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)

The effect of cyclosporine and steroids on early renal allograft function and eventual graft outcome was analyzed in 100 recipients; 33 recipients of living related donor (LRD) and 67 recipients of cadaveric donor (CAD) allografts were studied. A concurrent population of 47 CAD recipients treated with azathioprine and steroids was used for comparison. Recipients received oral cyclosporine (14 mg/kg) 48 hours (LRD) or 6-12 hours (CAD) pretransplant. No cases of acute tubular necrosis (ATN) were observed in the LRD recipients. The incidence of posttransplant ATN was similar in the cyclosporine-treated (41%) and in the azathioprine-treated (45%) CAD recipients (P = ns). Cyclosporine-treated CAD kidneys preserved less than 24 hr experienced a lower rate of ATN (P less than .01) using simple cold storage (31%), as compared with hypothermic pulsatile perfusion (57%). One-month creatinine nadirs were higher in cyclosporine-treated than in azathioprine-treated recipients, using median values for each group. One-year actuarial patient survival for cyclosporine-treated LRD recipients was 97%; CAD recipients, 94%, and azathioprine-treated CAD recipients, 91%. Graft survival rates in the same groups were 91%, 76%, and 55%, respectively. The major causes of graft loss in cyclosporine-treated patients were nonimmunologic. It is concluded that cyclosporine and prednisone are a safe, efficacious combination for LRD and CAD renal transplantation. The possibility of nephrotoxicity leading to impaired graft function in the early posttransplant period should not preclude the administration of cyclosporine prior to alloantigen presentation.
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PMID:The effect of cyclosporine on early graft function in human renal transplantation. 635 68

Of 2457 patients in the North American Pediatric Renal Transplant Cooperative Study registry who were followed for 5481 patient-years after the index transplantation, we observed 136 deaths, for an average annual rate of 24.8 deaths per 1000 patient-years. Death resulted primarily from infection (n = 55, 40%), cardiovascular causes (n = 28, 21%), hemorrhage (n = 16, 12%), and malignancies (n = 9, 7%). Cadaver-donor source was associated with greater mortality (6.7%) than a living-donor source (4.0%) (P < 0.005). Recipients aged 0-1, 2-5, 6-12, and 13-17 years old had mortality rates of 17.5, 8.0, 3.6, and 4.5%, respectively (P < .001). Mortality rates increased substantially when examined by recipient and cadaver donor ages (mortality rates of up to 45%), the greater the concordance between young donor and recipient ages. Interestingly, acute tubular necrosis and graft failure less than 30 days after transplantation (GH30) were each associated with markedly elevated mortality rates. (The risk ratio for ATN was 3.1 [P < 0.001] and for GF30 it was 6.4 [P < 0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n = 21, 33.3%), congenital nephrotic syndrome (n = 79, 15.2%), pyelo/interstitial nephritis (n = 54, 11.1%), and Drash syndrome (n = 14, 21.4%). When the joint effect of these risk factors was examined in a Cox proportional hazards model, young recipient age (0-1 years old) and GF30 were significant (P < .001) risk factors of mortality for recipients of living-donor organs. For recipients of cadaver kidneys, young recipient age--0-1 years old (P < .001) and 2-5 years old (P = .002)--ATN (P = .029), and GF30 (P < .001) were all significant risk factors. Recipient age is the major determinant of increased mortality after renal transplantation. Avoidance of acute tubular necrosis by reducing cold time and preventing early graft failure by better matching techniques in this vulnerable population may improve the mortality rate.
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PMID:Posttransplant deaths and factors that influence the mortality rate in North American children. 811 40

