Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial natriuretic factor (ANF) ameliorates renal damage in animal models of acute ischemic renal failure. Consequently, ANF could blunt acute tubular necrosis related to ischemia that occurs frequently in cadaveric renal transplants. Ten pairs of cadaveric kidneys were transplanted into 20 recipients. Paired recipients received either alpha-human ANF (hANF) or vehicle alone in a prospective, double-blind protocol. Upon revascularization of the allograft, either hANF or vehicle was administered intravenously as a 50-micrograms bolus, followed by a 4-h infusion (0.1 microgram/kg/min). Glomerular filtration rate ([125I]iothalamate clearance) was measured between 4 and 7 days posttransplant and again between 14 and 21 days posttransplant. Serum creatinine was measured daily when patients were in the hospital, then twice weekly as patients were examined in the outpatient clinic. Between the groups, there was no significant difference in age of the recipients or donors, cold ischemia time, or histocompatibility leukocyte antigen match. Infusion of hANF had no adverse effects. When subjects receiving hANF were compared with those treated with vehicle alone, there were no significant differences in serum creatinine or glomerular filtration rate. Three hANF and four vehicle recipients required dialysis postoperatively. At 1 month posttransplant, 19 of 20 patients had functioning allografts; an allograft from one hANF recipient never functioned. It was concluded that hANF, when given by the protocol of this study, had no beneficial effect on the outcome of cadaveric renal transplantation in humans.
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PMID:Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation. 183 82

Because of the deleterious effects of acute tubular necrosis (ATN) after kidney transplantation, the search for new and effective means of protecting the kidneys from ischemic or nephrotoxic injuries continues. The beneficial effects of hyperhydration with mannitol or furosemide infusions in renal allograft recipients have now been well documented. The recent discovery by De Bold and coworkers that hypervolemia (by atrial distension) induces the release of atrial natriuretic factor (ANF) suggests an important physiopathological, and perhaps therapeutic, role for this natriuretic peptide in kidney transplantation. In addition to providing an overview of the current knowledge about ANF and its effects on both intact and ischemically injured kidneys, the physiological role of ANF in various situations, similar to those found in kidney transplantation, is analyzed. The effects of ANF on arachidonic acid metabolites and on the nephrotoxic side effects of cyclosporin are also reported. If the results of the preliminary experimental studies appear to be effective, further prospective clinical trails must be carried out to confirm them.
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PMID:Atrial natriuretic factor: a protective role after acute renal ischemia? Is there room for it in kidney transplantation? 214 25

Because of the deleterious effects of acute tubular necrosis (ATN) after kidney transplantation, the search for new and effective means of protecting the kidneys from ischemic or nephrotoxic injuries continues. The beneficial effects of hyperhydration with mannitol or furosemide infusions in renal allograft recipients have now been well documented. The recent discovery by De Bold and coworkers that hypovolemia (by atrial distension) induces the release of atrial natriuretic factor (ANF) suggests an important physiopathological, and perhaps therapeutic role for this natriuretic peptide in kidney transplantation. In addition to providing an overview of the current knowledge about ANF and its effects on both intact and ischemically injured kidneys, the physiological role of ANF in various situations, similar to those found in kidney transplantation, is analyzed. The effects of ANF on arachidonic acid metabolites and on the nephrotoxic side effects of cyclosporin are also reported. If the results of the preliminary experimental studies appear to be effective, further prospective clinical trials must be carried out to confirm them.
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PMID:Atrial natriuretic factor: a protective role after acute renal ischaemia? A room for it in kidney transplantation? 214 48

