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)

Since gender can influence the renal toxicity of a drug in a given species, the present study was undertaken to evaluate the role of sex in the protection against gentamicin (G)-induced nephrotoxicity afforded by diabetes mellitus (DM) in the rat. We have compared the effects of administration of G (40 mg/kg/day, for 14 days) on male and female DM Sprague-Dawley rats. Non-diabetic animals of both sexes receiving identical doses of G served as controls. At the end of the experiment on day 14, both female (F) and male (M) control groups had similar and marked evidence of nephrotoxicity: elevation of plasma creatinine (F 1.7 +/- 0.7; M 2.8 +/- 0.6 mg/dl), decrease in endogenous 24-h creatinine clearance (Ccr) (F0.3 +/- 0.1; M 0.2 +/- 0.1 ml/min/100 g BW), and histological evidence of severe acute tubular necrosis. In marked contrast, the DM rats showed no functional or morphological evidence of renal damage throughout the study regardless of their gender (day 14: plasma creatinine: F 0.2 +/- 0.03; M 0.2 +/- 0.02; Ccr: F 1.2 +/- 0.1; M 1.6 +/- 0.1 ml/min/100 g BW), and they also accumulated less G in their kidney cortex than the C rats. The male controls exhibited higher renal cortex accumulation of G than the female controls (p < 0.05), whereas the opposite occurred in the DM groups (p < 0.01). Because the validity of using Ccr for the evaluation of GFR changes in experimental nephrotoxicity has been questioned, we have compared, in a separate experiment, three different methods of estimation of GFR (simultaneous short clearances of inulin and Ccr, and 24-h Ccr) in conscious female Sprague-Dawley rats undergoing the same treatment with G described above. At no time during the study did the method used for estimation of the GFR influence the results. We conclude that male and female Sprague-Dawley rats with diabetes are functionally and morphologically equally protected against G. Furthermore, no gender-related differences in the magnitude of G-induced nephrotoxicity was demonstrated in the non-diabetic control animals.
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PMID:The protection against gentamicin nephrotoxicity in the streptozotocin-induced diabetic rat is not related to gender. 143 83

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and CNa/GFR X 100 were in group 1 0.80 +/- 0.05 ml/min and 0.68 +/- 0.06, in group 2 0.14 +/- 0.02 and 1.46 +/- 0.35, and in group 3 0.04 +/- 0.01 and 0.46 +/- 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 +/- 2 X 10(-11) mol/mm/min, in group 2 20 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 24 +/- 2 X 10(-11), P less than 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 +/- 2 X 10(-11), in group 2 33 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 27 +/- 2 X 10(-11), P less than 0.001 versus groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced Na-K-ATPase in distal nephron in glycerol-induced acute tubular necrosis. 215 4

In a prospective randomized trial we evaluated the influence of the calcium antagonist diltiazem (Dil) on the development of acute tubular necrosis (ATN) in cadaveric kidney transplantation. Dil was added to Eurocollin's solution (20 mg/l) at donor nephrectomy. The graft recipient received a preoperative bolus injection of Dil (0.28 mg/kg) which was followed by an infusion of Dil (0.0022 mg/min/kg) for 2 days. Thereafter, Dil was applied orally. Immunosuppressive therapy consisted of ciclosporin (CS) and low-dose steroids. There were no significant differences between the groups with respect to donor characteristics, HLA matching and ischemic periods. In the control group (n = 22), 9 patients (41%) developed ATN compared to 2 patients (10%) in the Dil group (p less than 0.05). In the control group, 3.5 +/- 0.4 HD per patient were necessary compared to 0.6 +/- 0.2 in the Dil group (p less than 0.05). Although CS blood levels were significantly higher in the Dil group (1st week 1,150 vs. 728 ng/ml; p less than 0.01), the GFR of grafts with primary function was significantly higher in the Dil group (day 7:39 vs. 24 ml/min; p less than 0.05). A significant reduction of the CS dose by 30% (p less than 0.01) led to comparable CS levels. In the Dil group, significantly fewer rejection episodes occurred during the first month. Our data indicate that the application of the calcium antagonist Dil lowered the incidence of posttransplant ATN. In addition, there is a possibility that Dil not only ameliorates ischemic damage in the kidney, but also reduces CS nephrotoxicity.
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PMID:Prevention of posttransplant acute tubular necrosis by the calcium antagonist diltiazem: a prospective randomized study. 331 61

