Stroke Risk and Predictors in Kidney Transplant Recipients

Kidney transplantation is the gold standard treatment for patients with end-stage renal disease (ESRD). The prevalence of mortality and major cardiovascular events in kidney transplant recipients has declined in recent years, and is lower among transplant recipients than in a matched chronic kidney disease (CKD) population. However, kidney transplant recipients continue to have an increased mortality and cardiovascular event risk compared with the general population, due in part to the conventional cardiovascular risk factors such as diabetes, hypertension, and renal dysfunction. There are also associations between transplant-specific factors such as immunosuppression medication, inflammation, and anemia and increased risk of cardiovascular events in kidney transplant recipients.

Stroke, while not as prevalent as other cardiovascular diseases, is a contributor to comorbidity and mortality in this patient population. However, there are few data on the epidemiology, risk pattern, and modification of stroke risk following renal transplantation. Researchers in Taiwan, led by Shih-Ting Huang, MD, recently conducted a retrospective study designed to estimate the absolute and relative risk of stroke among a large cohort of recent kidney transplant recipients in Taiwan. The study also sought to describe the predictors and mortality implications of stroke in kidney transplant recipients. Results were reported online in the International Journal of Environmental Research and Public Health [2019;doi:10.3390/ijerph16030326].

The study utilized data from the National Health Insurance Research Database in Taiwan from the years 2000 through 2010 to identify kidney transplant recipients (n=4635), patients with ESRD (n=69,297), and patients from the general population who were free of CKD and matched by comorbidities (n=69,297). Univariate and multivariate Cox regression models were used to examine the risk of stroke; the stroke risk was compared between the study cohorts.

Median age of patients at the time of ESRD diagnosis and undergoing kidney transplantation was 65.0 and 47.0 years, respectively. In the kidney transplant group, 52.6% were men; in the ESRD group the percentage of men was 49.3. Mean follow-up for patients with stroke in the kidney transplant group was 5.89 years, for patients in the CKD-free control subgroup it was 5.78 years, and in the ESRD subgroup it was 5.06 years.

Chronic obstructive pulmonary disease, congestive heart failure, and a history of stroke were more prevalent in the ESRD subgroup than in the non-CKD control subgroup and in the kidney transplant subgroup. In the transplant subgroup, hypertension and hyperlipidemia were prevalent (84.9% and 34.3%, respectively). At 1 year following kidney transplant, most transplant recipients received prednisone (99.6%), mycophenolate mofetil (85.5%), and tacrolimus (80.0%). The median time on dialysis prior to kidney transplantation was 2.9 years.

Compared with the CKD-free control group, the risk of overall stroke was significantly higher among patients with ESRD (adjusted hazard ratio [aHR], 2.11; 95% confidence interval [CI].2.03-2.20). Patients in the ESRD group also had a higher risk of ischemic stroke (aHR, 1.84; 95% CI, 1.76-1.93) and a higher risk of hemorrhagic stroke (aHR, 3.38; 95% CI, 3.09-3.69).

Compared with the ESRD group, the risk of overall stroke was significantly lower in the kidney transplant group (aHR, 0.37; 95% CI, 0.31-0.44). The risks of ischemic stroke and hemorrhagic stroke were also lower in the kidney transplant group (aHR, 0.45; 95% CI, 0.37-0.55 and 0.20, 95% CI, 0.14-0.29, respectively). There were no significant differences between the risk patterns for each of the stroke types among kidney transplant recipients and among the CKD-free control group.

The cumulative incidence of stroke was significantly higher in the ESRD subgroup than in the CKD-free control subgroup (log-rank, P<.0001). Kidney transplant recipients had a significantly lower incidence of stroke than those in the ESRD group (log-rank, P<.0001). There was no significant difference in the cumulative incidence of stroke between the kidney transplant recipient subgroup and the CKD-free control subgroup.

When the data were analyzed according to age (20-49 years, 50-64 years, and ≥65 years), the ESRD group had a significantly higher risk of overall, ischemic, and hemorrhagic stroke compared with the CKD-free control group across all of the age stratifications. Those 20 to 49 years of age had the highest overall risk of stroke. With the exception of the risk of hemorrhagic stroke in kidney transplant recipients >65 years of age, the risk of overall, ischemic, and hemorrhagic stroke was significantly lower among kidney transplant recipients compared with the ESRD subgroup across all age stratifications. Also across all age stratifications, there were no significant differences in the overall and ischemic stroke risk in kidney transplant recipients compared with those in the CKD-free control subgroup.

The researchers divided the kidney transplant recipients into two groups: those who experienced stroke and those who did not to compare their characteristics. Of the kidney transplant recipients with stroke, 91.8% had hypertension, 37.3% had hyperlipidemia, and 32.9% reported underlying coronary artery disease. There was a significant increase in the risk of stroke with age (adjusted odds ratio [aOR], 1.02; 95% CI, 1.01-1.04 for each year of age) and the presence of diabetes (aOR, 2.08; 95% CI, 1.42-3.03) among the kidney transplant recipient patients.

Limitations cited by the authors included the retrospective design of the study and unpredictable confounding factors that may have influenced the outcomes; relying on administrative data regarding smoking, donor characteristics, and other transplantation factors; and the patients being predominately Asian, possibily limiting the generalizability of the findings to other ethnic populations.

In conclusion, the researchers said, “We discovered that the risk for all types of stroke was lower among kidney transplant recipients than patients with ESRD, and was approximate to that of the general population. We also concluded that stroke was relatively uncommon after kidney transplantation,  but it predicted an increased risk for death in kidney transplant recipients. We believe that vigilance in detecting and controlling modifiable cardiovascular event risk factors may be critical for reducing the risk of stroke and eventual death among kidney transplant recipients.”

Takeaway Points

  1. Researchers in Taiwan conducted a retrospective cohort study to examine the incidence and predictors of stroke and stroke-associated mortality in kidney transplant recipients.
  2. Compared with patients with end-stage renal disease, transplant recipients have a significantly lower risk of overall stroke, ischemic stroke, and hemorrhagic stroke.
  3. The predictors of stroke in kidney transplant recipients were age and diabetes.