Maladaptive Repair and AKI to CKD Transition

Manjeri A. Venkatachalam, Hui Geng, Rongpei Lan, Prajjal Singha, Pothana Saikumar, Joel M. Weinberg

Producción científica: Chapter


During recovery from acute kidney injury (AKI), regenerating tubules may become growth arrested, fail to differentiate, and undergo atrophy. These tubules exhibit pathological signaling and paracrine activity that perturbs normal interactions of pericytes with peritubular capillary endothelium. The resulting dissociation of pericytes from capillaries is associated with capillary disintegration and rarefaction, pericyte to myofibroblast transformation, and fibrosis – the AKI to chronic kidney disease (CKD) transition. Although signals from injured endothelium and inflammatory-immune cells also contribute, selective tubule injury is sufficient to initiate the interstitial pathology that leads to fibrosis. Tissue hypoxia caused by vasoconstriction and capillary rarefaction prevents tubule recovery and maintains the profibrotic tubule phenotype in a vicious cycle. However, capillary rarefaction after AKI develops only around damaged tubules and tubulointerstitial fibrosis is not intrinsically progressive; therefore, further deterioration of kidney structure after the AKI to CKD transition requires new acute injury. On the other hand, additional loss of parenchyma caused by failed repair of AKI in kidneys with prior renal mass reduction and attendant hypertension can trigger hemodynamic processes that damage glomeruli to cause disease progression. The AKI to CKD transition is clinically important; investigation of the responsible signaling mechanisms could reveal molecular targets for intervention to prevent the development of CKD after AKI and retard further progression.

Idioma originalEnglish (US)
Título de la publicación alojadaComprehensive Toxicology, Third Edition
Subtítulo de la publicación alojadaVolume 1-15
ISBN (versión digital)9780081006122
ISBN (versión impresa)9780081006016
EstadoPublished - ene 1 2018

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Environmental Science


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