Severe renal failure (GFR less than or equal to 20 ml/min/1.73 m2) complicated the clinical course in 27 of 146 children (18.5%) admitted for orthotopic liver transplantation (OLT). Hepatorenal syndrome (HRS) was the cause of renal failure in 12 of 15 patients in whom renal failure preceded OLT while acute tubular necrosis, pre-renal factors and cyclosporine nephrotoxicity were the major causes of renal failure post-OLT. Eight patients died from hemorrhage, infection or other complications of hepatic failure before OLT could be performed. Survival in the remaining 19 patients undergoing OLT was significantly lower compared to 114 patients with OLT and no renal failure (53% vs 81%, p less than 0.025). Dialysis therapy in 13 of the 27 patients with renal failure (10 hemodialysis and 3 peritoneal dialysis) was frequently complicated by severe gastrointestinal hemorrhage and hypotension, and directly contributed to the death of two patients prior to OLT. Among the 19 patients with renal failure who were actually transplanted, the survival rate was similar whether dialysis was used or not (5/10 vs 5/9) even though the mean GFR was significantly lower in dialyzed patients (p less than 0.05). However, although small patient numbers precluded meaningful statistical analysis, dialysis appeared to be beneficial for the subgroup of 12 patients with HRS, 4 of whom had complete recovery of renal function after successful OLT. We conclude that, renal failure is common in children with advanced liver failure; dialysis in such patients may increase morbidity and does not improve overall mortality; and dialysis support may improve survival in the subgroup of patients with HRS.
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PMID:Renal failure and dialysis therapy in children with hepatic failure in the perioperative period of orthotopic liver transplantation. 352 24

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.
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PMID:Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction. 1087 67

Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.
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PMID:Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial. 1591 62

Acute renal failure that is associated with macroscopic hematuria (ARF-MH) is a widely known complication of IgA nephropathy (IgAN). Although spontaneous recovery of renal function after cessation of MH has been described, no long-term outcome studies have been performed. The outcome of patients who had biopsy-proven IgAN and presented an ARF-MH episode in the period 1975 through 2005 was studied. Thirty-six episodes of ARF-MH that occurred in 32 patients were identified. A complete recovery of baseline renal function after cessation of MH was observed in 27 (group 1); in the remaining nine episodes (25%; group 2), estimated GFR (eGFR) did not reach the baseline value. Final eGFR was 89 +/- 28 ml/min per 1.73 m(2) in group 1 patients and 38 +/- 12 ml/min per 1.73 m(2) in group 2 patients (P = 0.0005). The duration of MH was significantly longer in group 2 patients: 33.7 +/- 25.3 versus 15.4 +/- 18.4 d (P = 0008). A high proportion of tubules that were filled by red blood cell casts and had signs of acute tubular necrosis were the most striking histologic abnormalities. In conclusion, a significant proportion (25%) of ARF-MH in IgAN did not recover the baseline renal function after the disappearance of MH. Duration of MH longer than 10 d, age >50 yr, decreased baseline eGFR, absence of previous episodes of MH, and the severity of tubular necrosis were significant risk factors for an incomplete recovery of renal function.
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PMID:Factors that determine an incomplete recovery of renal function in macrohematuria-induced acute renal failure of IgA nephropathy. 1769 87

