Comparative Analysis of Left Ventricular Geometry in Adult Nigerians with and without Chronic Kidney Disease: Results from Ibadan CRECKID STUDY.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular morbidity and mortality. Left ventricular hypertrophy (LVH) is considered the strongest independent predictor of cardiovascular disease and events among CKD patients. We reported the echocardiographic left ventricular geometry in CKD patients compared to non-CKD hypertensive and apparently healthy controls in Ibadan. MATERIALS AND METHODS: A total of 683 participants in the CRECKID STUDY comprising 220(32.2%) CKD patients, 281(41.1%) non-CKD hypertensive patients and 182(26.6%) healthy controls were included in this analysis. Basic demographic and clinical information with echocardiographic parameters were obtained. RESULTS: Study participants in the non-CKD hypertensive group were on average older than the CKD and the healthy controls (56.2±13.1 vs 47.2±14.6, and 46.8±13.3 years, respectively; p<0.01). Compared with other groups, greater proportions of participants with CKD were men (40.5% vs.38.1% and 21.3%; p<0.0001). The left atrial and left ventricular dimensions were significantly higher in CKD compared with others. LVH was significantly more prevalent among CKD patients (68.2%) compared to hypertensive (43.9%) and normotensive (19.5%) group (p<0.01). The participants with CKD had a greater proportion of abnormal LV geometry with concentric LVH predominating (p<0.0001). Having LVH was associated with lower mean estimated glomerular filtration rate (eGFR) (40.6±37.71 vs 67±37.38, p<0.0001). CONCLUSION: In our study, patients with CKD had the highest prevalence of abnormal LV geometry and functions. A unit decrease in eGFR was associated with increased left ventricular mass. Early detection and prompt management of abnormal LV geometry may help in reducing adverse cardiovascular outcome in patients with CKD.

CONTEXTE: L'insuffisance rénale chronique (MRC) est associée àrisque accru de morbidité et de mortalité cardiovasculaires. Gauche l'hypertrophie ventriculaire (LVH) est considérée comme la plus forte prédicteur indépendant des maladies cardiovasculaires et des événements chez Patients atteints d'IRC. Nous avons rapporté l'échocardiographie ventriculaire gauche géométrie chez les patients atteints d'IRC par rapport aux patients hypertendus non atteints d'IRC etcontrôles apparemment sains à Ibadan. MATÉRIAUX ET MÉTHODES: Un total de 683 participants à la ÉTUDE CRECKID portant sur 220 (32.2%) patients atteints d'IRC,281 (41.1 %) patients hypertendus non atteints d'IRC et 182 (26.6 %) en bonne santé ont été inclus dans cette analyse. Démographie et clinique de base des informations avec des paramètres échocardiographiques ont été obtenues. RÉSULTATS: Participants à l'étude dans le groupe hypertendu non atteint d'IRC étaient en moyenne plus âgés que l'IRC et les témoins sains(56.2±13.1 vs 47.2±14.6 et 46.8±13.3 ans, respectivement; p<0.01). Par rapport à d'autres groupes, plus grande proportion de participants avec l'IRC étaient des hommes (40.5 % contre 38.1 % et 21.3 %; p<0.0001). Les dimensions auriculaire gauche et ventriculaire gauche étaient significativement plus élevées chez CKD par rapport à d'autres. La LVH était significativement plus répanduechez les patients atteints d'IRC (68.2 %) par rapport aux patients hypertendus (43.9 %) et le groupe normotensif (19.5 %) (p<0.01). Les participants avec CKD avait une plus grande proportion de géométrie LV anormale avec LVH concentrique prédominante (p<0.0001). Avoir LVH était associé à un débit de filtration glomérulaire estimé moyen plus faible (DFGe)(40.6±37.71 contre 67±37.38, p<0,0001). CONCLUSION: Dans notre étude, les patients atteints d'IRC avaient le plus haut prévalence d'une géométrie et de fonctions LV anormales. Une diminution unitaire de Le DFG était associé à une augmentation de la masse ventriculaire gauche. Tôt la détection et la gestion rapide de la géométrie LV anormale peuvent aider à réduire les résultats cardiovasculaires indésirables chez les patients atteints de CKD. Mots-clés: Maladie rénale chronique, Hypertensives, ventriculaire gauche géométrie.

Impact of cytomegalovirus disease in D+/R- kidney transplant patients receiving 6 months low-dose valganciclovir prophylaxis.

