Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268494 (ATN)
 694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To compare the effect of type of induction immunosuppression on the quality of initial renal allograft function, we identified 35 cadaver donor kidney pairs in which one recipient of a kidney from a given pair received induction immunosuppression with Minnesota antilymphocyte globulin (MALG group) while the recipient of the contra-lateral kidney received cyclosporine from day zero (CsA group). In the absence of an existing quantitative measure to assess and compare the status of those grafts that function primarily, we defined the half-life of creatinine elimination (t1/2SCr) as such an outcome measure based on a review of creatinine elimination kinetics. All organs were procured with in-situ perfusion and en-bloc removal. Total cold storage times, rewarm times, and perioperative management were comparable for the two groups. In the MALG group, the mean t1/2SCr) was not different from that in the CsA group (1.38 +/- 0.96 days vs 1.35 +/- 1.2 days P = NS). Multiple regression analysis performed on the differences in recipient age, number of DR-B locus matches, total cold ischemia time, rewarm time, and central venous pressure at reperfusion of a given donor pair demonstrated no significant impact of any of these differences on the difference in t1/2SCr for the same pair set in this sample. The nadir of serum creatinine achieved in the first five days posttransplant was somewhat higher in the CsA group (234 +/- 131 mumol/L) as compared with the MALG group (200 +/- 132 mumol/L) but the difference was not significant. A similar nonsignificant trend was observed in the comparison of mean serum creatinine values at 30 days posttransplant (MALG group: 158 +/- 62 mumol/L vs. CsA group: 200 +/- 141 mumol/L). Only one of seventy recipients (CsA group) was dialyzed within the first 5 days posttransplant for an overall incidence of ATN of less than 2%. Fourteen of 35 (40%) recipients in both groups received treatment for acute rejection. The mean time to first treatment for acute rejection episode was shorter in the CsA group than the MALG group (10 +/- 8 days vs 23 +/- 24 days, P = 0.055). Graft survival at one year was not different for the two groups (92% vs. 87% for the MALG and CsA groups respectively, P = NS).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The quality of initial function following renal transplantation determined by creatinine elimination kinetics. Comparison of Minnesota antilymphocyte globulin and cyclosporine induction immunosuppression. 175 62

In many studies of renal transplant recipients, acute tubular necrosis has been shown to predispose to a higher rate of graft loss, apparently due to rejection, but the mechanism of this effect is unknown. One possibility is an increased immunogenicity of the graft. To study this possibility, we examined the expression of major histocompatibility complex antigens in kidneys damaged by ischemia, using a mouse model of ischemic ATN. ATN was produced in the left kidney of male CBA mice by temporary clamping of the vascular pedicle for up to 60 min. Class I and II MHC expression was quantified by the extent of binding of monoclonals in radioimmunoassay, after 1 to 35 days in both kidneys. MHC induction was localized by indirect immunoperoxidase staining. Specific steady state mRNA for beta 2 microglobulin and class II were quantified by northern blotting using 32P-labeled probes. Changes in MHC expression were assessed by comparing the ischemically injured left kidney to the control right kidney. By day 1, ATN was evident by histology but there was no change in MHC expression. By day 3, class I was increased in the left kidney by 3-6-fold over the right. In tissue sections, the class I increase was localized to tubular epithelial cells. Starting on day 7 and persisting to day 35, class II was increased by 1.5 to 3 times for the ischemic kidney over the control, primarily in interstitial cells but also in tubular cells. This increase in class II was associated with the appearance of Thy 1.2-positive cells in the interstitial areas. Increased antigen expression was preceded by increased steady state mRNA. Thus unilateral ischemic ATN causes increased MHC expression in tubular cells and the accumulation of an inflammatory infiltrate, both of which may contribute to the increased rate of rejection and graft loss in ischemically injured kidneys.
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PMID:Increased major histocompatibility complex antigen expression in unilateral ischemic acute tubular necrosis in the mouse. 210 46

