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)

Sodium diethyldithiocarbamate (DDTC) administered following cis-diamminedichloroplatinum(II) (DDP) has been reported to attenuate structural renal damage and elevation of blood urea nitrogen in rats. Since DDP damages primarily proximal tubular epithelium in this species, we compared proximal tubular function, glomerular function, and histology in male Sprague-Dawley rats treated with DDP followed by either DDTC or 0.9% NaCl solution (NS) rescue. Male Sprague-Dawley rats received a single i.p. injection of DDP (7.5 mg/kg)-mannitol (75 mg/kg)-NaCl (67.5 mg/kg). Forty-five min later, rats were given i.p. injections of either DDTC (750 mg/kg) dissolved in 0.5 ml of NS (DDP + DDTC group; ten rats) or 0.5 ml NS (DDP + NS group; nine rats); additional rats received either DDTC only (DDTC group; six rats) or no treatment (untreated control group; six rats). All groups were sacrificed 5 days later by ether anesthesia and exsanguination. Compared to the untreated control group, the DDTC group had slightly lower mean blood urea nitrogen at sacrifice [12.5 +/- 0.5 (S.E.) versus 15.4 +/- 0.8 mg/dl; p less than 0.025 by unpaired Student's t test]; there was no difference in serum creatinine. The DDP + DDTC group had no diarrhea and no presacrifice deaths in contrast to diarrhea and three presacrifice deaths in the DDP + NS group. Blood urea nitrogen was also lower in the DDP + DDTC group at sacrifice (187 +/- 30 versus 383 +/- 39 mg/dl; p less than 0.005). However, weight loss and serum creatinine were not different. Structural acute tubular necrosis was marked in both DDP groups but was less severe in the DDP + DDTC group than in the DDP + NS group. Proximal tubular function was indexed by the uptake of the organic base N-[14C]methyl nicotinamide (NMN) and the organic acid p-aminohippurate in renal cortical slices incubated 90 min in Cross and Taggart medium. NMN uptake (expressed as slice to medium ratio) was slightly lower in the DDTC group than in untreated controls (4.1 +/- 0.2 versus 5.0 +/- 0.2; p less than 0.025). Marked depression of p-aminohippurate and NMN uptake occurred in both DDP + DDTC and DDP + NS groups. There was no difference in NMN uptake, but depression of p-aminohippurate uptake was slightly less severe in the DDP + DDTC group (5.3 +/- 0.7 versus 3.1 +/- 0.3; p less than 0.005). We conclude that DDTC rescue attenuates structural DDP injury in this animal model. DDP-mediated proximal tubular dysfunction was only marginally attenuated by DDTC; glomerular filtration rate, as indexed by serum creatinine, was not protected. DDTC attenuation of DDP toxicity may be mediated in part via reducing volume depletion due to DDP-associated diarrhea.
Cancer Res 1983 Aug
PMID:cis-diamminedichloroplatinum(II) nephrotoxicity: tubular function after rescue with sodium diethyldithiocarbamate in rats. 630 93

Bilateral internal iliac artery infusion of chemotherapeutic agents in patients with advanced bladder carcinoma, Stage D, resulted in a 50% response or greater in nine of 15 patients with a median survival, thus far, of 52 weeks. Hematuria was controlled in eight of ten patients, and pain was relieved in 12 of 15 patients. Three additional patients were treated as adjuvants after their residual tumor was removed surgically or irradiated before chemotherapy. Cis-diamminedichloroplatinum (CDDP) was infused at a dose of 80--120 mg/m2 over a 24-hour period. When CDDP failed or in the presence of impaired renal function, a combination of 5-fluorouracil (5-FU) infused intraarterially while Adriamycin and mitomycin C were delivered intravenously, salvaged two patients. Complications were tolerable, consisting of transient acute tubular necrosis in two patients, a lower extremity embolus in one, and skin reactions due to 5-FU in two patients.
Cancer 1982 Feb 15
PMID:Transcatheter intraarterial infusion of chemotherapy in advanced bladder cancer. 679 83

2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.
Cancer Res 1981 Sep
PMID:Phase I study of 2'-deoxycoformycin in acute lymphoblastic leukemia. 697 90

Calcium antagonists block calcium entry into cells, resulting in relaxation of smooth muscle and limitation of the cytotoxic effects of ischaemia in various organ systems. They are most frequently used for clinical conditions requiring vasodilatation, i.e. hypertension and Raynaud's phenomenon, and this also suggests that the most common adverse effect of these drugs for noncardiovascular indications is an unwanted decline in blood pressure. Other uses include treatment of supraventricular arrhythmias and angina. There is some evidence that these drugs retard the development of atherosclerosis. Calcium channel blockers also improve renal reperfusion and may reduce renal insufficiency due to various nephrotoxins, and are particularly useful in renal transplantation for protection against cyclosporin toxicity and post-transplant acute tubular necrosis. These drugs are also useful in pregnancy-induced hypertension and unwanted uterine contraction. Affective disorders and malignancies may be other conditions which benefit from calcium antagonist therapy. Calcium antagonists, in particular nimodipine which is most selective for the cerebral vasculature, have been approved for treating vasospasm after subarachnoid haemorrhage. They are probably also effective for treatment of migraine. Calcium channel blockers may be effective for treating acute cerebral infarction, but results of clinical trials to date have been equivocal, largely because it has been difficult to recruit patients within the short interval after the onset of stroke when these drugs would be most effective, and because of the unwanted hypotensive effect of high doses.
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PMID:New uses for calcium channel blockers. Therapeutic implications. 751 Jun 13

