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)

A 33-year-old woman without evidence of previous liver disease developed fulminant hepatic failure following the therapeutic dose of acetaminophen 3 days prior to admission. At admission, liver and renal function revealed hepatocellular injury with jaundice, and acute renal failure, total serum bilirubin 12.5 mg/ dL, direct serum bilirubin 8.1 mg/dL, aspartate aminotransferase 8460 IU/L, alanine aminotransferase 4640 IU/L, blood urea nitrogen 36 mg/dL, and serum creatinine 5.2 mg/dL. Two days later she developed multiorgan failure including hemodynamic disturbance with irreversible shock, and expired. Autopsy was performed, liver pathology showed severe centrilobular and midzonal necrosis, compatible with toxic hepatic necrosis, and renal pathology showed focal loss of tubular epithelial cells and partial occlusion of tubular lumen by cellular debris, compatible with acute tubular necrosis. Physicians should be aware of potential hepatotoxicity and nephrotoxicity of acetaminophen, even if given at therapeutic dosage in acute febrile illness.
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PMID:Therapeutic dose of acetaminophen with fatal hepatic necrosis and acute renal failure. 1762 27

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

Paraphenylene diamine (PPD) is a major component of hair dyes. The aim is to study the renal manifestations and outcome of PPD consumption. During a four-year period from 2002 to February 2006, 10 persons were admitted to our Institute after consuming a hair dye in a suicidal bid. The percentage of ARF due to PPD at our Institute was 0.95%. Seven patients out of 10 (70%) who consumed PPD developed ARF. All 10 patients, including the patients who had normal renal function had features of rhabdomyolysis. Two patients required ventilator support for respiratory distress and two more required tracheostomy due to upper airway tract edema. One patient has expired after two sessions of dialysis. Renal biopsy in two patients (one, postmortem) showed acute tubular necrosis along with presence of casts in tubules due to myoglobin.
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PMID:Paraphenylene diamine ingestion: an uncommon cause of acute renal failure. 1829 14

Yucca schidigera juice in doses of 1.5 g (63 mg sapogenin) and 3.0 g (126 mg sapogenin) per kg live weight was administered intraruminally to 30 lambs for 21 days to investigate whether the saponins in Y. schidigera were toxic to lambs and whether they could cause hepatogenous photosensitisation. Twelve lambs died or had to be euthanised. The main pathological findings in the diseased lambs were acute tubular necrosis in the kidneys, dehydration and watery content in the gastrointestinal tract. Fifteen lambs were euthanised at the end of the study, and the main pathological findings in dosed animals were accumulation of homogeneous pale PAS-positive material in the hepatocytes. There was a rise in serum creatinine and urea concentrations in the lambs with renal lesions the day before they died. Major Y. schidigera-related saponins were found in the liver and kidney samples from all lambs that were dosed with Y. schidigera juice. The results of the present study demonstrate that un-hydrolysed saponins can be absorbed from the gastrointestinal tract. The possible role of saponins in causing nephrotoxicity is discussed.
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PMID:Toxicity testing of saponin-containing Yucca schidigera Roetzl. juice in relation to hepato- and nephrotoxicity of Narthecium ossifragum (L.) Huds. 1794 32

We report two children with hemolytic anemia during the course of hepatitis A infection. On admission, the patients had high blood urea nitrogen, creatinine, and uric acid levels, as well as anemia, leucocytosis, and direct and indirect hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on admission. Inadvertent administration of vitamin K could have been related to an acute reduction in hemoglobin concentration. To prevent renal damage, plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute tubular necrosis complicated the clinical course in one patient, and several sessions of hemodialysis were required. In conclusion, intravascular hemolysis should be considered in patients with hepatitis A infection, marked hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet recommended for routine administration, high-risk patients, including those with a G6PD deficiency, should be vaccinated against hepatitis A.
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PMID:Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia. 1832 Feb 20

Activated neutrophils have been implicated in the development of ischemia/reperfusion (I/R)-induced renal failure. Cytokine-induced neutrophil chemoattractant-1 (CINC-1), a major factor in acute inflammation, is responsible for the activation of neutrophils and for neutrophil chemotaxis to sites of injury. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators. We examined whether the human form of ANP attenuates I/R-induced renal injury by reducing neutrophil activation in a rat model. Male Wistar rats weighing 200-240 g were observed for 24 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP, 0.2 microg/kg/min) beginning immediately after ischemia and continuing for 2 h after reperfusion. CINC-1 and myeloperoxidase (MPO) concentrations were measured to assess activation of the infiltrating neutrophil. Blood urea nitrogen and serum creatinine and urinary N-acetyl beta-d-glucosaminidase (NAG) were measured as indicators of glomerular function and as a specific indicator of proximal tubular function, respectively. alpha-hANP significantly inhibited I/R-induced increases in renal CINC-1 and MPO concentrations. alpha-hANP also reduced I/R-induced increases in the concentrations of blood urea nitrogen and serum creatinine, and improved histopathologic changes, including acute tubular necrosis. These findings indicate that alpha-hANP attenuates I/R-induced acute renal injury, at least in part by reducing neutrophil activation, and may be useful in surgeries, associated with renal ischemia, as well as in renal transplantation.
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PMID:Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. 1864 86

