Late steroid withdrawal and cardiovascular events in kidney transplant recipients.

INTRODUCTION: Cardiovascular events (CVE) are the leading cause of mortality in kidney transplant recipients. The adverse effects of long-term therapy with steroids on cardiovascular risk have motivated increasing interest in steroid withdrawal (SW). The objective of this study was to compare the incidences of CVE and all-cause mortality between patients who had undergone SW at 1 year posttransplant and control patients who continued on steroids. METHODS: A cohort of 400 consecutive adult recipients of a kidney transplant between 1993 and 1998 who qualified for late SW was studied. At 1 year posttransplant 188 patients underwent SW, whereas 212 patients continued on steroids. Cox proportional-hazards analysis was used to estimate CVE (cardiac and cerebrovascular events) and all-cause mortality hazard ratios (HR) for patients who had undergone SW versus controls who continued on steroids beyond 1 year. RESULTS: The average follow-up was 61 months. There were 44 (11%) cardiac events, 18 (4.5%) cerebrovascular events, and 41 deaths (10.3%). The composite outcome of CVE and all-cause mortality was reached in 26 (13.8%) subjects who had undergone SW and 50 (23.6%) controls (P=0.013). In adjusted analyses, SW was associated with decreased risk for the composite outcome (HR 0.46, 95% confidence interval [CI] 0.28-0.76), cardiac events (HR 0.48, 95% CI 0.28-0.84), and all-cause mortality (HR 0.27, 95% CI 0.12-0.59). There was no association of SW with the risk for cerebrovascular events (HR 1.76, 95% CI 0.45-7.01). CONCLUSION: In this retrospective analysis, SW at 1 year posttransplant was associated with decreased risk for future CVE and all-cause mortality.

Long-term kidney regraft survival from deceased donors: risk factors and outcomes in a single center.

BACKGROUND: Although survival of kidney regrafts is similar to that of primary grafts, risk factors associated with regraft survival have not been defined clearly. The aim of this study was to investigate risk factors for regraft outcome, including characteristics of the previous and current transplant, and time to retransplant. METHODS: In a historical cohort study, 966 primary and 176 repeat deceased donor kidney graft recipients transplanted between January 1, 1990 and December 31, 2004 were studied. Cox regression analysis was used to estimate graft loss hazard ratios (HR) for regrafts versus primary grafts. Adjustments were made for recipient and donor demographics, transplant-related factors (transplant era, panel reactive antibodies, human leukocyte antigens mismatches, immunosuppression, delayed graft function, acute rejection [AR]), previous transplant characteristics (graft survival, graft loss because of AR), and time to retransplant. RESULTS: A total of 508 kidney grafts were lost in the period between January 1990 and May 2007: 427 primary grafts and 81 regrafts. Regraft recipients had a covariate-adjusted 6% increase in graft loss (HR=1.06; P=0.69). Regraft loss was significantly associated with previous graft survival less than or equal to 1 year (HR=2.01; P=0.004), previous graft loss because of AR (HR=2.26; P=0.017) and time to retransplant more than 1 year (HR=2.42; P=0.002). Other significant predictors of regraft loss were diabetes (HR=1.81), donor age more than 50 years (HR=1.86) and delayed graft function after retransplant (HR=1.95). CONCLUSIONS: Kidney regrafts seem to have similar long-term outcome as primary grafts. However, additional risk factors significantly associated with regraft survival are previous graft survival, graft loss because of rejection, and time to retransplant.

Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease.

PURPOSE: An algorithm was developed for performing bilateral nephrectomies for specific indications before or at renal transplantation in patients with autosomal dominant polycystic kidney disease. Outcomes for the living donor arm of the algorithm are reported. MATERIALS AND METHODS: Patients with autosomal dominant polycystic kidney disease and end stage renal disease were evaluated for transplantation. Patients with recurrent pyelonephritis, hemorrhage, pain, early satiety or kidneys that extended into the true pelvis underwent bilateral nephrectomies. Bilateral nephrectomies with concurrent renal transplantation were performed if a living renal donor was identified. If no living donor was identified, pre-transplantation bilateral nephrectomies were done and the patients were listed for cadaveric donor renal transplantation. The living renal donor arm of the algorithm was evaluated by comparing certain parameters for 15 and 17 patients with autosomal dominant polycystic kidney disease who underwent pre-transplantation and concurrent bilateral nephrectomies, respectively, including patient and graft survival, delayed graft function, graft function, length of stay for each surgery, transfusions and complications. RESULTS: No deaths, graft failures or delayed graft function occurred. In the delayed renal transplant group median time from nephrectomy to living donor transplantation was 124 days. Serum creatinine at discharge home and 1 year after transplantation for the pre-transplantation nephrectomy cohort was 2.0 and 1.3 mg/dl, respectively. Seven of the 17 patients with concurrent nephrectomy underwent transplantation before starting renal replacement therapy. A longer mean total hospital stay in the pre-transplantation nephrectomy cohort was the only statistically significance outcome variable. CONCLUSIONS: Selective bilateral nephrectomies at living donor renal transplantation results in decreased total length of stay without compromising patient or graft outcomes and it allows preemptive renal transplantation. Concurrent nephrectomy is safe and it further validates the algorithm for selective, concurrent bilateral nephrectomies for patients with autosomal dominant polycystic kidney disease who undergo living donor renal transplantation.

