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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.
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PMID:Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure. 259 59

An initial event in cell response to growth factors is the change in the state of phosphorylation of a number of cellular proteins playing a role in cell proliferation. The effects of a single dose of exogenously administered epidermal growth factor (EGF) on renal serine/threonine protein kinases such as ribosomal protein S6 kinase(s) and protein kinase C (PKC) and on [3H]thymidine incorporation into tubule cell nuclei have been studied during the regenerative repair response after temporary renal ischemia in the rat, followed by reperfusion for up to 72 h. During the postischemic reflow, the PKC and S6 kinase activities increased at 24 and 72 h, respectively. EGF anticipated both increases: the PKC at 4 and the S6 kinase(s) at 24 h. Associated with this EGF-induced rise of S6 kinase activity, a significant increase in renal tubule cell proliferation was observed. These studies suggest the presence of a growth factor-activated serine/threonine phosphorylation cascade in the rat kidney participating in the regulation of cell growth during recovery from an ischemic insult.
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PMID:Ribosomal protein S6 kinase and protein kinase C activation by epidermal growth factor after temporary renal ischemia. 832 65

Kidneys of newborn (but not adult) mice are normally high permissive for polyomavirus (Py) infection and readily establish persistent infections. We have proposed that ongoing cellular differentiation, which occurs in newborn mice, may be necessary for a high level of in vivo Py replication (R. Rochford, J. P. Moreno, M. L. Peake, and L. P. Villarreal, J. Virol. 66:3287-3297, 1992). This cellular differentiation requirement may also be necessary for the reactivation of a persistent Py kidney infection and could provide an alternative to the accepted view that reactivation results from immunosuppression. To examine this proposal, the ability of adult BALB/c mouse kidneys to support primary acute Py infection or to reactivate previously established persistent Py infections after kidney-specific damage was investigated. Kidney damage was induced by both chemical (glycerol, cisplatin, or methotrexate) and mechanical (through renal artery clamping to produce unilateral renal ischemia) treatments. We also examined the effects of epidermal growth factor (EGF), which enhances the rate of kidney regeneration, on Py replication. Using histopathologic techniques, in situ hybridization for Py DNA, and immunofluorescence for Py VP1 production, we established that both chemical damage and damage through renal artery clamping of adult kidneys promoted high levels of primary Py replication in these normally nonpermissive cells. This damage also promoted the efficient reactivation of Py replication from persistently infected kidneys, in the absence of immunosuppression. EGF treatment significantly increased acute Py replication and also reactivation in damaged kidneys. These results support the view that ongoing cellular division and differentiation may be needed both for high levels of acute Py replication and for reactivation of persistent infections in vivo.
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PMID:Adult mouse kidneys become permissive to acute polyomavirus infection and reactivate persistent infections in response to cellular damage and regeneration. 838 4

The renin-angiotensin system plays an important role in renal growth and development: exposure of the fetus or neonate to angiotensin-converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. This study was designed to investigate the effects of ACE inhibition in the neonatal rat on the expression of genes known to modulate renal cellular proliferation, cell interactions, and extracellular matrix. Newborn rat pups were treated with enalapril (30 mg/kg/d) or vehicle for 14 d, and kidneys were removed for Northern analysis of mRNA for transforming growth factor-beta1 (TGF-beta1), prepro epidermal growth factor (EGF), clusterin, and renin. Distribution of TGF-beta1, EGF, and clusterin was also determined by immunohistochemistry. Enalapril treatment resulted in 40% mortality by d 14, reduced body and kidney weight, decreased glomerular area, and caused tubular dilatation (p < 0.05 versus vehicle group). Enalapril decreased renal TGF-beta1 and EGF mRNA expression, and increased renal clusterin and renin expression (p < 0.05). Renal tubular immunoreactive EGF was decreased, and clusterin was increased by enalapril treatment. These results indicate that ACE inhibition in the developing kidney reduces the renal expression of critical growth factors, which may account for renal growth impairment. Clusterin expression may increase either due to blockade of tonic angiotensin-mediated inhibition, or as an adaptive response to renal ischemia.
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PMID:Angiotensin-converting enzyme inhibition decreases growth factor expression in the neonatal rat kidney. 935 28

Determinations of renal clearance of fluorescein isothiocyanate (FITC)-inulin were used for assessing the glomerular filtration rate (GFR) in rats and to characterize factors influencing the glomerular filtration capacity. In anesthetized rats, GFR develops after birth up to day 30. Thereafter, GFR remains relatively constant for up to 3 months of age and drops continuously until the 8th month. GFR can be determined in utero, already one day before birth, however, only at a very low level. It increases significantly on the first day of life. Even at this time the effect of furosemide on GFR can be proven. After reduction of renal mass, GFR is decreased in dependence on the extent of kidney tissue removal. However, within 2 days after unilateral nephrectomy (NX) or one week after 5/6 NX, GFR reaches values about 3/4 of the controls with two intact kidneys. Furthermore, the compensation of GFR after renal ischemia reaches 80% of baseline values after one week. On the other hand, GFR is enhanced after bile duct ligation as a model of hepato-renal failure. It has been shown in previous experiments that pretreatment with hormones can stimulate renal tubular transport processes. Pretreatment with dexamethasone or triiodothyronine after 5/6 NX improves glomerular filtration capacity whereas in animals with ligated bile ducts dexamethasone seems to prevent the increase in GFR. After subchronic treatment with epidermal growth factor (EGF) GFR is significantly reduced. A continuous infusion of amino acids does not change GFR in the controls but enhances the filtration capacity in EGF-treated rats. But immediately after bolus injection of amino acids GFR also increases significantly in the controls. Diuretics such as furosemide, most nephrotoxic agents (cyclosporine A [CsA], heavy metals) and imidazole reduce the GFR significantly. Diltiazem reported to act nephroprotectively in CsA nephrotoxicity in human beings was without beneficial effect in rats. This could be due to species differences in GFR because the rat is one of the species with the highest glomerular filtration capacity.
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PMID:Determination of the glomerular filtration rate (GFR): methodological problems, age-dependence, consequences of various surgical interventions, and the influence of different drugs and toxic substances. 1063 78

Recovery from ischemic acute kidney injury requires the replacement of damaged tubular cells. This repair process involves epidermal growth factor (EGF) synthesized in medullary the thick ascending limbs (mTAL) of Henle. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, increases glomerular filtration rate and renal medullary blood flow. However, the effects of ANP on renal recovery after I/R-induced renal injury remain unclear. We therefore examined whether human ANP enhances recovery from I/R-induced renal injury by reducing damage to EGF-producing kidney cells in a rat model. Male Wistar rats weighing 200-240 g were observed for 48 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP) at 0.2 microg/kg/min beginning immediately after ischemia and continuing for 2 h after reperfusion. Outer medullary blood flow (OMBF), EGF mRNA, serum blood urea nitrogen (BUN) and creatinine levels as indicators of glomerular function were measured, while urinary N-acetyl beta-D-glucosaminidase (NAG) was used as a specific indicator of proximal tubular function. OMBF was increased by alpha-hANP after reperfusion and maintained significantly higher mRNA level of EGF in the kidney 24 h after reperfusion. I/R-induced increases in serum concentrations of BUN and creatinine and urinary concentrations of NAG were also reduced by alpha-hANP, with improved histopathological changes, including acute tubular necrosis at 24-48 h after reperfusion. This report is the first to demonstrate that alpha-hANP accelerates recovery following renal ischemic insult by reducing the damage to EGF-producing kidney cells.
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PMID:Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. 2047 88