Ischemic-reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin-3 is a multi-functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro-inflammatory cytokines. The aim of this study was evaluate the role of galectin-3 in the inflammation triggered by IRI. Galectin-3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP-1, IL-6 and IL-1beta were studied by real-time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 +/- 85.21 mg/dl vs. gal-3 KO = 123.74 +/- 29.64 mg/dl, P = 0.001). Galectin-3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP-1, IL-6, IL-1beta, less macrophage infiltration and lower ROS production at early time points. Galectin-3 seems to play a role in renal IRI involving the secretion of macrophage-related chemokine, pro-inflammatory cytokines and ROS production.
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PMID:A Role for galectin-3 in renal tissue damage triggered by ischemia and reperfusion injury. 1865 91

Renal ischemia/reperfusion (I/R) injury is one of the main causes of postoperative renal failure. Activated neutrophils are implicated in the development of I/R-induced renal failure. JTE-607 has been reported to be a potent inhibitor of the multiple inflammatory cytokines in the endotoxic shock mouse model and heart Langendorff perfusion model. In this study, we examined whether JTE-607 attenuates I/R-induced renal injury by reducing neutrophil activation. Male wistar rats were intravenously administered JTE-607 (JTE group, 30 mg/kg) or 5% mannitol (control group) 30 min before ischemia. JTE-607 reduced the I/R-induced increases in the serum concentrations of blood urea nitrogen and creatinine, and improved the histopathologic changes, including acute tubular necrosis. I/R-induced an increase in neutrophil activation, reflected by increases in renal cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase (MPO) concentrations which were significantly reduced by JTE-607. These findings indicate that JTE-607 attenuates I/R-induced acute renal injury, probably by inhibiting neutrophil activation. JTE-607 might be a novel therapeutic strategy for the protection of postoperative renal failure in surgery associated with renal ischemia as well as renal transplantation.
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PMID:JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. 1869 26

IL-18 function is neutralized in IL-18 binding protein transgenic (IL-18BP Tg) mice. First, we determined whether IL-18BP Tg mice are protected against ischemic acute kidney injury (AKI). Ischemic AKI was induced by bilateral renal pedicle clamping. IL-18BP Tg mice were functionally and histologically protected against ischemic AKI as determined by blood urea nitrogen, serum creatinine, and acute tubular necrosis score. We have demonstrated that the injurious effect of IL-18 in the kidney is independent of neutrophils and lymphocytes. Thus the effect of IL-18 inhibition on renal macrophage infiltration was determined. The number of macrophages was significantly reduced in IL-18BP Tg compared with wild-type kidneys. To determine the cytokines and chemokines that are dependent on IL-18, we performed flow cytometry based assays. Multiple chemokines/cytokines, IL-3, IL-6, IL-15, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, macrophage inflammatory protein-2, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1 were significantly increased in AKI vs. sham kidneys. Only CXCL1 (also known as KC or IL-8) was significantly increased in AKI vs. sham kidneys and significantly reduced in IL-18BP Tg AKI vs. wild-type AKI kidneys. To determine whether macrophages are the source of CXCL1 in the kidney, we depleted macrophages with liposomal encapsulated clodronate. CXCL1 was significantly decreased in macrophage-depleted vs. control AKI mice. In summary, in ischemic AKI in mice, 1) IL-18BP Tg mice are functionally and histologically protected, 2) macrophage infiltration in the kidney and CXCL1 are significantly reduced in IL-18BP Tg mice, and 3) macrophage depletion significantly reduces CXCL1 in the kidney. In conclusion, protection against ischemic AKI in IL-18BP Tg mice is associated with less macrophage infiltration and less production of CXCL1 in the kidney.
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PMID:Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury. 1875 96

Ischemia/reperfusion (I/R) injury in organ transplantation significantly contributes to graft failure and is untreatable using current approaches. I/R injury is associated with activation of the complement system, leading to the release of anaphylatoxins, such as C5a, and the formation of the membrane attack complex. Here, we report a novel therapy for kidney I/R injury through silencing of the C5a receptor (C5aR) gene using siRNA. Mice were injected with 50 microg of C5aR siRNA 2 days before induction of ischemia. Renal ischemia was then induced through clamping of the renal vein and artery of the left kidney for 25 minutes. The therapeutic effects of siRNA on I/R were evaluated by assessment of renal function, histopathology, and inflammatory cytokines. siRNA targeting C5aR efficiently inhibited C5aR gene expression both in vitro and in vivo. Administering C5aR siRNA to mice preserved renal function from I/R injury, as evidenced by reduced levels of serum creatinine and blood urea nitrogen in the treated groups. Inhibition of C5aR also diminished in vivo production of the pro-inflammatory cytokine tumor necrosis factor-alpha and chemokines MIP-2 and KC, resulting in the reduction of neutrophils influx and cell necrosis in renal tissues. This study demonstrates that siRNA administration represents a novel approach to preventing renal I/R injury and may be used in a variety of clinical settings, including transplantation and acute tubular necrosis.
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PMID:Gene silencing of complement C5a receptor using siRNA for preventing ischemia/reperfusion injury. 1877 41


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