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Loss of Subpodocytic Space Predicts Poor Response to Tacrolimus in Steroid-Resistant Calcineurin Inhibitor-Naïve Adult-Onset Primary Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult-onset nephrotic syndrome, but its pathophysiology is poorly understood. The question as to why only a subset of patients responds to treatment in unanswered. In the past few years, change of podocytic phenotype from stationary type in health to migratory type in disease has been described, of which loss of subpodocytic space is a surrogate marker. Diagnostic biopsies of adult-onset steroid-resistant calcineurin inhibitor-naïve primary FSGS cases, which were subsequently treated with tacrolimus were included in this retrospective study conducted from 2011 to 2013. The ultrastructure of all cases was studied in detail, especially in context to the presence or absence of subpodocytic space. In the present study, we have compared presence or absence of subpodocytic space in tacrolimus-responsive versus tacrolimus-resistant cases to identify potential electron microscopic features predictive of response to treatment, of which loss of subpodocytic space indicating migratory phenotype is the most important and consistent feature. The present series included 7 tacrolimus responsive cases (includes two cases with partial response) and seven tacrolimus-resistant cases. The tacrolimus-resistant patients were of older age, had a longer duration of illness, and a lower eGFR as compared to tacrolimus responsive cases. The subpodocytic space was preserved in patients on tacrolimus with complete remission and lost in patients with partial response and tacrolimus-resistant cases.