Rare nephrotic syndromes: Relevance for future treatment strategies

Nephrotic syndrome (NS) is an entity of diseases with the clinical features of proteinuria (>3.5 g/day), edema, hypoalbuminemia and hypercholesterolemia. Histologically, a focal segmental glomerulosclerosis (FSGS) is found as an expression of podocyte damage. Many nephrotic syndromes, particularly in FSGS are based on a genetic mutation. More than 60 genes have now been identified that can cause nephrotic syndrome when a mutation is present. Increasing use of whole-exome sequencing (WES) has led to the discovery of new genes that cluster around specific signalling pathways in podocyte structures, providing insights into treatable forms of nephrotic syndrome. The treatment strategy for nephrotic syndrome is currently still based on the histological lesions present and afterwards on the response of the disease to glucocorticoids and not based on genetic testing. Genetic testing is also increasingly being used in adult patients but has not yet become established as part of standard care. Genetic testing should be carried out at an early stage, with the goal of adjusting the treatment in individual patients and also to minimize unnecessary exposure to immunosuppressant drugs in the future. In the long run individualized treatment in patients with nephrotic syndrome is expected to occur as long as knowledge on gene mutation continues to progress and new treatment strategies can be used in a tailored manner; however, for this further new therapeutic targets must be identified.