atrial-natriuretic-factor and Kidney-Tubular-Necrosis--Acute

Topics: Acute Kidney Injury; Atrial Natriuretic Factor; Diuretics; Dopamine; Humans; Kidney Medulla; Kidney Tubular Necrosis, Acute; Oxygen; Renal Dialysis

Topics: Atrial Natriuretic Factor; Controlled Clinical Trials as Topic; Humans; Kidney Tubular Necrosis, Acute

Topics: Animals; Atrial Natriuretic Factor; Calcium Channel Blockers; Diuretics; Dopamine; Hemodynamics; Humans; Kidney Tubular Necrosis, Acute; Mannitol

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Erythrocyte Transfusion; Glomerular Filtration Rate; Hemodynamics; Kidney Tubular Necrosis, Acute; Mannitol; Rats

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.

Topics: Animals; Atrial Natriuretic Factor; Humans; Ischemia; Kidney; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Middle Aged

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.

Topics: Adult; Aged; Atrial Natriuretic Factor; Blood Pressure; Data Interpretation, Statistical; Diuretics; Double-Blind Method; Female; Heart Rate; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Oliguria; Peptide Fragments; Placebos; Prospective Studies; Renal Dialysis; Risk Factors; Survival Rate; Treatment Outcome

We compared the clinical outcomes of patients with (n = 71) and without (n = 185) diabetes mellitus enrolled into the placebo arm of a large, multicenter clinical trial of patients with acute tubular necrosis (ATN). Compared with the nondiabetic patients, diabetic patients were older (65.5 +/- 12.9 versus 60.7 +/- 18.0 years, P < 0. 05), had higher usual serum creatinine concentration (1.7 +/- 0.6 versus 1.4 +/- 0.5 mg/dL, P < 0.001), and had a higher prevalence of underlying hypertension, coronary artery disease, and congestive heart failure (all P < 0.007). By day 21 after enrollment, neither mortality nor dialysis-free survival was different between the groups. Length of stay for surviving patients, in both the intensive care unit and the hospital, were significantly shorter for the diabetics. Among acute comorbidities predicting mortality or the need for dialysis, sepsis was more prevalent among the nondiabetic patients (18% versus 35%, diabetics versus nondiabetics, P < 0.05). In conclusion, clinical outcomes for diabetic patients with ATN were no worse than for nondiabetic patients, despite their older age and worse underlying renal function. Patients with diabetes mellitus had more chronic cardiovascular disease but were less acutely ill. We speculate that cardiovascular disease is a risk factor for ATN in patients with diabetes mellitus. These results fail to implicate the increasing prevalence of diabetes mellitus in the persistently poor prognosis of patients with ATN.

Topics: Aged; Atrial Natriuretic Factor; Diabetes Complications; Diabetes Mellitus; Diuretics; Humans; Kidney Tubular Necrosis, Acute; Middle Aged; Peptide Fragments; Prognosis; Renal Dialysis; Risk Factors; Survival Rate

Atrial natriuretic peptide, a hormone synthesized by the cardiac atria, increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles. It has been shown to improve glomerular filtration, urinary output, and renal histopathology in laboratory animals with acute renal dysfunction. Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide.. We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis. The patients received a 24-hour intravenous infusion of either anaritide (0.2 microgram per kilogram of body weight per minute) or placebo. The primary end point was dialysis-free survival for 21 days after treatment. Other end points included the need for dialysis, changes in the serum creatinine concentration, and mortality.. The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group (P = 0.35). In the prospectively defined subgroup of 120 patients with oliguria (urinary output, < 400 ml per day), dialysis-free survival was 8 percent in the placebo group (5 of 60 patients) and 27 percent in the anaritide group (16 of 60 patients, P = 0.008). Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most. Conversely, among the 378 patients without oliguria, dialysis-free survival was 59 percent in the placebo group (116 of 195 patients) and 48 percent in the anaritide group (88 of 183 patients, P = 0.03).. The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis. However, anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis.

Topics: Atrial Natriuretic Factor; Diuretics; Double-Blind Method; Female; Humans; Infusions, Intravenous; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Oliguria; Peptide Fragments; Prospective Studies; Renal Dialysis; Survival Analysis; Treatment Outcome

Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed.. To test the hypothesis that the cause of ATN affects its clinical outcome.. The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes.. Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysis-free survival improved significantly and mortality tended to decline with advancing age.. Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious commorbidities in the ischemic ATN group. Advancing age was associated with improved dialysis-free survival and a tendency toward reduced mortality in patients with ischemic ATN.

