, which medication class
has been shown to reduce the risk of kidney disease progression
and cardiovascular events?
A) ACE inhibitors or ARBs
B) SGLT2 inhibitors
