Renal Graft Survival Research Articles

Renal graft survival is not influenced by a positive flow B‐cell crossmatch

The influence of a positive B-cell crossmatch on graft outcome in renal transplantation is controversial. We analyzed graft survival using Kaplan-Meier estimates for recipients of deceased donor kidneys who were either regraft transplant patients (n = 198) from 1990 to August 20, 2004, or primary transplant patients (n = 361) from December 15, 2000 to August 8, 2004, each of whom had a flow T- and B-cell IgG crossmatch performed before transplantation. The flow B-cell crossmatch (FBXM) was not used to decide whether or not to transplant. Graft survival was analyzed by whether the patient's FBXM was positive or negative. We also evaluated creatinine levels and graft survival of 131 transplant patients (June 1, 2004 to July 1, 2005) by their FBXM result and by their HLA class II flow-defined IgG PRA. One- and three-yr graft survival for the primary transplant patient group with a positive FBXM (98% and 84%) was not significantly different from the group with a negative FBXM (96% and 93%) (log-rank = 0.9). Similarly, graft survival at one, five, and 10 yr for the regraft transplant group whose FBXM was positive (91%, 76%, and 61%) was not significantly different from the group whose FBXM was negative (91%, 79%, and 77%) (log-rank = 0.4). Creatinine levels in the group of patients whose FBXM was positive (1.4 +/- 0.4 mg/dL; n = 76) were not significantly different from the group with a negative FBXM (1.4 +/- 0.4 mg/dL; n = 42). Even in the presence of class II PRA, a positive FBXM did not impact a patient's creatinine levels or graft outcome. Neither short nor long-term graft survival of deceased donor kidneys is influenced by a positive flow B-cell IgG crossmatch, even when caused by HLA class II antibody.

Effective Immunoprophylaxis With Basiliximab Plus Triple Therapy in Renal Transplantation: Five-Year Single-Center Experience

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of ≥1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 ± 0.9 (mean ± SD), and the cold ischemia time was 22.0 ± 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 ± 46 μmol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 ± 26 μmol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.

Comparison of Renal Allograft Outcomes in Combined Liver-Kidney Transplantation Versus Subsequent Kidney Transplantation in Liver Transplant Recipients: Analysis of UNOS Database

There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. Renal half-life of KALT allografts was shorter than CLKT group (6.6+/-0.9 vs. 11.7+/-1.3 years, P < 0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P < 0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P < 0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P < 0.001). Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.

Mycophenolate Mofetil Tolerability and Dose Changes in Tacrolimus-Treated Renal Allograft Recipients

Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss ( n = 7), death with a functioning graft ( n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea ( n = 33, 28.7% of all patients), leukopenia ( n = 22, 19.1%), both of these ( n = 7, 6.1%), or other events ( n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 ± 2.42 vs 7.37 ± 2.23 ng/mL; P = .051 and 1.75 ± 0.71 vs 1.48 ± 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.

Outcome of Pregnancy in Renal Allograft Recipients: SIUT Experience

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months’ postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8–86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

The Natural Course of Cytomegalovirus Infection and Disease in Renal Transplant Recipients

A series of prospective studies of a large cohort population of renal transplant recipients who did not receive cytomegalovirus (CMV) prophylaxis or preemptive therapy examined the effects of CMV infection and disease on renal allograft rejection, long-term recipient and graft survival, and new-onset diabetes mellitus. CMV infection and disease were found to be independent risk factors for allograft rejection and new-onset diabetes mellitus within 100 days posttransplantation, and for recipient mortality and uncensored graft loss beyond 100 days posttransplantation. Additional studies are needed to determine whether CMV prophylaxis or preemptive therapy may be of benefit in preventing these complications.

