Question 1
What is the most common type of glomerulonephritis that is associated with malignancy in adults?
(A) Minimal change
(B) Focal segmental Glomerulonephritis
(C) Thin basement membrane disease
(D) Pauci-immune crescentic glomerulonephritis
(E) Membranous glomerulonephritis
E: Membranous nephropathy is the most common glomerular disease that is associated with solid cancers. Lung, gastrointestinal, prostate, and breast cancers are the cancers that have most commonly been associated with membranous nephropathy. There are only a few reported cases of membranous nephropathy with concurrent renal-cell carcinoma. The incidence of malignant tumors among patients with histologically proven membranous nephropathy is in the range of 5 to 10%. This rate may be increased in elderly patients N Engl J Med 2015; 373:1958-1967.
Question 2
What is the most common type of glomerulonephritis associated with chronic kidney disease?
(A) IgA nephropathy
(B) membranous nephropathy
(C) minimal change disease
(D) post-streptococcal glomerulonephritis
(E) focal segmental glomerulosclerosis
A: According to RPA course 2015
Question 3
Which autoantibody is associated with idiopathic membranous nephropathy?
(A) PLA4R
(B) PLA2R
(C) ANA
(D) Jo-1
(E) Mi-2
B: Approximately 75 to 80% of cases of membranous nephropathy are idiopathic, without a known, specific, identifiable inciting event, such as a medication, infection, or cancer. Membranous nephropathy is characterized by deposits that develop on the subepithelial surfaces of the glomerular capillary wall, mainly on the podocytes. An autoantibody targeting the M-type phospholipase A2 receptor (PLA2R), an antigen normally expressed on the surface of podocyte-cell membranes, has been discovered; it has been suggested that cases of idiopathic membranous nephropathy may actually be cases of an autoimmune disease targeting podocytes with autoantibodies to PLA2R. Approximately 75 to 80% of cases of primary membranous nephropathy are associated with a positive test for antibodies to PLA2R at the time of diagnosis. Another antigen that may be found is Thrombospondin Type-1 domain containing 7A. This is highly concentrated on glomerular podocytes. N Engl J Med 2014; 371:2277-2287
Question 4
Which of the following drugs is NOT associated with minimal change disease?
(A) gold
(B) meloxicam
(C) ibuprofen
(D) alendronate
(E) hydralazine
E: The most common drugs that are associated with minimal change disease include NSAIDS, COX-2 inhibitors and bisphosphonates. Gold is also associated. It is the most common GN in children, but accounts for only 10% of adult cases of GN. Highly responsive to steroids, however in adults the cumulative doses required to obtain a response are higher, with a decreased chance of responding. PEP 2014
Question 5
HIV associated nephropathy is associated with what histological subtype of glomerulonephritis
(A) collapsing variant of focal segmental glomerulonephritis
(B) focal glomerulosclerosis
(C) proliferative variant of focal segmental glomerulonephritis
(D) minimal change disease
(E) mesangiocapillary glomerulonephritis
A: MKSAP16 and PEP 2014
Question 6
What lipid abnormality is NOT associated with nephrotic syndrome?
(A) Unchanged HDL
(B) Increased LDL
(C) Increased triglycerides
(D) Increased chylomicrons
(E) Increased Lipoprotein A
D: The mechanism of dyslipidaemia is unknown. Statins may be used in order to decrease the cardiovascular event rate. HDL is usually unchanged, however the cardioprotective fraction HDL2 is reduced. PEP 2014, J Lipid Res. 1992;33(12):1817, Kidney Int. 2003;63(5):1964.
Question 7
What vascular bed is characteristically involved in thrombosis secondary to nephrotic syndrome?
(A) sagital sinus
(B) portal vein
(C) renal vein
(D) hepatic vein
(E) testicular vein
C: Renal vein, 10 - 40% of cases. The risk of thrombosis is greatest in membranous nephropathy and appears to be proportional to the severity of the hypoalbuminemia. A serum albumin concentration ≤2.8 g/dL (28 g/L) is the threshold level for increased risk in membranous nephropathy with a 2.13-fold increase in risk for every 1 g/dL (10 g/L) decrease in albumin below this level. Uptodate, PEP2014, Clin J Am Soc Nephrol. 2012;7(1):43. Kidney Int. 2012;81(2):190
Question 8
Which pathophysiological mechanism does NOT contribute to the increased coagulopathy associated with nephrotic syndrome?
