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

Abstract

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.