Arsalan N. Habib

Role of Socioeconomic Status in Kidney Transplant Outcome

There is controversy regarding the influence of genetic versus environmental factors on kidney transplant outcome in minority groups. The goal of this project was to evaluate the role of certain socioeconomic factors in allograft and recipient survival. Graft and recipient survival data from the United States Renal Data System were analyzed using Cox modeling with primary variables of interest, including recipient education level, citizenship, and primary source of pay for medical service. College (hazard ratio [HR] 0.93, P < 0.005) and postcollege education (HR 0.85, P < 0.005) improved graft outcome in the whole group and in patients of white race. Similar trends were observed for recipient survival (HR 0.9, P < 0.005 for college; HR 0.88, P = 0.09 for postcollege education) in the whole population and in white patients. Resident aliens had a significantly better graft outcome in the entire patient population (HR 0.81, P < 0.001) and in white patients in subgroup analysis (HR 0.823, P < 0.001) compared with US citizens. A similar effect was observed for recipient survival. Using Medicare as a reference group, there is a statistically significant benefit to graft survival from having private insurance in the whole group (HR 0.87, P < 0.001) and in the black (HR 0.8, P < 0.001) and the white (HR 0.89, P < 0.001) subgroups; a similar effect of private insurance is observed on recipient survival in the entire group of patients and across racial groups. Recipients with higher education level, resident aliens, and patients with private insurance have an advantage in the graft and recipient outcomes independent of racial differences.

Effect of donors' intravenous drug use, cigarette smoking, and alcohol dependence on kidney transplant outcome.

Background. The shortage of organ donors for kidney transplants has made the expansion of the kidney donor pool a clinically significant issue. Previous studies suggest that kidneys from donors with a history of intravenous (IV) drug, cigarette, and/or alcohol use are considered to be a risky choice. However, these kidneys could potentially be used and expand the kidney supply pool if no evidence shows their association with adverse transplant outcomes. Methods. This study analyzed the United Network for Organ Sharing dataset from 1994 to 1999 using Kaplan-Meier survival analysis and Cox modeling. The effects on transplant outcome (graft and recipient survival) were examined with respect to the donors’ IV drug use, cigarette smoking, and alcohol dependency. Covariates including the recipient variables, the donor variables, and the transplant procedure variables were included in the Cox models. Results. The results show that the donors’ history of cigarette smoking is a statistically significant risk factor for both graft survival (hazard ratio = 1.05, P < 0.05) and recipient survival (1.06, P<0.05), whereas neither IV drug use nor alcohol dependency had significant adverse impact on graft or recipient survival. Conclusions. Assuming that adequate testing for potential infections is performed, there is no evidence to support avoiding the kidneys from donors with IV drug use or alcohol dependency in transplantation. Utilizing these kidneys would clearly expand the potential pool of donor organs.

Role of pre‐transplant marital status in renal transplant outcome

Abstract:  Background:  End‐stage renal disease is associated with illness‐induced disruptions that challenge patients and their families to accommodate and adapt. However, the impact of patients’ marital status on kidney transplant outcome has never been studied. This project, based on data from United States Renal Data System (USRDS), helps to answer how marriage affects renal transplant outcome.

The association between length of post-kidney transplant hospitalization and long-term graft and recipient survival

Abstract: Background: There has been a general trend towards shortened length of post‐kidney transplant hospitalization (LOH). The decision regarding patientss discharge from the hospital theoretically may be based on several factors, including, but not limited to, patient well being, insurance status, family situation and other, mostly socio‐economic factors, as opposed to hard medical evidence. However, the appropriate LOH in kidney transplant recipients is not well studied regarding long‐term outcomes.

Role of maintenance immunosuppressive regimen in kidney transplant outcome.

Data of long-term immunosuppressive protocol comparison are lacking. The goal of this study was to compare kidney transplant outcome using three common immunosuppressive protocols. A retrospective study was performed of the graft and recipient survival using US Renal Data System data (n = 31,012) between January 1, 1995, and December 31, 1999, with the follow-up through December 31, 2000, on prednisone + cyclosporine + mycophenolate mofetil (PCM; n = 17,108), prednisone + tacrolimus + mycophenolate mofetil (PTM; n = 7225), or prednisone + cyclosporine + azathioprine (PCA; n = 6679). Compared with PCM, there is an increased risk for allograft failure associated with PTM (hazard ratio [HR] 1.09; P < 0.05) and PCA (HR 1.15; P < 0.001). Similar associations were demonstrated in the following subgroups: Early (before 1997) and late (in or after 1997) transplant periods, in living-donor transplants, and in adult and kidney-only recipients. This association also was found between PCA regimen and graft survival in the entire patient population (HR 1.15; P < 0.001) and in the studied subgroups. PCA (HR 1.15; P < 0.005), but not PTM (HR 1.01; P = 0.816), regimen was associated with increased recipient mortality in the entire patient population and in patient subgroups. Secondary outcomes (serum creatinine values at given time points, acute rejection rate, and posttransplantation malignancies) are also discussed. These data suggest that a PCM regimen is associated with lower risk for graft failure compared with a PTM regimen and with lower risk for graft failure and recipient death compared with a PCA regimen.

