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)

The presence of delayed graft function (DGF) following cadaver donor renal transplantation is associated with inferior graft survival as well as decreased patient survival. Delay in onset of function eliminates a valuable indicator of allograft viability, which is not easily replaced by standard diagnostic procedures. The purpose of this study was to demonstrate that a new clearance technique could be used to measure renal function minute to minute and under conditions similar to those observed in humans in the immediate posttransplantation period. A monkey model was used to provide controlled conditions. Increasing levels of ischemic injury were produced in 12 Rhesus monkeys by renal hilum cross-clamping. Real-time measurements of glomerular filtration rate (GFR) were obtained from the rate of clearance of the extracellular fluid of the GFR agent 99mTc-DTPA, as measured with a specially designed external radioactivity counting device called the ambulatory renal monitor, or ARM. GRF was measured every 2-5 min as the slope (k) of the log of activity measured minute to minute versus time. GFR measurements were correlated with blood urea nitrogen (BUN), plasma creatinine (Cr), routine light microscopy, and measurement of proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Large changes in renal function due to ischemia or ureteral obstruction were observed within minutes. In addition, the rate constant on Day 1 was predictive of peak serum Cr(R =--0.86, R2=.74, p = .0001). Acute tubular necrosis (ATN) resolution was reflected more quickly when using the rate constant (Day 1) than when using either BUN or plasma Cr (Day 3-4). Because of renal functional reserve, BUN and plasma Cr were relatively insensitive indicators of mild to moderate reductions in GFR as compared with the rate constant. We conclude that ARM is a simple method which provide an accurate, near real-time GFR readout with potential applications not only for the clinical management of patients with DGF, but also as a research tool in acute renal failure (ARF).
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PMID:Real-time monitoring of renal function during ischemic injury in the rhesus monkey. 857 Aug 62

Renal changes that occur with aging mainly consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increase the risk of volume depletion and the prerenal type of acute renal failure (ARF) in elderly people. Bladder outlet obstruction caused by benign prostatic hypertrophy is a common cause of ARF in elderly men. Another frequent cause of ARF in the elderly is drug-induced nephropathy. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics are most often implicated in the development of ARF in the elderly. However, considering the high usage of these drugs, the incidence of drug-induced nephropathy is relatively small. NSAIDs are more likely to cause ARF in patients with congestive heart failure, chronic renal disease (including diabetic nephropathy) or chronic liver disease than in otherwise healthy individuals. NSAID-induced ARF is often of the prerenal type, but may be caused by acute interstitial nephritis (AIN). The presence of heavy proteinuria or nephrotic syndrome differentiates NSAID-induced AIN from AIN caused by other drugs. Antibiotics, especially semisynthetic penicillins, more commonly give rise to AIN associated with peripheral blood eosinophilia and eosinophiluria than NSAIDs. Ciprofloxacin is increasingly reported to cause AIN. Fever commonly accompanies AIN, especially when induced by antibiotics. Aminoglycosides produce ARF by inducing acute tubular necrosis (ATN), which results from the excessive accumulation of myeloid bodies in the tubules. In all cases of ARF it is essential to obtain a good history, to perform a through physical examination, with particular attention to skin turgor, and to measure blood pressure, pulse rate (supine and upright), urinary electrolyte and creatinine levels. Fractional excretion of sodium and the urine:plasma creatinine ratio are reliable indices that distinguish prerenal ARF from ATN. A prompt response to fluid challenge, with an increase in urine output and urinary sodium excretion, and a rapid decrease in blood urea nitrogen, constitutes strong evidence for prerenal ARF. However, these indices are unreliable when prerenal ARF has progressed to ATN or when ARF has an obstructive pattern to begin with. In all cases of ARF, especially in elderly men, urinary tract obstruction should be suspected unless the history is otherwise clear cut. Ultrasound of the kidneys and bladder is a simple, non-invasive and meaningful test that can be used to rule out obstructive causes of ARF. If obstruction is the cause of ARF, ultrasound will be positive; in contrast, urinary obstruction is very unlikely if ultrasound findings are normal in a patient who has been oliguric or anuric for 48 hours or more. Similarly, acute glomerulonephritis, including rapidly progressive glomerulonephritis, should be suspected when ARF is associated with heavy proteinuria. In such instances, percutaneous renal biopsy is essential to document the diagnosis. It is of utmost importance to establish whether ARF is of prerenal or postrenal type, both of which are potentially fully reversible. In contrast, patients with ATN or rapidly progressive glomerulonephritis may not recover, or may only partially recover, their renal function. Haemodialysis and nutritional support are common measures for patients with severe ATN and a highly catabolic state. Corticosteroids and immunosuppressive therapy should be instituted for rapidly progressive glomerulonephritis, in addition to haemodialysis. haemodiafiltration instead of haemodialysis is recommended for patients who are haemodynamically unstable [i.e., with a persistently low blood pressure (systolic < or = 100 mm Hg)]. Haemodiafiltration has been shown to improve acid-base balance and uraemia better than standard haemodialysis. However, despite dialysis, mortality in patients with ARF associated with ischaemic ATN remains high.
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PMID:Management of acute renal failure in the elderly. Treatment options. 889 22