Late-onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R-) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6-month low-dose valganciclovir (VGCV) prophylaxis, risk factors for late-onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R- kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow-up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively. The use of an induction agent with rabbit antithymocyte globulin and older donor age were factors associated with the risk of late-onset CMV disease (AHR 2.91, 95% CI 1.18-7.20, p = 0.021 and AHR 1.03, 95% CI 1.01-1.06, p = 0.016, respectively). Late-onset CMV disease was associated with increased risk for death-uncensored graft loss (AHR 2.95, 95% CI 1.15-7.61, p = 0.025). In conclusion, late-onset CMV disease continues to negatively impact kidney transplant outcome despite 6-month low-dose VGCV prophylaxis. Investigations focusing on novel preventive approaches should be emphasized.

Impact of MELD-based allocation on end-stage renal disease after liver transplantation.

The proportion of patients undergoing liver transplantation (LT), with concomitant renal dysfunction, markedly increased after allocation by the model for end-stage liver disease (MELD) score was introduced. We examined the incidence of subsequent post-LT end-stage renal disease (ESRD) before and after the policy was implemented. Data on all adult deceased donor LT recipients between April 27, 1995 and December 31, 2008 (n = 59 242), from the Scientific Registry of Transplant Recipients, were linked with Centers for Medicare & Medicaid Services' ESRD data. Cox regression was used to (i) compare pre-MELD and MELD eras with respect to post-LT ESRD incidence, (ii) determine the risk factors for post-LT ESRD and (iii) quantify the association between ESRD incidence and mortality. Crude rates of post-LT ESRD were 12.8 and 14.5 per 1000 patient-years in the pre-MELD and MELD eras, respectively. Covariate-adjusted post-LT ESRD risk was higher in the MELD era (hazard ratio [HR]= 1.15; p = 0.0049). African American race, hepatitis C, pre-LT diabetes, higher creatinine, lower albumin, lower bilirubin and sodium >141 mmol/L at LT were also significant predictors of post-LT ESRD. Post-LT ESRD was associated with higher post-LT mortality (HR = 3.32; p < 0.0001). The risk of post-LT ESRD, a strong predictor of post-LT mortality, is 15% higher in the MELD era. This study identified potentially modifiable risk factors of post-LT ESRD. Early intervention and modification of these risk factors may reduce the burden of post-LT ESRD.

Influence of recipient race on the outcome of simultaneous pancreas and kidney transplantation.

Racial differences on the outcome of simultaneous pancreas and kidney (SPK) transplantation have not been well studied. We compared mortality and graft survival of African Americans (AA) recipients to other racial/ethnic groups (non-AA) using the national data. We studied a total of 6585 adult SPK transplants performed in the United States between January 1, 2000 and December 31, 2007. We performed multivariate logistic regression analyses to determine risk factors associated with early graft failure and immune-mediated late graft loss. We used conditional Kaplan-Meier survival and multivariate Cox regression analyses to estimate late death-censored kidney and pancreas graft failure and death between the groups. Although there was no racial disparity in the first 90 days, AA patients had 38% and 47% higher risk for late death-censored kidney and pancreas graft failure, respectively (p = 0.006 and 0.001). AA patients were twice more likely to lose the kidney and pancreas graft due to rejection (OR 2.31 and 1.86, p = 0.002 and 0.008, respectively). Bladder pancreas drainage was associated with inferior patient survival (HR 1.42, 95% CI 1.15, 1.75, p = 0.001). In the era of modern immunosuppression, AA SPK transplant patients continue to have inferior graft outcome. Additional studies to explore the mechanisms of such racial disparity are warranted.

Organ donation and utilization in the United States, 1999-2008.

Despite the Organ Donation Breakthrough Collaborative's work to engage the transplant community and the suggested positive impact from these efforts, availability of transplanted organs over the past 5 years has declined. Living kidney, liver and lung donations declined from 2004 to 2008. Living liver donors in 2008 dropped to less than 50% of the peak (524) in 2001. There were more living donors that were older and who were unrelated to the recipient. Percentages of living donors from racial minorities remained unchanged over the past 5 years, but percentages of Hispanic/Latino and Asian donors increased, and African American donors decreased. The OPTN/UNOS Living Donor Transplant Committee restructured to enfranchise organ donors and recipients, and to seek their perspectives on living donor transplantation. In 2008, for the first time in OPTN history, deceased donor organs decreased compared to the prior year. Except for lung donors, deceased organ donation fell from 2007 to 2008. Donation after cardiac death (DCD) has accounted for a nearly 10-fold increase in kidney donors from 1999 to 2008. Use of livers from DCD donors declined in 2008 to 2005 levels. Understanding health risks associated with the transplantation of organs from 'high-risk' donors has received increased scrutiny.