To assess the impact of cadaver donor age on posttransplant renal function and graft survival, we analyzed our clinical results in 17 recipients of younger donor kidneys (less than 10 years) and 48 recipients of older donor kidneys (greater than 50 years) and compared them with a control group of 598 patients who received kidneys from donors between 11 and 50 years of age. The 3 groups were comparable with respect to recipient age, duration of dialysis, prior transfusions, previous transplants, cold ischemia time, HLA AB mismatches, cytotoxic antibody profile, posttransplant ATN, and prophylactic ALG treatment. The cumulative patient survival at 1, 2, and 3 years was not significantly different among the 3 groups, but the graft survival in recipients of older donor kidneys was significantly lower than the control (71% vs. 62% at 2 years, P = .09 and 66% vs. 55% at 3 years, P = .0003. The short-term renal function assessed at 1 month posttransplant was significantly lower in the older donor group compared with the control (creatinine clearance 45 mL/min vs. 59 mL/min, P = .0003). Likewise, the long-term renal function assessed at the last follow-up was also lower in the older donor group than the control (creatinine clearance 40 mL/min vs. 49 mL/min, P = .07). There were no significant differences in graft survival or short- or long-term renal function between the younger donor group and the control group. These observations suggest that transplantation of a kidney from an older cadaver donor is associated with an inferior posttransplant outcome. The practical decision whether or not to use an older donor kidney should be individualized taking this as well as other factors into account.
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PMID:Influence of cadaver donor age on posttransplant renal function and graft outcome. 230 Oct 36

The results of 61 cadaveric allografts preserved for 30 to 76 hours were analyzed to determine the effect of cold ischemia time, the method of preservation, and the type of immunosuppression on early graft viability and long-term graft survival. Preservation in cold storage up to 50 hours gave a low incidence of nonfunction (4%) and of posttransplant dialysis (20%) and a high rate of function both at 1 month (96%) and at 2 years (60%). Cold ischemia time greater than 50 hours caused a significantly increased need for dialysis (58%) but without appreciable difference in graft function at 1 month or at 2 years. Preservation by machine had no advantage over preservation by simple cold storage when the cold ischemia time was less than 50 hours. When cold ischemia time exceeded 50 hours, machine preservation was associated with a significantly reduced incidence of posttransplant dialysis but without significant differences in long-term function at 2 years. With up to 50 hours of cold ischemia and providing there was no ATN, CsA had little nephrotoxicity and gave excellent graft function at 1 month and at 2 years. However, the nephrotoxicity of CsA was markedly increased when the preservation interval exceeded 50 hours, resulting in a significantly increased rate of primary nonfunction and the need for dialysis with a significant decrease in graft function at 1 month and at 2 years. The nephrotoxicity of CsA was considerably decreased or eliminated without affecting its powerful immunosuppressive property when initial immunosuppression was begun with azathioprine with sequential conversion to CsA when graft function was fully established. It is recommended that when cold ischemia is long or when there is ATN, CsA should be used as a sequential therapy to azathioprine after graft diuresis or, alternatively, in much smaller doses as part of a combination therapy with azathioprine.
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PMID:Limiting factors in successful preservation of cadaveric kidneys with ischemia time exceeding 50 hours. 354 9

Post-transplant cure tubular necrosis (ATN) represents the most frequent cause of delayed graft function in the immediate post-transplant period. Several causes have been associated with the development of post-transplant ATN such as donor and recipient ages, cold-warm ischemia times, HLA mismatches, and postoperative hypotension. In the present study, we retrospectively evaluated the role of secondary hyperparathyroidism and high parathyroid hormone (PTHi) blood levels in the development of post-transplant ATN. One hundred patients submitted to cadaveric renal transplant between January 1992 and March 1993 in our unit were included. Twenty-seven patients (27%) developed post-transplant ATN and seventy-three (73%) did not. Post-transplant ATN was significantly associated with gender (p < 0.01), recipient age (p < 0.01), number of transplantations (p < 0.01), time on hemodialysis (p < 0.001), cold ischemic time (p < 0.05) and PTHi levels (p < 0.001). The bivariate and multivariate statistical analyses demonstrated that the development of post-transplant ATN was significantly more frequent in females; retransplanted patients, patients with a time on dialysis of more than 5 years, recipients over 60 years old, patients with a PTHi blood level higher than 240 pg/ml (4 times normal level) and a cold ischemia time of more than 18 h. Based on these results, we conclude that high PTHi blood levels in the renal transplant recipients represent a relevant factor in the development of post-transplant ATN. The administration of intravenous pulsed of 1,25(OH)2D3 and/or a calcium channel blocker in the perioperative period could be useful to decrease the incidence and severity of post-transplant ATN in these patients.
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PMID:Role of secondary hyperparathyroidism in the development of post-transplant acute tubular necrosis. 874 60