High risk renal transplant recipients experience excess graft loss despite overall improvements in the results of cadaveric renal transplantation. We evaluated a novel immunosuppression regimen consisting of simultaneous administration of OKT3, cyclosporine, azathioprine and prednisone. Of the 12 high risk patients studied 5 received 2 transplants, 1 received 3 transplants and 8 had peak panel reactive antibodies of greater than 60%. The protocol consisted of cyclosporine (7 mg./kg. orally or 3 mg./kg. intravenously per day) starting from the day of transplant regardless of graft function; 5 mg. OKT3 per day for 10 to 14 days starting intraoperatively; 5 mg./kg. azathioprine per day for 2 days, then 1.5 mg./kg. per day and adjusted according to white blood cell counts, and prednisone taper at 2 to 0.4 mg./kg. per day on day 10. The dose of cyclosporine was increased to 14 mg./kg. per day orally when serum creatinine was less than 3 mg./dl. The cyclosporine whole blood levels (measured by high performance liquid chromatography) were maintained between 250 and 400 ng./ml. in the first 3 months. Followup evaluations ranged from 3 to 28 months (median 8.5). Seven patients (58.3%) had acute tubular necrosis and required dialysis support for 2 to 5 weeks. Six patients (including 5 with acute tubular necrosis) experienced 1 episode of acute rejection in the first 3 months (2 of these were due to accelerated vascular rejection). Two rejections responded to pulse steroid treatment, while 4 (including 2 with vascular rejection) were treated with antilymphoblast globulin rescue therapy for 10 to 14 days. Symptomatic cytomegalovirus pneumonia occurred in 3 patients (25%). There were no deaths or graft losses. No case of malignancy was observed to date. The serum creatinine is less than 2 mg./dl. in 9 patients, and 2.5 to 2.9 mg./dl. in the remaining 3. We conclude that simultaneous quadruple immunosuppressive regimen that includes induction cyclosporine and OKT3 is a highly effective therapy for high risk patients, yielding excellent short-term and intermediate success rates. Long-term results of this regimen, including neoplastic potentiation, cannot be addressed because of the limited followup of these patients.
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PMID:Simultaneous quadruple immunosuppression with cyclosporine induction therapy in high risk renal transplant recipients. 801 58

Of 2457 patients in the North American Pediatric Renal Transplant Cooperative Study registry who were followed for 5481 patient-years after the index transplantation, we observed 136 deaths, for an average annual rate of 24.8 deaths per 1000 patient-years. Death resulted primarily from infection (n = 55, 40%), cardiovascular causes (n = 28, 21%), hemorrhage (n = 16, 12%), and malignancies (n = 9, 7%). Cadaver-donor source was associated with greater mortality (6.7%) than a living-donor source (4.0%) (P < 0.005). Recipients aged 0-1, 2-5, 6-12, and 13-17 years old had mortality rates of 17.5, 8.0, 3.6, and 4.5%, respectively (P < .001). Mortality rates increased substantially when examined by recipient and cadaver donor ages (mortality rates of up to 45%), the greater the concordance between young donor and recipient ages. Interestingly, acute tubular necrosis and graft failure less than 30 days after transplantation (GH30) were each associated with markedly elevated mortality rates. (The risk ratio for ATN was 3.1 [P < 0.001] and for GF30 it was 6.4 [P < 0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n = 21, 33.3%), congenital nephrotic syndrome (n = 79, 15.2%), pyelo/interstitial nephritis (n = 54, 11.1%), and Drash syndrome (n = 14, 21.4%). When the joint effect of these risk factors was examined in a Cox proportional hazards model, young recipient age (0-1 years old) and GF30 were significant (P < .001) risk factors of mortality for recipients of living-donor organs. For recipients of cadaver kidneys, young recipient age--0-1 years old (P < .001) and 2-5 years old (P = .002)--ATN (P = .029), and GF30 (P < .001) were all significant risk factors. Recipient age is the major determinant of increased mortality after renal transplantation. Avoidance of acute tubular necrosis by reducing cold time and preventing early graft failure by better matching techniques in this vulnerable population may improve the mortality rate.
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PMID:Posttransplant deaths and factors that influence the mortality rate in North American children. 811 40

