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)

Rats were injected intraperitoneally with HgCl2 at doses of 2.5, 5, 7.5, and 10 mumol of Hg/kg. Urine was collected over a 24-hr period. At this time, plasma samples were taken and kidney damage was assessed by histological examination. Urinary gamma-glutamyltransferase levels were significantly elevated at Hg2+ doses of 7.5 and 10 mumol/kg, consistent with the detection of acute tubular necrosis by light microscopy. Resonances for a large number of low molecular weight metabolites were assigned in high resolution 1H NMR spectra of rat urine. Spectra from small volumes of urine (about 0.5 ml) were obtained in less than 5 min with no pretreatment. Significant Hg2+ dose-related decreases in the excretion of creatinine and citrate and increases of glucose, glycine, alanine, alpha-ketoglutarate, succinate, and acetate were detected. Elevated levels of lactate and creatinine in plasma of rats receiving the two highest doses were found by 1H NMR. There was a good correspondence between the histopathology, enzyme excretion, and 1H NMR urinary metabolite fingerprints in the assessment of Hg2+-induced renal damage. 1H NMR provided a sensitive measure of mercury-induced nephrotoxic lesions, and information on the molecular basis of mercury cytotoxicity was derived from the abnormal patterns of metabolite excretion. These suggested that primary metabolic effects of mercury were upon mitochondrial metabolism, in particular inhibition of certain citric acid cycle enzymes leading to decreased utilization of alpha-ketoglutarate and succinate by the renal tubular cells. The decrease in urinary citrate associated with Hg2+ dosing was attributed to intracellular, tubular acidosis with concomitant enhanced citrate reabsorption. The acidosis was assumed to arise from a combination of the inhibition of tubular carbonic anhydrase and a mild metabolic lactic acidosis due to increased activity of anaerobic pathways in the kidney. The possible extension of the 1H NMR techniques to the investigation of the nephrotoxic potential of other compounds and drugs is discussed.
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PMID:Proton NMR spectra of urine as indicators of renal damage. Mercury-induced nephrotoxicity in rats. 286 May 59

In a multicenter trial we investigated the effect of immunosuppressive therapy on graft and patient survival, renal function, and complications in 291 recipients of cadaveric renal transplants. One hundred forty-two patients were randomly assigned to treatment with cyclosporine and prednisone, and 149 to control immunosuppressive therapy (azathioprine and prednisone, with or without antilymphocyte globulin). At three years graft survival was 69 percent in the cyclosporine-treated patients and 58 percent in the controls (P = 0.05). The number of episodes of graft rejection was similar in the two groups, but the severity of rejection was significantly worse among the controls. Patients survival after three years was 90 percent in the cyclosporine group and 82 percent in the control group (P = 0.04). Acute tubular necrosis was an important risk factor for graft loss in both groups. Risk factors for death included diabetes and older age of the recipient. Renal function as indicated by the serum creatinine concentration or creatinine clearance was poorer in the cyclosporine-treated patients than in the controls, but has remained stable in both groups since the sixth month after transplantation. We conclude that, among recipients of cadaveric renal transplants, those treated with cyclosporine, despite having poorer (but stable) renal function, have better graft and patient survival at three years than those treated with alternative forms of immunosuppressive therapy.
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PMID:A randomized clinical trial of cyclosporine in cadaveric renal transplantation. Analysis at three years. 287 86

Splenectomy (SPLX) prevents ischemic acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion. This study attempts to reverse the protective effect of splenectomy in the ischemic model of ATN by increasing hematocrit before inducing ATN. Sham-SPLX, SPLX, and SPLX dogs given packed red cells to elevate hematocrit by 30% (SPLX-high hematocrit) received bilateral renal artery obstruction (RAO) for 120 minutes. Renal function was tested for 6 days post-RAO. Hematocrit in the SPLX-high hematocrit group was greater (p less than .05) than the SPLX-RAO group but did not differ from the non-SPLX group. All groups had different (p less than .05) serum creatinine levels for 48 hours post-RAO, and untreated animals differed from all the others at 144 hours. Serum creatinine was highest in untreated, lowest in SPLX-high hematocrit, and intermediate in noninfused SPLX animals. The same pattern was observed in blood urea nitrogen, creatinine clearance and renal histopathology. Fractional excretion of sodium in the SPLX groups was six times that in the intact animals (p less than .05), irrespective of hematocrit level. We conclude that increased hematocrit is protective in ischemic ATN, and does not promote PTC congestion or ATN in the SPLX animal. In addition, the protective effect of splenectomy may be mediated, in part, by mechanism(s) that alter sodium transport or osmolar excretion.
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PMID:Increased hematocrit mitigates ischemic renal damage in the splenectomized dog. 292 39