There are few studies on the relationship between the morphology of acute tubular necrosis (ATN) in native kidneys and late functional recovery. Eighteen patients with acute renal failure (ARF) who had undergone renal biopsy were studied. All had the histological diagnosis of ATN and were followed for at least six months. Clinical characteristics of ARF were analyzed, and histological features were semi-quantitatively evaluated (tubular atrophy, interstitial inflammatory infiltrate, interstitial fibrosis, and ATN). According to the maximal GFR achieved during the follow-up, patients were divided into two groups: complete recovery (GFR >or= 90 mL/min/1.73 m(2)) and partial recovery (GFR < 90 mL/min/1.73 m(2)). Only 39% of the patients achieved complete recovery. Patients with partial recovery achieved their maximal GFR (63 +/- 9 mL/min/1.73 m(2)) 37 +/- 14 months after ARF, a period of time similar to those patients with complete recovery (i.e., 54 +/- 22 months). Patients with partial recovery had more severe ARF: oliguria was more frequent (90 versus 17%, p < 0.01), and they had higher peak creatinine (13.85 +/- 1.12 versus 8.95 +/- 1.30 mg/dL, p = 0.01), and longer hospitalization (45 +/- 7 versus 20 +/- 4 days, p = 0.03). No single histological parameter was associated with partial recovery, but the sum of all was when expressed as an injury index [4.00 (2.73-5.45) versus 2.00 (1.25-3.31), p < 0.05]. In conclusion, among patients with atypical ATN course, those with more severe ARF and tubule-interstitial lesions are more prone to partial recovery.
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PMID:Histological features of acute tubular necrosis in native kidneys and long-term renal function. 1870 14

During normal pregnancy, renal blood flow and GFR increase gradually until they reach a peak of about 150% of their normal values by the end of the 1(st) trimester. This increase in GFR is secondary to the extra-cellular compartment expansion caused by a positive sodium balance of about 500-900 mmol which is in turn associated with a water retention amounting 6 to 8 liters. Blood pressure decreases during a normal pregnancy because of the decrease in peripheral vascular resistance. This drop in blood pressure is limited by the renin-angiotensin system. Blood pressure gradually recovers during the 3(rd) trimester. Systemic hypertension, proteinuria >0.3 g/day and edema are the usual signs leading to the diagnosis of PE. However, any of the above listed signs found in isolation can be a tell tale sign of PE and must therefore prompt for the identification of a possible fetal effect The differential diagnosis of PE includes essential hypertension and hypertension secondary to a pre-existing renal failure. In the latter, signs of renal impairment early in the pregnancy, or (and) renal failure prior to the pregnancy are of important diagnostic clues. Causes of acute renal failure during pregnancy are numerous. PE associated acute renal failure presents in 5-10% of severe forms of PE. This is always a bad prognostic sign with a predicted mortality of 10%. Histological features are those of acute tubular necrosis with "endotheliosis" an inflammation of the glomerular endothelium. This renal impairment is frequently complicated by pulmonary edema. Passed the acute phase, the recovery of the renal function is usually complete. An acute renal failure during pregnancy can also be secondary to a pre-existing renal impairment suddenly aggravated by PE. In this setting, the probability of these patients requiring long term dialysis is high. Post-partum Haemolytic-Uremic Syndrome (HUS), although rare, is a serious condition which, following delivery, will require an early diagnosis (haemolysis, hypertension, acute renal failure) and urgently require symptomatic, perhaps specific, treatment (Plasma exchange transfusion).
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PMID:[Kidney and preeclampsia]. 2035 4

Highly active antiretroviral therapy (HAART) and other medical therapies for HIV-related infections have been associated with toxicities. Antiretroviral therapy can contribute to renal dysfunction directly by inducing acute tubular necrosis, acute interstitial nephritis, crystal nephropathy, and renal tubular disorders or indirectly via drug interactions. With the increase in HAART use, clinicians must screen patients for the development of kidney disease especially if the regimen employed increases risk of kidney injury. It is also important that patients with chronic kidney disease (CKD) are not denied the best combinations, especially since most drugs can be adjusted based on the estimated GFR. Early detection of risk factors, systematic screening for chronic causes of CKD, and appropriate referrals for kidney disease management should be advocated for improved patient care. The interaction between immunosuppressive therapy and HAART in patients with kidney transplants and the recent endorsement of tenofovir/emtricitabine by the Centers for Disease Control (CDC) for preexposure prophylaxis bring a new dimension for nephrotoxicity vigilance. This paper summarizes the common antiretroviral drugs associated with nephrotoxicity with particular emphasis on tenofovir and protease inhibitors, their risk factors, and management as well as prevention strategies.
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PMID:Nephrotoxicity of HAART. 2186 Jul 87


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