Database comparison of the adult-to-adult living donor liver transplantation cohort study (A2ALL) and the SRTR U.S. Transplant Registry.

Data submitted by transplant programs to the Organ Procurement and Transplantation Network (OPTN) are used by the Scientific Registry of Transplant Recipients (SRTR) for policy development, performance evaluation and research. This study compared OPTN/SRTR data with data extracted from medical records by research coordinators from the nine-center A2ALL study. A2ALL data were collected independently of OPTN data submission (48 data elements among 785 liver transplant candidates/recipients; 12 data elements among 386 donors). At least 90% agreement occurred between OPTN/SRTR and A2ALL for 11/29 baseline recipient elements, 4/19 recipient transplant or follow-up elements and 6/12 donor elements. For the remaining recipient and donor elements, >10% of values were missing in OPTN/SRTR but present in A2ALL, confirming that missing data were largely avoidable. Other than variables required for allocation, the percentage missing varied widely by center. These findings support an expanded focus on data quality control by OPTN/SRTR for a broader variable set than those used for allocation. Center-specific monitoring of missing values could substantially improve the data.

Choice of induction regimens on the risk of cytomegalovirus infection in donor-positive and recipient-negative kidney transplant recipients.

BACKGROUND: Late occurrence of cytomegalovirus (CMV) infection remains a concern in CMV-seronegative kidney and/or pancreas transplant recipients of CMV-seropositive organs (donor positive/recipient negative, D+/R-) despite the use of prophylaxis. We investigated the impact of various antibody induction regimens on CMV infection in this group of patients. METHODS: A total of 254 consecutive D+/R- kidney and/or pancreas transplant patients were studied. The induction agents rabbit anti-thymocyte globulin (rATG) or basiliximab were used according to the center practice. All patients received prophylaxis with valganciclovir (VGCV) for either 3 or 6 months. The occurrence of CMV infection was confirmed by positive DNA viremia. Multivariate Cox regression analyses were performed to determine risk factors for CMV infection. RESULTS: The cumulative incidence of CMV infection was 58, 112, and 59 cases per 1000 patient-years for patients who received no antibody induction, induction with rATG, or basiliximab induction, respectively (P=0.02). The use of rATG but not basiliximab was associated with an increased risk for CMV infection (adjusted hazard ratio [AHR] 2.13, 95% confidence interval [CI] 1.24-3.54, P=0.006). Acute rejection and its treatment with rATG were not associated with an increased risk for CMV infection when an additional course of VGCV was given following the treatment. Longer duration of prophylaxis was associated with a reduced risk for CMV infection (AHR 0.54, 95% CI 0.33-0.87, P=0.011). CONCLUSIONS: Induction with rATG is associated with increased risk of CMV infection. Longer duration of prophylaxis is beneficial.

Reimbursing live organ donors for incurred non-medical expenses: a global perspective on policies and programs.

Methods to reimburse living organ donors for the non-medical expenses they incur have been implemented in some jurisdictions and are being considered in others. A global understanding of existing legislation and programs would help decision makers implement and optimize policies and programs. We searched for and collected data from countries that practice living organ donation. We examined legislation and programs that facilitate reimbursement, focusing on policy mechanisms, eligibility criteria, program duration and types of expenses reimbursed. Of 40 countries, reimbursement is expressly legal in 16, unclear in 18, unspecified in 6 and expressly prohibited in 1. Donor reimbursement programs exist in 21 countries; 6 have been enacted in the last 5 years. Lost income is reimbursed in 17 countries, while travel, accommodation, meal and childcare costs are reimbursed in 12 to 19 countries. Ten countries have comprehensive programs, where all major cost categories are reimbursed to some extent. Out-of-country donors are reimbursed in 10 jurisdictions. Reimbursement is conditional on donor income in 7 countries, and recipient income in 2 countries. Many nations have programs that help living donors with their financial costs. These programs differ in operation and scope. Donors in other regions of the world are without support.

