Impact of Pre-Transplant Vascular Disease on Long-Term Outcomes after Transplantation

Vascular disease is associated with an increased risk of death among dialysis patients on the transplant waiting list. Among candidates for transplantation on the deceased donor waiting list, the annual rate of vascular-related deaths is >8%; the rate increases with cumulative time on dialysis therapy. Even with the modest survival benefit of transplantation for patients with vascular disease, vascular-disease–related death remains a significant impediment to improvement in long-term outcomes associated with transplantation. In Australia and New Zealand, cardiovascular disease (CVD) and other vascular diseases are associated with >30% of deaths in patients with a functioning transplant; similar mortality rates are observed worldwide.

Short-term outcomes for transplant recipients have improved with advances in kidney transplantation, but there are few data on long-term outcomes among patients with comorbid vascular conditions. Wai H. Lim, MD, and colleagues recently conducted a population cohort study designed to examine the association of vascular disease prior to transplantation with graft and patient survival following transplantation. The study also evaluated whether diabetes status modified that association. Results were reported in the American Journal of Kidney Diseases [2018;71(1):102-111].

The researchers utilized data from the Australia and New Zealand Dialysis and Transplant Registry to identify primary adult deceased donor kidney transplant patients ≥18 years of age for 1990 to 2012. Exclusion criteria included receipt of multiple organ transplants and transplants prior to the index date.

The primary clinical outcome of interest was all-cause mortality. Secondary outcomes were overall transplant loss, death-censored transplant loss, death with a functioning transplant, and cause-specific mortality (CVD, infection mortality, cancer, and other vascular disease–related mortality). Other vascular disease–related morality was defined as death from cerebrovascular accident, withdrawals resulting from cerebrovascular or peripheral vascular disease (PVD)–related comorbid conditions, pulmonary embolus, bowel infection, and ruptured aortic aneurysm.

The total cohort included 7128 transplant recipients. Of those, 84.3% (n=6011) had no recorded vascular disease at the time of transplantation; 12.0% (n=854) had vascular disease at one site; and 3.7% (n=263) had vascular disease at two or more sites. Mean age of patients with no vascular disease, vascular disease at one site, and vascular disease at two or more sites was 46.7, 54.4, and 56.9 years, respectively. Median follow-up was 7.3 years (58,120 patient-years).

Patients with vascular disease were more likely to have diabetes (P<.001). CVD was the most prevalent type of vascular disease (67.9%; n=759), followed by PVD (38.5%, n=430), and cerebrovascular disease (21.4%, n=239), P<.001. Over successive transplantation eras, the proportion of recipients with any vascular disease increased (range, 14.3% during 1990-1997 to 17.4% during 2006-2012 (P=.003).

With increases of the burden of vascular diseases, there was an increase in the cumulative increase of all-cause mortality. Among patients with vascular disease at two or more sites, overall mortality rates at 0-1, >1-5, and >5-10 years after transplantation were 8, 18, and 20 per 100 recipients, respectively, compared with 3, 5, and 7 per 100 patients among those without vascular disease (P<.001).

Recipients with any vascular diseases had lower overall survival up to 20 years following transplantation compared with those without vascular disease. Patients with vascular disease at two or more sites had the poorest survival (log-rank test P<.001). Recipients with one and two or more vascular diseases were at increased risk for death by at least 1.4 times compared with recipients without vascular disease (adjusted hazard ratios of 1.40; 95% confidence interval [CI], 1.21-1.63; and 1.75; 95% CI, 1.39-2.20; P<.001 for both), for one and two or more sites, respectively.

At 20 years following transplantation, overall transplant survival was lower in patients without vascular diseases; the poorest transplant survival was seen in patients with two or more vascular diseases. There were differences between recipients with and without vascular disease in primary causes of loss of transplant (P<.001). A greater proportion of recipients with one and two or more vascular diseases died with a functioning transplant compared with recipients without vascular disease (57.1% and 59.4% vs 37.7%, respectively). Incidences of other causes of transplant loss were 22.6% and 15.0% versus 34.1% for chronic allograft nephropathy/interstitial fibrosis and tubular atrophy, 4.9% and 5.4% versus 4.7% for rejection, and 3.9% and 3.9% versus 4.8% for glomerulonephritis-related transplant loss, respectively.

There was an interaction between diabetes status and vascular disease burden for all-cause mortality (P for interaction=.002), overall transplant loss (P=.01), death with a functioning transplant (P=.01), and CVD mortality (P=.01). Associations between vascular disease burden and those outcomes were stratified by diabetic status. For recipients without diabetes mellitus, respective mortality rates for recipients without vascular disease between >1 and 5 and >5 and 10 years after transplantation were 5 and 7 per 100 recipients, compared with 23 and 22 per 100 recipients, respectively, among those with vascular disease at two or more sites. For those with diabetes mellitus, mortality rates for those without vascular disease at >1 and 5 and >5 and 10 years following transplantation were 9 and 13 per 100 recipients, respectively, compared with 14 and 19 per 100 recipients among those with vascular disease at two or more sites.

Selection bias and unmeasured residual confounders, including the severity/extent of comorbid conditions likely to be present were cited by the researchers as limitations to the study.

In conclusion, the researchers said, “The impact of vascular disease on long-term outcomes was modified by the presence of diabetes, whereby excess risks for death and transplant loss are more apparent in recipients without diabetes.”

Takeaway Points

  1. A recent population cohort study examined the association between vascular disease prior to transplantation and transplant and patient survival following transplantation.
  2. At 15 years after transplantation, overall survival for recipients without vascular disease was 65% compared with 35% and 22% among recipients with vascular disease at one and two or more sties, respectively.
  3. The impact of vascular disease on long-term outcomes was modified by the presence of diabetes; excess risks for death and transplant loss were more apparent in recipients without diabetes.