Following acute tubular necrosis (ATN), kidney plasma membrane insulin-like growth factor-I (IGF-I) receptor number increases markedly, although IGF-I receptor mRNA levels do not change. To determine whether this increase could represent a redistribution of intracellular receptors and whether receptor function is intact in acute uremia, rats with ATN of 2 days duration and pair-fed controls were studied. Skeletal muscle receptor binding was unchanged. In contrast, binding to receptors in solubilized cortex and isolated cortical plasma membranes increased significantly due to an increase in receptor number. However, the increase in membrane binding was threefold greater than the increase in solubilized cortex binding. This indicates that the increase in total cellular IGF-I receptors can only account for a minor portion of the increase in abundance of plasma membrane receptors number and is consistent with a redistribution of receptors from an intracellular to a membrane location as the major mechanism. Autophosphorylation and receptor kinase activity were unaffected by the uremia (blood urea nitrogen of approximately 198 mg/dl). Since these early steps of IGF-I receptor signaling are intact early in acute uremia, it is likely that at this time in the course of the disease the increase in receptor number will heighten the sensitivity to IGF-I and may thus favor its participation in renal repair.
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PMID:IGF-I receptor binding, autophosphorylation, and kinase activity in kidney and muscle of acutely uremic rats. 908 75

NSAID use is pervasive in our society. Existing NSAIDs pose little risk to patients who tolerate them early during their administration. Among persons with normal renal function who have no other risk factors (dehydration) for an acute hemodynamic effect, there is no risk. However, NSAID administration to susceptible persons may cause decrements in renal plasma flow and glomerular filtration rate within hours. This acute hemodynamic effect is the most common renal syndrome caused by NSAIDs. With careful monitoring, this effect is readily detected with routine clinical laboratory tests (serum creatinine and/or blood urea nitrogen concentrations). However, patients who continue administration of NSAIDs in this setting risk acute tubular necrosis and permanent damage to the kidney. Newer NSAIDs that selectively inhibit cyclooxygenase-2: cyclooxygenase-1 ratio may provide a more favorable risk profile for patients who cannot tolerate existing drugs.
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PMID:Effects of NSAIDs on the kidney. 938 87

Here, we report a 35-year-old man with non-fulminant acute non A, non B, non C hepatitis which developed into acute renal failure. The patient was admitted to hospital with the chief complaints of general fatigue, nausea and a high-grade fever of 40 degrees C. Laboratory examination revealed severe liver dysfunction and renal insufficiency on admission: his serum glutamic oxaloacetic transaminase was 3.203 IU/ml, serum glutamic pyruvic transaminase was 3.825 IU/ml, lactic dehydrogenase was 2.840 IU/ml, blood urea nitrogen was 65 mg/dl, and creatinine was 7.6 mg/dl. Hemodialysis was conducted during the initial 19-day period after admission because anuria was manifested on admission. On the 36th day after onset, renal functions returned to normal and the patient was negative for IgM-HA antibody. HBs antigen, IgM-HBC antibody, HCV antibody, cytomegalovirus antibody, and Epstein-Barr virus antibody. However, liver biopsy for histological examination on the 44th day after onset revealed no specific findings except the healing stage of acute hepatitis. Renal biopsy on the 49th day showed the healing stage of acute tubular necrosis without any glomerular change. It has been infrequently reported that acute renal failure develops following a non-fulminant acute state without hepatitis A, B or C virus infection. It is necessary to take acute renal failure into account in the clinical course of non-fulminant non A, non B, non C hepatitis.
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PMID:[Acute renal failure in non-fulminant acute hepatitis without hepatitis A, B or C virus infection]. 951 78

