Kidney Outcomes after Hematopoietic Cell Transplantation in Children and Young Adults with Sickle Cell Disease

Background:

Kidney damage in children with sickle cell disease (SCD) begins in the first decade of life with development of chronic kidney disease (CKD), a sequalae progressive kidney injury. CKD contributes to an increased morbidity and mortality, with early development of end stage kidney disease which contributes to early death in SCD. Hematopoietic cell transplantation (HCT) serves as a potentially curative therapy for patients with SCD with the possibility of stabilization or improvement in end organ function, however conditioning and other transplant therapies can be nephrotoxic. We sought to 1) assess the prevalence of acute kidney injury (AKI) in the first 48 hrs and 7 days after HCT, 2) determine kidney function at baseline, 1-, 6-, 12- and 24-months after HCT, 3) assess the prevalence of hyperfiltration defined by an eGFR > 135 mL/min/1.73m², and 4) assess prevalence of chronic kidney disease after HCT by an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m².

Methods

Children and young adults with SCD received either a matched sibling donor (MSD) or a haploidentical donor (HAPLO) HCT following a reduced toxicity conditioning with alemtuzumab, thiotepa and low dose total body irradiation (NCT04362293). Patients were receiving either hydroxyurea (HU) or chronic transfusion therapy (CTT) before HCT. All patients received a fresh apheresis derived peripheral blood hematopoietic cell graft. Sirolimus was used for graft versus host disease prophylaxis for 6-12 months post-HCT, with additional post-transplant cyclophosphamide for HAPLO recipients. The prevalence of AKI was assessed in the first 48hrs and 7 days post-HCT using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline; 0.3 mg/dL increase of serum creatinine or 1.5x increase from baseline. Kidney function was determined at baseline, 1-, 6-, 12- and 24-months after HCT by calculating eGFR using the bedside Schwartz formula.

Results

Twenty patients with SCD underwent HCT of which eleven received HAPLO HCT and nine received MSD HCT. Participants were majority male (60%) with a median age of 15.3 years (range: 6.5-23.5 years) at time of HCT. All patients engrafted and had expected HCT related acute toxicities. AKI was not observed in the first 48 hrs or 7 days after the cellular infusion in any participant. At baseline, median eGFR was 145 [range 98.5-264] mL/min/1.73m² and decreased to 129 [range 86.5-199] mL/min/1.73m² by 6 months. The median eGFR at 12-months was 137 [range 88.5-195] mL/min/1.73m². The prevalence of hyperfiltration decreased from baseline, with 80% (16/20) at baseline versus 33.33% (6/18) at 6 months and 58.82% (10/17) at 1 year. With 8 patients having 2-year follow-up, the median eGFR at 2 years after HCT was 118 mL/min/1.73m² with only a 25% (2/8) prevalence of hyperfiltration. At baseline there was no evidence of CKD, with a 2-year prevalence of 12.5% (1/8).

Discussion

This study demonstrates that this reduced toxicity conditioning HCT regimen is not associated with AKI early after HCT. Chronic kidney disease compromised a small percent of our population and long-term kidney function stabilized with decrease in prevalence of hyperfiltration. These findings need to be confirmed in a larger SCD HCT patient cohort.