State of the art in childhood nephrotic syndrome: concrete discoveries and unmet needs

Abstract

Nephrotic syndrome (NS) is a clinical entity characterized by proteinuria, hypoalbuminemia, and peripheral edema. NS affects about 2-7 per 100,000 children aged below 18 years old yearly and is classified, based on the response to drugs, into steroid sensitive (SSNS), steroid dependent, (SDNS), multidrug dependent (MDNS), and multidrug resistant (MRNS). Forms of NS that are more difficult to treat are associated with a worse outcome with respect to renal function. In particular, MRNS commonly progresses to end stage renal failure requiring renal transplantation, with recurrence of the original disease in half of the cases. Histological presentations of NS may vary from minimal glomerular lesions (MCD) to focal segmental glomerulosclerosis (FSGS) and, of relevance, the histological patterns do not correlate with the response to treatments. Moreover, around half of MRNS cases are secondary to causative pathogenic variants in genes involved in maintaining the glomerular structure. The pathogenesis of NS is still poorly understood and therapeutic approaches are mostly based on clinical experience. Understanding of pathogenetic mechanisms of NS is one of the 'unmet needs' in nephrology and represents a significant challenge for the scientific community. The scope of the present review includes exploring relevant findings, identifying unmet needs, and reviewing therapeutic developments that characterize NS in the last decades. The main aim is to provide a basis for new perspectives and mechanistic studies in NS.

Keywords: focal-segmental glomerulosclerosis; minimal change disease; monoclonal antibodies; nephrotic syndrome; post-transplant recurrence; proteinuria; rituximab.

Figure 1

Classification of NS occurring in childhood based on the response to treatments..

Figure 2

Primary and secondary childhood NS. Inherited forms of NS, caused by pathological variants in genes transcribing for the main protein of glomerular tuft, represent a unique group of NS for which a clear mechanism has been defined. NS associated with either virus infections or drugs are reported as secondary NS on the basis of both the temporal association and reversibility of proteinuria. All other mechanisms are supposed and require further confirmatory results..