This study further highlights disparities in health outcomes and access to transplant for children and young adults with SCD- ESKD. First, children and young adults with SCD-ESKD have worse survival than matched individuals with non-SCD-ESKD. Second, SCD individuals experience longer wait times for kidney transplant than matched controls. Third, despite adjusting for pre-nephrology care, children, and young adults with SCD-ESKD had overall higher mortality. The recent American Society of Hematology guidelines for the management of SCD suggests early referral for renal transplant and highlights the need for studies to evaluate disparities in access to care for SCD patients with ESKD[6]. This study provides additional evidence to support the need to further understand and address the reasons for this marked healthcare disparity.
Kidney transplantation in children is well-recognized to provide a long-term survival advantage in all patients with ESKD, however racial disparities in transplantation can lead to unequitable transplantation rates [7]. Two adult SCD studies suggest that transplantation is associated with a decrease in mortality [8, 9]. However, in this study, the time from the development of ESKD to kidney transplant remained longer for patients with SCD. This disparity is further highlighted by findings that these individuals have a higher mortality within the first and subsequent years after developing ESKD. Therefore, children, and young adults with SCD should not be precluded from early referral to access to kidney transplantation. A study published in 2021, examined the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplant Network (OPTN) database, found that patient and allograft survival in SCD kidney recipients did not improve between recent era (2010–2019) and early era (2000–2009). However, the authors note that these findings should not discourage kidney transplantation due to the overall survival benefits that transplantation confers [10]. Several of these more recent studies point towards graft loss secondary to poorly controlled SCD-related disease. Strategies to reduce post-transplant complications due to SCD should therefore be evaluated. Disease modifying agents such as hydroxyurea, is both effective in reducing increased sickle hemoglobin concentration and decreasing albuminuria in children and adults with SCD [11] [12] and could be continued post-transplant. Initiating automated blood transfusion in adult recipients during and after kidney transplantation has also demonstrated the ability to improve allograft and patient outcomes [8]. The mammalian target of rapamycin (mTOR) pathway has been identified as a regulator of red blood cell growth and proliferation[13]; one case report found use of mTOR inhibitor, everolimus, post-transplant improved fetal hemoglobin and decreased SCD pain[14]. Lastly, allogenic hematopoietic stem cell transplantation remains the only curative therapy for SCD, but this can be limited by the cost, suitable matched donors as well as significant morbidity[15]. An approach of dual stem cell and organ transplantation may be an option for patients in the foreseeable future as advances in stem cell transplantation are made. Larger prospective studies are needed to confirm these medications and modalities on allograft survival.
Our study has several limitations inherent to a retrospective study of administrative data. We can only identify associations between SCD status and mortality/transplantation but cannot speak directly to causal relationships between delayed transplantation and mortality. We only identified SCD-ESKD individuals and cannot calculate the prevalence or incidence of ESKD within the SCD population at large. Additionally, due to the limited number of participants within the SCD-ESKD cohort and the small number of patients in many subgroups, we were unable to further stratify the data. We have limited information about care prior to developing ESKD, particularly regarding the use and duration of disease modifying therapies prior to development of ESKD and transfusions post-transplant. Future studies need to evaluate approved therapies for treatment of SCD to understand how these interventions influence the progression of kidney disease.
It is vital that the transplant community identify and reduce the barriers to kidney transplantation in children and young adults with SCD-ESKD. Future research should consider qualitative assessment of the barriers to transplantation among kidney transplant centers. Equitable access to transplantation may mitigate the decreased survival seen in this study. The risk of SCD-related kidney disease must be balanced with improvement in the quality of life and possible improved survival when compared to those who remain on dialysis. Use of hydroxyurea, mTOR inhibitors and exchange transfusions need to be further studied in the post-transplant period. However, in the immediate future, nephrology centers can start to work towards improving access to transplantation and establishing sickle cell specific transplant protocols to improve post-transplant allograft survival by working with their hematology colleagues and sharing protocols.