A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A [99mTc]dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.
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PMID:Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function. 301 25

Treatment with thromboxane (Tx) synthase inhibitors or free radical scavengers has been shown to afford protection from renal ischemia. Since free radicals are closely associated with thromboxane (Tx) synthesis, this study examines the thesis that free radical scavengers inhibit formation of Tx. Anesthetized rats (n = 42) underwent right nephrectomy. By random choice, before 45 min of left renal pedicle clamping, rats received: 0.5 ml dextrose placebo IV (n = 6); the hydroxyl radical scavenger dimethyl-thiourea (DMTU), 500 mg/kg IV (n = 10); or the superoxide scavenger superoxide dismutase (SOD), 24,000 Sigma Units (SU)/kg IV (n = 12). This dose of SOD was repeated before release of the clamp. Treatment with DMTU and SOD decreased plasma TxB2 levels following 5 min of reperfusion from 2,480 pg/ml in dextrose treated controls to 1,155 pg/ml (p less than 0.01) and 1,419 pg/ml (p less than 0.03), respectively. At 24 hr, DMTU and SOD therapy decreased creatinine from 3.0 mg/dl in controls to 1.6 mg/dl (p less than 0.01) and 2.1 mg/dl (p less than 0.05), respectively. At 24 hr, DMTU but not SOD decreased left renal weight from 113 to 94% (p less than 0.0003) of the weight of the previously removed right kidney, and histologically prevented acute tubular necrosis (p less than 0.05). In nephrectomized but nonischemic sham control rats (n = 7) plasma TxB2 and 6-keto-PGF1 alpha concentrations were 757 pg/ml and 82 pg/ml, creatinine level 0.9 mg/dl and kidney weight 94% of the previously removed right kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of thromboxane (Tx) synthesis by free radical scavengers. 312 99

With PHP as an oxygen carrier, histologic studies in ET showed changes of renal tubular epithelial cells at 2 weeks post ET, with normal structure by 3-12 months post ET. The renal functional effects of PHP were evaluated by ET (30%, N = 3; 50%, N = 1; 80%, N = 3) in seven healthy mongrel dogs. Blood, urine, and renal biopsy specimens were taken pre ET and at 0, 1, and 2 days, 2, 4, and 6 weeks, and 3, and 6 months post ET. Data were compared to modified criteria of acute tubular necrosis. All dogs tolerated the procedure well and survived for 1 year. Urine output was normal with elevation during the first 2 days in the 50 and 80% ET, followed by stable output by 2 weeks, ranging from 12 to 60 ml/kg/day. Blood urea nitrogen (BUN) and serum creatinine (SCr) were normal. BUN/SCr was normal. The urine to plasma osmolality ratios were 2.6 to 8.3 (normal greater than 1), and fractional percent excretions of sodium (FES) were stable throughout. No existence of broad granular pigmented casts (BGPC) in urine sediment were noted. Renal histologic evaluation of vacuolization in the renal tubules were seen to be dose-dependent and transient, with normal histology by 3-6 months post ET. Dose-dependent vacuole formation observed in the early weeks post ET with PHP showed no renal functional changes. Based upon the modified criteria for acute tubular necrosis, no histologic abnormalities were noted.
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PMID:Renal effects of a pyridoxalated-hemoglobin-polyoxyethylene conjugate solution as a blood substitute in exchange transfusions. 319 21

Thirteen patients developed a renal disease after using heroin alone or in combination with other drugs, for a period of 3 to 12 years. Eleven were IV drug addicts, 2 were sniffers. Six patients had acute tubular necrosis, due to rhabdomyolysis in 5 and to prolonged gentamicin therapy for bacterial endocarditis in 1. Five patients manifested a nephrotic syndrome, and renal biopsy showed various types of glomerulonephritis (GN) without glomerular sclerosis. The two last patients had hypertension with intrarenal vascular lesions and HBsAg was present in their serum. Chronic hemodialysis and/or renal transplantation were required in 2 cases with GN; all other patients recovered normal serum creatinine. There was no specific pathologic picture of heroin abuse in this series.
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PMID:[Renal disease associated with heroin abuse]. 321 43

