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Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: the cytokine effect on transplantation.

BACKGROUND: Our group has previously described five different size alleles of an interferon (IFN)-gamma microsatellite. Analyzing this polymorphism, this study correlated high IFN-gamma production with a 12 CA repeat allele (allele 2). Further, our group has described interleukin (IL)-10 polymorphism defining in vitro high and low IL-10 producer status. METHODS: Samples from 88 of 115 consecutive cadaveric renal transplants were used to define polymorphism of both IFN-gamma and IL-10. Patients were separated into high and low genotypes based on the previously reported association between certain genotypes and in vitro production. Graft survival, acute rejection, and serum creatinine at 5 years were analyzed for comparison between groups. RESULTS: The genotype associated with high IFN-gamma production was found in 70 patients. The incidence of acute rejection was 54.3% in the high IFN-gamma genotype group, compared with 44.4% in the low IFN-gamma group. Requirement for antithymocyte globulin therapy was greater in the high IFN-gamma group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-gamma genotype was more strongly associated with rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high IFN-gamma genotype had a 61% incidence of rejection compared with only 20% in the low IFN-gamma genotype patients (OR=3.06). Graft survival was similar between the two groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-gamma genotype patients had serum creatinine levels above 200 micromol/L compared with only 14.3% of the low IFN-gamma genotype recipients at 5 years after transplantation (P=0.05). The high IL-10 genotype was shown to be associated with better graft function at 5 years (75 vs. 50%, P=0.09). CONCLUSION: In this study we have shown that high producer genotype for IFN-gamma may have an influence on acute rejection of kidney transplants, particularly in patients on cyclosporine monotherapy. It is also associated with worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.

Acute Disease↗

Cold ischemia time: an independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft.

BACKGROUND: Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). METHODS: We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. RESULTS: By multivariate analysis, a CIT of 15 hr or more (vs. < 15 hr) independently increased the risk of the AHG Class I PRA level being > or = 20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT < 15 hr group (25.9%+/-33.9; n=24) compared with the CIT > or = 15 hr group (46.3%+/-36.5; n=66) (P<0.001). CONCLUSION: Longer CIT induces a humorally more immunogenic kidney.

Adult↗

Cohort study of the prognostic significance of acute transplant glomerulitis in acutely rejecting renal allografts.

BACKGROUND: Acute transplant glomerulitis is a unique lesion in renal allografts, the prognostic significance of which is controversial. We conducted this retrospective cohort study to examine the independent prognostic significance of moderate-to-severe transplant glomerulitis in acute rejection. METHODS: Renal allograft survival for patients with acute rejection were studied, comparing one group with significant glomerulitis (G, n=28) with those with no glomerulitis (NG, n=35). Clinical, biopsy, and demographic data and renal graft survival were compared, and the association of G with graft failure was examined. RESULTS: In the G versus NG group, a greater percentage of patients were highly sensitized (peak panel reactive antibody value >80%; P=0.009), had had a previous renal transplant (40% vs. 11%; P=0.02), or had suffered from delayed graft function (P=0.03). The G group had a trend toward earlier rejection episodes (P=0.07), a significantly higher serum creatinine at the time of index biopsy (P=0.01), a higher prevalence of vascular rejection (P=0.02), and less improvement in mean reciprocal serum creatinine at 1-2 weeks after biopsy (P=0.02). Although there was a trend toward shorter allograft survival in the G group (P=0.09), the level of significance of which increased with adjustment for transplantation time period and the duration of the transplant-biopsy interval (P=0.06), the relative risk for graft loss was no longer significant when additionally adjusted for index biopsy Banff score (relative risk, 0.97; P=0.97). CONCLUSION: In this study, G was significantly more common in highly sensitized patients and was strongly associated with vascular rejection biopsies but was not an independent predictor of graft survival.

Acute Disease↗

Tumor necrosis factor beta gene polymorphisms associated with urinary tract infections after renal transplantation.