The aim of the prospective study was to assess the exact kidney temperature and the effect of surface cooling of the kidney during the time of vascular anastomosis. Twenty-two renal graft recipients were incorporated into our study. We used an electronic temperature measurer provided with a needle-shaped probe pierced into the body of the kidney. The temperature was recorded every 5 min. The mean temperature of the kidney at the beginning of anastomosis (T0) was 8.87 +/- 3.97 degrees C and 17.95 +/- 5.1 degrees C at the end (Tend). The striking finding of this study was that the mean Tend delayed kidney function-negative in [ATN(-)] recipients was significantly lower than in the ATN(+) group; respectively, 14.86 +/- 3.6 degrees C and 19.71 +/- 5.07 degrees C. Therefore, we have divided all recipients according to Tend (< 15 degrees C and > 15 degrees C) in an attempt to assess the direct influence of kidney temperature on early graft function. In nine cases, a temperature below 15 degrees C was recorded and in 13 cases it exceeded 15 degrees C at the end of anastomosis. The mean cold ischemia time and anastomosis time were not different in these recipients. Delayed graft function occurred in 14 recipients; in 3 of 9 (33.3%) recipients from group Tend < 15 degrees C; and in 11 of 13 (85%) from group Tend > 15 degrees C. One case of primary non-function was observed (Tend > 15 degrees C). This study documents the value of effective cooling of the kidney during the time of vascular anastomosis. Since in most clinical reports the significance of the second warm ischemia was assessed only by the duration of the anastomosis, without measurement of the actual organ temperature, this may explain the different findings in our studies.
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PMID:Effective surface cooling of the kidney during vascular anastomosis decreases the risk of delayed kidney function after transplantation. 895 98

Previous experimental and human data suggests a detrimental effect on the course of acute renal failure related to exposure of blood to artificial dialysis membranes of poor biocompatibility. We performed a 2.5-year prospective randomized trial to compare the clinical course of acute renal failure (post-operative ischemic acute tubular necrosis, ATN) in patients receiving a cadaveric renal transplant requiring supportive hemodialysis in the immediate post-transplant setting. Patients were randomized to either a cuprophane or polymethylmethacrylate (PMMA) conventional hollow fiber dialyzer. All patients received a standard immunosuppressive regimen which included induction therapy with either horse anti-thymocyte gamma globulin (ATGAM) or the murine anti-CD3 monoclonal antibody (OKT3). Of 53 patients randomized, 17 were excluded (2 for intervening biopsy-proven rejection prior to recovery from ATN, 10 for primary graft nonfunction and 5 for other reasons), leaving 36 evaluable cases of uncomplicated ATN, 18 in each group. There was no difference by age, race, gender, cause of ESRD, immunosuppressive regimen, cold or warm ischemia time, use of pre-transplant dialysis, percent oliguria or the incidence of intra-dialytic hypotension between the 2 groups. There was no difference in the mean time to recovery from ATN posttransplant (8.9 days in the cuprophane group vs 9.5 days in the PMMA group, p = NS) or in the average number of hemodialysis treatments required (3.6 in both groups, p = NS). There was also no difference in long term allograft outcome in terms of the nadir serum creatinine, the number of episodes of subsequent acute rejection or in the development of chronic rejection. An intent-to-treat analysis of all 53 originally randomized patients similarly yielded no significant differences. A subsequent, non-randomized study using a membrane of intermediate biocompatibility (Hemophan) also showed no difference in recovery time from ATN. Bioincompatible membranes do not seem to have a significant clinical impact on the course of recovery of this form of acute renal failure. The striking benefits of biocompatibility in the course of ARF seen in other human trials may relate more to the non-renal systemic toxic effects of bioincompatibility.
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PMID:Biocompatible dialysis membranes and acute renal failure: a study in post-operative acute tubular necrosis in cadaveric renal transplant recipients. 898 57