Improving Utilization of Deceased Donor Kidneys by Matching Recipient and Graft Survival

Younger renal transplant recipients often outlive their allografts, whereas older recipients often die before their allograft fails. Thus, our aim was to assess the utility of matching recipient and graft survival to improve allocation of deceased donor kidneys. We reviewed the records of 49,206 patients (United Network for Organ Sharing, 1995-2002). Donor grafts were stratified by Deceased Donor Score (DDS). We observed a disparity between recipient survival and renal graft survival which contributed to an annual gap between supply and demand of renal transplants. Utilization of DDS and distribution of marginal kidneys to older recipients would improve allocation.

Long-Term Renal Allograft Function on a Tacrolimus-Based, Pred-Free Maintenance Immunosuppression Comparing Sirolimus vs. MMF

It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF.

GalT knockout pig to baboon xenotransplantation

The success and widespread acceptance of clinical allotransplantation has led to a shortage of cadaveric organs and a resurgence of interest in xenotransplantation. Although swine are generally regarded as the preferred source of xenogeneic organs, the severe immunologic response to swine organs has so far precluded their clinical use. However, we have recently obtained pigs not expressing the alpha 1,3-galactosyltransferase gene (GalT-KO swine). We have reported initial results using GalT-KO swine as donors to baboons which demonstrated survival of a life-supporting renal graft for up to 83 days without rejection when combined with a regimen designed to induce tolerance by vascularized donor thymic grafts. Although further improvements will be needed to warrant a clinical trial of xenotransplantation, the initial results are encouraging. In addition to genetic modification of donor pigs, it is hoped that our tolerance-inducing regimen will allow successful clinical xenotransplantation by overcoming additional xenogeneic immunological barriers.

Prolongation of Renal Allograft Survival in Rats by Replication-Defective Recombinant Adenovirus-Mediated Coexpression of CD40L and CTLA4Ig

Background Blockade of costimulatory signals has been shown to prolong allograft survival. The aim of the present study was to investigate the effect of simultaneous blockade of CD40/CD40L and CD28/B7 costimulatory pathways by replication-defective adenovirus-mediated expression of secretable extracellular domain of human CD40L (shCD40L) and CTLA4Ig to prolong rats renal allograft survival. Methods We constructed Adv-shCD40L-IRES 2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding human CD40L and CTLA4Ig. Coexpression of shCD40L and CTLA4Ig was evaluated by confocal laser scanning microscopy. The function of these two molecules was examined in human mixed lymphocyte reactions (MLRs) in vitro and in experimental BN-to-LEWIS rat renal transplantation in vivo. Results Successful construction of Adv-shCD40L-IRES 2-CTLA4Ig was confirmed by polymerase chain reaction. Coexpression of shCD40L and CTLA4Ig on human kidney cell line HK-2 cells after transfection was detected by direct immunofluorescence staining. Human MLR was inhibited to 52.2% ± 0.6% and 42.1% ± 0.2% of the vehicle control by Adv-shCD40L and Adv-CTLA4Ig, respectively. Adv-shCD40L-IRES 2-CTLA4Ig resulted in further inhibition of MLR to 22.0% ± 0.2% of vehicle control. Transfection with Adv-shCD40L or Adv-CTLA4Ig alone prolonged renal graft survival to 24.8 ± 2.5 days and 27.3 ± 3.6 days, respectively, as compared to vehicle-treated controls (7.8 ± 0.3 days). Cotransfection of both genes extended graft survival to 41.8 ± 3.7 days. Conclusions Adv-shCD40L-IRES 2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding human CD40L and CTLA4Ig, achieved simultaneous blockade of CD40/CD40L and CD28/B7 costimulatory pathways, Adv-shCD40L-IRES 2-CTLA4 by Ig synergistically inhibited human T-cell proliferation in MLR, and prolonged rats renal allograft survival.

