Renal dysplasia in the neonate

Abstract

Purpose of review: Renal dysplasia is classically described as a developmental disorder whereby the kidneys fail to undergo appropriate differentiation, resulting in the presence of malformed renal tissue elements. It is the commonest cause of chronic kidney disease and renal failure in the neonate. Although several genes have been identified in association with renal dysplasia, the underlying molecular mechanisms are often complex and heterogeneous in nature, and remain poorly understood.

Recent findings: In this review, we describe new insights into the fundamental process of normal kidney development, and how the renal cortex and medulla are patterned appropriately during gestation. We review the key genes that are indispensable for this process, and discuss how patterning of the kidney is perturbed in the absence of these signaling pathways. The recent use of whole exome sequencing has identified genetic mutations in patients with renal dysplasia, and the results of these studies have increased our understanding of the pathophysiology of renal dysplasia.

Summary: At present, there are no specific treatments available for patients with renal dysplasia. Understanding the molecular mechanisms of normal kidney development and the pathogenesis of renal dysplasia may allow for improved therapeutic options for these patients.

Figure 1. Nephron differentiation and patterning during kidney development

In response to Wnt9b signaling from the ureteric tips, the surrounding nephron progenitors condense into pre-tubular aggregates (PA), and undergo a mesenchymal to epithelial transition to form the renal vesicles (RV). These RV subsequently differentiate into comma (CSB) and s-shaped bodies (SSB). Migrating perivascular cells enter into the cleft of the s-shaped bodies, followed by tubular elongation and patterning into a mature nephron with establishment of an appropriate cortical-medullary axis. Images have been obtained from the GUDMAP database (http://www.gudmap.org/Schematics). Originally designed by Kylie Georgas, University of Queensland) (5).