Vascular thrombosis remains a major cause of graft failure, accounting for 12.2% of failed index transplants and 19.2% of repeat transplants. We conducted a special study to identify the risk factors for vascular thrombosis. A total of 4394 transplants (2060 living donor [LD] transplants and 2334 cadaver donor [CAD] source transplants) were evaluated. The respective vascular thrombosis rates for LD and CAD transplants were 38/2060 (1.8%) and 100/2334 (4.2%) (P<0.001). Univariate analysis showed that the rate of graft loss due to thrombosis was significantly higher in younger children (less than 2 years of age) as compared with older age groups (2-5 years, 6-12 years, and more than 12 years of age) (9.0% vs. 5.5%, 4.4%, and 3.5% for CAD transplant recipients and 3.5% vs. 3.4%, 0.7%, and 1.9% for LD graft recipients). Recipients of kidneys from cadaver donors less than 5 years of age had a significantly higher thrombosis rate (8.3%) than did recipients from older donor groups (5-10 years, 4.5%; greater than 10 years, 3.2%). Recipients of kidneys with cold ischemia time greater than 24 hr also had a higher thrombosis rate (5.6%), as compared with recipients of kidneys with a shorter cold ischemia time (3.2%). Recipients of antilymphocyte therapy on day 0 or day 1 were at dimished risk of graft loss due to thrombosis (2.2% vs. 4.1%, P=0.001). Comparable trends were seen for both LD and CAD organ recipients. LD organ recipients with a history of prior transplantation had a significantly higher rate of thrombosis as compared with those who received a primary transplant (4.6% vs. 1.6%, P=0.005). For both LD and CAD organ recipients, the occurrence of acute tubular necrosis was a significnat risk factor for the development of thrombosis. Regression analysis showed that for LD organ recipients, a history of prior transplantation increased the risk for thrombosis, whereas increasing recipient age had a linear decreasing risk effect. The use of antilymphocyte antibody or cyclosporine on day 0/1 decreased the risk for thrombosis. For CAD kidney recipients, organ cold ischemia time greater than 24 hr increased the risk for thrombosis. The use of antibody induction therapy, donors greater than 5 years of age, and increasing recipient age were factors that decreased the risk for thrombosis.
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PMID:Risk factors for vascular thrombosis in pediatric renal transplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. 915 19

The shortage of cadaver kidneys available for organ donation compared to growing demand has led to an increase in the use of living-unrelated donors (LURD) for renal transplantation (Tx). Results from trials in adults show that 1-year graft survival rates in LURD are similar to living-related donor (LRD) rates and superior to those of cadaver renal donor (CAD) transplants. We report our experience with 38 LURD transplants for children enrolled in NAPRTCS that were performed between 1987 and 1997. Ages of recipients at Tx were 0-5 years (n=8), 6-12 (n=10), and >12 years (n=20). Twenty nine were primary Tx, seven were second Tx, and two were third Tx. HLA antigen data showed that the number of 2-antigen mismatches for each locus was 44.7% for HLA-A, 71.1% for HLA-B, and 55.3% for HLA-DR. There were 7 donor/recipient pairs with a 6-antigen mismatch, 12 pairs with a 5-antigen mismatch, while there were 6 pairs with a 3-antigen match of which 3 pairs had at least one match at each of the A, B, and DR loci. A total of 38 acute rejection episodes occurred in 25 LURD recipients. Among primary grafts the incidence of first acute rejection at 30 d post-Tx was 46% in LURD vs. 29% in LRD and 37% in CAD recipients; at 1 year post-Tx it was 76% in LURD vs. 48% in LRD and 62% in CAD recipients. Acute tubular necrosis (ATN) was reported in four or 10.5% of LURD transplants compared with 5.4% in LRD and 19.0% in CAD recipients. There were 12 LURD graft failures, due to vascular thrombosis (3), acute rejection (2), recurrence of original disease (1), infection (3), and patient death (3). Estimated primary graft survival probabilities (+/- SE) at 12 months post-Tx are 0.825 +/- 0.071 for LURD, compared to 0.911 +/- 0.006 for LRD, and 0.815 +/- 0.009 for CAD. We conclude that data from this study show that LURD Tx in children have a low rate of ATN that is similar to that of LRD Tx. However, LURD Tx have a high incidence of acute rejection, and the graft survival at 12 and 24 months post-Tx is inferior to LRD Tx. There is a high frequency of graft loss due to causes other than rejection, and these may be related to adverse recipient selection criteria.
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PMID:Living-unrelated renal transplantation in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 1008 40