Proteinuria in Thrombotic Microangiopathy (TMA) Can Be Associated with Adaptive Partial Podocytopathy with Focal Podocyte Hyperplasia
Background: TMA associated renal failure is easy to understand, but it has been difficult to explain the significant proteinuria in some cases of TMA. We recently confirmed that 100% of hyperplastic podocytes in collapsing glomerulopathy stained positively for CD133 (a stem cell/progenitor marker) as previously reported. The goal of this study was to determine if there was significant fusion of foot processes (FFP) and CD133-positive hyperplastic podocytes in TMA to correlate with the proteinuria. Design: The study included 12 negative controls (renal parenchyma away from renal cell carcinoma) and 25 TMA cases, either induced by drugs or due to other etiologies (preeclampsia, TTP, atypical HUS, malignant hypertension, etc). The percentage of FFP was estimated and proteinuria levels were obtained for TMA cases. Both groups of cases were stained for CD133 by immunohistochemical methods and the # of glomeruli with CD133-positive hyperplastic podocytes was analyzed. Results: In total, 19 of 25 TMA cases had elevated protein/creatinine ratio more than 2 (Table). The TMA group had significantly higher levels of serum creatinine (2.81 ± 0.40 mg/dl) than the control group (0.95 ± 0.12 mg/dl). All controls showed positive CD133 staining only in the parietal epithelial cells (PEC), but none of them revealed positive CD133 staining in podocytes. In addition to positive CD133 staining in the PEC, 19 of 25 (76%) TMA cases showed positive CD133 staining in small clusters of hyperplastic podocytes within Bowman’s space (Figure, orange arrows in B and D). The average percentage of glomeruli with CD133-positive hyperplastic podocytes was 12 % in the TMA group. This was significantly higher than in the control group (0 %) (p = 0.0002), although this positivity did not show significant correlation with proteinuria in TMA group (r = 0.30, p = 0.1537). The percent of FFP (56 ± 4 %) was significantly correlated with proteinuria (protein/creatinine ratio 4.4 ± 0.6) (r = 0.46, p = 0.0237) in the TMA group. Conclusions: Our data indicate that the proteinuria in TMA can be associated with significant FFP. Small clusters of CD133- positive hyperplastic podocytes can be seen in the majority of TMA cases of this cohort, which supports an adaptive partial podocytopathy in some TMA cases.
Moore M, Afolayan-Oloye O, Li W, Kanaan H, Zhang P. Proteinuria in thrombotic microangiopathy (TMA) can be associated with adaptive partial podocytopathy with focal podocyte hyperplasia. Lab Invest. 2022 Mar;102(Suppl 1):1178-1179.