Steroid-free immunosuppression after renal transplantation—long-term experience from a single centre

A steroid-free immunosuppressive protocol may improve the general well-being of patients, but long-term renal graft survival has been a concern. In a retrospective clinical study, 329 consecutive transplantations with renal grafts at our centre during the period 1995-2004, were followed for up to 9.3 years. Patients mainly received steroid-free immunosuppression with an initial induction with antithymocyte globulin or basiliximab and maintenance therapy with ciclosporin and mycophenolate mofetil (MMF). Steroids were given after rejection, or if the physician judged it necessary, for instance because of primary kidney disease or when calcineurin inhibitor toxicity was suspected. About 71% of the patients did not take steroids at all. Nevertheless, graft survival rates at 1, 5 and 7 years were 95, 77 and 72% for all grafts, including 27% living donor transplants and 27% second or subsequent grafts. Ten patients (3.2%) died with functioning grafts. Within the first year of transplantation there were 69 acute rejections in 63 patients (19%). Four cases (1.3%) of post-transplant lymphoproliferative disorder (PTLD) occurred with one graft loss and no deaths. Owing to a high PTLD rate in a previous patient cohort, total immunosuppression was lessened after 1998. Steroid avoidance is possible with good results with respect to acute rejection and long-term graft survival. After introducing MMF, largely avoiding muromonab-CD3 mouse raised monoclonal antibody against CD (OKT3), and reducing doses of calcineurin inhibitor, the rates of PTLD did not differ from what is usually found. For the present, induction and use of MMF, together with a calcineurin inhibitor, is probably to be preferred.

Early measurement of interstitial fibrosis predicts long-term renal function and graft survival in renal transplantation.

This study investigated the relationships between renal allograft interstitial fibrosis, renal function and graft survival. A total of 107 consecutive renal transplant recipients immunosuppressed with cyclosporin were studied. Needle core transplant biopsies were performed before operation and at 1, 6 and 12 months after transplantation. Allograft fibrosis was assessed by histomorphometric analysis of graft interstitial volume fraction. Renal function was measured by isotopic glomerular filtration rate (GFR) measurement at the same time points. Interstitial volume fraction was already high in preperfusion biopsies, significantly increased with time but stabilized at 6 months after transplantation. GFR correlated negatively with interstitial volume fraction at 6 months (P = 0.05). Interstitial volume fraction at 1 month was not a useful predictor of subsequent graft survival but for allografts surviving to 6 months an interstitial volume fraction above 25 per cent predicted significantly poorer survival (P = 0.04). It provides an objective measure of chronic allograft damage and may prove to be a useful surrogate endpoint in the study of therapeutic intervention.

Calcineurin-Inhibitor–Sparing Immunosuppressive Protocols

Calcineurin inhibitors (CNI) have played an important role in improving graft survival. However, the balance between preventing immunologic allograft losses and the management of CNI-related nephrotoxicity is still an issue in renal transplantation. There are three major CNI-sparing strategies. CNI Minimization The advent of mycophenolate mofetil (MMF) allows cyclosporine (CsA) reduction to ameliorate renal function in patients with chronic renal allograft dysfunction, without increasing acute rejection rates. In combination with mTOR inhibitors, very low CNI levels may be sufficient to prevent acute rejection. However, in this association, CNI nephrotoxicity is magnified by pharmacokinetic interaction. CNI Withdrawal CNI withdrawal has been attempted in regimens containing MMF or sirolimus (SRL). Introduction of MMF in patients with chronic allograft nephropathy (CAN) followed by CNI withdrawal resulted in stabilization or improvement of renal function and hypertension profile, although there is some risk of acute rejection. In regimes based on SRL, CNI withdrawal is a safety strategy, achieving a sustained improvement of renal function, histology, and graft survival. There is not consensus at all whether MMF should be added or not in patients converted from CNI to mTOR inhibitor. CNI Avoidance Polyclonal-based regimens with MMF and steroids have shown acceptable acute rejection rates, but high rates of cytomegalovirus (CMV) and opportunistic infections. Conversely, anti–IL-2R in combination with MMF and steroids resulted in 50% incidence of acute rejection, thus suggesting that CNI avoidance is not feasible in a regimen based on MMF. Alternatively, a protocol based on anti–IL-2R induction therapy combined with SRL, MMF, and prednisone has shown an efficient prevention of acute rejection, higher creatinine clearance and lower rate of CAN in comparison with a group treated with CNI. New strategies using costimulation blockade may help in the development of safe CNI-free regimens. In summary, in renal transplantation the new immunosuppressive medications have made feasible old aspirations such as minimization, withdrawal, or even avoidance of CNI.