(A) Antithrombin III deficiency
(B) Decreased intravascular volume
(C) Increased platelet activation
(D) Presence of high molecular weight fibrinogen moieties in the circulation
(E) Decreased Protein C
E: Anticoagulation with warfarin is not unreasonable if albumin <20. Treatment is similar to any other thrombosis and should be continued for 3 months after albumin rises above 20g/L N Engl J Med. 2013 Mar;368(10):956-8
Question 9
A 46 year old female with a long standing history of psoriatic arthritis presents with worsening oedema, shortness of breath, hypertension and macroscopic haematuria. Urinalysis reveals the presence of red cell casts and active urinary sediment. Physical examination also reveals evidence of left ventricular failure co-incident with volume overload. There is also evidence of purpuric lesions. With regards to the most likely diagnosis, what will a renal biopsy reveal?
(A) membranoproliferazive glomerulonephritis secondary to immune-complex deposition (type 3 immunopathology), with mesangial cell hypercellularity, increased lymphocytes,double contour basement membrane, sub-epithelial immune complex deposition, staining for classical complement proteins and immunoglobulins
(B) membranoproliferazive glomerulonephritis secondary to non immune complex complement mediated damage, with mesangial cell hypercellularity, increased lymphocytes, double contour basement membrane, staining for alternate complement components, C3 and negative staining for immunoglobulins
(C) minimal change disease, with normal light microscopy but electron microscopy showing podocyte effacement
(D) focal segmental glomerulosclerosis
(E) Stage Immunofluorescence staining showing IgG, C3, C4 basement membrane staining with immune complexes, multiple crescents, involvement of >50%
A: This is a case of immune complex deposition causing membranoprolierative glomerulonephritis and nephritic syndrome. PEP 2014
Question 10.
Which of the following has no benefit in the treatment of primary membranous glomerulonephritis?
(A) cyclophosphamide AND prednisolone
(B) prednisolone alone
(C) Rituximab
(D) tacrolimus + MMF + prednisolone
(E) anti-coagulation
B: Prednisolone alone has no role in the treatment of primary membranous glomerulonephritis. Anticoagulation has some benefit if albumin <20 JASN 1995; 5: 1553, Kidney International (1995); 47: 1130
Question 11
Which of the following is a pathological hallmark of IgA nephropathy
(A) Aneurysmal dilatation of the afferent arteriole supplying juxtaglomerular nephrons
(B) Abnormal glycosylation in IgA2 and IgM with resultant immune complex formation and deposition in mesangium
(C) Abnormal glycosylated IgA1 dimers resulting in neo-epitopes recognised by IgG, resulting in IgG-IgA1 immune complex deposition in mesangium
(D) Lymphocytic predominant infiltration in the proximal tubule
(E) CD8 class restricted dendritic cells with CD40 hyper-expression
C: N Engl J Med 2013; 368: 2404-2414
Question 12
A 24 year old female presents with decreased exercise tolerance, day time somnolence and intermittent confusion. She has a chest X-ray which shows pulmonary infiltrates, and an increased DLCO. There is no history of asthma. She previously had an episode of viral meningitis. Renal function tests reveal hyperkalaemia, a serum creatinine of 480, and phosphate of 3.25. A renal biopsy shows crescents, interstitial inflammation, and immune fluorescence reveals linear IgG staining. What is the serological test that will help define the likely diagnosis based on the clinical information presented?
(A) pANCA, anti MPO
(B) anti-GBM
(C) c-ANCA, anti PR3
(D) anti-SCL70, anti-RNA polymerase
(E) dsDNA, reduced C3, reduced C4, anti-Sm
B: The linear IgG staining with pulmonary-renal syndrome is highly suggestive of anti-GBM. SLE would show IgG, IgA, lots of complement staining and immune complex deposition. Wergners, microscopic polyangitis and charge-strauss will show ANCA. Systemic sclerosis will show anti-SCL70 and anti-RNA polymerase PEP 2014, RPA course 2015
What is the most common type of glomerulonephritis that is associated with malignancy in adults?
