title: Suicide of the nephron.
abstract: There are various causes of renal disease. However, progressive renal disease is closely linked to the degree and duration of proteinuria. At first sight, this seems a perverse response in which a compromised organ unleashes a coordinated series of reactions that exacerbate the damage already done. Although the nephron has mechanisms whereby it can compensate for damage both by hypertrophy and hyperfunction after renal injury or ablation, these changes seem to provide only a temporary compensation. I and my colleagues found altered renal telomere shortening in the male rat linked to increased or decreased proteinuria and longevity, which suggests a mechanism whereby this compensatory process may be limited. I hypothesise that when the damaging or hypertrophic processes shorten renal telomeres to a critical length, the cells senesce with loss of function. I also suggest that the complex series of responses triggered in a protein-leaking nephron is normally a beneficial and limited process. It leads to the replacement by fibrosis of a malfunctioning unit in an otherwise healthy organ that has substantial spare capacity. The response only becomes life threatening when there is widespread nephron damage, the acceleration of which results in the ablation of all nephron function.
authors.affiliation: Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, UK. cnh1000@cam.ac.uk
authors.forename: C N
authors.initials: CN
authors.lastname: Hales
mesh_terms: D000818:Animals; D016923:Cell Death; D002455:Cell Division; D007668:Kidney / Q000503:physiopathology; D008297:Male; D009399:Nephrons / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D016615:Telomere / Q000235:genetics