RPS Case of the Month
Dr. Preethi Sekar MD, DNB, PDCC
(Renal & Transplant Pathology)Fellowship in Renal Pathology (UChicago)
KMCH Institute of Health Sciences & Research
Coimbatore, Tamil Nadu, India
Clinical HistoryA 38-year-old male with hypertension (BP 240/120 mm Hg) was being evaluated for rise in serum creatinine-3.3 mg/dL at the time of biopsy, it was previously normal during his last follow up visit six months ago. He also had hematuria and proteinuria (UPCR 4.4:1). He was anemic (Hb 9.8 g/dL) and his serologic studies showed low C3 levels (60 mg/dL). C4 levels were normal. He was being managed with ACEi/ARBs.
Kidney Biopsy Findings:
Figure 4. Immunofluorescence showing granular mesangial IgA (3+) staining of the glomerulus. There was also staining for C3 (2+) and kappa (2+) and lambda (3+) light chains. Other antibodies were negative.
Thrombotic microangiopathy (TMA) is a pathological process characterized by thrombocytopenia, microangiopathic hemolytic anemia, and microvascular occlusion leading to organ injury, including acute kidney injury . TMA is a feature of a number of clinical disorders including haemolytic uraemic syndrome (HUS) associated with shiga toxin, atypical HUS (aHUS), thrombotic thrombocytopenic purpura (TTP) and other disorders including malignant hypertension .
In acute TMA, there are fibrin thrombi often with fragmented red blood cells involving the renal arteries, arterioles, or glomerular capillaries. These are accompanied by mesangiolysis, endothelial swelling, and a bloodless appearance of the glomeruli. Arteries can show prominent myxoid alteration of the intima with entrapped red blood cell fragments or leukocytes. Prominent tubular injury secondary to the vascular injury is often present and even cortical necrosis can be observed in severe cases .
When injury is chronic, there is duplication of the glomerular basement membranes. The interlobular arteries and arterioles may show concentric proliferation of intimal cells giving rise to “onion skin” appearance. Occasionally, recanalized thrombi may be seen.
Collapsing glomerulopathy, a variant of focal segmental glomerulosclerosis can be commonly observed in the setting of TMA. This pattern of glomerular injury is usually associated with nephrotic-range proteinuria, which could result in a misdiagnosis if the vascular injury is either not prominent or not sampled .
Lesions of TMA are frequent in IgA nephropathy and are usually attributed to associated hypertension. However, certain studies reveal that TMA can be observed in cases of IgA nephropathy patients who are normotensive as well, but the pathophysiologic mechanism remains undetermined .
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