Effect of Chronic Viral Hepatitis on Graft Survival in Saudi Renal Transplant Patients

Background: In Saudi Arabia the prevalence of hepatitis C among hemodialysis patients is very high ranging from 60 to 80%. A large number of these dialysis patients go for renal transplant, resulting into a higher prevalence of hepatitis C virus (HCV) infection in renal transplant patients. Yet no current systematic report is available on the influence of hepatitis C status on patient and graft survival. The present study was therefore undertaken to address this objective. Methods: Retrospective analysis of data of 448 renal transplantation subjects was undertaken. The mean follow-up period was 5.85 ± 2.7 (median 5.3) years. The factors associated with renal graft survival were reviewed and these include: age, sex, and type of donor, immunosuppressive medication, episodes of infection, blood pressure, serum creatinine, and status of hepatitis. The primary end-points were renal graft function and patient survival. Logistic regression, COX regression analysis, and Kaplan-Meier survival estimates were used to evaluate the influence of hepatitis C on the above parameters. Results: Among 448 recipients of first kidney transplant patients, 286 (63.8%) were positive for HCV infection. In the HCV-positive group, 204 (71.32%) were males. Kaplan-Meier survival analysis showed a significantly better graft survival for HCV-negative patients than HCV-positive patients (p < 0.001; log-rank test). Logistic regression analysis and COX regression analysis have shown different grades of graft dysfunction were present in HCV-positive patients after adjustment for covariates: age, sex, blood pressure, type of donor, and immunosuppressive medication; the presence of HCV was a major predictor of bad outcome and significantly influenced graft survival (odds ratio = 4.37; 95% Cl = 1.81–4.77). Significant deterioration of liver function was noted in HCV-positive patients at the last follow-up, taking ALT as a marker (ALT level 80.6 ± 5.8 U/l at the last follow-up versus 49.5 ± 32 U/l at baseline p ≤ 0.0001). Sixteen patients had a chronic active course and 1 patient developed biopsy-proven liver cirrhosis and portal hypertension. A serious and significantly greater incidence of fatal chest infections was seen in HCV-positive patients. Although mortality was greater in HCV-positive versus HCV-negative patients (20 vs. 7), the difference did not attain statistical significance (p = 0.23) and none of the patients died as a result of hepatic failure. Conclusion: The presence of HCV infection greatly influenced graft survival in renal transplant patients and a higher proportion of infected patients had renal and hepatic dysfunction. A significant increase in fatal chest infections was noted in HCV-positive patients. Overall mortality was higher in HCV-positive patients, but it was not statistically significant. All measures should be taken to prevent HCV transmission in the dialysis population. Renal transplant recipients with HCV infection need close monitoring for both graft and liver function.