Living unrelated donor renal transplantation: a single center experience.

PURPOSE: Living, genetically unrelated donor renal transplantation (LURT) is being performed with increasing frequency. We evaluated our single center experience with LURT and compared this to a cohort of living related donor renal transplants (LRT) to evaluate the short-term success of LURT at our center. MATERIALS AND METHODS: We identified 99 consecutive patients who underwent LURT at our center and had at least 1 year of followup data. A control cohort of 99 patients who underwent LRT at our center matched for age, number of transplants and date of transplant was also identified. One-year graft and patient survival, and serum creatinine levels at 1, 3, 6 and 12 months were compared between the groups. Our data were compared with national and international data. RESULTS: At our center 1-year graft survival was 95% in the LURT and LRT cohorts. One-year LURT patient survival was 99% compared with 97% in the LRT group and the serum creatinine levels were not significantly different. CONCLUSIONS: Patients undergoing LURT at our center have excellent 1-year graft and patient survival compared with LRT performed at our center, and national and international LURT. Genetically unrelated kidney donors should continue to be used to expand the kidney donor pool.

Autosomal-dominant polycystic kidney disease as a risk factor for diabetes mellitus following renal transplantation.

BACKGROUND: Posttransplant diabetes mellitus is an important complication of renal transplantation that is associated with a significant impact on quality of life and an increase in long-term morbidity and mortality. Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary disease that commonly leads to end-stage renal disease (ESRD) in adulthood. The association between ADPKD and posttransplant diabetes mellitus has not been previously studied in a large cohort of patients. METHODS: To address this question, we studied a cohort of 135 patients with ADPKD who received a first renal-only transplant between January 1985 and December 1999. An age, race, and date of transplant-matched cohort of 135 non-ADPKD subjects were used as the control population. RESULTS: The cohorts were similar at baseline for gender distribution, body mass index (BMI), proportion of obese subjects (BMI greater than 30 kg/m(2)), family history of diabetes mellitus, and type of donor (deceased or living). At 12 months, the incidence of posttransplant diabetes mellitus was significantly higher in patients with ADPKD when compared to the controls (17% vs. 7.4%) (P= 0.016), despite no significant differences in the BMI, percent increase in BMI, number of acute rejections, prednisone dose at 3 and 6 months, use of diuretics or beta blockers, delayed graft function, or serum creatinine levels. The proportion of subjects requiring insulin was significantly higher in the ADPKD group (11.1% vs. 3%) (P= 0.009). Variables significantly associated with posttransplant diabetes mellitus at 1 year by bivariate analyses were the diagnosis of ADPKD (P= 0.02), BMI at transplant (P= 0.04), obesity at 12 months (P= 0.01), and delayed graft function (P= 0.02). Gender of recipient (P= 0.9), family history of diabetes (P= 0.3), prednisone dose at 3 months (P= 0.9) and 6 months (P= 0.7), acute rejection (P= 0.9), use of beta blockers or tacrolimus (P= 0.8), deceased donor transplant (P= 0.2), and serum creatinine at 1 year (P= 0.5) were not associated with posttransplant diabetes mellitus. A trend toward increased incidence of posttransplant diabetes mellitus was found with the use of diuretics post transplant (P= 0.054). By multivariable analyses, in patients with ADPKD, the adjusted (by all the variables listed above) relative risk for development of posttransplant diabetes mellitus was 2.87 (95% CI = 1.24-6.65) (P= 0.014). Only the diagnosis of ADPKD (RR = 2.9) (P= 0.01), obesity at 1 year (RR 2.5) (P= 0.017), and delayed graft function (RR 2.4) (P= 0.03) contributed significantly to the fit of a stepwise logistic regression model. Patient survival was significantly worse in the cohort of patients who developed posttransplant diabetes mellitus (median survival 109.3 vs. 121 months) (P= 0.008). CONCLUSION: In our study patients with ADPKD were at a threefold increased risk for development of posttransplant diabetes mellitus within the first year following renal transplantation. Development of posttransplant diabetes mellitus was associated with a significant detrimental impact on patient survival. Further studies are needed to provide insight into the mechanisms of the association between ADPKD and posttransplant diabetes mellitus.

Protecting patient privacy in clinical data mining.

This paper investigates whether HIPAA de-identification requirements--as well as proposed AAMC de-identification standards--were met in a large clinical data mining study (1997-2001) conducted at Duke University prior to the publication of the final rule. While HIPAA has improved de-identification standards, the study also shows that privacy issues may persist even in de-identified large clinical databases.