Topics: Adult; Aged; Atrial Natriuretic Factor; Diuretics; Double-Blind Method; Female; Humans; Ischemia; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Natriuresis; Peptide Fragments; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Survival Analysis

The efficacy and safety of (1-28) alpha-human ANP in preventing acute tubular necrosis (ATN) in cadaveric renal transplantation was tested by comparing ANP infusion with a maximal hydration (MH) regimen which we previously reported as effective in lowering the incidence of ATN (1, 2). Since the production of endogenous ANP increases with volume overloading (3), we hypothesized that increased endogenous ANP production may contribute to the beneficial effects of MH in renal transplant recipients. We thus conducted an open randomized study comparing the effect on early renal allograft function of MH (control group) versus moderate hydration plus ANP infusion (ANP group). Forty patients were blindly paired in two groups of 20 according to the duration of cold ischemia time (mean +/- 2 h). The demographic characteristics of donors and recipients were similar. Using a Swan-Ganz catheter, hemodynamic parameters were monitored for 4 h after transplantation. The group receiving ANP and moderate hydration was perfused to a mean pulmonary arterial pressure (PAP) of < or = 20 mmHg. The PAP in patients receiving MH was driven to > or = 25 mmHg. In the ANP group, a bolus of 100 micrograms of ANP was infused into the graft's renal artery at the time of unclamping, followed by 24 h of continuous intravenous infusion at 0.03 microgram/kg/min. Thereafter, the patients received ANP at a rate of 0.01 microgram/kg/min until the serum creatinine reached < 2 mg/dl. As a consequence of the hydration regimen, the PAP at unclamping was lower in the ANP group than in the control group; 20 +/- 3 and 26 +/- 4 mmHg, respectively (p < 0.05). The ANP plasma levels were significantly higher during the first 3 d in the ANP group (p < 0.001). The median recovery rate of renal function was similar in both groups. No patients in the ANP group experienced ATN while 4 patients (20%) in the control group did (p = 0.125). The need for hemodialysis was markedly reduced in the ANP group compared to the control group (1 ANP-treated patient required dialysis once whereas 5 patients from the control group underwent dialysis a total of 26 times; p = 0.068). ANP administration was well-tolerated and no hypotensive episodes were reported. This preliminary study suggests that ANP infusion is at least as effective as maximal hydration in preventing ATN and represents an efficient alternative for transplantation centers which do not use maximal hydration as a standard regimen in managing kidney allograft r

Topics: Acute Kidney Injury; Adult; Atrial Natriuretic Factor; Blood Pressure; Cadaver; Female; Fluid Therapy; Humans; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Male; Pulmonary Artery

Seventeen Sprague-Dawley rats had ischemic nonoliguric acute renal failure (ARF) induced by vascular clamping resulting in their preischemic blood urea nitrogen (BUN) and creatinine levels of 16 +/- 1 and 0.56 +/- 0.05 mg/dl to increase to 162 +/- 4 and 8.17 +/- 0.5 mg/dl, P < 0.001, respectively, at day 4 of postischemia. Vessel dilator, a 37-amino-acid cardiac peptide hormone (0.3 microg x kg(-1) x min(-1) ip), decreased the BUN and creatinine levels to 53 +/- 17 mg/dl and 0.98 +/- 0.12 mg/dl (P < 0.001) in another seven animals where ARF had been established for 2 days. Water excretion doubled with ARF and was further augmented by vessel dilator. Transthoracic echocardiography revealed left ventricular dilation as a probable cause of the increase in vessel dilator in the circulation with ARF, and vessel dilator infusion reversed this dilation. At day 6 of ARF, mortality decreased to 14% with vessel dilator from 88% without vessel dilator. Acute tubular necrosis was <5% in the vessel dilator-treated rats compared with 25% to >75% in the placebo-treated ARF animals. We conclude that vessel dilator improves acute tubular necrosis and renal function in established ARF.

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Disease Models, Animal; Echocardiography; Heart; Hemodynamics; Ischemia; Kidney; Kidney Function Tests; Kidney Tubular Necrosis, Acute; Male; Peptide Fragments; Protein Precursors; Rats; Rats, Sprague-Dawley; Vasodilator Agents

Topics: Atrial Natriuretic Factor; Diuretics; Humans; Integrins; Kidney Tubular Necrosis, Acute; Peptide Fragments

Topics: Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Growth Substances; Humans; Intensive Care Units; Kidney Tubular Necrosis, Acute; Kidney Tubules; Regeneration