Risk of Venous Thromboembolism in Kidney Transplant Recipients with Autosomal Dominant Polycystic Kidney Disease

BACKGROUND: Kidney transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) may be at higher risk of venous thromboembolism than non-ADPKD recipients. METHODS: We conducted an observational study of adult kidney transplant recipients at a single center, the University Medical Center Groningen (UMCG; n=1179, 393 with ADPKD), and replicated key analyses in the multicenter Swiss Transplant Cohort Study (STCS; n=4415, 710 with ADPKD). The primary endpoint was time to first venous thromboembolism after transplantation or death related to venous thromboembolism (identified through medical record review), analyzed using Kaplan-Meier estimates and Cox regression. Data were pooled for subgroup analyses and to assess determinants of post-transplant venous thromboembolism risk. RESULTS: Venous thromboembolism occurred more often in ADPKD than non-ADPKD kidney transplant recipients (log-rank p=0.04 and p<0.001 for UMCG and STCS, respectively). The 10-year cumulative venous thromboembolism incidence was 13.5% [95% CI: 9.4, 17.5], versus 9.6% [95% CI: 7.0, 12.1] in ADPKD versus non-ADPKD recipients in UMCG, and 21.0% [95% CI: 17.0, 24.7] versus 15.1% [95% CI: 13.5, 16.6] in STCS. Median [Q1, Q3] time to venous thromboembolism were similar across cohorts (UMCG: 1.7 [0.4, 4.9], STCS: 1.4 [0.2, 4.8] years). Venous thromboembolism risk was highest in the early (<2 years) post-transplant period. After adjustment for venous thromboembolism risk factors, ADPKD remained independently associated with post-transplant venous thromboembolism in both cohorts (UMCG HR 1.80 [95% CI: 1.21, 2.69]; STCS HR 1.39 [95% CI: 1.13, 1.72]). The association between ADPKD and risk of venous thromboembolism was more pronounced in males. Hemoglobin levels after kidney transplantation were approximately 7.0 ± 0.8% higher in ADPKD recipients, particularly in males, with corresponding higher risks of erythrocytosis during follow-up. Incorporating longitudinal hemoglobin as a time-varying covariate attenuated the association between ADPKD and venous thromboembolism, suggesting that the association was at least partially driven by higher hemoglobin levels. CONCLUSIONS: Kidney transplant recipients were at high risk for venous thromboembolism, and those with ADPKD are at an even higher risk.