(A) Minimal change
(B) Focal segmental Glomerulonephritis
(C) Thin basement membrane disease
(D) Pauci-immune crescentic glomerulonephritis
(E) Membranous glomerulonephritis
E: Membranous nephropathy is the most common glomerular disease that is associated with solid cancers. Lung, gastrointestinal, prostate, and breast cancers are the cancers that have most commonly been associated with membranous nephropathy. There are only a few reported cases of membranous nephropathy with concurrent renal-cell carcinoma. The incidence of malignant tumors among patients with histologically proven membranous nephropathy is in the range of 5 to 10%. This rate may be increased in elderly patients N Engl J Med 2015; 373:1958-1967.
Question 2
What is the most common type of glomerulonephritis associated with chronic kidney disease?
(A) IgA nephropathy
(B) membranous nephropathy
(C) minimal change disease
(D) post-streptococcal glomerulonephritis
(E) focal segmental glomerulosclerosis
A: According to RPA course 2015
Question 3
Which autoantibody is associated with idiopathic membranous nephropathy?
(A) PLA4R
(B) PLA2R
(C) ANA
(D) Jo-1
(E) Mi-2
B: Approximately 75 to 80% of cases of membranous nephropathy are idiopathic, without a known, specific, identifiable inciting event, such as a medication, infection, or cancer. Membranous nephropathy is characterized by deposits that develop on the subepithelial surfaces of the glomerular capillary wall, mainly on the podocytes. An autoantibody targeting the M-type phospholipase A2 receptor (PLA2R), an antigen normally expressed on the surface of podocyte-cell membranes, has been discovered; it has been suggested that cases of idiopathic membranous nephropathy may actually be cases of an autoimmune disease targeting podocytes with autoantibodies to PLA2R. Approximately 75 to 80% of cases of primary membranous nephropathy are associated with a positive test for antibodies to PLA2R at the time of diagnosis. Another antigen that may be found is Thrombospondin Type-1 domain containing 7A. This is highly concentrated on glomerular podocytes. N Engl J Med 2014; 371:2277-2287
Question 4
Which of the following drugs is NOT associated with minimal change disease?
(A) gold
(B) meloxicam
(C) ibuprofen
(D) alendronate
(E) hydralazine
E: The most common drugs that are associated with minimal change disease include NSAIDS, COX-2 inhibitors and bisphosphonates. Gold is also associated. It is the most common GN in children, but accounts for only 10% of adult cases of GN. Highly responsive to steroids, however in adults the cumulative doses required to obtain a response are higher, with a decreased chance of responding. PEP 2014
Question 5
HIV associated nephropathy is associated with what histological subtype of glomerulonephritis
(A) collapsing variant of focal segmental glomerulonephritis
(B) focal glomerulosclerosis
(C) proliferative variant of focal segmental glomerulonephritis
(D) minimal change disease
(E) mesangiocapillary glomerulonephritis
A: MKSAP16 and PEP 2014
Question 6
What lipid abnormality is NOT associated with nephrotic syndrome?
(A) Unchanged HDL
(B) Increased LDL
(C) Increased triglycerides
(D) Increased chylomicrons
(E) Increased Lipoprotein A
D: The mechanism of dyslipidaemia is unknown. Statins may be used in order to decrease the cardiovascular event rate. HDL is usually unchanged, however the cardioprotective fraction HDL2 is reduced. PEP 2014, J Lipid Res. 1992;33(12):1817, Kidney Int. 2003;63(5):1964.
Question 7
What vascular bed is characteristically involved in thrombosis secondary to nephrotic syndrome?
(A) sagital sinus
(B) portal vein
(C) renal vein
(D) hepatic vein
(E) testicular vein
C: Renal vein, 10 - 40% of cases. The risk of thrombosis is greatest in membranous nephropathy and appears to be proportional to the severity of the hypoalbuminemia. A serum albumin concentration ≤2.8 g/dL (28 g/L) is the threshold level for increased risk in membranous nephropathy with a 2.13-fold increase in risk for every 1 g/dL (10 g/L) decrease in albumin below this level. Uptodate, PEP2014, Clin J Am Soc Nephrol. 2012;7(1):43. Kidney Int. 2012;81(2):190
Question 8
Which pathophysiological mechanism does NOT contribute to the increased coagulopathy associated with nephrotic syndrome?
