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)

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.
 ...
PMID:Proton NMR spectra of urine as indicators of renal damage. Mercury-induced nephrotoxicity in rats. 286 May 59

We examined the protective effects of medical castration by means of gonadotropin-releasing hormone analogue (GnRHA) on the toxic effects of cisplatin in rats. Twelve days after a s.c. injection of a slowly-releasable form of leuprolide acetate (GnRHASR), rats were injected i.p. with cisplatin daily (3 mg/kg body weight (BW) for males and 4 mg/kg BW for females) for four days and sacrificed 24 h after the last injection. The doses caused acute tubular necrosis and gastrointestinal (GI) symptoms, i.e., diarrhea and fluid retention and bleeding in GI tract. GnRHASR pretreatment reduced serum urea nitrogen (SUN) and serum creatinine (SCre) increase and the incidence of GI symptoms. Histological analysis showed that rats pretreated with GnRHASR had noticeably less kidney damage. GnRHA thus demonstrated its ability to protect the kidneys and GI tract against cisplatin toxicity in both male and female rats. This finding suggests a potential clinical application of GnRHA in antineoplastic chemotherapy.
 ...
PMID:Leuprolide acetate prevents toxic effects of cisplatin on the kidneys and gastrointestinal tract. 767 May 59

Chronic heart failure (CHF) is often associated with impaired renal function due to hypoperfusion. Such patients are very sensitive to changes in renal perfusion pressure, and may develop acute tubular necrosis if the pressure falls too far. The situation is complicated by the use of diuretics, ACE inhibitors and spironolactone, all of which may affect renal function and potassium balance. Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia and hypertension in CRF contribute to the development of left ventricular hypertrophy (LVH), which carries a poor prognosis, so correction of these factors is important.
 ...
PMID:Influence of progressive renal dysfunction in chronic heart failure. 1195 39

Despite major advances in nutritional support, membrane technology and dialytic techniques, the mortality of patients with acute renal failure (ARF) who require dialysis is still almost 50% (1). Increased patient age and co-morbidity confer a poorer prognosis, and the condition is certainly commoner in this patient group. Hence, one study showed that the age-related annual incidence of ARF increased from 17 per million in adults under 50 years to 949 per million in the 80-89 age group (2). Over 60% of cases of ARF ultimately result from renal hypoperfusion and consequent intra-renal ischaemic damage, which leads to acute tubular necrosis (ATN) (3). Ischaemic ARF may thus result from a diversity of systemic and intra-renal circulatory stresses including acute losses of blood and extra-cellular fluids, from low cardiac output states such as following ischaemic or toxic myocardial damage, and even from drug-induced renal perfusion shutdown (ACE inhibitors, non-steroidal anti-inflammatory agents). Many cases of ARF have a multi-factorial aetiology (e.g. post-surgical sepsis with hypovolaemia, hypotension and injudicious antibiotic use), and these patients, who often have other organ failure, fit into the poorer prognostic category. A large number of patients with ischaemic ARF pass through a phase of potentially reversible pre-renal oliguria; early recognition and prompt, appropriate treatment of these pre-renal factors can prevent progression to established ARF, with the genuine prospect of improved patient morbidity and mortality, and this is the main scope of this article. Early diagnosis in other patients with ARF, such as those with acute inflammatory renal disease (e.g. vasculitis) or urinary tract obstruction, will allow appropriate prompt treatment and the possibility for reversal of the ARF. The following account, which is composed of personal experience, that of colleagues, and the literature (1,4), is not intended to provide a comprehensive guide to the management of ARF, but seeks to highlight important common pitfalls and fundamental principles in the recognition and subsequent preventive treatment of these patients.
 ...
PMID:Early management and prevention of acute renal failure. 1237 20

We report a case of a 46-year-old white male with renal graft artery stenosis who developed acute renal shutdown with total anuria while on the ACE inhibitor lisinopril, one week following the discontinuation of aspirin. The serum creatinine was 8.5 mg/dl. Doppler ultrasound and MAG3 scintigraphy of the grafted kidney were highly suggestive of a viable but nonfunctioning kidney. A femoro-femoral bypass for total thrombosis of the right common iliac artery was performed distal to the occlusion. Immediate diuresis was obtained after establishing the bypass. Serum creatinine dropped to 1.35 mg/dl three days later. In this case we believe that the collateral circulation played a significant role in immediate recovery of kidney function by maintaining renal perfusion pressure and preventing acute tubular necrosis (ATN). We also believe that the ACE inhibitor might have contributed to salvaging the kidney by improving medullary oxygen balance and maintaining adequate medullary blood flow.
 ...
PMID:A transplanted kidney surviving total vessel occlusion and anuria. 1611 94

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance will be investigations of stem cell kinetics, including local presence, bloodborne migration, activation, seeding, and its role in renal remodeling (psychological, pathological, and therapy induced). Methods also could be established for investigating the role of receptors and oncoproteins in cellular proliferation, apoptosis, tubular atrophy, and interstitial fibrosis; monitoring ras gene targeting in kidney diseases, assessing cell therapy devices (bioartificial filters, renal tubule assist devices, and bioarticial kidneys), and targeting of signal transduction moleculas with growth factors and cytokines. These potential new approaches are, at best, in an experimental stage, and more research will be needed for their implementation.
 ...
PMID:Future direction of renal positron emission tomography. 1635 95

