Collapsing Glomerulopathy in Advanced Diabetic Nephropathy
Steven P Salvatore, Surya V Seshan. Weill Cornell Medical College, New York City
Background: Collapsing glomerulopathy (CG) is a pattern of severe podocytic injury which is rapidly progressive, presenting with massive proteinuria, and relatively resistant to therapy. Other associated etiologies include viral infections, drug therapy, autoimmune conditions, and in transplants with obliterative arteriopathy, previously proposed to be due to podocytic ischemic injury. Significant glomerular ischemia also occurs in cases of diabetic nephropathy (DN) with severe hyalin vascular disease.
Design: Of 4264 native kidney biopsies from our institution from 2003-2011, 534 (12.5%) had DN, and 26 of those (4.8%) had at least one glomerulus showing features of CG. Analysis of the clinicopathologic features of this cohort as well as immunohistochemical staining for vascular endothelial growth factor (VEGF) and podocytic markers WT1, synaptopodin, podocin, and beta-dystroglycan was performed.
Results: The 26 patients ranged in age from 26-80 years (mean 53), 14 male and 13 female. Most patients were type 2 diabetics (78%) with long-standing disease (mean 14 years), insulin dependent (67%), and hypertensive in 83%. Serum creatinine (Cr) levels were typically elevated, mean 3.75mg/dL (1.1-10.4), and had nephrotic range proteinuria, mean 9.8 g/d (2-29). Two patients had hepatitis C, none had HIV, autoimmune disease, or were on pamidronate or interferon. Renal biopsy showed segmental or global glomerulosclerosis (GS) in 2% (0-23) and 33% (0-80) of glomeruli, respectively. DN classification according to Tervaert et al (JASN 2010) was Class IV (>50% global GS) in 12 cases, III (nodular GS) in 8, IIb (severe diffuse mesangial (mes) sclerosis) in 4, and IIa (mild diffuse mes sclerosis) in 2. Segmental or global CG was present in 2-30% (mean 16%) of glomeruli, with 1 having 100% CG. Vascular disease was prominent, moderate in 44% and severe in 56%. Extensive arteriolar hyalinosis with >50% luminal stenosis in more than half of the arterioles was seen in 85.2% of cases. Markers of podocytic differentiation were lost in the glomeruli with CG for 100% synaptopodin and podocin, 75% beta-dystroglycan, and 70% WT-1. VEGF overexpression was seen in 43%. Follow-up on 12 patients: 9 (6 Class IV, 2 - III, 1 – IIb) developed chronic renal failure on average 9.7 months from the biopsy (0-36). The 3 remaining, 5 months to 2 years follow-up, had progressively increasing Cr with stable proteinuria.
Conclusions: CG contributes to the increased level or new onset of proteinuria in DN. Identification of CG in advanced DN with significant hyalin vascular disease is presumably due to podocytic ischemia and is of prognostic significance.
Category: Kidney (does not include tumors)
Tuesday, March 20, 2012 11:45 AM
Platform Session: Section H, Tuesday Morning