Graft and patient survival in kidney transplant recipients selected for de novo steroid-free maintenance immunosuppression.

Steroid-free regimen is increasingly employed in kidney transplant recipients across transplant centers. However, concern remains because of the unknown impact of such an approach on long-term graft and patient survival. We studied the outcomes of steroid-free immunosuppression in a population-based U.S. cohort of kidney transplant recipients. All adult solitary kidney transplant recipients engrafted between January 1, 2000 and December 31, 2006 were stratified according to whether they were selected for a steroid-free or steroid-containing regimen at discharge. Multivariate Cox regression models were used to estimate graft and patient survival. The impact of the practice pattern on steroid use at individual transplant centers was analyzed. Among 95 755 kidney transplant recipients, 17.2% were steroid-free at discharge (n = 16 491). Selection for a steroid-free regimen was associated with reduced risks for graft failure and death at 1 year (HR 0.78, 95% CI 0.72-0.85, and HR 0.73, 95% CI 0.65-0.82, respectively, p < 0.0001) and 4 years (HR 0.83, 95% CI 0.78-0.87, and HR 0.76, 95% CI 0.71-0.83, respectively, p < 0.0001). This association was mostly observed at individual centers where less than 65% of recipients were discharged on the steroid-containing regimen. De novo steroid-free immunosuppression as currently practiced in the United States appears to carry no increased risk of adverse clinical outcomes in the intermediate term.

New ecosystems in the deep subsurface follow the flow of water driven by geological activity.

Eukarya have been discovered in the deep subsurface at several locations in South Africa, but how organisms reach the subsurface remains unknown. We studied river-subsurface fissure water systems and identified Eukarya from a river that are genetically identical for 18S rDNA. To further confirm that these are identical species one metazoan species recovered from the overlying river interbred successfully with specimen recovered from an underlying mine at -1.4 km. In situ seismic simulation experiments were carried out and show seismic activity to be a major force increasing the hydraulic conductivity in faults allowing organisms to create ecosystems in the deep subsurface. As seismic activity is a non-selective force we recovered specimen of algae and Insecta that defy any obvious other explanation at a depth of -3.4 km. Our results show there is a steady flow of surface organisms to the deep subsurface where some survive and adapt and others perish. As seismic activity is also present on other planets and moons in our solar system the mechanism elucidated here may be relevant for future search and selection of landing sites in planetary exploration.

Comparative risk of impaired glucose metabolism associated with cyclosporine versus tacrolimus in the late posttransplant period.

New onset diabetes after transplantation (NODAT) and impaired fasting glucose (IFG) are common in kidney transplant recipients (KTRs). Calcinuerin inhibitor (CNI) therapy is a causal risk factor. NODAT is associated with increased mortality and diminished graft survival. We studied the incidence of NODAT and IFG in KTRs before and after a medically indicated switch of CNI therapy from cyclosporine (CsA) to tacrolimus (Tac). The study population consisted of 704 nondiabetic KTRs. Of them, 171 underwent conversion from CsA to Tac (group I) and 533 remained on the CsA since transplantation (Group II). Time-dependent Cox regression and generalized estimating equations were used to account for sequential CNI exposure. NODAT and IFG occurred in 15.2% and 22.1% of group I subjects and 15.6% and 25.8% of group II subjects, respectively (p = 0.90 for NODAT and p = 0.38 for IFG). Accounting for equal follow-up time since conversion from CsA to Tac, the adjusted 5-year NODAT-free survival was 87.4% and 91.4% in group I and group II, respectively (p = 0.90). In conclusion, conversion to Tac, compared to continuous exposure to CsA, carries quantitatively similar risk of impaired glucose metabolism in KTRs in the late posttransplant period.

Soil Fertility, Phosphorus Fractions, and Maize Yield as Affected by Poultry Manure and Single Superphosphate.

A field experiment was conducted in 2007 and 2008 on a slightly acidic alfisol. Poultry manure (PM) was applied at 0, 5 t ha(-1), 10 t ha(-1), 15 t ha(-1), and 20 t ha(-1) in combination with SSP at 0, 15 kg P ha(-1), 30 kg P ha(-1), 45 kg P ha(-1), and 60 kg P ha(-1), which was replicated three times. The pH and organic C were significantly increased by the application of PM alone while available P was highly increased by the sole application of SSP. Plant tissue P was significantly increased with the application of 30 kg P ha(-1) while the largest grain yield was obtained when PM at 20 t ha(-1) was combined with SSP at 60 kg P ha(-1). The buildup of organic P was observed when PM was applied at 15 t ha(-1) while the combination of the two treatments increased residual P and Fe-P. However, P occlusion was effectively reduced with the sole application of PM. Organic P and residual P however had a strong positive relationship with the grain yield. Comparing the sole and combined application of the treatments, the combined application was more effective for most of the parameters observed.