We report of a 71-year-old woman with a history of chronic analgesic nephropathy, who underwent coronary angiography. Because of anterior ventricular aneurysm, anticoagulation with nadroparine was installed. Continued ACE-inhibitor and ASA with additional intravenous contrast substance lead to acute tubular necrosis with rapid decline of the renal function. Due to accumulation of the low molecular weight heparin, the patient developed an extensive retroperitoneal haematoma with circulatory shock and temporary anuric kidney failure. Low molecular weight heparins are commonly used during percutaneous coronary interventions. They are as safe and efficient compared to unfractioned heparin. But due to their renal elimination, they have to be monitored by measuring anti-factor Xa-activity if creatinine-clearance is <30 ml/min.
 ...
PMID:[Bleeding complication due to accumulation of low-molecular-weight heparin in a patient with renal insufficiency]. 1752 Aug 42

Numerous anatomical and functional changes occurring in the aging kidney lead to reduced glomerular filtration rate, lower renal blood flow and impaired renal autoregulation. The elderly are especially vulnerable to the development of renal dysfunction and in this population acute renal failure (ARF) is a common problem. ARF is often iatrogenic and multifactorial; common iatrogenic combinations include pre-existing renal dysfunction and exposure to nephrotoxins such as radiocontrast agents or aminoglycosides, use of NSAIDs in patients with congestive cardiac failure and use of ACE inhibitors and diuretics in patients with underlying atherosclerotic renal artery stenosis. The aetiology of ARF is classically grouped into three categories: prerenal, intrinsic and postrenal. Prerenal ARF is the second most common cause of ARF in the elderly, accounting for nearly one-third of all hospitalized cases. Common causes can be grouped into true volume depletion (e.g. decreased fluid intake), decreased effective blood volume (e.g. systemic vasodilation) and haemodynamic (e.g. renal artery stenosis, NSAID use). Acute tubular necrosis (ATN) is the most common cause of intrinsic ARF and is responsible for over 50% of ARF in hospitalized patients, and up to 76% of cases in patients in intensive care units. ATN usually occurs after an acute ischaemic or toxic event. The pathogenesis of ATN involves an interplay of processes that include endothelial injury, microvascular flow disruption, tubular hypoxia, dysfunction and apoptosis, tubular obstruction and trans-tubular back-leak. Vasculitis causing ARF should not be missed as this condition is potentially life threatening. The likelihood of a postrenal cause for ARF increases with age. Benign prostatic hypertrophy, prostatic carcinoma and pelvic malignancies are all important causes. Early identification of ARF secondary to obstruction with renal imaging is essential, and complete or partial renal recovery usually ensues following relief of the obstruction.A comprehensive medical and drug history and physical examination are all invaluable. Particular attention should be paid to the fluid status of the patient (skin turgor, jugular venous pressure, lying and standing blood pressure, urine output). Urinalysis should be performed to detect evidence of proteinuria and haematuria, which will aid diagnosis. Fractional excretion of sodium and urine osmolality may be measured but the widespread use of diuretics in the elderly gives rise to unreliable results. Renal imaging, usually ultrasound scanning, is routinely performed for assessment of renal size and to exclude urinary obstruction. In some cases, renal biopsy is necessary to provide specific diagnostic information. The general principles of managing ARF include treatment of life-threatening features such as shock, respiratory failure, hyperkalaemia, pulmonary oedema, metabolic acidosis and sepsis; stopping and avoiding administration of nephrotoxins; optimization of haemodynamic and fluid status; adjustment of drug dosage appropriate to glomerular filtration rate; early nutritional support; and early referral to nephrologists for diagnosis of ARF cause, timely initiation of dialysis and initiation of specific treatment. The treatment of prerenal and ATN ARF is largely supportive with little evidence of benefit from current pharmacological therapies. Despite advances in critical care medicine and renal replacement therapy, the mortality of ARF has not changed significantly over the last 40 years, with current mortality rates being up to 75%.
 ...
PMID:Management of acute renal failure in the elderly patient: a clinician's guide. 1854 Jun 87

In this case report, a patient is described with an unusual cause of renal artery stenosis (RAS). The patient presented with acute anuric renal failure and hypertensive urgency, following a nephrectomy, which was complicated by massive blood loss. Because the acute renal failure was first presumed to be due to acute tubular necrosis, the diagnosis of a nearly complete iatrogenic RAS was not made until 6&emsp14;weeks after surgery. The stenosis was caused by five misplaced surgical clips on the artery of the remaining kidney. The hypertension was initially treated with ACE inhibitor. Eight weeks after the initial surgery, a successful revascularisation procedure was performed, leading to the recovery of kidney function.
 ...
PMID:Renal artery stenosis: a classic presentation, a rare cause... 2289 Oct 24