An Emerging Molecular Understanding and Novel Targeted Treatment Approaches in Pediatric Kidney Diseases

Abstract

The evaluation and treatment of the heterogeneous group of kidney diseases poses a challenging field in pediatrics. Many of the pediatric disorders resulting in severe renal affection are exceedingly rare and therapeutic approaches have remained symptomatic for most of these disease entities. The insights obtained from cellular and molecular studies of rare disorders by recent genetic studies have now substantially changed our mechanistic understanding of various important pediatric renal diseases and positive examples of targeted treatment approaches are emerging. Three fields of recent breathtaking developments in pediatric nephrology are the pathophysiology of nephrotic syndrome and proteinuria, the molecular mechanisms underlying atypical hemolytic uremic syndrome, and the genetics and cellular biology of inherited cystic kidney diseases. In all three areas, the combined power of molecular basic science together with deeply characterizing clinical approaches has led to the establishment of novel pathophysiological principles and to the first clinical trials of targeted treatment approaches.

The expanding phenotypic spectra of kidney diseases: insights from genetic studies

“…The identification of mutations in podocyte-specific genes can influence decisions on immunosuppressive treatment in patients with FSGS and inform post-transplantation prognostics 116,117 . Similarly, the post-transplantation recurrence rate of aHUS is much lower in patients with mutations in MCP and DGKE than in patients with mutations in other genes 42,118 and ACE inhibitors can be used to slow the progression of renal failure in patients with Alport syndrome without the need for immunosuppressants 119,120 .…”

Proteinurie und Hämaturie

“…Arbeiten der vergangenen 20 Jahre weisen darauf hin, dass einer wesentlichen Albuminurie vor allem ein Defekt der Podozyten zugrunde liegt [1,3]. Bei den Podozyten handelt es sich um hochdifferenzierte Zellen mit einem begrenzten Regenerationspotenzial, die sich durch einen kräftigen Zellkörper auszeichnen, von dem tubulinbasierte Ausläufer, sog.…”

Ciliopathies - from rare inherited cystic kidney diseases to basic cellular function

“…In summary, cilia have become a central topic in cellular research. The novel cellular insights have led to the establishment of a novel molecular understanding in pediatric cystic kidney diseases and various clinical trials, again underlining the importance of basic science for the progress in disease-oriented research [ 29 ].…”