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)

Immunosuppressant-induced nephrotoxicity, in particular chronic progressive tubulointerstitial fibrosis/arteriopathy induced by the calcineurin inhibitors cyclosporin and tacrolimus, has become the 'Achilles heel' of immunosuppressive agents. The use of calcineurin inhibitors as primary immunosuppressants in hepatic and cardiac transplantation has led to end-stage renal disease and dialysis. Calcineurin inhibitor-induced acute renal failure may occur as early as a few weeks or months after initiation of cyclosporin therapy. The clinical manifestations of acute renal dysfunction are caused by vasoconstriction of renal arterioles, and include reduction in glomerular filtration rate, hypertension, hyperkalaemia, tubular acidosis, increased reabsorption of sodium and oliguria. The acute adverse effects of calcineurin inhibitors on renal haemodynamics are thought to be directly related to the cyclosporin or tacrolimus dosage and blood concentration. However, new clinical data indicate that calcineurin inhibitor-induced chronic nephropathy can occur independently of acute renal dysfunction, cyclosporin dosage or blood concentration. Several strategies have been evaluated to attenuate cyclosporin-induced nephropathy, but their efficacy remains unknown. Cytokine release syndrome associated with the use of muronomab-CD3 (OKT-3) can also contribute to the pathogenesis of transient acute tubular necrosis and renal dysfunction following renal transplantation. Continued research and clinical experience should provide information regarding the aetiology of cyclosporin-induced chronic progressive tubulointerstitial fibrosis/arteriopathy and its potential treatment.
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PMID:Immunosuppressant-induced nephropathy: pathophysiology, incidence and management. 1061 71

A total of 107 cadaveric kidneys from non-heart-beating donors (NHBDs) have been transplanted between 1974 and 2000 at Kitasato University Hospital, Sagamihara, Japan. The patient survival of the 107 recipients of cadaveric renal transplants at 1, 5 and 10 yr was 0.857, 0.770 and 0.746, respectively. The 50% graft survival was 3.8 yr. The 5 and 10-yr graft survival was 0.457 and 0.337, respectively. Twenty of the 107 recipients of non-heart-beating cadaveric renal transplantation had graft survival longer than 10 yr. Of these 20 patients, 14 survivors still maintain functioning renal grafts and two died with functioning graft, although the remaining four reverted to dialysis because of chronic rejection and nephropathy. The average graft survival of these 20 patients at the time of study was 13.3 yr and the longest was 21.4 yr. The average serum creatinine level at 10 yr after transplantation was 1.63 mg/dL, almost identical to that at 5 yr post-transplant. The donors aged on average 40.2 yr; 13 were male and seven were female. The youngest donor was 9-yr-old and the oldest was 66. The graft survival was significantly better in the group with donor age younger than 55 yr (Log-rank: p=0.007). The average weight of the renal graft was not different between the long and shorter graft survival groups. The average warm ischemic time and total ischemic time were 9.7 and 539.7 min, respectively. The duration of post-transplant acute tubular necrosis averaged 9.2 days. These parameters tended to be shorter than those in recipients with graft survival >10 yr, but with no statistical significance. The mean numbers of acute rejection (AR) episode within 3 months after transplantation were 0.25 +/- 0.66 and 0.92 +/- 0.90 (p=0.020) in long survival and shorter survival groups, respectively. Long survivors had a significantly lower incidence of AR. Two of 20 cases received conventional immunosuppression with prednisolone, azathioprine and mizoribin, and 18 had prednisolone and calcineurin inhibitor (CNI). Kaplan-Meier analysis showed a significant contribution of CNI to graft survival (p=0.036). However, the graft survival reduction rate after 1 yr post-transplant did not differ between conventional and CNI immunosuppression. These data suggest that renal grafts retrieved with proper organ procurement procedures from NHBDs may survive long-term and help to overcome donor shortage.
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PMID:Factors contributing to long graft survival in non-heart-beating cadaveric renal transplantation in Japan: a single-center study at Kitasato University. 1243 17