INTRODUCTION: We investigated whether tumor necrosis factor (TNF) beta(low) or TNFbeta(high) alleles predicted susceptibility to infection or rejection after renal transplantation. METHODS: TNFbeta alleles were determined in 137 (ESRD) patients and correlated with urinary tract infections and rejection within 60 days among 75 consecutive renal transplant recipients. RESULTS: TNFbeta low was more prevalent among African-Americans than caucasians (83 vs. 63%, P=0.02). After renal transplantation, patients with TNFbeta low experienced more urinary tract infections (50 vs. 10%, P=0.002). The incidence of TNFbeta low and urinary tract infections were equivalent in patients treated with mycophenolate mofetil/cyclosporine (CsAA) (n=37) versus mycophenolate mofetil/tacrolimus (n=38). TNFbeta low was not associated with the incidence of delayed graft function (5 vs. 2, P=NS), early rejection (21 vs. 18%, P=NS) or actuarial 1-year graft survival (96 vs. 90%, P=NS). CONCLUSIONS: TNFbeta low was associated with urinary tract infections and TNFbeta high was associated with freedom from urinary tract infections. Neither gene correlated with rejection or l-year graft survival.

Adult↗

Prospective trial of a predictive algorithm to transplant cadaver kidneys into highly sensitized patients.

BACKGROUND: The difficulty of transplanting sensitized patients increases proportionally to the panel reactive antibody (PRA) titer. Because of the high likelihood of a positive final crossmatch, these patients are often excluded from a prospective transplant unless there is a 0 HLA-A, -B, -DR mismatch. To address this problem, we developed a computerized algorithm, termed the Kentucky Antibody Testing System (KATS), that predicts class I HLA antigens that would be both "unacceptable" and "acceptable" to the recipient. This report describes the results of a prospective trial among voluntarily participating centers that agreed to share kidneys based on the KATS predictions for patients whose PRA exceeded 40%. METHODS: The results of three antibody screens on each patient were compared with the HLA phenotypes of the cells in the panel in 2x2 tables with calculation of chi-square and correlation coefficient statistics. Private, broad, and public antigens were identified and a list of acceptable and unacceptable antigens were entered into the UNOS computer for each patient listed in the KATS sharing algorithm. RESULTS: Of the total 418 patients meeting the inclusion/exclusion criteria, the largest single group submitted was Black-not-of-Hispanic-origin females. The mean PRA of the patients was 72%. The first transplant via KATS allocation was performed on March 8, 1997. Between that time and the last transplant on July 31, 2000, 145 kidneys were offered to the participating centers and 48 transplants were performed. Of the many reasons listed for not accepting an offer or not transplanting the shared kidney into its intended recipient, only two occurred because of a positive T cell crossmatch and six because of a positive B cell crossmatch. As compared to all other high PRA patients within Southeastern Organ Procurement Foundation who were transplanted during the study period, they were more likely to be non-Caucasian, to be less well matched for private HLA-A, B, and DR antigens, and to have waited for a longer time than the other groups. Although there was a higher incidence of delayed graft function, there was no significant difference in cold ischemia, rejection episodes, or patient or graft survival. CONCLUSIONS: We conclude that KATS, or some other system to prospectively identify a list of acceptable and unacceptable HLA antigens, could improve the access of highly sensitized patients to a successful kidney transplant.

Adult↗

Kidney transplantation in the elderly: age-matching as compared to HLA-matching: a single center experience.

BACKGROUND: We report the short-term outcome of our patients participating within the Eurotransplant age-matching program, where kidneys from donors >65 years are transplanted to recipients >65 years regardless of human leukocyte antigen (HLA) compatibility but with short cold ischemia times, in comparison with patients >60 years transplanted with HLA-matching. METHODS: Twenty-five patients (66.7+/-2.6 years) (donors 69+/-4.3 years) participated in this program (group A). The control group consisted of 21 patients (63+/-2.6 years) (group B) (donors 47.6+/-17.3 years). RESULTS: Despite significant differences in donor age, cold ischemia time (12.3+/-4.6 hr in A, 22.8+/-4.8 hr in B, P<0.001) and a mean of 4.4+/-1.4 vs. 2.3+/-1.6 HLA-mismatches (P<0.001), there was no difference regarding the incidence of delayed graft function (64 vs. 57%), rejections (52 vs. 66.7%), infections (56 vs. 52.4%), and other complications (80 vs. 71.4%). Mean serum creatinine after 6 months was 1.94+/-0.49 and 1.83+/-0.67 mg/dl (NS). CONCLUSION: The short-term results of the age-matching program are promising and comparable with results from patients of similar age with HLA-matching.

Age Factors↗

The effect of obesity on renal transplant outcomes.