(A) Antithrombin III deficiency
(B) Decreased intravascular volume
(C) Increased platelet activation
(D) Presence of high molecular weight fibrinogen moieties in the circulation
(E) Decreased Protein C
E: Anticoagulation with warfarin is not unreasonable if albumin <20. Treatment is similar to any other thrombosis and should be continued for 3 months after albumin rises above 20g/L N Engl J Med. 2013 Mar;368(10):956-8
Question 9
A 46 year old female with a long standing history of psoriatic arthritis presents with worsening oedema, shortness of breath, hypertension and macroscopic haematuria. Urinalysis reveals the presence of red cell casts and active urinary sediment. Physical examination also reveals evidence of left ventricular failure co-incident with volume overload. There is also evidence of purpuric lesions. With regards to the most likely diagnosis, what will a renal biopsy reveal?
(A) membranoproliferazive glomerulonephritis secondary to immune-complex deposition (type 3 immunopathology), with mesangial cell hypercellularity, increased lymphocytes,double contour basement membrane, sub-epithelial immune complex deposition, staining for classical complement proteins and immunoglobulins
(B) membranoproliferazive glomerulonephritis secondary to non immune complex complement mediated damage, with mesangial cell hypercellularity, increased lymphocytes, double contour basement membrane, staining for alternate complement components, C3 and negative staining for immunoglobulins
(C) minimal change disease, with normal light microscopy but electron microscopy showing podocyte effacement
(D) focal segmental glomerulosclerosis
(E) Stage Immunofluorescence staining showing IgG, C3, C4 basement membrane staining with immune complexes, multiple crescents, involvement of >50%
A: This is a case of immune complex deposition causing membranoprolierative glomerulonephritis and nephritic syndrome. PEP 2014
Question 10.
Which of the following has no benefit in the treatment of primary membranous glomerulonephritis?
(A) cyclophosphamide AND prednisolone
(B) prednisolone alone
(C) Rituximab
(D) tacrolimus + MMF + prednisolone
(E) anti-coagulation
B: Prednisolone alone has no role in the treatment of primary membranous glomerulonephritis. Anticoagulation has some benefit if albumin <20 JASN 1995; 5: 1553, Kidney International (1995); 47: 1130
Question 11
Which of the following is a pathological hallmark of IgA nephropathy
(A) Aneurysmal dilatation of the afferent arteriole supplying juxtaglomerular nephrons
(B) Abnormal glycosylation in IgA2 and IgM with resultant immune complex formation and deposition in mesangium
(C) Abnormal glycosylated IgA1 dimers resulting in neo-epitopes recognised by IgG, resulting in IgG-IgA1 immune complex deposition in mesangium
(D) Lymphocytic predominant infiltration in the proximal tubule
(E) CD8 class restricted dendritic cells with CD40 hyper-expression
C: N Engl J Med 2013; 368: 2404-2414
Question 12
A 24 year old female presents with decreased exercise tolerance, day time somnolence and intermittent confusion. She has a chest X-ray which shows pulmonary infiltrates, and an increased DLCO. There is no history of asthma. She previously had an episode of viral meningitis. Renal function tests reveal hyperkalaemia, a serum creatinine of 480, and phosphate of 3.25. A renal biopsy shows crescents, interstitial inflammation, and immune fluorescence reveals linear IgG staining. What is the serological test that will help define the likely diagnosis based on the clinical information presented?
(A) pANCA, anti MPO
(B) anti-GBM
(C) c-ANCA, anti PR3
(D) anti-SCL70, anti-RNA polymerase
(E) dsDNA, reduced C3, reduced C4, anti-Sm
B: The linear IgG staining with pulmonary-renal syndrome is highly suggestive of anti-GBM. SLE would show IgG, IgA, lots of complement staining and immune complex deposition. Wergners, microscopic polyangitis and charge-strauss will show ANCA. Systemic sclerosis will show anti-SCL70 and anti-RNA polymerase PEP 2014, RPA course 2015
