IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

Abstract

Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.

Keywords: Children; Chronic kidney disease; Genetics; Immunosuppressive treatment; Outcome; Pediatrics; Steroid-resistant nephrotic syndrome.

Fig. 1

Matrix for grading of evidence and assigning strength of recommendations as currently used by the American Academy of Pediatrics. Reproduced with permission from [15]

Fig. 2

Algorithm for the management of children with nephrotic syndrome. Patients are characterized according to response to a 4-week treatment with oral prednisolone (PDN). Patients showing no complete remission enter the confirmation period in which responses to further oral prednisolone (PDN) with or without methylprednisolone (MPDN) pulses in conjunction with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) are ascertained and genetic and histopathological evaluation is initiated. Patients with non-genetic SRNS should be candidates for further immunosuppression, whereas those with monogenetic forms are not (further details are given in the text). In the setting of low resource countries where genetic and/or histopathology assessment is not available, immediate immunosuppressive treatment with CNI may be started. If CNI are not available intravenous or oral cyclophosphamide may be started. * = We suggest tapering PDN after CNI initiation as follows: 40 mg/m² QOD for 4 weeks, 30 mg/m² QOD for 4 weeks, 20 mg/m² QOD for 4 weeks, 10 mg/m² QOD for 8 weeks, and discontinuing thereafter; ** = CNI may be continued in case of partial remission; *** = in cases of no complete response within 4 weeks, frequent relapses or side effects of medications, we recommend following the refractory SRNS protocol; SRNS, steroid-resistant nephrotic syndrome; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; PDN, prednisolone; IV, intravenous; CNI, calcineurin inhibitor; MMF, mycophenolate mofetil