Background

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common complications following allogeneic hematopoietic stem cell transplantation (HSCT). The development of renal complications has been consistently associated with poor clinical outcomes. Identifying the risk factors for AKI and CKD, and understanding their contribution to non-relapse mortality (NRM), is essential for optimizing patient management and outcomes. Our study aims to underscore the determinants of post-transplant renal dysfunction and their association with NRM in HSCT patients.

Methods

We conducted a large-scale, multi-center observational cohort study involving adult patients (aged ≥18 years) who underwent their first allogeneic HSCT at National Taiwan University Hospital and National Taiwan University Cancer Center between January 2015 and September 2023. Patients were not enrolled if they had a history of prior HSCT, received autologous transplantation, or had undergone renal replacement therapy prior to HSCT. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. AKI developed within the first 100 days post HSCT was defined and classified according to the KDIGO criteria. CKD was defined as an eGFR <60 mL/min/1.73 m². Continuous variables were compared using the Mann–Whitney U test. Categorical variables were analyzed using chi-square or Fisher's exact tests, as appropriate.

Results

This retrospective study included 963 patients which consisted of 53.6% males with a median age of 51 years. Non-myeloablative conditioning was used in 60.8% of cases. Related HLA-matched donors accounted for 33.0% of transplants. The median CD34+ cell dose was 4.88 × 10⁶/kg. Antithymocyte globulin was used in 65.4% of conditioning regimens, and cyclosporin was the primary graft-versus-host disease (GvHD) prophylaxis (94.6%). 70.8% of individuals (682) developed AKI and 22.3% of individuals (215) developed CKD. Those with AKI had a significantly higher proportion of male sex (34.9% vs. 18.7%, P < 0.001), lower BMI (median 23.0 vs. 23.8, P = 0.001), lower albumin levels (median 3.8 vs. 4.0 g/dL, P < 0.001), higher infection rates (42.5% vs. 27.3%, P < 0.001) and higher baseline eGFR (median 108.1 vs. 105.8 mL/min/1.73m², P = 0.007). Age, HCT-CI scores, and pre-existing CKD did not differ significantly between groups. Development of CKD after HSCT was associated with prior AKI (HR 1.88, 95% CI: 1.08–3.28), prior AKD (HR 2.11, 95% CI: 1.19–3.74), and prior dialysis (HR 4.10, 95% CI: 1.00–16.78). Acute GvHD was also associated with CKD (HR 1.58, 95% CI: 1.09–2.30, P < 0.05), with higher hazard ratios observed in grade III (HR 3.20, 95% CI: 1.85–5.59, P < 0.001) and grade IV aGvHD (HR 4.06, 95% CI: 2.08–7.95, P < 0.001). Chronic GvHD (cGvHD) also significantly increased CKD risk (HR 1.69, 95% CI: 1.14–2.52, P < 0.05), especially in cases with extensive involvement (HR 1.48, 95% CI: 1.02–2.16, P < 0.05). In the unadjusted analysis of NRM following allogeneic HSCT, several risk factors overlapped with those associated with AKI. Male sex (HR 1.41, 95% CI: 1.04–1.93, P < 0.05), reduced baseline serum albumin (HR 0.26, 95% CI: 0.17–0.40, P < 0.001) and higher infections rates (HR 1.82, 95% CI: 1.11–3.00, P < 0.05) were all associated with higher NRM.

Conclusions

Several baseline factors associated with AKI, such as male sex, low albumin levels, and higher infection rates, were also independently linked to increased NRM. Renal complications represent major contributors to NRM in HSCT patients. These findings highlight the need for early intervention and integrated renal care in HSCT management.

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2025
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