Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group

Abstract

Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders characterized by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. The main cause of CNS is genetic defects in podocytes; however, it can also be caused, in rare cases, by congenital infections or maternal allo-immune disease. Management of CNS is very challenging because patients are prone to severe complications, such as haemodynamic compromise, infections, thromboses, impaired growth and kidney failure. In this consensus statement, experts from the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Paediatric Nephrology (ESPN) summarize the current evidence and present recommendations for the management of CNS, including the use of renin-angiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis. Therapeutic management should be adapted to the clinical severity of the condition with the aim of maintaining intravascular euvolaemia and adequate nutrition, while preventing complications and preserving central and peripheral vessels. We do not recommend performing routine early nephrectomies but suggest that they are considered in patients with severe complications despite optimal conservative treatment, and before transplantation in patients with persisting nephrotic syndrome and/or a WT1-dominant pathogenic variant.

Fig. 1. Opinion-based management algorithm for CNS.

At presentation with congenital nephrotic syndrome (CNS), a clinical and biological assessment including screening for congenital infections and genetic analysis is recommended. Initial treatment should be based on the results of these assessments. Patients should be managed at diagnosis by a specialized paediatric nephrology team. Blood volume should be assessed and symptomatic treatments instituted to maintain blood volume and prevent complications. Follow-up must be managed by a multidisciplinary team. Nephrectomy can be considered for children with persistent, severe CNS despite optimal management. Stable children can be managed on an outpatient basis with spacing or even stopping of albumin infusions. All children should be referred promptly to a kidney transplant team. Bilateral nephrectomy is recommended at the time of kidney failure (chronic kidney disease (CKD) G5) if nephrotic syndrome persists and/or if the patient has a WT1 pathogenic variant. *Preventive measures: prophylaxis for thrombosis, infection and anaemia, adequate nutrition and growth hormone substitution. RAS, renin–angiotensin system, CVL, central venous line.