BACKGROUND: Although obesity has been associated with improved survival on dialysis, its effects on renal transplant outcomes remain unclear. Previous studies have reported conflicting findings and have been limited by the use of outdated patient data, univariate analyses, and liberal transplant selection criteria. The present study aimed to evaluate the effect of obesity on renal transplant outcomes in a rigorously screened population. METHODS: A retrospective analysis was undertaken of all patients transplanted at the Princess Alexandra Hospital from 1 April 1994 to 31 March 2000. Patients were rigorously screened for cardiovascular disease before acceptance for transplantation. The effects of obesity on renal transplant outcomes were assessed by logistic and multivariate Cox regressions. RESULTS: Of the 493 patients transplanted, 59 (12%) were obese (body mass index [BMI] 30 kg/m ). Obese patients were more likely to experience superficial wound breakdown (14% vs. 4%, P<0.01) and complete wound dehiscence (3% vs. 0%, P<0.01). Wound infections also tended to be more frequent in obese recipients (15% vs. 8%, P=0.11). There were no significant differences between the two groups with respect to operative duration, postoperative complications, hospitalization, delayed graft function, or acute rejection episodes. Five-year actuarial survival rates were comparable between the two groups with respect to graft survival (83% vs. 84%, P=NS) and patient survival (91% vs. 91%, P=NS). On multivariate analysis, BMI was an independent risk factor for wound breakdown (odds ratio 1.21, 95% CI 1.09-1.34, P<0.001), but not for other posttransplant complications, hospitalization, graft loss, or patient survival. CONCLUSIONS: The only significant adverse effect of obesity on renal transplant outcomes was an increase in wound complications, which were generally of minor consequence. Provided that adequate care is taken to avoid transplanting patients with significant cardiovascular disease, obese recipients can achieve excellent long-term patient and graft survivals that are on par with their nonobese counterparts. Denying patients access to renal transplantation on the basis of obesity per se does not appear to be justified.

Adult↗

Cytomegalovirus seromismatching increases the risk of acute renal allograft rejection.

BACKGROUND: There is an association between cytomegalovirus (CMV) infection or disease and acute allograft rejection in the setting of renal transplantation. There is, however, debate regarding the nature of this association, with evidence supporting both a "forward" relationship (CMV infection or disease precedes acute rejection) and a "backward" relationship (CMV infection or disease follows acute rejection). The objective of this study was to determine whether CMV matching had an independent effect on the risk of acute renal allograft rejection, which would support the view that CMV infection or disease is a risk factor for acute rejection. METHODS: Retrospective single center study (using a prospectively maintained database) of 333 first cadaveric transplant recipients from January 1st 1991 to December 31st 1997. Primary end-point was incidence of acute rejection, diagnosed clinically or by renal biopsy, for different groups formed on the basis of CMV seromatching. RESULTS: One hundred and ninety-four patients (58.3%) had at least one acute rejection episode. CMV seromismatched patients (donor +/recipient-) had a significantly higher rate of acute rejection than non-seromismatched patients (72.6% vs. 54.2%, P=0.005). Using multiple logistic regression, CMV seromismatch, delayed graft function, and biological induction were identified as independent predictors of acute rejection. The adjusted odds ratios for these were 2.28, 1.65, and 0.52, respectively. CONCLUSIONS: Patients who are CMV seromismatched are at higher risk of acute renal allograft rejection. This finding suggests that CMV infection or disease is a risk factor for acute rejection.

Acute Disease↗

Modulation of peripheral-type benzodiazepine receptor levels in a reperfusion injury pig kidney-graft model.

BACKGROUND: Ischemia-reperfusion injury is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria play a central role in this process. METHODS: Using an autotransplantation pig kidney model, both early (40 min and 7 days) and late (2-16 weeks) changes in renal function and morphology were determined after different periods of cold ischemia in University of Wisconsin or Euro-Collins solutions. We have also investigated the expression of the peripheral-type benzodiazepine receptor (PBR), which is also critical in maintaining outer mitochondrial membrane stability. RESULTS: Function of the kidneys was better preserved after 1 hr and 24 hr than after 48 hr and 72 hr in Euro-Collins and University of Wisconsin solutions. Medulla injury was reduced in 1 hr-preserved and 24 hr-preserved groups. PBR was found to be present in epithelial cells of the deep cortical and outer medulla in both normal human and well-preserved pig kidneys. PBR expression was modulated by ischemia-reperfusion injury and the concurrent tubular injury and repair processes. CONCLUSION: This study indicates that PBR expression correlates with the quality of kidney preservation and might serve as an index of kidney and mitochondria viability. Moreover, these data suggest that PBR might be involved in membrane biogenesis during reperfusion. In addition, considering the identical localization of PBR in human and pig kidneys, these findings could have a direct application in human clinical settings of kidney pathology.

