Kidney Disease with Hematuria

Question 1

1. Review important glomerular physiology.

Answer 1

.

Question 2

2,3,4. Describe the pathophysiology, morphology and correlating presentation of IgA neprhopathy.

Answer 2

hypercellularity in the mesangium on LM and crescents (focal proliferative lesions), immunofloresence for IgA deposit, EM shows electron dense deposits

hematuria, preceding URTI, normal renal function with ensuing proteinuria

pathophysiology is unknown as the most common primary GN can be asymptomatic or progress to renal failure, no effective therapy

Question 3

2,3,4. Describe the pathophysiology, morphology and correlating presentation of AntiGBM disease (ie. Good pasture)

Answer 3

patients present with hematuria and rapidly progressive real failure (medical emergency) due to autoimmunity against NC1 a3 collagen IV

binding of antigen and antibody in the BM can activate complement cascade, lead to inflammation and cause the escape of fibrin into urinary space

LM shows cellular crescents, immunoflorescence denotes a linear pattern of IgG, diagnosis can be confirmed with anti-GBM antibody

treatment with plasmapharesis, steroids and immunosuppressive agents, can recur in transplant, pulmonary hemorrhage accompanies called Goodpasture syndrome

Question 4

5. Describe disease entities presenting with primarily hematuria.

Answer 4

IgA nephropathy
Anti-GBM disease
Vasculitis
Thrombotic Microangiopathy
Membranoproliferative Glomerulonephritis
Post-infectious glomerulonephritis

Lupus nephritis
Hypertensive nephropathy

Question 5

2,3,4. Describe the pathophysiology, morphology and correlating presentation of vasculitis.

Answer 5

older patients with rapidly progressive renal failure and hematuria due to antineutrophil cytoplasmic autoantibodes (ANCA- with granulomas is granulomatosis with polyangiitis)

LM capillary wall necrosis, cellular proliferation and formation of crescents with inflammation of vessels (cellular infiltrate); **immunofluorescence negative for immunoglobulins and complement

tx. with prednisone and immunosuppressive drugs

Question 6

2,3,4. Describe the pathophysiology, morphology and correlating presentation of thrombotic microangiopathy.

Answer 6

damage to endothelium or inappropriate thrombus respectively due the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura (inhibition of ADAMTS13)

LM reveals glomerular and vascular deposition of fibrin IMF confirms deposition of fibrin; hemolysis of RBC and thrombocytopenia present on UA, treatment includes plasmapheresis

Question 7

2,3,4. Describe the pathophysiology, morphology and correlating presentation of SLE.

Answer 7

mixed nephrotic and nephritic syndrome where immune complexes are present in both serum and glomeruli, antibodies are directed against DNA; deposition of complex is heterogeneous

LM shows many morphologic variants, IMF stains for immunoglobulins and complement diffusely, EM shows electron dense deposits throughout the glomeruli and micro tubular particles

tx. with steroids and immunosuppressive drugs

Question 8

2,3,4. Describe the pathophysiology, morphology and correlating presentation of membranoproliferative GN.

Answer 8

a pattern of glomerular injury seen in a variety of conditions due to immune and complement mediated damage

LM shows accentuated lobularity and mesangial and expansion (increased matrix and cells), duplicated GBM, sub endothelial immune deposits with neutrophils and monocytes

presents with hematuria and nephrotic syndrome with slow unremitting course with no effective treatments (recurrent in transplant kidneys)

Question 9

2,3,4. Describe the pathophysiology, morphology and correlating presentation of post-infectious GN.

Answer 9

circulating immune complexes IgG- group A strep with spontaneous recover (>95% cases)

LM shows diffuse proliferation and inflammation, IMF shows granular deposition of complex, EM shows sub epithelial large domed deposits (eventually reabsorbed)

Question 10

2,3,4. Describe the pathophysiology, morphology and correlating presentation of hypertension.

Answer 10

renal parenchymal lesions associated with arterial atherosclerosis and arteriolosclerosis (shear stress)

presents with small kidney with granular surface with cortical scarring and atrophy
intimal and SM thickening of arterioles with hyaline deposition gross section shows fibrin clots; onion skin lesions and LM shows expansion of sub endothelial space

NOTE: malignant hypertension diastolic BP>130, cause tissue injury to multiple organs