Risk Factors and Clinical Impact of Chronic Kidney Disease (CKD) after Allogeneic Stem Cell Transplant (allo-SCT)
Authors: Shimizu Hiroaki , Ishizaki Takuma , Hatsumi Nahoko , Takada Satoru , Yokohama Akihiko , Saitoh Takayuki , Nojima Yoshihisa , Handa Hiroshi 
Published: October 2019

Abstract
Background: Although the number of long-term survivors after allo-SCT has been increasing with the recent improvements of transplant procedures, late complications have emerged as an important unsolved issue in these transplant recipients. CKD is generally recognized as a stage prior to end-stage renal disease, which requires renal replacement therapy, and the incidence of CKD among transplant recipients has been reported to be around 30%. We recently reported that administration of low-dose carperitide in the early phase of transplant had the potential to prevent development of CKD after allo-SCT. However, risk factors for CKD after allo-SCT have not been fully elucidated, so that suitable candidates for this preventive approach are unclear. To this end, this retrospective study was conducted. Patients and methods: In this study, 149 consecutive patients who underwent allo-SCT for the first time at Gunma University and Saiseikai Maebashi Hospital between 2006 and 2013 and survived without a relapse of underlying disease three months after transplant were included. There was no restriction on underlying disease, donor source, or conditioning regimen. CKD was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2 lasting more than three months, according to the KDIGO guideline. Overall survival (OS) was defined as the interval from the date of transplant to the date of death. Non-relapse mortality (NRM) was defined as any death without a relapse of underlying disease. Fisher's exact test was used for comparison of binary variables. Cumulative incidences (CIs) of CKD were compared using the stratified Gray test, considering death without the event as a competing risk. The Fine-Gray proportional hazard model was used for multivariate analysis of risk factors for CKD. In the analysis of OS and NRM, CKD was treated as a time-dependent covariate. P < 0.05 was considered significant. Results: Of the 149 transplant recipients included in this study, 80 were male and 69 were female. The median age was 48 years (range, 18-72 years), and the median baseline eGFR was 92.2 ml/min/1.73 m2 (range, 19.4 - 172.8 ml/min/1.73 m2). Underlying diseases were acute myeloid leukemia in 77 patients, acute lymphoblastic leukemia in 39, and myelodysplastic syndrome in 20. Stem cell donors were related donors in 30 patients, unrelated donors in 78, and cord blood in 41, and almost all patients were conditioned with total body irradiation (TBI)-containing myeloablative conditioning (MAC) regimens. The 2-year cumulative incidence of CKD after transplant was 35.6%. On univariate analysis, age > 50 years, baseline eGFR < 90 ml/min/1.73 m2, use of FK506 for GVHD prophylaxis, prolonged calcineurin inhibitor use (> 6 months), and acute kidney injury (AKI) development within 90 days after transplant were significant risk factors for CKD development. Multivariate analysis showed that age > 50 years (hazard ratio [HR] = 3.322; p-value < 0.001), baseline eGFR < 90 ml/min/1.73 m2 (HR = 2.088; p-value = 0.018), use of MAC regimens (HR = 2.122; p-value = 0.035), prolonged calcineurin inhibitor use (HR = 2.078; p-value = 0.035), and AKI development within 90 days after transplant (HR = 2.697; p-value < 0.001) were independent risk factors for CKD development, but disease type, disease risk, donor type, HLA mismatch, TBI-containing conditioning regimen, transplant year, acute GVHD, and chronic GVHD were not. CKD development showed no significant impact on OS (HR = 1.063; p-value = 0.823), and CKD development was not associated with increased NRM (HR = 1.439; p-value = 0.335). Conclusion: These findings suggest that transplant recipients with some of the features mentioned above, including higher age, lower baseline eGFR, and use of MAC regimens, should be recognized as patients at high risk for CKD at the time of transplant. Thus, we plan to conduct a prospective trial to explore whether low-dose carperitide treatment can reduce the incidence of CKD after allo-SCT among such high-risk transplant recipients.

Disclosures
No relevant conflicts of interest to declare.