Animals↗

Renal transplantations performed using non-heart-beating organ donors: going back to the future?

BACKGROUND: As more expanded-criteria organ donors are used to bridge the widening gap between organ supply and demand, non-heart-beating (NHB) donors will become increasingly important. The purpose of this study was to analyze renal transplant outcomes using this source of cadaveric (CAD) organs and compare the results with heart-beating organ sources. METHODS: Data from 98,698 adult CAD renal transplant recipients and 34,531 living donor renal transplant recipients registered in the U. S. Renal Data System database between January 1993 and June 2000 were analyzed. Kaplan-Meier survival curves were used to compare graft and patient survival rates between NHB, CAD, and living donor transplant recipients. Cox proportional hazards models were used to identify risk factors for NHB donor recipients, while adjusting for potential confounding variables. RESULTS: Recipients of NHB donor organs experienced nearly twice the incidence of delayed graft function (DGF) compared with heart-beating donors (42.4% vs. 23.3%, respectively). NHB donor transplants experienced comparable allograft survival when compared with CAD transplants at 6 years (73.2% vs. 72.5%, respectively; P=NS); patient survival was greater at 6 years for NHB compared with CAD renal transplant recipients (80.9% vs. 77.8%, respectively; P=NS). Significant factors for allograft loss for NHB donor organ recipients included the following: organ used for repeat transplants; DGF; donor age older than 35 years; and head trauma as a cause of initial injury (relative risk 2.74, 1.90, 1.78, and 1.41, respectively). CONCLUSIONS: Although exhibiting elevated DGF rates, allograft and patient survival rates of transplants from NHB donor sources are equivalent to those from conventional CAD sources. Donor age, recipient transplant number, female recipient, mechanism of injury, and DGF were the most pertinent variables leading to poor outcomes.

Adult↗

Improved freedom from rejection after a loading dose of sirolimus.

BACKGROUND: Sirolimus (SIR) in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients. Limited data are available regarding SIR in combination with tacrolimus (TAC). METHODS: A single-center, retrospective review of renal transplant recipients receiving SIR, TAC, and corticosteroids postoperatively was conducted. A total of 118 consecutive renal transplant recipients were included on the basis of availability of day 1 SIR dose information. Seventy-seven patients received an SIR loading dose (SIR-LD) immediately posttransplantation, and 41 patients did not (SIR no loading dose [SIR-NLD]). RESULTS: The two groups showed similar demographic and transplant characteristics. SIR doses and trough levels were significantly higher in the SIR-LD patients at 1 and 7 days posttransplantation; however, no differences occurred beyond day 7. Patients receiving an SIR-LD experienced significantly better freedom from rejection at 1, 3, and 6 months posttransplantation (P<0.05). This rejection benefit in the SIR-LD group was independent of donor source and use of antibody induction. SIR-LD patients experienced fewer serious infections (12% SIR-LD vs. 27% SIR-NLD, P=0.04) and a lower incidence of delayed graft function (21% SIR-LD vs. 39% SIR-NLD, P<0.05). No significant differences in serum creatinine, hemoglobin, and platelet counts occurred in the first 180 days posttransplantation, but the patients in the SIR-NLD group experienced lower hemoglobin levels at day 30 than those in the SIR-LD group (10.8 g/dL SIR-LD vs. 9.7 g/dL SIR-NLD, P=0.03). CONCLUSION: SIR-LD significantly improves early posttransplantation freedom from rejection in renal transplant recipients without increasing other complications.

Adult↗

Death in the first year after kidney transplantation: implications for patients on the transplant waiting list.

BACKGROUND: As the kidney transplant waiting list continues to expand, maintaining the medical fitness of transplant candidates will become increasingly difficult. METHODS: To identify patients who are at greatest risk during the wait-list period, we performed a Cox regression analysis to determine risk factors for mortality in the first posttransplantation year among 23,546 adult first kidney transplant recipients recorded in the United States Renal Data System between January 1995 and September 1997. RESULTS: In this study population, 4.6% of the patients died in the first posttransplantation year, and cardiac causes were the leading cause (27%) of death. Patients with diabetes (hazard ratio [HR]=1.58; 95% confidence interval [CI], 1.39-1.80), peripheral vascular disease (HR=1.41; 95% CI, 1.11-1.80), or angina (HR=1.38; 95% CI, 1.15-1.65), and patients with a longer duration of end-stage renal disease (HR=1.06 per year; 95% CI, 1.04-1.09) had a higher risk for mortality. Additionally, patients with early acute rejection (HR=1.47; 95% CI, 1.23-1.76), delayed graft function (HR=1.46; 95% CI, 1.25-1.71), and a lower glomerular filtration rate after transplantation were also at increased risk for death within the first posttransplantation year. CONCLUSIONS: Patients with comorbid disease, patients with a long duration of end-stage renal disease, and potential recipients of organs at high risk for graft dysfunction should be carefully screened for medical complications before transplantation to achieve the most favorable outcomes. Alternate organ allocation strategies that facilitate patient assessment close to the time of transplantation or that prioritize high-risk patients may also improve outcomes.