Pretransplant renal failure is a well-known risk factor which adversely affects the prognosis after liver transplantation. We report a case with pretransplant renal failure and discuss the perioperative management of such patient. The patient was 62 year-old-woman who was diagnosed with end-stage liver disease due to primary biliary cirrhosis, for which living donor liver transplantation (LDLT) was indicated. Her pretransplant serum creatinine was 9.4 mg/dl due to combination of drug-induced (antibiotics) acute tubular necrosis and hepatorenal syndrome. The management of renal failure consisted of the avoidance of calcineurin inhibitor as an induction immunosuppression and the use of perioperative continuous hemodiafiltration (CHDF). The postoperative course of the patient was complicated with CMV pneumonia and acute rejection, however she recovered and discharged on 94 POD with well-preserved graft function and normal renal function without any adverse sequela. LDLT for patients with renal failure can be performed successfully by careful management.
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PMID:[Living donor liver transplantation for a patient with renal failure]. 1263 31

Platelet accumulation in glomerular capillaries (GC) and peritubular capillaries (PC) has pathogenetic importance in antibody-mediated hyperacute renal allograft rejection. CD61 is expressed constitutively by platelets, by platelet microparticles arising from platelet activation, and is readily detectable by immunohistochemistry. This study examined the immunohistochemical localization of CD61 in acute humoral rejection (AHR) of renal allografts to explore the relationship of platelet accumulation to antibody-mediated rejection. Two observers graded the extent of CD61 staining in PC and GC from 0 (none) to 2+ (>50%) in 15 renal allograft biopsy specimens with AHR and compared these with tissues from allografts with acute cellular rejection (ACR) (n = 23); acute calcineurin inhibitor toxicity (ACIT) (n = 21) with thrombotic microangiopathy (TMA) (n = 11) and tubular toxicity only (n = 10); acute tubular necrosis (ATN) (n = 16); acute renal vein thrombosis (RVT) (n = 4); and histologically unremarkable native kidneys (n = 26). Selected tissues were examined by electron microscopy and stained for CD34 by immunohistochemistry. Histologically unremarkable native kidney tissues had CD61 only in scattered small lumenal granules in GC and PC. Mural and occlusive lumenal CD61 deposits (>0.5+) were observed in 13 of 13 (100%) allograft tissues with GC thrombi due to AHR (1) and ACIT TMA (9) and RVT (3). Twenty-seven of 66 allografts (40.9%) without glomerular thrombi had >0.5+ GC CD61 in AHR (60%), ACR (26%), tubular ACIT (60%), and ATN (44%). More than trace (>0.5+) PC mural and lumenal CD61 deposits were seen only in AHR (53.3%) and ACR (30%). PC CD61 correlated with interstitial hemorrhage (r = 0.64), neutrophilic capillaritis (r = 0.47), and interstitial inflammation (r = 0.47) (P <0.001 for each). PC CD61 was observed in 11 of 11 foci of necrosis due to AHR, RVT, and ischemia. In AHR, capillaries with CD61 deposits had few platelets, numerous microvesicles and membrane fragments, severe endothelial injury seen on electron microscopy, and reduced capillary CD34 expression. CD61 detection by immunohistochemistry revealed products of capillary platelet activation in allograft biopsy specimens without light microscopic thrombi. Observations in this study suggest that intracapillary platelet activation occurs in response to graft capillary injury from many causes and may not be specific for antibody-mediated rejection.
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PMID:Platelets and capillary injury in acute humoral rejection of renal allografts. 1282 6

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.
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PMID:Sirolimus in kidney transplantation from marginal donors. 1511 May 69

The relationship between acute renal allograft rejection and histopathologic biopsy alterations recognized by the Banff Schema as "borderline changes" is not clear. Some evidence supports the contention that about one third of patients with borderline infiltrates and clinical evidence of graft dysfunction do indeed have acute rejection, which, if left untreated, progresses to a histologically more advanced stage of rejection. Several investigators recognize that not all patients with mild tubulitis respond clinically to antirejection therapy; a significant number of these biopsy specimens display additional histological alterations. The most common concurrent lesions are chronic allograft nephropathy, arteriolar lesions consistent with calcineurin inhibitor toxicity, acute tubular necrosis, and obstructive nephropathy. Management of patients with borderline changes must tightly correlate the pathologic features and the clinical information.
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PMID:Borderline changes in the Banff schema: rejection or no rejection? 1511 Jun 52

