Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.
 ...
PMID:Postischemic renal injury is mediated by neutrophils and leukotrienes. 254 28

Foscarnet is a pyrophosphate analogue that has been successfully used in severe cytomegalovirus (CMV) infections. Little is known of the incidence and mechanisms of foscarnet-induced nephrotoxicity as most data comes from recipients of renal allografts or from patients with severe underlying disease or with other nephrotoxic drugs. We have retrospectively analyzed the evolution of renal function after 56 courses of foscarnet. In addition, we have prospectively studied the protective effects of hydration on foscarnet nephrotoxicity (2.5 liters of saline/day during the night before the foscarnet therapy and throughout the course of treatment). Foscarnet-induced acute renal failure was defined as a rise in serum creatinine of at least 25% from the basal value. An increase in serum creatinine occurred in 37 cases out of the 56 courses of foscarnet (66%). The mean serum creatinine prior to foscarnet was 80.5 +/- 3.3 mumol/l and the mean increase was 190 +/- 28.3 mumol/l (range 80-1,000). Peak serum creatinine was higher than 200 and 300 mumol/l in 16 and 13 patients, respectively. Kidney obtained at autopsy from a 30-year-old male with AIDS, CMV pneumonitis and acute renal failure secondary to foscarnet administration showed an extensive tubular necrosis. In the group which was prospectively hydrated only 1 patient had an acute renal failure. The mean serum creatinine at the peak (96 +/- 4 mumol/l) and at the end of the treatment (83 +/- 4 mumol/l) was significantly lower (p less than 0.05) than in non hydrated patients. In conclusion, foscarnet is a highly nephrotoxic drug which induces acute tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Foscarnet nephrotoxicity: mechanism, incidence and prevention. 255 31

Monitoring of immunoglobulin-secreting cells in peripheral blood was performed in 88 renal transplant recipients using a reverse hemolytic plaque-forming cell assay. Comparison with other in vitro tests for rejection (plasma neopterin, CD4/CD8 ratio) demonstrated that the number of immunoglobulin-secreting cells in peripheral blood provides a highly sensitive rejection marker. Evidence of rejection was obtained 1.7 +/- 0.4 (mean +/- SEM) days before a rise in creatinine, with a significant PFC rise in 95% (73/77) of rejection episodes. The PFC response was not influenced by HLA matching, number of preoperative blood transfusions, acute tubular necrosis, or uremia. A significant PFC rise in the absence of an ongoing rejection episode occurred in the presence of bacterial or viral infections, in case of posttransplant surgical complications, and regularly during the early posttransplant period (days 4-9). However, even early posttransplant the PFC peak was significantly higher in patients with an ongoing rejection episode than in patients without rejection (P less than 0.001).
 ...
PMID:B lymphocyte response as an indicator of acute renal transplant rejection. I. Immunoglobulin-secreting cells in peripheral blood. 257 82

This study reports clinical evaluation of a newly-discovered protein, alpha-2 glycomicroglobulin (A2GM), for monitoring renal function and in the identification and characterization of rejection episodes in kidney transplant recipients. Using a sensitive enzyme-linked immunosorbent assay technique, plasma levels of A2GM were measured prior to, and following, transplantation. There was an initial decrease in plasma A2GM in all patients following transplantation, but the decrease was significantly (P less than 0.023) greater in patients with initial good function than in those with initial poor function associated with initial acute tubular necrosis or rejection. The decrease in A2GM did not correlate with subsequent graft function and viability. Levels of A2GM were found to be sensitive to changes in renal function and correlated well with creatinine. A sustained rise in A2GM was indicative of rejection. A2GM predicted rejection episodes 48-72 h before any significant rise in plasma creatinine in five of seven rejections studied. It is concluded that plasma A2GM levels may be clinically useful in assessing allograft function and in predicting rejection crises in kidney transplant recipients.
 ...
PMID:Plasma alpha-2 glycomicroglobulin in monitoring allograft function and in predicting rejection episodes in kidney transplantation (preliminary results). 263 65

