Evidence that inhibition of tubular cell apoptosis protects against renal damage and development of fibrosis following ureteric obstruction.
Ureteric obstruction is frequently encountered in primary care urology and can lead to damage to the ipsilateral kidney. Relief of all types of obstruction generally leads to the normalization of any deterioration in renal function noted at diagnosis. However, some evidence from animal models suggests that obstruction can cause progressive deleterious effects on renal function and blood pressure control, especially in the presence of preexisting pathologies such as essential hypertension. The last 10 years have seen a proliferation of studies in rodents wherein complete unilateral ureteric obstruction has been used as a model of renal fibrosis. However, the relevance of the findings to human obstructive uropathy has, in many cases, not been the primary aim. In this review, we outline the major events linking damage to the renal parenchyma and cell death to the evolution of fibrosis following obstruction. Special focus is given to the role of apoptosis as a major cause of cell death during and post-complete ureteric obstruction. Several interventions that reduce tubular apoptosis are discussed in terms of their ability to prevent subsequent progression to end-organ damage and fibrosis.
Docherty
Neil G
NG
Department of Surgery, Conway Institute of Biomolecular and Biomedical Sciences, Univ. College Dublin, Belfield, Dublin 4, Republic of Ireland.
O'Sullivan
Orfhlaith E
OE
Healy
Declan A
DA
Fitzpatrick
John M
JM
Watson
R William G
RW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005355:Fibrosis / Q000473:pathology*; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control*; D007684:Kidney Tubules / Q000473:pathology*; D008954:Models, Biological; D016212:Transforming Growth Factor beta / Q000502:physiology; D014517:Ureteral Obstruction / Q000473:pathology* / Q000503:physiopathology
D016212:Transforming Growth Factor beta