Race/Ethnicity, Poverty Status, and Renal Transplant Outcomes

There are known racial disparities in renal graft survival. Data are lacking comparing associations of race/ethnicity and socioeconomic status with graft failure and functional status after transplantation. Our goal was to test if African-American and Hispanic race/ethnicity and poverty are associated with worse outcomes following renal transplantation. We performed a retrospective cohort study using a nationwide registry (United Network for Organ Sharing). We studied 4,471 adults who received renal transplants in 1990. Outcomes were graft failure and functional status over 10 years. Cumulative incidence of graft failure was higher among African-Americans and Hispanics than whites (77% vs. 64% vs. 60 %; P<0.001) and among transplant recipients living in the poorest areas (70% vs. 58% in the richest; P<0.001). African-American and Hispanic race/ethnicity were independently predictive of graft failure (RR 1.8, 95% CI 1.6-1.9; RR 1.3, 95% CI 1.2-1.6, respectively) in multivariate analyses but poverty status was not (RR 1.0, 95% CI 0.9-1.1). Days with impaired functional status were higher for African-Americans compared to whites (RR 1.6, 95% CI 1.3-1.9) but not independent of poverty. Poverty was independently associated with impaired functional status (RR 1.3, 95% CI 1.0-1.6). African-Americans and Hispanics had higher rates of graft failure compared to whites after adjustment for poverty and other covariates whereas poverty, but not race/ethnicity, was related to functional status following renal transplantation. National datasets should include individual-level measures of socioeconomic status in order to improve evaluation of social and environmental causes of disparities in renal transplant outcomes.

The impact of donor spontaneous intracranial haemorrhage vs. other donors on long‐term renal graft and patient survival

Donor cause of death has a significant impact on transplant survival in heart transplants recipients. The objective of this study was to determine if long-term renal allograft and patient survival differed between grafts donated by donors who died of spontaneous intracranial haemorrhage (SIH) compared with those with other causes of death (OCOD). Between 1990 and 2001, 1526 renal transplants were performed (711 SIH donors and 815 OCOD donors) at our unit. Serum creatinine levels at 1 yr, graft half-life and annual graft failure rate were measured for both groups. Renal graft and patient survivals between the groups were compared. Relative risk for SIH donors and other confounding variables was measured using Cox proportional hazards models. Graft half-life results were obtained for SIH (8 yr) and OCOD (10.13 yr) recipients. Graft and patient survival at 5 and 10 yr was 68.5% and 39.3% respectively for the SIH group vs. 76.8% and 51.9% respectively for the OCOD group (p < 0.001). However, SIH graft recipients were significantly older with more females. After adjustment for differences in baseline variables between the groups, donor cause of death did not have an independent effect on long-term graft or patient survival. Spontaneous intracranial haemorrhage as a cause of donor death, failed to have a significant independent effect on long-term allograft and patient survival.

Angiotensin-Converting Enzyme and Endothelial Constitutive Nitric Oxide Synthase Polymorphisms in Turkish Renal Transplant Population and Possible Influence on Renal Artery Atherosclerosis and Graft Survival

Background Renal transplant recipients are prone to accelerated atherosclerosis secondary to immunsuppressants, which may decrease graft survival. We sought to analyze the effects on renal graft survival of atherosclerotic degeneration in the renal artery and the influence of angiotensin-converting enzyme (ACE) endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms. Methods and patients Thirty three renal transplant recipients (25 men) of mean age 28.4 ± 9.6 years, received organs from 11 living related donors and were followed for at least 36 months. Genotyping was performed for the insertion/deletion ACE (I/D), angiotensin (AGT) (M→T, 235), angiotensine 1 receptor (A→C, 1166), angiotensin 2-receptor (A→G, 1223), and ecNOS (b→a, intron4) gene polymorphisms. Renal artery biopsies were performed during transplantation surgery to analyze the presence of atherosclerosis. Results Pathological examination indicated that 18 donor specimens and nine recipient specimens had atherosclerotic degeneration. Survival analysis (36 months) indicated that graft survival rates of recipients who had atherosclerosis in the renal artery and who received an organ from donors with an atherosclerotic renal artery were shorter than in their counterparts ( P = .02, P = .04, respectively). Comparison of genetic variations of recipients revealed that CC/TC variation of AGT was higher in patients with atherosclerosis (81% vs 53%, P = .03). There was no significant difference between groups in means of other gene polymorphisms. Conclusion Renin-angiotensin system gene polymorphism analysis of patients in renal transplantation waiting list may provide information about allograft survival and posttransplant atherosclerotic degeneration at graft vasculature of young transplant recipients.