Renal failure secondary to CDDP is due to acute tubular necrosis and is usually reversible. We report 4 cases of definitive renal failure secondary to administration of cisplatin (CDDP). Three women and one man, mean age 40 +/- 8 years (24 to 64 years), at onset of dialysis are reported. They had received 1 to 4 courses of CDDP for an endometrial carcinoma (n = 2), a breast carcinoma or a thymoma. The mean total dose of CDDP was 447 +/- 169 mg (160 to 900 mg). There was no additional nephrotoxic drug. Before treatment serum creatinine concentration was normal (77 +/- 7 mumol per liter) in all patients. In 2 cases dehydration (due to vomiting and use of mannitol) occurred during CDDP treatment. One patient was treated 30 days after a nephrectomy. At the onset of dialysis, renal ultrasound was normal. In 3 cases dialysis was necessary within 15 days following chemotherapy. In one case renal function deteriorated progressively to end stage renal failure 12 months after CDDP treatment. Dialysis was performed in 3 cases by hemodialysis and in one patient by peritoneal dialysis. All patients remained more than 6 months on dialysis. Three patients died from their cancer. One patient, being considered cured from his thymoma, is currently being evaluated for a kidney transplantation. Our observations outline the potential severity of CDDP nephrotoxicity. Systemic hydration with serial serum creatinine measurements are mandatory during and after CDDP administration these patients.
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PMID:[Definitive end-stage chronic kidney failure after cisplatin treatment]. 815 52

The population of aged people is increasing in number all over the world along with the problems associated with senescence. The functional and morphological changes that occur with ageing are accompanied by an increased risk of certain conditions like drug-induced nephrotoxicity and acute tubular necrosis. Elderly patients of end-stage renal disease can undergo renal replacement therapy with acceptably good results. If free from any medical and other illnesses, elderly persons can be considered for kidney donation without any increased risk for surgery or anaesthesia. However, such kidneys are functionally not as good as kidneys from young individuals. Prostatic diseases like prostatic hyperplasia and cancer are more a concern of the aged than the younger population. Besides, there is an apprehension about the increased risk of anaesthesia due to the frequent presence of other co-existent illnesses in the senile population. Less morbid therapeutic methods are available to deal with prostatic disorders but one should not hesitate to undertake major open or endoscopic surgeries in such patients, should it be necessary.
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PMID:Renal & prostatic disorders in the elderly. 936 62

Non-bacterial thrombotic endocarditis (NBTE) commonly occurs in patients with wasting disease (e.g. malignancy) or with valves damaged following trauma due to intra-cardiac foreign body, scarring or marked turbulence. Although disseminated intravascular coagulation (DIC) is well documented following viperine bite and the underlying mechanism of NBTE is thought to be DIC, there is no report of NBTE in humans following snake bite. We report a young male who following viperine bite developed local swelling, superficial gangrene of tissues at the site of bite, and oliguria and died following multiple cerebral infarcts and acute renal failure. The post-mortem examination showed NBTE of the aortic valve, multiple embolic infarcts of brain, spleen and kidneys, acute tubular necrosis and features of DIC in the brain in the form of fibrin thrombi in the capillaries, perivascular hemorrhages and necrosis.
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PMID:Fatal non-bacterial thrombotic endocarditis following viperine bite. 961 77

Gadolinium Texaphyrin (Gd-Tex) is a radiation sensitizer with a novel mechanism of action that sensitizes both oxic and hypoxic cells, localizes selectively in tumors, and is detectable by magnetic resonance imaging (MRI). This Phase I single-dose trial of Gd-Tex administered concurrently with radiation therapy was carried out to determine the maximally tolerated dose (MTD), dose-limiting toxicities, pharmacokinetics, and biolocalization of Gd-Tex as determined by MRI. Adults with incurable cancers of any histology requiring radiation therapy were eligible. A single i.v. dose of Gd-Tex was followed at least 2 h later by radiation therapy. The Gd-Tex dose was escalated in cohorts of 3 to 5 patients. Thirty-eight patients (median age, 58 years; range, 35-77 years) with incurable cancers of the lung (26), cervix (3), or other solid tumors (9) received a total of 41 single administrations of Gd-Tex. The Gd-Tex dose was escalated from 0.6 to 29.6 mg/kg. Irradiated sites included the thorax, brain, pelvis, bone, soft tissue, and sites of nodal metastases. The MTD was 22.3 mg/kg, determined by reversible acute tubular necrosis as the dose-limiting toxicities. Gd-Tex selectively accumulated in primary and metastatic tumors as demonstrated by MRI. No increase in radiation toxicity to normal tissues was seen. The median half-life of Gd-Tex after single-dose administration is 7.4 h. This study demonstrates that Gd-Tex is well tolerated in doses below the MTD, and that there is selective biolocalization in tumors. The maximum recommended dose for single administrations is 16.7 mg/kg.
Clin Cancer Res 1999 Apr
PMID:A phase I single-dose trial of gadolinium texaphyrin (Gd-Tex), a tumor selective radiation sensitizer detectable by magnetic resonance imaging. 1021 7


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