The impact of recipient history of cardiovascular disease on kidney transplant outcome.

Cardiovascular disease (CVD) leads to increased mortality rates among renal transplant recipients; however, its effect on allograft survival has not been well studied. The records from the United States Renal Data System and the United Network for Organ Sharing from January 1, 1995, through December 31, 2002, were examined in this retrospective study. The outcome variables were allograft survival time and recipient survival time. The primary variable of interest was CVD, defined as the presence of at least one of the following: cardiac arrest, myocardial infarction, dysrhythmia, congestive heart failure, ischemic heart disease, peripheral vascular disease, and unstable angina. The Cox models were adjusted for potential confounding factors. Of the 105,181 patients in the data set, 20,371 had a diagnosis of CVD. The presence of CVD had an adverse effect on allograft survival time (HR 1.12, p < 0.001) and recipient survival time (HR 1.41, p < 0.001). Among the subcategories, congestive heart failure (HR 1.14, p < 0.005) and dysrhythmia (HR 1.26, p < 0.05) had adverse effects on allograft survival time. In addition to increasing mortality rates, CVD at the time of end-stage renal disease onset is also a significant risk factor for renal allograft failure. Further research is needed to evaluate the role of specific forms of CVD in allograft and recipient outcome.

A Population-Based Assessment of the Familial Component of Chronic Kidney Disease Mortality

Background/Aim: While the familial nature of chronic kidney disease (CKD) has been recognized, it has primarily been defined from studies of first-degree relatives of selected sets of cases. The goal of this study is an evaluation of the familial clustering of end-stage renal disease (ESRD) and CKD mortality using a population-based genealogy of Utah. This is the first population-based analysis of the familial component of ESRD and non-ESRD CKD. Methods: We have defined two distinct patient groups for this analysis, using individuals with death certificates in the Utah Population Database indicating ESRD (n = 192) and non-ESRD CKD (n = 335) as the cause of death. Two measures of familiality were used: (1) relative risk (RR) of CKD or ESRD death in relatives of cases and (2) an average relatedness statistic, i.e., the Genealogical Index of Familiality. Results: The RR for dying with ESRD among the first-degree relatives of individuals dying with ESRD is estimated to be 10.1 (p = 0.0007, 95% confidence interval CI 2.76–25.95), but is not significantly elevated among second-degree relatives. The RR for dying with non-ESRD CKD among first- and second-degree relatives of individuals dying with non-ESRD CKD was 3.89 (p = 0.0051, 95% CI 1.43–8.46) and 3.11 (p = 0.04, 95% CI 0.85–7.95), respectively. The Genealogical Index of Familiality statistic demonstrated that the individuals dying with ESRD are significantly more related than expected in this population (p = 0.013); significant excess relatedness was also observed for individuals dying with non-ESRD CKD (p = 0.006), suggesting a familial component for both, with evidence for common environmental and genetic effects. Conclusion: The results of this analysis of individuals dying with ESRD and non-ESRD CKD supports a significant and independent familial component to both conditions, suggesting a heritable factor playing a role.

A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy

Background: In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease. Objective: The objective of this study is to examine whether reduction of plasma uric acid with febuxostat, a xanthine oxido reductase inhibitor, impacts adipose tissue oxidative stress, adipokines, and markers of systemic inflammation or kidney fibrosis. Design: This was a double-blinded randomized controlled trial. Setting: Academic university setting was used. Patients: Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included. Measurements: Adipose tissue thiobarbituric acid reducing substances (TBARS) and adiponectin concentrations and urinary transforming growth factor–β (TGF-β) were primary endpoints. Plasma C-reactive protein, high molecular weight–adiponectin, interleukin–6, tumor necrosis factor–α, and TBARS and albuminuria were among predefined secondary endpoints. Methods: Participants were randomly assigned to febuxostat (n = 40) or matching placebo (n = 40) and followed for 24 weeks. Results: Baseline plasma uric acid levels were 426 ± 83 µmol/L; 95% completed the study. Estimated glomerular filtration rate (eGFR) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks (P = .05). In separate mixed-effects models, compared with placebo, febuxostat reduced uric acid by 50% (P < .001) but had no significant effects on subcutaneous adipose tissue TBARS (−7.4%, 95% confidence interval [CI], 57.4%-101.4%) or adiponectin (6.7%, 95% CI, 26.0%-53.8%) levels or urinary TGF-β/creatinine ratio (18.0%, 95% CI, 10.0%-54.8%) or secondary endpoints. Limitations: Relatively modest sample size and short duration of follow-up. Conclusions: In this population with progressive diabetic nephropathy, febuxostat effectively reduced plasma uric acid. However, no detectable effects were observed for the prespecified primary or secondary endpoints. Trial Registration: The study was registered in clinicaltrials.gov (NCT01350388).