Compared with other etiologies of kidney failure, patients who initiate dialysis due to kidney failure associated with sickle cell disease have a 1.5 to 2.8-fold hazard of mortality. Kidney transplantation is a potential treatment option to reduce the high risk of mortality in this patient population. However, it is unclear whether transplantation is desirable in patients with kidney failure associated with sickle cell disease due to higher post-transplant mortality.
Access to transplantation may be affected by the high post-transplant mortality rate in patients with sickle cell disease and, according to Sunjae Bae, MPH, PhD, and colleagues, transplant centers are disincentivized to perform transplantation in those patients due to the close monitoring of each center’s aggregate post-transplant mortality rate.
While post-transplant mortality is higher in recipients with sickle cell disease, the decrease in mortality associated with transplantation may be similar or greater in that patient population due to the significant increase in dialysis mortality compared with non-sickle cell counterparts. There are few available data on lower mortality associated with transplantation in patients with sickle cell disease.
The researchers conducted a national cohort study to (1) examine mortality rates and measured decreased in mortality associated with transplantation in patients with kidney failure due to sickle cell disease compared with other etiologies, and (2) compare access to transplantation between populations with and without sickle cell disease, from initiation of dialysis to transplant waitlist registration, to receipt of a kidney transplant. Results of the study were reported online in the Clinical Journal of the American Society of Nephrology [doi:10.2215/CJN.02720320].
To quantify the decrease in mortality associated with transplantation, the researchers measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, hazard ratios (HRs) for receiving transplantation in the sickle cell and control groups were estimated, treating death as a competing risk.
The study utilized data from the United States Renal Disease System (USRDS) and the Scientific Registry of Transplant Recipients (SRTR). The dialysis cohort included all adults ≥18 years of age who initiated maintenance dialysis with incident diagnosis of kidney failure between January 1, 1998, and December 31, 2017, from USRDS data. Patients who had sickle cell disease as the “primary cause of renal failure” on the end-stage kidney disease Medical Evidence Report (Form CMS-2728), with International Classification of Diseases, Ninth Edition, Clinical Modification diagnosis code 282.6 or International Classification of Diseases, Tenth Edition, Clinical Modification diagnosis code D57. All others were included in the controls. The waitlist cohort included all adults added to the national kidney transplant waiting list between January 1, 1998, and December 31, 2017, from SRTR data. Candidates whose primary diagnoses were sickle cell disease (diagnosis code 3029) or other (diagnosis code 99), were identified. All others were included in the controls.
The dialysis cohort included 1970 patients in the sickle cell group and 2,047,790 in the control group. Compared with controls, the sickle cell group was younger (median, 44 vs 65 years), more likely to be Black (92% vs 27%), and had fewer comorbidities. The waitlist cohort included 507 patients in the sickle cell group and 463,298 in the control group. The sickle cell group was younger (median, 39 vs 53 years), more likely to be Black (94% vs 28%) or have panel reactive antibody ≥80% (19% vs 10%), and less likely to have diabetes (3% vs 42%) compared with the control group.
In all analyses, the sickle cell group showed higher mortality. The 10-year Kaplan-Meier estimates for dialysis, waitlist, and post-transplant mortality were 85%, 61%, and 50%, respectively, in the sickle-cell group, and 81%, 41%, and 32%, respectively, in the control group.
In model 1 (before any adjustments), the sickle-cell group showed 1.21-fold (95% confidence interval [CI], 1.15-1.27) dialysis mortality, 1.98-fold (95% CI, 1.75-2.23) waitlist mortality, and 1.81-fold (95% CI, 1.45-2.27) post-transplant mortality. Model 3 (fully adjusted) indicated greater differences in mortality, with adjusted HRs of 2.14 (95% CI, 2.03-2.25) for dialysis mortality, 3.21 (95% CI, 2.84-3.62) for waitlist mortality, and 3.03 (95% CI, 2.42-3.80) for post-transplant mortality.
Of the 507 patients with sickle cell disease in the waitlist cohort, 192 subsequently received a transplant. Of the 463,298 candidates from the controls, 243,045 received a transplant. There was an association between kidney transplantation and similar decreases in mortality in the sickle cell and control groups.
In the sickle cell group, transplant recipients had lower mortality, with absolute risk differences of 6.1 (98.75% CI, –0.8 to 13.0) percentage points at 1-year post-transplant, 15.3 (98.75% CI, 3.9-26.7) at 3 years post-transplant, 23.8 (98.75% CI, 9.6-38.0) at 5 years post-transplant, and 20.3 (98.75% CI, 0.9-39.8) at 10 years post-transplant as compared with candidates on the waitlist. In the control group, transplantation was associated with absolute risk differences at 1, 3, 5, and 10 years post-transplant of 0.7 (98.75% CI, 0.5-0.8), 6.6 (98.75% CI, 6.4-6.9), 12.7 (98.75% CI, 12.4-13.1), and 19.8 (98.75% CI, 19.2-20.4), respectively. Following adjustment for race and clinical characteristics, the estimates remained overall similar.
The sickle cell group had lower access to transplantation overall. Beginning at initiation of dialysis, the sickle cell group was less likely to receive a transplant (subdistribution HR, 0.73; 95% CI, 0.68-0.97). After waitlist registration, the sickle cell group was also less likely to receive a transplant compared with the control group (subdistribution HR, 0.62; 95% CI, 0.53-0.72).
Limitations to the study cited by the authors included the possibility of confounding due to the observational study design, restricting the analyses on the decreases in mortality associated with transplantation to waitlisted candidates, and the lack of details on certain clinical factors.
In conclusion, the researchers said, “In this national study, kidney transplantation was associated with similar and substantial decreases in mortality in the sickle cell and control groups. Nonetheless, the sickle cell group had worse access to transplantation compared with the control group, even after being placed on the national kidney transplant waiting list. Our findings suggest that access to transplantation in the sickle cell population should be improved.”
- Researchers conducted a national, observational cohort study to examine the decrease in mortality associated with kidney transplantation in patients with kidney failure associated with sickle cell disease.
- Compared with matched candidates on the kidney transplant waitlist, transplant recipients with sickle cell disease and a group of controls with other kidney failure etiologies had similar post-transplant mortality.
- Even after waitlist registration, patients with sickle cell disease were less likely to receive transplantation compared with the control group.