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)

There is a growing number of hospitalised patients who develop a drug-induced renal problem because increasing numbers of potent drugs have been added to the therapeutic arsenal in recent years. The 3 clinical syndromes that can be recognised in drug-induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. The first can be caused by prerenal problems, acute interstitial nephritis, acute tubular necrosis and intratubular obstruction. The most important drugs that cause prerenal failure are NSAIDs, captopril and cyclosporin. NSAIDs inhibit the synthesis of prostaglandins, and consequently vasoconstriction of the afferent arteriole leads to lowering of the glomerular filtration rate (GFR); captopril blocks the formation of angiotensin II (which also leads to a lower GFR), and should be used with caution in patients with stenotic renal arteries; cyclosporin causes vasoconstriction of the afferent arteriole, which is probably mediated by the sympathetic system. Combinations of these drugs result in increased nephrotoxicity. The drugs most likely to cause acute interstitial nephritis are antibiotics and NSAIDs. Normally, signs of an allergic reaction are also present. Acute interstitial nephritis is usually self-limiting, but in some studies it is claimed that steroids may promote recovery. Four important causal agents of acute tubular necrosis are aminoglycosides, amphotericin B, radiocontrast agents and cyclosporin. Approximately half of the cases of drug-induced renal failure are related to the use of aminoglycosides: generally, 10 days after start of treatment a nonoliguric renal failure develops, with recovery after withdrawal of the drug in almost all cases. The aminoglycosides are particularly nephrotoxic when combined with other nephrotoxic drugs. 80% of amphotericin B-treated patients develop renal insufficiency, a percentage that increases as the cumulative dose exceeds 5g. It is because of its unique antifungal properties that there are still some indications for the use of this highly nephrotoxic drug; the high percentage of nephrotoxicity can probably be prevented in part by sodium loading. The nephrotoxicity of radiocontrast agents is largely dependent on renal function: from 0.6% in patients with normal renal function to 100% in patients with a serum creatinine above 400 mumol/L. Diabetes mellitus does not add greatly to the risk of radiocontrast nephrotoxicity. The nephrotoxicity of cyclosporin is dose-dependent and reversible, although there are some reports of irreversibility after long term use. Cyclosporin can also result in nephrotoxicity in combination therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Drug-induced nephrotoxicity. Aetiology, clinical features and management. 204 84

Acute renal failure (ARF) associated with idiopathic nephrotic syndrome has been reported in adults with advanced age but is a rare event in children. We have reviewed the literature on this subject and report an additional pediatric case. The pathogenetic mechanisms which may lead to ARF during the course of idiopathic nephrotic syndrome are reviewed with a brief discussion of the role of angiotensin II and angiotensin converting enzyme inhibition in this setting. Although no consensus has emerged for the prevention and treatment of ARF in patients with nephrotic syndrome, a combination of salt-poor albumin and diuretics to reduce interstitial edema may be beneficial as a preventive measure. Once acute tubular necrosis is diagnosed, dialysis may be indicated. In the majority of reports the prognosis for recovery of renal function has been good even in patients in whom long-term dialysis was required.
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PMID:Acute renal failure in idiopathic nephrotic syndrome. 904 53

Mercury chloride (HgCl2) has a potent nephrotoxic effect. Most of Hg2+ existing in plasma following HgCl2 exposure forms a complex with sulfhydryl-containing ligands such as albumin and glutathione (GSH). The Hg(2+)-GSH complex is filtered in the glomeruli of the kidney and degraded into Hg(2+)-cysteine in the proximal tubules by the combined action of gamma-glutamyl transpeptidase and dipeptidase present in the epithelial cells. The degradation product is then incorporated and accumulated into the proximal tubule epithelial cells. The accumulated Hg2+ in the epithelial cells finally causes acute tubular necrosis (ATN) by its cytotoxic effect. At present, it is believed that tubular obstruction resulting from ATN triggers the onset of HgCl2-induced acute renal failure (ARF). A progressive fall in glomerular filtration rate (GFR) contributes to the progression of HgCl2-induced ARF. The fall in GFR may be caused by an increment in afferent arteriole resistance (RA) and a decrement in the ultrafiltration coefficient (Kf) due to mesangial cell contraction. These changes in RA and Kf may be attributed to the increased action of the vasoconstrictors, angiotensin II and endothelin-1 and to the decreased action of the vasodilator, nitric oxide observed at the glomerulus level of HgCl2-induced ARF. Accordingly, the imbalance between these vasoactive substances appears to play an important role in the progression of HgCl2-induced ARF due to reducing GFR. Further studies, however, remain to elucidate the mechanisms involved.
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PMID:[HgCl2-induced acute renal failure and its pathophysiology]. 952 59