To the extent that age-related declines in kidney function are caused by intrarenal alterations, donor age should affect glomerular filtration rate (GFR) after renal transplantation. Although some investigations have suggested that transplantation of aging kidneys may cause an increased incidence of primary allograft failure, the effects of donor age on GFR are unknown. In the present study, 201 patients who had allografts that survived for at least 24 months were investigated. The age range of the donors was 7 to 61 years. Multivariate regression analysis demonstrated that both donor and recipient age had significant, independent effects on creatinine clearance at 1 year, and at last follow-up, 5.0 +/- 1.9 years (mean +/- SD) after transplantation. The effect of donor age on renal function could not be attributed to differences in the number of rejection episodes, the frequency or duration of posttransplant acute tubular necrosis, age of the recipient, or other factors. Donor age had no effect on allograft survival, and did not affect the rate of decline in creatinine clearance between 1 year and last follow-up. Thus, these results suggest that donor age is associated with intrarenal alterations that lead to reductions in renal function after transplantation, but donor age may not affect long-term prognosis or allograft survival in the late posttransplant period.
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PMID:The influence of donor age on renal function in transplant recipients. 327

To examine the mechanisms of the nephrotoxic synergy of bacterial cell wall lipopolysaccharide (LPS) (or endotoxin) and the cephalosporin antibiotics, we have studied: 1) the effects on mean arterial blood pressure and the clearances of inulin, p-aminohippurate and cephaloridine (Cld) of a 12%-lethal dose of Escherichia coli 0111-B4 LPS (0.05 mg/kg b.wt.i.v.), with both low and high rates of saline infusion (0.1 ml/min vs. a 7.5-ml/kg load followed by 0.4 ml/min, respectively, in approximately 2-kg rabbits); 2) the separate and combined effects of LPS and saline infusion on the concentrations of Cld in renal cortex and serum; and 3) the separate and combined effects of LPS and saline infusion on the nephrotoxicity of Cld, quantified by acute tubular necrosis scoring and serum creatinine concentrations 48 hr after treatment with 90 mg/kg of Cld i.v. and by mitochondrial respiratory toxicity, depletion of reduced glutathione and production of lipid peroxidation products in renal cortex 1 hr after treatment with 90 to 360 mg/kg of Cld i.v. The following was found: 1) the increased saline infusion (saline) largely prevented an LPS-induced fall of inulin clearance and partially prevented a fall of blood pressure and p-aminohippurate and Cld clearance; 2) as a result, saline prevented slightly elevated late serum and cortical Cld concentrations in LPS-treated animals; 3) the tubular necrosis and elevation of serum creatinine caused by Cld alone was reduced slightly and that produced by the combination of LPS plus Cld was reduced greatly by saline; 4) the comparable mitochondrial respiratory toxicity found after Cld and LPS-plus-Cld was prevented by saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of the bacterial endotoxin-cephaloridine toxic synergy and the protective effects of saline infusion in the rabbit kidney. 334 35

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were studied three and seven days after ischemic acute tubular necrosis (ATN). Creatinine clearance was decreased three days after clamping the renal arteries (0.42 +/- 0.03 ml/min/100 g, N = 6 in ATN vs. 0.68 +/- 0.09, N = 7 in sham controls; P less than 0.001). Plasma concentrations (24.1 +/- 1.9 pg/ml) and PR of calcitriol (9.8 +/- 0.91 ng/kg/day) were significantly lower in ATN rats three days after ischemic insult when compared to sham control rats, respectively (76.6 +/- 7.3 pg/ml, and 29.6 +/- 3.3 ng/kg/day; both P less than 0.01). The MCRs of calcitriol were not different between ATN (0.28 +/- 0.02 ml/min/kg) and sham control rats (0.27 +/- 0.01). By the seventh day after ischemic injury, when creatinine clearance of ATN rats returned to normal, both the PR and plasma concentrations of calcitriol also returned to normal values in these animals. In order to assess the effect of uremia on calcitriol metabolism, MCR and PR of calcitriol were measured in rats with reinfusion of their urines for 24 hours. The PR of calcitriol was significantly decreased (9.42 +/- 1.21; vs. controls, 20.5 +/- 2.9 ng/kg/day, P less than 0.001) in uremic animals. Since decreased PR of calcitriol was also accompanied by decreased MCR of calcitriol, plasma concentrations of calcitriol of the uremic rats with intact kidneys remained within normal values. We conclude that the PR of calcitriol is decreased early in ATN rats. Although the MCR was not decreased in mild ATN rats, it may decrease in severe acute renal failure.
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PMID:Production and metabolic clearance of calcitriol in acute renal failure. 336 54


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