Interleukin-1 (IL-1) is a central component of many acute inflammatory processes. Blocking IL-1 receptor (IL-1R) with IL-1R antagonist (IL-1Ra) has attenuated ischemic reperfusion injury in brain, heart, and liver models. However, the role of IL-1 in renal ischemic reperfusion injury (IRI) is not known. Therefore, the role of IL-1 in renal IRI was evaluated using the complementary approaches of IL-1R blockade in wild-type mice in addition to the study of renal IRI in IL-1R knockout (KO) mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. IL-1Ra was administered at 10 mg/kg every 4 h, high doses that have been protective in previous organ injury models in mice. IL-1R KO animals, previously characterized as insensitive to IL-1, had the absence of IL-1R1 confirmed by DNA blots. IL-1Ra, IL-1R KO, and control groups had similar elevations of blood urea nitrogen (114 +/- 13, 133 +/- 11, and 120 +/- 11 mg/dl) and serum creatinine (1.7 +/- 0.3, 2.1 +/- 0.2, and 1.6 +/- 0.3 mg/dl) 24 h after ischemia. Furthermore, acute tubular necrosis scores were also similar in IL-1Ra-treated mice (3.0 +/- 0.3), IL-1R KO mice (2.7 +/- 0.3), and control mice (3.1 +/- 0.2). However, both IL-1Ra and IL-1R KO groups, compared with control animals, developed significantly less infiltration of polymorphonuclear leukocytes per 10 high-power fields in postischemic renal tissue (1111 +/- 228 and 967 +/- 198 versus 1820 +/- 190, P < 0.05). In contrast to the comparable renal functions at 24 h, recovery of renal function was significantly accelerated in the IL-1R KO group compared with control at both 48 (P < 0.05) and 72 (P < 0.05) h. Recovery in the IL-1Ra group was similar to that in the control animals. These data demonstrate that IL-1 is unlikely to be beneficial in the recovery of renal function after ischemia and may play a deleterious role.
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PMID:Role of IL-1 in renal ischemic reperfusion injury. 955 64

Gliclazide, a sulfonlyurea class molecule, is used to control glycaemic levels in non-insulin-dependent diabetes mellitus. Acute and chronic toxicity studies, conducted in various animal species, have demonstrated a very low toxicity. We report a patient who developed acute renal failure due to acute tubular necrosis following a massive ingestion of gliclazide in an suicide attempt. The patient ingested 28 grams of gliclazide; the normal dose of gliclazide is 80 mg one or twice a day. At admission the patient was hypoglycaemia and in a few days became oliguric with an increase in the serum creatinine concentration, but with a normal blood urea nitrogen level. He underwent dialysis and ten days after ingestion of gliclazide, his renal function improved rapidly.
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PMID:Acute renal failure after massive ingestion of gliclazide in a suicide attempt. 960 41

To examine the mechanisms involved in the progression of mercury chloride (HgCl2)-induced acute tubular necrosis (ATN), we investigated the histopathological changes and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in renal cortices of rats at 20 hours after exposure to HgCl2. The expression of iNOS mRNA was significantly augmented in renal cortices of rats with HgCl2-induced acute renal failure (ARF). Likewise, the induction of iNOS protein was observed in damaged proximal tubule epithelial cells of rats with HgCl2-induced ARF. Pretreatment of rats with iNOS inhibitor aminoguanidine, however, suppressed the development of proximal tubule epithelial cell injury and prevented an increase in blood urea nitrogen and serum creatinine as well as resulting in a marked fall in iNOS mRNA and protein in rats with HgCl2-induced ARF. These observations indicate that the induction of iNOS may play a role in the progression of HgCl2-induced ATN through the exacerbation of proximal tubule epithelial cell damage.
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PMID:Inducible nitric oxide synthase expression in mercury chloride-induced acute tubular necrosis. 981 Jan 45

