A multi-national study examined the response sustainability to calcineurin inhibitors and long-term kidney survivals in children with genetic podocytopathies.

INTRODUCTION

While calcineurin inhibitors (CNIs) reduce proteinuria in a subgroup of children with genetic podocytopathies, previous reports suggest that the response is short-lived and of no benefit to long-term outcomes. Here, we assess CNI response sustainability and the association between different patterns of response preservation and kidney survival.

METHODS

We performed a retrospective cohort study of patients aged 0-18 years with genetic podocytopathies treated with CNIs for at least three months from 34 pediatric nephrology centers worldwide. Response status was defined in accordance with International Pediatric Nephrology Association Clinical Practice Recommendations.

RESULTS

We analyzed 136 patients with genetic podocytopathies over a median follow-up period of 42.1 months (between CNI initiation and last follow-up or commencement of kidney replacement therapy, whichever occurred first). At least partial response was attained in 28% and 22% of patients at six months post-CNI initiation and last follow-up, respectively. Compared to no response group, patients with at least partial response at six months had significantly lower urine protein-to-creatinine ratios across various time points post-CNIs. 71%, 11% and 18% exhibited no response, non-sustained and sustained response, respectively, throughout the observation period. Both sustained and non-sustained responses were significantly associated with superior kidney survival compared to no response. Importantly, no patients with sustained response developed kidney failure over a follow-up period of 42 (interquartile range 19-62) months. Patients with non-sustained response had a 92% lower risk of kidney failure compared to non-responders.

CONCLUSIONS

A subset of children with genetic podocytopathies experienced a sustained response to CNIs, and none developed kidney failure. Children with non-sustained response still demonstrated superior kidney survival compared to non-responders. Our findings may support a trial of CNIs in genetic podocytopathies, and continuing therapy among those showing clinical response.