Adult↗

Long-term outcomes of renal transplantation: a result of the original endowment of the donor kidney and the inflammatory response to both alloantigens and injury.

Recent data suggest that long-term allograft survival might be affected by two factors. The first is the endowment of the allograft, which consists of two elements: the nephron mass and the ability of these nephrons to repair injuries sustained during the transplant process. The second factor is renal inflammation. Although inflammation is traditionally ascribed to alloreactivity, recent data have shown that there is also a renal inflammatory response to early injury after transplantation, to brain death in the donor, and as part of the maladaptive response to nephron loss. These two factors contribute to the detrimental effects of delayed graft function or acute rejection on the long-term survival seen in most studies, and the beneficial effects of anti-inflammatory agents on the maladaptive response to nephron loss.

Animals↗

Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States.

The current organ shortage has led to the utilization of double kidney transplants from marginal adult donors, but outcomes data are limited. The United Network for Organ Sharing registry database was used to compare the outcomes of 403 dual adult kidney transplantations (DKT) and 11,033 single kidney transplantations (SKT) from 1997 to 2000. Graft and patient survival and the effect of multiple risk factors were evaluated. It was found that DKT patients were older, less sensitized, and received grafts from older, more mismatched donors with longer cold ischemia times. There was also a greater percentage of donors with a history of diabetes or hypertension and African-American recipients and donors in the DKT group. Graft survival was inferior in the DKT group, with a 7% lower graft survival rate at 1 yr. There was a higher incidence of primary nonfunction in the DKT group, although the incidence of delayed graft function, early rejection treatment, and graft thrombosis did not differ. Multivariate analysis was used to identify African-American recipient ethnicity and retransplant as risk factors for graft loss. Graft survival was comparable in DKT and SKT with donors over 55 yr of age. DKT resulted in inferior graft outcomes compared with SKT. When compared with SKT with donors over 55 yr of age, DKT resulted in similar graft outcomes. These otherwise discarded kidneys should be cautiously considered as a source of marginal donors.

Adult↗

Ischemia-reperfusion induces glomerular and tubular activation of proinflammatory and antiapoptotic pathways: differential modulation by rapamycin.

Ischemia-reperfusion (I-R) injury in transplanted kidney, a key pathogenic event of delayed graft function (DGF), is characterized by tubular cell apoptosis and interstitial inflammation. Akt-mammalian target of rapamycin-S6k and NF-kappaB-inducing kinase (NIK)-NF-kappaB axis are the two main signaling pathways regulating cell survival and inflammation. Rapamycin, an immunosuppressive drug inhibiting the Akt axis, is associated with a prolonged DGF. The aim of this study was to evaluate Akt and NF-kappaB axis activation in patients who had DGF and received or not rapamycin and in a pig model of I-R and the role of coagulation priming in this setting. In graft biopsies from patients who were not receiving rapamycin, phosphorylated Akt increased in proximal tubular, interstitial, and mesangial cells with a clear nuclear translocation. The same pattern of activation was observed for S6k and NIK. However, in rapamycin-treated patients, a significant reduction of S6k but not Akt and NIK activation was observed. A time-dependent activation of phosphatidylinositol 3-kinase, Akt, S6k, and NIK was observed in the experimental model with the same pattern reported for transplant recipients who did not receive rapamycin. Extensive interstitial and glomerular fibrin deposition was observed both in pig kidneys upon reperfusion and in DGF human biopsies. It is interesting that the activation of both Akt and NIK-NF-kappaB pathways was induced by thrombin in cultured proximal tubular cells. In conclusion, the data suggest that (1) coagulation may play a pathogenic role in I-R injury; (2) the Akt axis is activated after I-R, and its inhibition may explain the prolonged DGF observed in rapamycin-treated patients; and (3) NIK activation in I-R and DGF represents a proinflammatory, rapamycin-insensitive signal, potentially leading to progressive graft injury.

