title: [Regeneration following acute kidney damage].
abstract: Acute renal failure was, and still is, a relative frequently observed disease (1% of the hospital population) with a bad prognosis (50% mortality). This prognosis remained unchanged over the last 40 years, on the one hand due to the changed, older patient population with his complex pathology, on the other hand the lack of efficient therapies capable to cure or prevent acute renal failure. Fortunately, the kidney, in contrast to some other organs, possess an important regeneration capacity after acute ischemic and/or toxic injury. This regeneration capacity manifests itself by a proliferation and migration of young cells along the denudated basal membrane of the injured segments within 24 hours after the acute insult. This proliferation is also seen at the interstitium and the non-injured distal tubule of the kidney. Some years ago intensive research was performed looking for possible renal growth factors, being the initiators of this important proliferation. Indeed, the kidney expresses several growth factors such as 'epidermal growth factor', 'insuling growth factor', 'platelet growth factor', 'hepatocyte growth factor', 'transforming growth factor alpha', and 'transforming growth factor beta'. However, studies performed in several models of acute renal injury observed an almost complete disappearance of these growth factors immediately after the insult, measurement at the level of mRNA and protein. On the other hand, the receptor-density for some growth factors at the level of the baso-lateral site of the cells of the injured segments is upregulated. The kidney itself is not the source of growth factors, she is eager to take up a number of growth factors, a possible mechanism for the repairing proliferation. Based on these findings and the fact that a clear cellular infiltrate goes along with each acute renal insult, the question was raised if there is a role for this cellular infiltration in the regeneration process? We and others could demonstrate that soon after the insult a fast interstitial infiltration/proliferation occurs and that this cellular infiltration is mainly surrounding the injured segments of the nephron. This infiltration does not consists of neutrophils but of macrophages and T-cells. Even in the case of an ischemic insult, in contrast to the current literature, the cellular infiltration does not contain neutrophils. We found that the contribution of the neutrophils is negligible compared to the macrophages and T-cells. An explanation could be found in the fact that the methods, used to identify the neutrophils, are not specific for this particular leukocyte subset. Several experiments were performed searching for a role of the cellular infiltrate using athymic rats (absence of T-cells), knock-out mice (ICAM1 or iNOS deficient) performing leukocyte depletion experiments with appropriate antibodies; applying antisense oligonucleotides (ICAM1), all point towards the same direction: prevention of the formation of an interstitial infiltrate results in almost no decrease of renal function after acute injury. This favourable effect on renal function does not preclude a role of this interstitial infiltrate in the regeneration process of the damaged nephron segments. Further research will have to show if the infiltrate can not be the source of the growth factor, initiating the important renal proliferation/regeneration. It is clear that this infiltrate has to disappear, a process in which apoptosis plays a central role. Indeed, it was shown that a maintained macrophage T-cell infiltrate can provoke interstitial fibrosis and finally chronic renal failure.
authors.affiliation: Dienst Nierziekten-Hypertensie, Universiteit Antwerpen (UIA), Universitair Ziekenhuis Antwerpen.
authors.forename: M E
authors.initials: ME
authors.lastname: De Broe
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000502:physiology / Q000503:physiopathology*; D051379:Mice; D051381:Rats; D012038:Regeneration
chemical_list: D006133:Growth Substances