IPNA Clinical Practice Recommendations for the Diagnosis and Management of Children with Steroid-resistant Nephrotic Syndrome

Individualizing Treatment of Steroid-Resistant Nephrotic Syndrome

“…Steroid resistance is believed to have a genetic or immune etiology. More than 80 monogenic disorders, involving structural and regulatory proteins of the glomerular filtration barrier, are associated with initial steroid resistance (1). Immune perturbations are postulated to result in generation of a "circulating factor" that increases the permeability of the glomerular filtration barrier, resulting in nephrotic-range proteinuria.…”

“…Immune perturbations are postulated to result in generation of a "circulating factor" that increases the permeability of the glomerular filtration barrier, resulting in nephrotic-range proteinuria. All patients with steroid resistance should undergo a kidney biopsy to delineate the histology, usually FSGS or minimal change disease (1). Therapy comprises a combination of calcineurin inhibitors (CNIs), prednisone, and angiotensin-converting enzyme inhibitors (1).…”

“…Therapy comprises a combination of calcineurin inhibitors (CNIs), prednisone, and angiotensin-converting enzyme inhibitors (1). Concerns in management include nonresponse to intensified immunosuppression, progressive kidney disease, and 30% risk of post-transplant FSGS (1,2). Late resistance, which comprises 5%-10% of patients with nephrotic syndrome, is not associated with a genetic cause but has higher risk of allograft recurrence (2).…”

“…The proportion of patients with a genetic etiology varies with ethnicity and indications for performing these investigations. Recent guidelines from the International Pediatric Nephrology Association emphasize that all patients with initial steroid-resistant nephrotic syndrome should undergo these studies (1). We prefer a focused approach, with studies limited to patients with onset of disease during infancy, family history of similar illness, syndromic features, or nonresponse to CNI or before transplant.…”

“…The rates for kidney failure were 44%-62% and 23%-50%, respectively (odds ratio, 3.05; 95% confidence interval, 2.28 to 4.08) (4-6). Although few patients with WT1 mutations may show partial response to CNI (4,5), there is consensus that patients with confirmed genetic etiology should not receive immunosuppressive medications (1). Genetic screening might enable specific therapy in few patients, including those with defects in coenzyme Q10 pathway and certain phenocopies (Fabry disease and cystinosis), and allow counseling on outcomes (Alport syndrome, Denys-Drash syndrome, and Dent disease) (1,3,4,6).…”