Adult↗

Hepatitis C, acute humoral rejection, and renal allograft survival.

The effect of recipient hepatitis C virus (HCV) infection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Compared with HCV Ab-negative patients, those with positive HCV Ab had longer time on dialysis before transplantation, higher percentage of panel-reactive antibodies (PRA), were more likely to receive a cadaveric transplant, and were more likely to develop delayed graft function (DGF). In univariate analyses, predictors of renal allograft loss included HCV, cadaveric graft, PRA >20%, HLA mismatch > or =5, retransplantation, DGF, induction therapy, and AHR. When adjusted for PRA >20%, HLA mismatch > or =5, and multiple transplant status, HCV was not a statistically significant predictor of allograft loss. HCV was also associated with AHR but lost significance when adjusted for PRA >20%. HCV Ab-positive patients were more likely to have longer duration of dialysis before transplantation prior to kidney transplants, higher PRA, and to receive cadaveric transplants. These characteristics likely resulted in more DGF and AHR after transplantation. After adjusting for these confounding factors, the association between HCV Ab positivity and renal allograft loss was notably attenuated and no longer statistically significant.

Adult↗

Clinical outcomes of renal transplantation using liquid chromatographic monitoring of tacrolimus.

It is suggested that specific methods of Tacrolimus monitoring rather than immunoassays which over-estimate Tacrolimus levels, should be used in transplant recipients. There is limited data, however, comparing clinical outcomes of renal transplantation using each of these techniques. In this study, 40 renal transplant recipients with Tacrolimus monitoring by Microparticle Enzyme Immunoassay (MEIA; target trough level 10-15 ng/ml) were compared with 40 patients monitored by High Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS; target trough level 8-13 ng/ml). All received anti CD25 antibody induction and Mycophenolate Mofetil in a steroid sparing protocol. No demographic differences were seen between MEIA and HPLC-MS groups. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying Tacrolimus levels within target range at three and six months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in 4 patients in the MEIA group and 1 patient in the HPLC-MS group (P = 0.17). Biopsy proven acute Tacrolimus nephrotoxicity occurred in 6 patients in the MEIA group, and 7 in the HPLC-MS group (P = NS). No difference was seen in serum creatinine or estimated creatinine clearance at 3 or 6 months. No difference between groups was seen in systolic or diastolic blood pressure, or total cholesterol at 3 or 6 months. 2 patients in the MEIA group developed CMV disease and 1 developed posttransplantation diabetes mellitus. CMV and posttransplantation diabetes were not seen in the HPLC-MS group. 2 patients in each group developed reversible tremor. This study suggests that renal transplantation with HPLC-MS monitoring of Tacrolimus is safe and effective.

Adult↗

Laparoscopic donor nephrectomy: the University of Maryland 6-year experience.

PURPOSE: We determined whether the results of laparoscopic donor nephrectomy warranted expansion of the availability of the technique. MATERIALS AND METHODS: Donor and recipient charts for 738 consecutive laparoscopic living donor nephrectomies have been reviewed. RESULTS: Renal donors were 69% white race and 57% female. Age range was 18 to 74 years. Neither age nor obesity alone were exclusionary criteria. Nephrectomy was left sided in 96%. Donors with body mass index greater than 33 had longer operative times. The extraction site changed from umbilical to suprapubic during the series. Warm ischemia time was 169 seconds. Conversion to open nephrectomy occurred in 1.6% of cases and blood transfusion was required in 1.2%. Major intraoperative complications occurred in 6.8% and major postoperative complications occurred in 17.1% of cases. Hospitalization lasted 64.4 hours. Postoperative donor creatinine was 1.5 times the preoperative level. Recipient serum creatinine averaged 2.0 mg% at 1 week and 1.6 mg% at 1 year. Delayed graft function occurred in 2.6%. However, 9.1% of recipients did not achieve a serum creatinine less than 3.0 mg% within 7 days. The endovascular stapler also created 37 extra arteries for implantation. CONCLUSIONS: Risks of laparoscopic donor nephrectomy to the donor must not be minimized. Rapid conversion to open surgery to control bleeding may be necessary. Nonvascular intraoperative injuries require recognition. Slow bowel function recovery prolongs hospitalization and may indicate unrecognized pancreatitis or small bowel herniation. Surgical technique and complication management have improved. Laparoscopic donor nephrectomy is now routine but still requires an intense level of attention to prevention of complications.

Adolescent↗