Chronologically different impacts of immunologic and non‐immunologic risk factors on renal allograft function

Upon analysis of the risk factors affecting renal graft survival and function, the time-dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1-haplotype-matched living-related donors. Until 5-yr post-transplantation (TX), yearly serum creatinine (Scr), 24-h urinary excretion of protein, and their yearly changes were compared by the episodes of acute rejection within 1 yr, the kidney weight to recipient body weight (KW/BW) ratio, the donor/recipient (D/R) age ratio, and the D/R gender pairing. The Kaplan-Meier method, Cox proportional hazard model, ANOVA, and repeated measures ANOVA were each applied for different purposes. Only the episodes of acute rejection were a significant risk factor affecting graft survival. The episodes of acute rejection, KW/BW ratio, D/R age ratio, and D/R gender pairing consistently and independently had significant influences on Scr. Recipients having the lowest KW/BW ratio (first quartile) or the highest D/R age ratio (fourth quartile) had rapid increments of Scr after 4-yr post-TX. After 3-yr post-TX, there were significant correlations between the number of non-immunologic risk factors present and the yearly changes in Scr. Non-immunologic factors had a detrimental effect on renal graft function, especially after 3-yr post-TX. If immunologic risks seem to be similar, size matching, age, and gender pairing should be considered for better long-term graft function in renal TX recipients.

Four‐year data after pediatric renal transplantation: A randomized trial of tacrolimus vs. cyclosporin microemulsion

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 yr) were randomly assigned (1:1) to receive either Tac (n = 103) or CyA (n = 93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection (intent-to-treat). Baseline characteristics were comparable between treatment groups. Excluding deceased patients (n = 9) and patients lost to follow-up (n = 31, mostly transferred to adult care), 95% of 2-yr data (159 of 167 possible patients), 87% of 3-yr data (142 of 163) and 73% of 4-yr data (114 of 156) were retrieved. At 1 yr Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA (59.1%, p = 0.003). The incidence of corticosteroid-resistant rejection was also significantly lower with Tac (7.8% vs. 25.8%, p = 0.001). At 4 yr, patient survival was similar (94% vs. 92%, p = 0.86) but graft survival significantly favored Tac (86% vs. 69%; p = 0.025, log-rank test), respectively. At 1 yr, the mean glomerular filtration rate (GFR) (Schwartz formula, ml/min/1.73 m(2)) was 64.9 +/- 20.7 (n = 84) vs. 57.8 +/- 21.9 (n = 77, p = 0.0355), at 2 yr 64.9 +/- 19.8 (n = 71) vs. 51.7 +/- 20.3 (n = 66, p = 0.0002), at 3 yr 66.7 +/- 26.4 (n = 81) vs. 53.0 +/- 23.3 (n = 55, p = 0.0022), and at 4 yr 71.5 +/- 22.9 (n = 51) vs. 53.0 +/- 21.6 (n = 44, p = 0.0001) for Tac vs. CyA, respectively. Cholesterol remained significantly higher with CyA throughout follow-up. Three patients in each arm developed post-transplant lymphoproliferative disease. Incidence of insulin-dependent diabetes mellitus was not different. Tac was significantly more effective than CyA in preventing acute rejection in pediatric renal recipients. Renal function and graft survival were also superior with Tac. Glomerular filtration rate appears to be an useful surrogate marker for long-term outcome.

Steroid Maintenance Therapy after Transplantation-Quo Vadis?: Long-Term Prospective Study of Steroid Withdrawal in Kidney and Heart Transplant Recipients. Am J Transplant 5: 720-728, 2005.

Steroid Maintenance Therapy after Transplantation-Quo Vadis?: Long-Term Prospective Study of Steroid Withdrawal in Kidney and Heart Transplant Recipients. Am J Transplant 5: 720-728, 2005.