Transforming growth factor (TGF)-beta1 is important in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy (CAN). The angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopressor angiotensin II. Angiotensin II is also a growth factor and a profibrogenic cytokine. It mediates the induction of TGF-beta1. We studied the relationship among the intragraft expression of AGT, TGF-beta1, and CAN in stable renal transplant patients (RTP). We used a competitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)-ELISA assay to identify intragraft amounts of AGT expression in RTP and correlated it with TGF-beta1 mRNA expression. We studied and performed kidney biopsies on 12 RTP with long-functioning grafts and 6 RTP in the immediate posttransplantation period (7 days) who had acute tubular necrosis as control. Histology was based on Banff working classification criteria. Total RNA was isolated from biopsy specimens. For RT-PCR-ELISA, we created heterologous RNA competitors that coamplified with the same primers as AGT and TGF-beta1. Six of 12 long RTP had proteinuria >1000 mg/24 hr and 6 had proteinuria <1000 mg/24 hr. The differences between Banff grades (P =0.03), AGT, and TGF-beta1 levels by RT-PCR-ELISA were statistically significant between both groups (106.2+/-60.7 vs. 34.1+/-11.9 pg/microg total RNA [P =0.01] and 5954+/-5612 vs. 436+/-517 transcripts/microg total RNA [P =0.01], respectively). The control group showed AGT levels of 25+/-12.2 pg/microg total RNA and TGF-beta1 levels of 228+/-111 transcripts/microg total RNA, significant only for the higher proteinuria group (P=0.01 and P=0.04, respectively). There was a correlation between AGT and TGF-beta1 in both groups (r=0.96, P=0.001). We showed a relationship between mRNA expression of AGT and TGF-beta1 in kidney transplant patients with different grades of CAN and proteinuria.
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PMID:Intragraft messenger RNA expression of angiotensinogen: relationship with transforming growth factor beta-1 and chronic allograft nephropathy in kidney transplant patients. 1235 92

Hypertonic glycerol injection is one of the most frequently used models of experimental acute renal failure. Late structural changes such as interstitial fibrosis in the renal cortex and tubular atrophy have been detected after severe acute tubular necrosis (ATN). The aim of this study was to investigate the expression of angiotensin II (AII) and endothelin during the evolution of the ATN induced by glycerol and their relationships with the late structural changes observed in the kidneys. Forty-nine male Wistar rats were injected with a 50% glycerol solution, 8 mL/kg, divided into equal amounts, each administered into one hind leg, and 18 with 0.15 M NaCl solution. Blood and urine samples were collected 1, 5, 30, and 60 days after the injections to quantify sodium and creatinine; the animals were killed and the kidneys removed for histologic and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining in the cortical tubulointerstitium. Glycerol-injected rats presented a transitory increase in plasma creatinine levels and in fractional sodium excretion. The immunohistochemical studies showed increased AII and endothelin staining in the renal cortex from rats killed 5 days after glycerol injection (p<0.001) compared with control that persisted until day 60. The animals killed on days 30 and 60 also presented chronic lesions (fibrosis, tubular dilatation, and atrophy) in the renal cortex, despite the recovery of renal function. AII and endothelin may have contributed to the development of renal fibrosis in these rats.
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PMID:Angiotensin II and endothelin in the renal cortex during the evolution of glycerol-induced acute tubular necrosis. 1635 Aug 30

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.
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PMID:Renal interstitial hyaluronan: functional aspects during normal and pathological conditions. 2251 43

Contrast-induced nephropathy (CIN) is regarded as acute tubular necrosis resulting from the cytotoxicity of contrast media and the medullary hypoxia linking to the interplay of vasoconstriction and vasodilatation. Saline infusion may prevent CIN by inhibiting renin release and thus production of angiotensin II (ANG II), a vasoconstrictor, from angiotensin I (ANG I). Yet the use of angiotensin converting enzyme inhibitor (ACEI) yields conflicting results in the prevention of CIN. We hypothesise that ACEI will be useful for CIN prevention when the saline infusion is insufficient, useless when the saline infusion is sufficient, and counterproductive when the saline infusion is excessive, respectively. When the production of ANG I and thus ANG II is insufficiently inhibited by insufficient saline infusion, ACEI may help prevent CIN by conferring extra inhibition on the production of ANG II from ANG I. The counterproductive effect may result from ACEI blocking the generation of angiotensin 1-7, a potent vasodilator, from angiotensin 1-9 whose precursor, ANG I, is excessively diminished by excessive saline infusion. Clinical data suggest that normal saline infusion at a rate of 1 ml/kg/h for 12 h, 1 ml/kg/h for 6 h, and 2 ml/kg/h for 6 h before and after contrast injection provide sufficient, insufficient, and excessive hydration in the prevention of CIN, respectively. The mainstream guideline is to stop ACEI and provide sufficient hydration for CIN prevention. Alternatively one may continue to have ACEI but the use of normal saline infusion must be limited to 1 ml/kg/h for 6 h before and after contrast injection.
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PMID:A hypothesis on the conflicting results of angiotensin converting enzyme inhibitor in the prevention of contrast-induced nephropathy. 2643 30