Improved Survival with Transplantation in Granulomatosis with Polyangiitis in the United States: Data from the US Renal Data System

Background/Purpose:

Granulomatosis with polyangiitis (GPA) is a common cause of glomerulonephritis and leads to end-stage renal disease (ESRD) in approximately 25% of patients. GPA is an accepted indication for transplantation and has comparable outcomes when compared to patients with ESRD due to other immune-mediated conditions. However, transplantation is a limited resource and the survival benefit of transplantation compared to remaining waitlisted has not been previously evaluated.

Methods:

We identified all incident cases of ESRD due to GPA (ICD9=446.4) in the United States Renal Data System (USRDS) who were waitlisted for a renal transplant between 1995 and 2014. The USRDS captures nearly all patients with ESRD in the US and requires that nephrologists report the ESRD cause (ICD-9 code). The USRDS includes details regarding demographics, comorbidities, and waitlist and transplant dates and statuses. It also includes details on date and cause of death. All patients were followed until death or January 1, 2016. We restricted our analysis to patients waitlisted for transplant to limit the potential bias of confounding by indication.  We used a pooled logistic regression with transplantation as a time-varying covariate to estimate the relative risk (RR) and 95% confidence intervals (CIs) of death among those transplanted compared to those who remained on the waitlist. We adjusted for sociodemographic covariates (e.g., age, gender) as well as comorbidities (e.g., diabetes, cardiovascular disease (CVD)).  We assessed differences in cause of death using cause-specific hazard models to estimate hazard ratios (HRs) and 95% CIs.   

Results:

During the study period, 1,556 patients with ESRD due to GPA were waitlisted for a renal transplant and 977 (63%) of these patients received a transplant. The majority were male (60%) and white (84%). Average age at ESRD onset, waitlisting, and transplant were 47.3 ±16.5 years, 49.3 ±16.4 years, and 47.8 ±17.2 years, respectively. The average time from ESRD diagnosis to being waitlisted was 1.5 ±2.2 years. Total follow up time was 6.8 ±4.7years. Overall, 444 deaths occured.  In fully-adjusted analyses, transplanted patients had a 59% lower risk of death compared to those who remained on the waitlist (RR 0.41, 95% CI 0.34-0.49).   In fully adjusted cause-specific analyses, patients transplanted had a lower risk of cause-specific death from CVD (HR 0.06, 95% CI 0.03-0.1) and infection (HR 0.3 95% CI 0.2-0.6).  There was no difference in the risk of cause-specific death from cancer (HR 0.5 95% CI 0.2-1.2).   

Conclusion:

In this nationwide study of ESRD due to GPA, renal transplantation was associated with a significantly reduced risk of death compared to remaining on the waitlist. Our findings highlight the importance of identifying barriers to transplantation in this patient population. Additionally, evaluating management strategies to reduce the risk of CVD and infection in patients on the waitlist will likely improve survival.