Ischemia-induced renal injury is prevented by inhibition of thromboxane (Tx) synthesis. This protection was believed to be secondary to a high prostaglandin (PG)/TxA2 ratio. This study tests whether increasing the PG/Tx ratio by administration of vasodilating PGs protects the reperfused ischemic kidney. Anesthetized rats underwent right nephrectomy and 45 minutes of left renal pedicle clamping. Beginning 10 minutes before clamp release, animals were treated intravenously with the following: saline placebo (n = 10); the cyclooxygenase inhibitor ibuprofen (Ibu), 12.5 mg/Kg in a bolus (n = 8); a stable analogue of prostacyclin (PGI2), 500 ng/kg/minute for 2 hours (n = 9); PGE1, 400 ng/kg/minute for 2 hours (n = 8); the combination Ibu and PGI2 (n = 8) or PGE1 (n = 8). In saline treated ischemic controls, 5 minutes after reperfusion plasma, thromboxane (TxB2) and 6-keto-PGF1 levels were 2537 and 317 pg/ml, respectively--higher than the TxB2 and 6-keto-PGF1 levels of 750 and 80 pg/ml, respectively, in nephrectomized but nonischemic sham controls (n = 7) (p less than 0.05). In ischemic control animals at 24 hours, creatinine levels were 4.6 mg/dl, relative to 0.9 ml/dl in sham animals (p less than 0.05); the weight of the left (L) ischemic kidney relative to the right (R) normal kidney was 118%, compared with 99% in sham animals (p less than 0.05); and renal histology of ischemic control animals at 24 hours showed acute tubular necrosis (ATN) relative to normal findings in sham animals. Pretreatment with Ibu led to: TxB2 and 6-keto-PGF1 levels of 116 and 40 pg/ml, lower than those of sham animals (p less than 0.05); creatinine levels of 4.6 mg/dl, L/R renal weight of 119%; and ATN similar to that of ischemic controls. Treatment with a PGI2 analogue or PGE1 was not protective and led to increases in TxB2, 6-keto-PGF1, creatinine, L/R renal weight, and ATN similar to that of ischemic controls. The combination of Ibu and either PGI2 or PGE1 led to: reduced levels of TxB2 and 6-keto-PGF1 (p less than 0.05); attenuated increases in creatinine to 2.2 and 2.3 mg/dl, respectively (p less than 0.05); and limited ATN (p less than 0.05). These data indicate that the vasodilating PG protect the ischemic reperfused kidney only when Tx is inhibited.
 ...
PMID:Vasodilating prostaglandins attenuate ischemic renal injury only if thromboxane is inhibited. 264 99

Although a wide variety of disease processes can result in a failure of renal excretory function, the vast majority of cases with "acute renal failure" (ARF) are due to the syndrome of acute tubular necrosis (ATN). The syndrome is usually initiated by an acute injury to the proximal renal tubular epithelial cells by ischemic or nephrotoxic events. This is followed by progressive and often rapid increases in the concentration of blood urea nitrogen (BUN) and serum creatinine. In the average case, the failure of renal excretory function persists for 1 to 3 weeks, to be followed by recovery. Oliguria (urine volume less than 400 ml) is present in about half of the patients. The pathogenesis of the retention of nitrogenous waste in human ATN is the subject of controversy, but the balance of data in most patients suggests that the predominant mechanism is a profound secondary vasoconstriction in response to tubular cell injury. This may represent a teleologically appropriate response to prevent catastrophic losses of fluid that would occur, if the normally high rates of glomerular filtration continued, in the face of reduced tubular reabsorptive capacity. The mechanisms by which the tubular cell injury is communicated to the vasculature, and the mediators of the hemodynamic changes, remain to be established. The differential diagnosis in a patient with ARF, usually involves exclusion of an obstruction to the urinary tract as an initial step. The next step is to differentiate the patients with ATN from those who have renal hypoperfusion in response to events in the systemic circulation, but who otherwise have functionally and structurally intact kidneys, i.e., prerenal ARF. The kidneys of patients with prerenal ARF exhibit the normal renal response to an acute reduction in renal blood flow and glomerular filtration rate (GFR). This consists of avid reabsorption of the filtered salt and H2O, so that a small amount of concentrated and NaCl-poor urine is elaborated. The tubular cell injury in ATN syndromes prevents this response from maximally occurring, so that the urine is isosmotic and relatively rich in NaCl.
 ...
PMID:Acute renal failure. 264 37

