Article

HSCT Does Not Cause Kidney Damage in Sickle Cell Patients

Author(s):

Patients with sickle cell disease often suffer from acute kidney injuries and chronic kidney disease.

Emily Limerick

Emily Limerick

New research presented at the American Society of Hematology (ASH) 2021 meeting shows hematopoietic stem cell transplantation (HSCT) does not cause kidney damage for patients with sickle cell disease (SCD).

A team, led by Emily Limerick, MD, Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, identified the effect of HSCT on renal function in people with SCD.

Hematopoietic stem cell transplantation (HSCT) has potential as a curative therapy for patients with sickle cell disease. However, the treatment has been linked to kidney issues, particularly acute kidney injury (AKI) and chronic kidney disease (CKD).

Exploring this link is important because sickle cell disease is associated with altered renal function.

In the study, the investigators examined 195 patients who received HLA-matched sibling or haploidentical HSCT for SCD at Imperial College London (ICL), National Institutes of Health (NIH), and University of Illinois Chicago (UIC). The UIC cohort is comprised of pediatric patients with sickle cell disease.

All 3 sites used a nonmyeloablative conditioning.

The investigators assessed renal function qat baseline and annually for up-to 3-years.

The team identified the prevalence of CKD both before and after HSCT, as well as the estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ration (UACR) trends following HSCT. Finally, they identified the incidence of AKI within 100 days of HSCT. AKI was defined and staged in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

The investigators calculated eGFR with the CKD- epidemiology collaboration (CKD-EPI) equation for adults and Bedside Schwartz for children.

Overall, the median eGFR declined annually. However, the median eGFR remained within the normal range throughout the follow-up period and the baseline median eGFR was 138 ml/min/1.73m2. This declined by 7 in the first year of follow-up and by additional decreases of 5 and 3.6 ml/min/1.73m2 in subsequent years (P of 0.07, 0.0002, and 0.0002 for years 1, 2, and 3 for comparison to baseline from regression model of eGFR).

There were no differences in eGFR found for covariates in the model, whether it was haploidentical compared to matched sibling, engraftment status, gender, or site.

Ultimately the study provides a reason for hope as the downward eGFR trend could represent a meaningful improvement in renal function toward normal because hyperfiltration (eGFR ≥150 ml/min/1.73m2) was present in 28% of patients at baseline and steadily declined to 7% by 3 years post-HSCT.

There was also a corresponding increase in patients with normal eGFR (60-149 ml/min/1.73m2) from 59% at baseline to 88% at 3 years post-HSCT. In the ICL and NIH cohorts, 58% of patients developed AKI in the early post-HSCT period. 67% of which were mild, stage 1, 25% were moderate, stage 2, and 8% were severe, stage 3 AKI.

“This study demonstrates that HSCT in patients with SCD is associated with a transient increase in UACR but not associated with a significant increase in CKD prevalence by 3-years post-HSCT,” the authors wrote. “The stability of UACR compared to baseline by the 3-year time point suggests that even more mild renal damage may stabilize after HSCT. Our data indicate that nonmyeloablative HSCT for SCD does not lead to significant kidney dysfunction post-HSCT.”

The study, “Nonmyeloablative Transplant for Sickle Cell Disease Does Not Lead to Kidney Dysfunction Post-HSCT,” was published online by ASH.

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