The paradigm that chronic rejection causes all progressive late allograft failure has been replaced by a hypothesis of cumulative damage, where a series of time-dependent immune and nonimmune mechanisms injure the kidney and lead to chronic interstitial fibrosis and tubular atrophy, representing a final common pathway of injury and its consequent fibrotic healing response. Allograft damage is common, progressive, time-dependent, clinically important and modified by immunosuppression. Early after transplantation, tubulointerstitial damage is predominantly related to ischemia reperfusion injury, acute tubular necrosis, acute and subclinical rejection and/or calcineurin inhibitor nephrotoxicity, superimposed on preexisting donor disease. Later, cellular inflammation lessens and is replaced by microvascular and glomerular injury from calcineurin inhibitor nephrotoxicity, hypertension, immune-mediated fibrointimal vascular hyperplasia, transplant glomerulopathy and capillary injury, polyoma virus and/or recurrent glomerulonephritis. Additional mechanisms of injury include internal architectural disruption of the kidney, cortical ischemia, persistent chronic inflammation, replicative senescence, cytokine excess and fibrosis induced by epithelial-to-mesenchymal transition. Current understanding of the etiology, pathophysiology and evolution of pathological changes are detailed. An approach to histological assessment of the individual failing graft are presented and a series of postulates are defined for future studies of chronic allograft nephropathy.
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PMID:Chronic allograft nephropathy: current concepts and future directions. 1653 63

Renal biopsy is currently the gold standard to assess the causes of renal allograft dysfunction. In the present study, we prospectively assessed the role of the renal allograft biopsy in the diagnosis and treatment of renal allograft dysfunction. Seven hundred and fifteen biopsies were performed in 399 patients. The anatomopathological results in group 1 (delayed graft function) were: 60.4% acute tubular necrosis, 17.6% acute rejection, 4.3% calcineurin inhibitor toxicity, and 17.7% other diagnoses; in group 2 (acute graft dysfunction): 42.3% acute rejection, 22% acute tubular necrosis, 8.4% calcineurin inhibitor toxicity, and 27.3% other diagnoses. Among patients with delayed graft function, 42.2% of biopsies led to a change in the treatment. In 60.5%, the biopsy of patients with acute dysfunction led to a change in the patient management. In our series, the result of the biopsy disagreed with the clinical diagnosis in 39.6% and 57.7% of cases, respectively. These results demonstrated that renal graft biopsy remains an indispensable tool for the accurate management of kidney transplant patients.
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PMID:Utility of biopsy in kidney transplants with delayed graft function and acute dysfunction. 1736 34

Acute renal failure (ARF) and chronic kidney disease (CKD) are common complications after liver transplantation (LTx). The incidence of ARF post-LTx varies between 48% and 94%; 8% to 17% of patients require renal replacement therapy (RRT). The most common cause of ARF early after LTx is ischemic acute tubular necrosis, followed later by cyclosporine toxicity and sepsis. Preoperative serum creatinine >1.5 mg/dL and early hepatic allograft dysfunction are risk factors for the occurrence of postoperative ARF. Of patients with ARF due to the hepatorenal syndrome, approximately two-thirds will recover, although recovery may be delayed 3 months or longer after LTx. Mortality after LTx is affected modestly by the presence of ARF pretransplant (<2-fold increase), but increases markedly (up to 8-fold) in the face of ARF posttransplant. Mortality does not appear to be influenced by the mode of RRT used. The risk of CKD after LTx is approximately 18% at 5 years and increases to approximately 25% by 10 years after transplantation. Calcineurin inhibitor toxicity is the most common cause. Specific prognosticators for predicting CKD after LTx are presently lacking. The occurrence of CKD after LTx markedly impairs long-term survival.
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PMID:Acute renal failure and chronic kidney disease following liver transplantation. 1789 11

Acute Renal Failure (ARF) in the immediate post transplant period is most commonly due to acute tubular necrosis, acute cellular rejection and calcineurin inhibitor toxicity apart from usual prerenal and post renal causes. In this report, we discuss an interesting and unusual cause of ARF due to thrombotic micro angiopathy in the immediate post transplant setting.
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PMID:Post transplant thrombotic microangiopathy causing acute renal failure. 2036 29


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