Research Viewpoints Thrombotic Micro-Angiopathy and Podocyte Injury

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Hu Y-F, Tan Y, Yu X-J, Wang H, Wang S-X, Yu F, Zhao M-H: Podocyte Involvement in Renal Thrombotic Microangiopathy: A Clinicopathological Study. American Journal of Nephrology DOI 10.1159/000510141

Traditionally, thrombotic micro-angiopathy (TMA) is believed to mainly be a consequence of events paying out at the interface of the endothelial cells of the vascular tree and the circulation, including the kidneys. Involvement of the glomerular podocyte, either primarily or secondarily, has not received a great deal of attention.

Hu and colleagues have addressed this issue in an interesting observational study of 63 subjects with kidney biopsy-proven TMA in order to better describe the pathophysiology of associated podocyte injury. The degree of podocyte effacement was studied morphometrically using the parameter of foot-process width (FPW, in nM). The underlying cause of TMA was quite diverse, with 50% being due to malignant hypertension and nephrotic range proteinuria. No patient received eculizumab, but 22% received PLEX, and 49% received some sort of immunosuppressive therapy.

The FPW was increased in these subjects and correlated with a decline in serum albumin levels and with eGFR and an increase in proteinuria. The degree of increase in FPW was an independent predictor of kidney failure, and a threshold value of >869 nM for FPW had a sensitivity of 78% and a specificity of 61% for predicting a composite outcome of death or kidney failure. Kidney failure was observed during follow-up in 52% of the cohort, especially in those with extensive foot-process effacement. Loss of synaptopodin and podocalyxin was seen with sclerotic lesions and crescents.

It appears that podocyte injury is a potential marker of a poor outcome in TMA, but the observational nature of the study precluded any mechanistic explanations and it is unknown if the degree of podocyte injury plays any role at all in the selection of therapeutic approaches. It is quite likely that cross-talk between endothelial cells and podocytes underlies many of the findings observed in this largely descriptive study.