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Hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD) may not be associated with a significant increase in chronic kidney disease incidence or prevalence at 2 and 3 years post-HSCT, according to study results presented by Emily Limerick, MD, of the National Heart, Lung, and Blood Institute, of the National Institutes of Health in Washington, DC, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“The characteristic sickling of red blood cells occurs in deoxygenated conditions, particularly in the hypoxic, acidotic, and hyperosmolar environment of the renal medulla,” said Dr Limerick. “[Sickle cell] nephropathy is common and a significant problem, among patients with sickle cell disease. One third of whom develop chronic kidney disease, and the overall survival for those with chronic kidney disease is reduced by 10 years.”
Though HSCT can be curative for patients with SCD, kidney dysfunction may be an unintended consequence following HSCT by potentially exacerbating acute renal injury (AKI) already present with SCD. Therefore, the investigators studied the prevalence of chronic kidney disease before and after HSCT and the incidence of chronic kidney disease after HSCT. They assessed estimated glomerular filtration rate (eGFR) and changes in urine albumin to creatinine ratio (UACR) after HSCT, as well as the incidence of AKI within 100 days of HSCT.
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In total, 106 patients with SCD (mean age, 32.5; range, 10-65; 56% men) who underwent HSCT at the National Institutes of Health Clinical Center were enrolled in the prospective cohort study. The HSCT regimens included HLA-matched sibling (n=71) and haploidentical HSCT (n=26) with nonmyeloablative conditioning, and gene therapy (n=9) with a myeloablative conditioning. Renal function was measured at baseline and compared to renal function 1 year after transplantation, and compared again annually for up to 3 years.
The baseline prevalence of chronic kidney disease (eGFR <60mL/min/1.73 m2) was 6%. After HSCT, an increase was noted after 1 year (48% at baseline vs 62% at 1 year; P =.02); this increase was attributed to the presence of albuminuria and not a decline in eGFR. No significant differences in the prevalence of chronic kidney disease occurred in years 2 and 3 (55% for both). The incidence of chronic kidney disease any time after HSCT was 1% (eGFR <60mL/min/1.73 m2) and 11% (eGFR <60mL/min/1.73 m2 and/or UACR >30 mg/g).
Following HSCT, the median eGFR remained within the normal range throughout the follow-up period with a declining trend over time (median eGFR, 139.7 mL/min/1.73 m2 at baseline, 130 mL/min/1.73m2 at 1 year, 126 mL/min/1.73 m2 at 2 years, and 119 mL/min/1.73 m2 at 3 years; P <.0001).
After HSCT, a statistically significant decrease in hyperfiltration (eGFR ≥150 mL/min/1.73 m2) occurred over time (34% at baseline to 11.7% at 3 years; P =.0006 for adjusted longitudinal model) and was accompanied by a corresponding increase in patients with normal eGFR (60-149 mL/min/1.73 m2; 60% at baseline to 80% at 3 years).
At 1 year following HSCT, median UACR increased relative to baseline (62.2 mg/g vs 24.3 mg/g; P =.007) but subsequently declined in years 2 and 3 (38.9 mg/g and 36.2 mg/g, respectively).
Within the 100 days following HSCT, 58% of patients experienced AKI, the majority of which were mild cases (77% mild/stage 1; 13% moderate/stage 2; and 10% severe/stage 3). In addition, AKI was not associated with an increased risk for mortality (P =.071).
The overall survival was 96%, with only 4 deaths in the cohort.
“In conclusion, transplant in patients with sickle cell disease is associated with a stable chronic kidney disease prevalence and incidence at both two and three years after transplant,” said Dr Limerick.
A noted limitation of the study was that 25% of participants had follow-up of 2 years or less.
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.
Reference
Limerick E, Jeffries N, Diamantidis C, et al. Renal function is preserved after hematopoietic stem cell transplantation for sickle cell disease. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 505.