Eukaryotic opportunists dominate the deep-subsurface biosphere in South Africa.

Following the discovery of the first Eukarya in the deep subsurface, intense interest has developed to understand the diversity of eukaryotes living in these extreme environments. We identified that Platyhelminthes, Rotifera, Annelida and Arthropoda are thriving at 1.4 km depths in palaeometeoric fissure water up to 12,300 yr old in South African mines. Protozoa and Fungi have also been identified; however, they are present in low numbers. Characterization of the different species reveals that many are opportunistic organisms with an origin due to recharge from surface waters rather than soil leaching. This is the first known study to demonstrate the in situ distribution of biofilms on fissure rock faces using video documentation. Calculations suggest that food, not dissolved oxygen is the limiting factor for eukaryal population growth. The discovery of a group of Eukarya underground has important implications for the search for life on other planets in our solar system.

Excess risk of renal allograft loss associated with cigarette smoking.

BACKGROUND: Cigarette smoking contributes to a number of health-related problems, but its impact on renal transplant survival beyond accelerated patient death is unclear. METHODS: We performed a cohort study of 645 adult renal allograft recipients from 1985 to 1995 to evaluate the relationship between smoking and graft outcome. RESULTS: Twenty-four percent of recipients (156/645) were smokers at the time of transplant evaluation. Of these, 90% continued to smoke after transplantation. Pretransplant smoking was significantly associated with reduced overall graft and death-censored graft survival. Patients who were smokers at the time of pretransplant evaluation had kidney graft survival of 84%, 65%, and 48% at 1, 5, and 10 years, respectively, compared with graft survival in nonsmokers of 88%, 78%, and 62% (P=0.007). Pretransplant smoking adversely affected death-censored graft survival in recipients of cadaveric (P=0.02) and of living donor kidneys (P=0.02). Reduced graft survival in pretransplant smokers could not be accounted for by differences in rejection (64% vs. 61%, P=0.35). In a multivariate analysis, pretransplant smoking was associated with a relative risk of 2.3 for graft loss. Among patients with a smoking history before transplantation, death-censored graft survival was significantly higher for those who quit smoking before transplant evaluation. CONCLUSIONS: Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival. These effects should be emphasized to patients with end-stage renal disease who are considering renal transplantation.

Posttransplant bone disease: a case illustrating dramatic improvements in bone density with vitamin D replacement therapy.

Although bisphosponates are proposed as first-line treatment for posttransplant bone disease they are not optimal in all situations. A kidney transplant recipient developed hypercalcemia from mobilization of extraskeletal calcium. He had low serum parathyroid hormone and vitamin D; high calcium excretion; and normal calcium intake. Bone biopsy revealed severe osteomalacia. Bisphosphonates, used in the early treatment of acute hypercalcemia, were not indicated to treat osteomalacia. However, over several months serum calcium declined sufficiently to allow treatment of the bone disease with oral calcitriol. Dual-energy radiographic absorptiometry over the next 2 years documented dramatic improvements in bone density (percent of young-normal controls) : from 63 to 85%, at the lumbar spine; from 38 to 67%, at the femoral neck. This response to treatment could not have been achieved with an antiresorptive strategy. Optimal management of posttransplant bone disease requires a diagnostic approach, which considers all plausible contributing factors.

Hepatitis C antibody status and outcomes in renal transplant recipients.

