Action Plan for Prolongation of Nephrogenesis in Preterm and Growth Restricted Babies: Explore Ultrastructure of the Nephrogenic Zone, Identify a Molecular Target, Select a Viable Drug and Find a Path for Administration

• Published in: Drug research Vol. 68; no. 1; pp. 5 - 16
• Main Author: Minuth, Will W.
• Format: Journal Article
• Language: English
• Published: Stuttgart · New York Georg Thieme Verlag KG 01.01.2018
• Subjects: Review; impaired nephrogenesis; morphogen; stem cell niche; nephrogenic zone; fetal kidney; drug delivery; preterm and low birth weight babies; prolongation of nephrogenesis
• ISSN: 2194-9379; 2194-9387
• DOI: 10.1055/s-0043-113637

Abstract A large amount of investigations informs about primary steps of mammalian kidney development such as anlage of the organ and initial nephron formation, while only few data exists about the late phase of human kidney development. In particular, little attention was up to date addressed to the decrease of morphogenic activity in the nephrogenic zone short before birth and the vanishing of all stem cell niches aligned beyond the organ capsule. There is evidence that molecular controlling of this normal but degenerative developmental process also plays a decisive role in the kidneys of preterm and growth restricted babies. Although they are born in a phase of active nephrogenesis, a substantial percentage of them evolves oligonephropathy, formation of atypical glomeruli and immaturity of parenchyma. Pathologic findings point out that independent from chemical nature all suspected hampering influences sublimate in the nephrogenic zone. However, it is unknown, whether impaired nephrogenesis is locally caused by harming interstitial fluid, disturbance of morphogen signaling, unbalanced synthesis of extracellular matrix or limited cell to cell communication. Thus, first of all these issues must be resolved, then save application of medicines prolonging nephrogenesis waits for realization. Due to the unexpectedly complex microanatomy and physiology of the nephrogenic zone, it will be a particular challenge for the future.