Pioglitazone enhances proteinuria reduction in complicated pediatric nephrotic syndrome

Background Nephrotic syndrome (NS) is a common pediatric kidney disease, yet current treatments for complicated NS are only partially effective and have significant toxicity. There is no Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-approved safe and effective treatment for NS. Thiazolidinediones (TZDs) have been shown to reduce proteinuria in both diabetic and non-diabetic kidney disease and in preclinical studies to directly protect podocytes from injury and reduce proteinuria. Here, we report on the potential utility of the addition of the TZD pioglitazone (PIO) to enhance proteinuria reduction in 8 children and young adults with steroid dependent NS and steroid resistant NS. Methods Clinical data were analyzed in comparable time periods before and after the addition of PIO to their medical regimens. Eight NS patients with minimal change NS ( n = 2), focal segmental glomerulosclerosis (FSGS) ( n = 4), or collapsing FSGS ( n = 2) were evaluated. Results Prior to PIO initiation, all children and young adults had already received multiple immunosuppressive medications (mean = 3.75). Five of eight patients (63%; “Responders”) had notable proteinuria reduction within 1 month of PIO initiation (62% reduction; P = 0.04) and normalization within 6 months (97% reduction; P = 0.04). PIO-related benefits among the responders included notable increases in serum albumin (2.5 to 3.7 g/dl; P = 0.08), dramatic reductions in hospitalizations for IV albumin infusions and diuresis (11 to 0; P 0.1). Importantly, no patients experienced any adverse events attributable to PIO during a total of 136 patient-months of treatment. Conclusions While confirmatory safety and efficacy studies are needed, these findings suggest pioglitazone (a non-immunosuppressive drug) may be useful to enhance proteinuria reduction in some children and young adults with complicated NS. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information