Prophylactic hemodialysis has been employed in the treatment of 15 patients with acute renal failure due to acute tubular necrosis (12), bilateral renal cortical necrosis (two), and poststreptococcal glomerulonephritis (one). Dialyses, usually lasting six hours each, were begun before clinical evidence of uremia developed in each patient and/or before the nonprotein nitrogen reached 200 mg.%, and were repeated daily or often enough to maintain the nonprotein nitrogen below 150 mg.%. The hypothesis underlying this technic postulates (1) that wasting, sepsis and impaired wound healing in these patients may reflect tissue injury by the same dialyzable toxic agents which produce the uremic symptoms that are readily reversible by dialysis, and (2) that repeated dialyses should therefore prevent both clinical uremia and the later, often lethal sequelae. The results contrast dramatically with our own past experience in treating patients with acute renal failure with a carefully executed medical regimen together with hemodialysis on conventional indications. Except in one instance of crush injury with progressive intracerebral damage, and one brief occasion in another individual, these patients experienced a stable, convalescent clinical course, remained free of uremic symptoms or chemical imbalances, ate at least three meals daily which were unrestricted in amount and composition, and were ambulatory between dialyses unless confined to bed by associated disease. Wounds healed well. Infection either did not occur, or subsided after appropriate therapy. Fluid restriction was liberalized by means of ultrafiltration with dialysis. Regional heparinization of only the extracorporeal circuit eliminated actual or impending bleeding as a contraindication to dialysis. Chronic vessel cannulation made the frequent dialyses possible, but may have provided the route for repeated, transient bacterial contamination of the blood stream in the first hour of many dialyses. Marked anemia, despite reticulocytosis, moderate to mild weight loss and some mental deficit persisted in spite of the general clinical improvement and well-being. Three patients with tubular necrosis died after seven, 11 and 26 days of oliguria; both patients with bilateral renal cortical necrosis also succumbed, on the seventy-third and ninety-second days of renal failure, and after 29 and 40 dialyses, respectively. At autopsy, evidence of sepsis was conspicuously absent. The remaining 10 patients survived. Thus some, but not all, clinical manifestations of acute renal failure appear to be favorably influenced by prophylactic dialysis treatment. Our initial experience in this group of 15 patients does not of course prove that freedom from complications and a significantly better outlook for survival can be assured to patients with acute renal failure by these methods. However, it seems to offer a reasonable hope of this possibility which we cannot attach to management by medical measures alone, or by dialysis on conventional indications. If this hope is realized in greatly extended, subsequent series, then it seems inevitable that some form of prophylactic dialysis, or some equally effective alternative, should be adopted in treating the majority of patients with acute renal failure.
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PMID:Prophylactic hemodialysis in the treatment of acute renal failure. Annals of Internal Medicine, 53:992-1016, 1960. 984 96

Regulation of fatty acid beta-oxidation (FAO) represents an important mechanism for a sustained balance of energy production/utilization in kidney tissue. To examine the role of stimulated FAO during ischemia, Etomoxir (Eto), clofibrate, and WY-14,643 compounds were given 5 days prior to the induction of ischemia/reperfusion (I/R) injury. Compared with rats administered vehicle, Eto-, clofibrate-, and WY-treated rats had lower blood urea nitrogen and serum creatinines following I/R injury. Histological analysis confirmed a significant amelioration of acute tubular necrosis. I/R injury led to a threefold reduction of mRNA and protein levels of acyl CoA oxidase (AOX) and cytochrome P4A1, as well as twofold inhibition of their enzymatic activities. Eto treatment prevented the reduction of mRNA and protein levels and the inhibition of the enzymatic activities of these two peroxisome proliferator-activated receptor-alpha (PPARalpha) target genes during I/R injury. PPARalpha null mice subjected to I/R injury demonstrated significantly enhanced cortical necrosis and worse kidney function compared with wild-type controls. These results suggest that upregulation of PPARalpha-modulated FAO genes has an important role in the observed cytoprotection during I/R injury.
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PMID:Etomoxir-induced PPARalpha-modulated enzymes protect during acute renal failure. 1075 Dec 29


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