BACKGROUND: Hepatitis occurs frequently in patients with end-stage renal disease. In 1997, 0.7% of patients receiving a renal transplant were positive for hepatitis C antibodies. Concern has been raised as to whether these patients are at an increased mortality risk after renal transplantation compared with patients who are hepatitis C antibody negative. To help answer this question, we analyzed data from the United States Renal Data System from October of 1988 through June of 1998. METHODS: Primary study endpoints were patient death and death censored graft loss. Secondary study endpoints included cardiovascular, infectious, malignant, and infection-related death. Kaplan-Meier survival estimates as well as Cox proportional hazard models were used to evaluate the impact of hepatitis C antibody status on the study endpoints. RESULTS: A total of 73,707 patients were analyzed. Patient survival by Kaplan-Meier analysis was higher in hepatitis C-positive patients, whereas death censored graft survival trended lower in the very long term. By the Cox model, hepatitis C-positive adjusted patient survival is slightly superior to that of hepatitis C-negative patients. CONCLUSIONS: Renal transplant recipients who are hepatitis C antibody positive do not have an increased risk of death after transplantation compared with hepatitis C-negative recipients. The current policy of transplanting hepatitis C-positive patients without active liver disease seems to incur no excess mortality risk.

Delayed graft function: risk factors and implications for renal allograft survival.

Delayed graft function (DGF) may be associated with diminished kidney allograft survival. We studied the risk factors that lead to nonimmediate function of a renal allograft and the consequences of DGF on short- and long-term renal transplant survival. Data from the U.S. Renal Data System were used to measure the relationships among cold ischemia time, delayed graft function, acute rejection, and graft survival in 37,216 primary cadaveric renal transplants (1985-1992). These relationships were investigated using the unconditional logistic and Cox multivariate regression methods. Cold ischemia time was strongly associated with DGF, with a 23% increase in the risk of DGF for every 6 hr of cold ischemia (P<0.001). Acute transplant rejection occurred more frequently in grafts with delayed function (37% vs. 20%; odds ratio=2.25, P=0.001). DGF was independently predictive of 5-year graft loss (relative risk=1.53, P<0.001). The presence of both early acute rejection and DGF portended a dismal 5-year graft survival rate of 35%. Zero-HLA mismatch conferred a 10-15% improvement in 1- and 5-year graft survival regardless of early functional status of the allograft. However, the 5-year graft survival rate in HLA-mismatched kidneys without DGF was significantly higher than that of zero-mismatched kidneys with DGF (63% vs. 51%; P<0.001). DGF independently portends a significant reduction in short- and long-term graft survival. Delayed function and early rejection episodes exerted an additive adverse effect on allograft survival. The deleterious impact of delayed function is comparatively more severe than that of poor HLA matching.

Interaction of mycophenolate mofetil and HLA matching on renal allograft survival.

INTRODUCTION: The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an analysis of the United States Renal Transplant Data Registry (USRDS). METHODS: All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. RESULTS: A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P<0.001). For both AZA and MMF three-year graft survival improved with fewer HLA donor-recipient mismatches. Comparing zero antigen mismatches to six antigen mismatches, the relative improvement was comparable for both patients on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard model the relative risk for graft loss decreased significantly in both the AZA and MMF treated patients with increased HLA matching. CONCLUSION: The use of MMF does not obviate the benefits of HLA matching, while HLA matching does not minimize the benefits of MMF on long term graft survival. Our study would suggest that HLA matching and MMF therapy are additive factors in decreasing the risk for renal allograft loss.

Gender differences in the risk for chronic renal allograft failure.

BACKGROUND: Despite the known differences in immunological reactivity between males and females, no differences in graft survival have been described among renal transplant recipients with regard to gender. To address this paradox, we analyzed data from 73,477 primary renal transplants collected in the US Renal Data System database. METHODS: Logistic regression and Cox proportional hazard models were used to investigate the primary study end points, graft loss secondary to acute rejection (AR) or chronic allograft failure (CAF). CAF was defined as graft loss beyond 6 months, not attributable to death, recurrent disease, acute rejection, thrombosis, infection, noncompliance, or technical problems. The models adjusted for 15 covariates including immunosuppressive regimen, and donor and recipient characteristics. RESULTS: The overall 8-year graft and patient survivals were significantly better in female renal transplant recipients compared with male recipients. However graft survival censored for death was not significantly different by gender. By multivariate analysis, females had a 10% increased odds of AR (OR=1.10, CI 1.02-1.12), but conversely a 10% lower risk of graft loss secondary to CAF (RR=0.9, CI 0.85-0.96). The risk for CAF increased significantly with increasing age for both males and females, but this effect was greater for males than for females (P<0.001). CONCLUSION: Although female renal transplant recipients have a similar death censored graft survival compared with males, there are important differences in immunological behavior. Females have a higher risk of AR while having a decreased risk of graft loss secondary to CAF.