Heme oxygenase-1 (HO-1) overexpression using gene transfer protects rat livers against ischemia/reperfusion (I/R) injury. This study evaluates the effects of Ad-HO-1 gene transfer in a rat renal isograft model. Donor LEW kidneys were perfused with Ad-HO-1, Ad-beta-gal, or PBS, stored at 4 degrees C for 24 h, and transplanted orthotopically into LEW recipients, followed by contralateral native nephrectomy. Serum creatinine, urine protein/creatinine ratios, severity of histologic changes, HO-1 mRNA/protein expression, and HO enzymatic activity were analyzed. Ad-HO-1 gene transfer conferred a survival advantage when compared with PBS- and Ad-beta-gal-treated controls, with median survival of 100, 7, and 7 d, respectively (P < 0.01). Serum creatinine levels were elevated at day 7 in all groups (range, 2.2 to 5.8 mg/dl) but recovered to 1.0 mg/dl by day 14 (P < 0.01) in Ad-HO-1 group, which was sustained thereafter. Urine protein/creatinine ratio at day 7 was elevated in both PBS and Ad-beta-gal, as compared with the Ad-HO-1 group (12.0 and 9.8 versus 5.0; P < 0.005); histologically, ATN and glomerulosclerosis was more severe in Ad-beta-gal group at all time points. Reverse transcriptase-PCR-based HO-1 gene expression was significantly increased before reperfusion (P < 0.001) and remained increased in the Ad-HO-1-treated group for 3 d after transplantation. Concomitantly, HO enzymatic activity was increased at transplantation and at 3 d posttransplant in the Ad-HO-1 group, compared with Ad-beta-gal controls (P < 0.05); tubular HO-1 expression was discernible early posttransplant in the Ad-HO-1 group alone. These findings are consistent with protective effects of HO-1 overexpression using a gene transfer approach against severe renal I/R injury, with reduced mortality and attenuation of tissue injury.
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PMID:Gene transfer-induced local heme oxygenase-1 overexpression protects rat kidney transplants from ischemia/reperfusion injury. 1259 12

In this study a method of elimination of the second warm ischemia is shown. The method is based on the application of a specially constructed polyethylene bag, in which the transplanted kidney is placed in the time course from a removal from ice to the reconstruction of vessel flow. The bag is built of polyethylene foil HDPE of low density produced under high pressure. Own construction of the bag (three spaces and polyethylene) enables the storage of a transplanted organ at the stable temperature +4 Celsius degrees. Thanks to the separation of containers for melting ice and for the kidney, possible becomes unrestrained performance of both venous and arterial anastomosis independently of existing operative conditions. Due to the applied method of the elimination of the second warm ischemia with the usage of own construction of polyethylene bag HDPE, one can expect better early renal function after transplantation--decrease in the number of cases and shortening of the time of acute tubular necrosis (ATN--Acute Tubular Necrosis).
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PMID:The modification of renal transplantation with the usage of own polyethylene receptacle. 1469 23

Fifty-one simultaneous pancreas-kidney transplants (SPKT) were performed between 1988 and 2004 in patients of mean age 34 years and 23 years duration of diabetes treatment. All kidney and pancreas recipients were on maintenance hemodialysis therapy prior to SPKT. The pancreas with duodenal segment and the kidneys were harvested from cadaveric heart-beating donors. Cold ischemia time in UW solution varied from 4 to 14 hours (mean, 9 hours 35 minutes). Twenty patients had the duodenal segment sutured to the urinary bladder, and the remaining 31 grafts were drained to an isolated ileal loop. Quadruple immunosuppression was administered as well as an anticoagulant and antibiotic prophylaxis. Forty-nine patients (49/51, 96%) regained insulin independence in the immediate postoperative period; 44 (86%) displayed immediate graft function. The remaining patients experienced postoperative ATN, the longest duration was 18 days. Of 51 patients, 38 (14.5%) are alive (follow-up, 6 to 180 months), 26 (68.5%) have good pancreatic function, and 34 (89%), good kidney function. Nineteen (50%) patients regard their quality of life as improved compared to their pretransplant status, which is mainly attributed to being dialysis and insulin free. Of 19 patients, 14 (74%) reported measuring glycemia regularly due to fear of losing the pancreas graft. Of 19 persons, seven (37%) returned to work after transplantation. Four (8.3%) lost their kidney graft secondary to vascular complications (n = 2) or rejection (n = 2). Four pancreas grafts with bladder drainage required conversion to enteric drainage owing to persistent urinary infections or urinary fistulae. Fifteen (29%) patients lost their pancreatic grafts within 1 year of transplantation due to the following: vascular complications (n = 12), septic complications (n = 1), or rejection (n = 2). Thirteen patients died within 1 year after transplantation, 5 of septic complications, 5 of neuroinfection, 1 of pulmonary embolism, and 2 of myocardial infarction. In conclusion, SPKT is a successful treatment for diabetic nephropathy, burdened by the possibility of serious complications.
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PMID:Surgical complications of simultaneous pancreas-kidney transplantation: a 16-year-experience at one center. 1629 59


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