Since August 1983, 115 patients have undergone live donor nephrectomy via an extraperitoneal flank approach with rib resection. Over-all hospital stay was short and morbidity was negligible. Early graft function was excellent as determined by urinary output in the first 20 hours postoperatively (mean 6,442 cc) and low nadir serum creatinine (mean 1.57 mg. per dl.). Acute tubular necrosis or urinary fistula developed in 3 kidneys (2.6 per cent). In the entire series, only 1 graft (0.8 per cent) was lost to technical complications. We conclude that an extraperitoneal flank approach to live donor nephrectomy is safe for the donor, and provides a structurally and functionally sound allograft for the recipient.
 ...
PMID:Flank donor nephrectomy: efficacy in the donor and recipient. 265 11

A group of 40 cadaveric kidneys was studied just prior to planned transplantation to further assess the applicability of 31P-MRS in the analysis of clinical renal transplant viability. Renal intracellular high-energy phosphorus metabolites (ATP [or NADP], phosphomonoester [PME] and inorganic phosphate [Pi]) and pH were measured noninvasively with MRS surface coils external to cold storage containers. Pretransplant MRS parameters were correlated with subsequent renal function in recipient patients (measured one week postoperatively by the need of dialysis, drop in serum creatinine, urine output, and 123I or 131I Hippuran assessed renal tubular function). ATP and NADP was detected in eleven kidneys and was significantly (P less than 0.001) associated with the best renal function posttransplantation. These kidneys also had the highest PME/Pi ratios (1.66-0.54), while lower ratios (0.36-0.10) were associated with prolonged acute tubular necrosis. The PME/Pi ratios significantly (P less than 0.0001) correlated with subsequent clinical renal function, whereas cold storage times (37 +/- 10 hr) or intracellular renal pH (6.53-7.91) did not. These preliminary data suggest that MRS is a noninvasive, nondestructive and sterile method for assessing clinical viability during hypothermic storage of human cadaver kidneys and the subsequent recovery of renal function postrenal transplantation.
 ...
PMID:Pretransplant assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy. Clinical experience in 40 recipient patients. 266 35

1. The effect of the methylxanthine aminophylline on cisplatin (5 mg kg-1 i.v.)-induced acute renal failure was investigated in the rat. Renal function was measured 5 days after cisplatin administration. 2. Cisplatin caused a polyuric acute renal failure. The creatinine clearance was significantly reduced. 3. Aminophylline (24 mg kg-1 12h-1) ameliorated the cisplatin nephrotoxicity when administered during the maintenance phase of acute tubular necrosis. However, it had no effect when only administered prophylactically before the cisplatin application. 4. Enprofylline (20 mg kg-1 4h-1 with dose adjustment), a methylxanthine lacking adenosine receptor antagonism in comparison to aminophylline, had no protective effect on cisplatin nephrotoxicity. 5. Adenosine is a renal vasoconstrictor and decreases glomerular filtration rate. Endogenous adenosine in the kidney is formed by degradation of ATP and is thought to be involved in various forms of acute renal failure. The results suggest that adenosine may be involved in the haemodynamic changes in the kidney induced by cisplatin.
 ...
PMID:Effect of aminophylline on cisplatin nephrotoxicity in the rat. 275 17

The effects of intramuscular glycerol on ischemic acute renal failure was investigated in dogs. Anesthetized dogs received a bilateral 120-min renal artery obstruction (RAO) alone, RAO plus 5 ml/kg of 50% glycerol or RAO plus 5 ml/kg of 75% glycerol. Control groups received the glycerol injection, but not RAO. Renal histopathology was minimal in dogs receiving glycerol alone. In RAO dogs, those receiving 50% glycerol showed diffuse acute tubular necrosis (ATN), while those receiving 75% glycerol had severe ATN with extreme mortality. Changes in serum creatinine, creatinine clearance, and fractional excretion of sodium were consistent with the histopathologic changes. We conclude that myoglobinuria, of a degree insufficient to cause renal failure itself, can interact with renal ischemia to significantly exacerbate the renal damage produced.
 ...
PMID:Myoglobinuria exacerbates ischemic renal damage in the dog. 279 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>