In order to determine the relationships between allograft function and the recipient's plasma concentrations of atrial natriuretic factor (ANF), plasma ANF was measured by radioimmunoassay for 14 days after cadaveric renal transplantation in 9 patients aged 19-64 years. All received immunosuppression with prednisolone, azathioprine, and cyclosporine. No patient was in heart failure. During the study period, six grafts functioned, and three were nonfunctioning--two due to rejection and one to acute tubular necrosis. Plasma ANF concentration at the time of transplantation was 48 +/- 16 pmol/L (mean +/- SEM) range 15-145 pmol/L. In the six patients with functioning grafts, ANF declined in parallel with the fall in serum creatinine (658 +/- 35 to 210 +/- 34 mumol/L). In the three with nonfunctioning grafts, serum creatinine and plasma ANF concentration both increased. There was overall a significant linear relation between serum creatinine and plasma ANF (r = 0.527, P less than 0.001). The changes in plasma ANF after renal transplantation bore no relationship to changes in body weight or blood pressure. However, plasma ANF concentration was related to allograft fractional sodium excretion (r = 0.687, p less than 0.001). We conclude that elevated plasma ANF concentrations in end-stage renal disease are restored to normal by successful renal transplantation, implying that renal function is a determinant of plasma ANF concentration. Circulating plasma ANF may also have a direct effect on allograft sodium excretion.
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PMID:Plasma atrial natriuretic factor and graft function in renal transplant recipients. 253 Jun 66

Atrial natriuretic peptide can increase glomerular filtration rate and filtration fraction and can promote natriuresis, effects that would logically seem to improve renal function after acute tubular necrosis from ischemic or toxic injury. Early human trials suggested a beneficial effect of atrial natriuretic peptide on creatinine clearance, and a reduction in the need for dialysis in treated patients. However, randomized, placebo-controlled trials have failed to show a clinically relevant benefit on survival, dialysis-free survival, or renal function in patients treated with this agent.
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PMID:The rise and fall of atrial natriuretic peptide for acute renal failure. 932 7

Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.
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PMID:Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group. 1115 96

Atrial natriuretic peptides (ANPs) are a family of peptide hormones, e.g., ANP, long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide synthesized by the ANP gene. Brain natriuretic peptide (BNP) and C-type natriuretic peptide are also members of this family but are synthesized by separate genes. Within the kidney, the ANP prohormone's posttranslational processing is different from that of other tissues, resulting in an additional four amino acids added to the NH2 terminus of ANP (e.g., urodilatin). Each of these natriuretic and diuretic peptides increases within the circulation with acute renal failure (ARF). Renal transplantation but not hemodialysis returns their circulating concentrations to those of healthy individuals. BNP and adrenomedullin, a 52-amino acid natriuretic peptide, have beneficial effects on glomerular hypertrophy and glomerular injury but do not improve tubular injury (i.e., acute tubular necrosis). Vessel dilator ameliorates acute tubular necrosis with regeneration of the brush borders of proximal tubules. Vessel dilator decreases mortality in ARF from 88 to 14% at day 6 of ARF, even when given 2 days after renal failure has been established.
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PMID:Natriuretic peptides and acute renal failure. 1284 58

Activated neutrophils have been implicated in the development of ischemia/reperfusion (I/R)-induced renal failure. Cytokine-induced neutrophil chemoattractant-1 (CINC-1), a major factor in acute inflammation, is responsible for the activation of neutrophils and for neutrophil chemotaxis to sites of injury. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators. We examined whether the human form of ANP attenuates I/R-induced renal injury by reducing neutrophil activation in a rat model. Male Wistar rats weighing 200-240 g were observed for 24 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP, 0.2 microg/kg/min) beginning immediately after ischemia and continuing for 2 h after reperfusion. CINC-1 and myeloperoxidase (MPO) concentrations were measured to assess activation of the infiltrating neutrophil. Blood urea nitrogen and serum creatinine and urinary N-acetyl beta-d-glucosaminidase (NAG) were measured as indicators of glomerular function and as a specific indicator of proximal tubular function, respectively. alpha-hANP significantly inhibited I/R-induced increases in renal CINC-1 and MPO concentrations. alpha-hANP also reduced I/R-induced increases in the concentrations of blood urea nitrogen and serum creatinine, and improved histopathologic changes, including acute tubular necrosis. These findings indicate that alpha-hANP attenuates I/R-induced acute renal injury, at least in part by reducing neutrophil activation, and may be useful in surgeries, associated with renal ischemia, as well as in renal transplantation.
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PMID:Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. 1864 86

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