Key Findings
- Purpose
To evaluate glomerular, tubular, and endothelial biomarkers in patients with SCD, focusing primarily on differences between hemolysis-dominant (HD) and vaso-occlusion–dominant (VOD) subphenotypes. - Population (Model)
This monocenter exploratory pilot study included 25 patients with SCD: 21 with HbSS and 4 with HbSC. Primary analyses focused on 12 adults with HbSS: 8 classified as HD and 4 as VOD. Blood and urine samples were collected during routine outpatient visits when participants were clinically stable and had no signs of a sickle cell crisis. Longitudinal sampling was available for 11 of the 12 adults, with samples collected over a median follow-up of approximately 13 months. - Headline Result
Moderately increased albuminuria, referred to in the study as microalbuminuria, was identified in 5 adults, including 4 of 8 participants in the HD subgroup and 1 of 4 in the VOD subgroup; no macroalbuminuria was observed. Urinary NGAL and KIM-1 were within reference intervals and did not distinguish between the HD and VOD subphenotypes, while urinary cystatin C was largely below the assay’s limit of quantification. Descriptive analyses suggested lower serum cystatin C, albuminuria, and urinary α1-microglobulin/creatinine ratios among hydroxyurea-treated participants, but the groups were small and the differences were not statistically significant. Serum soluble fms-like tyrosine kinase-1 (sFLT-1) correlated with lactate dehydrogenase (LDH), reticulocyte count, and direct bilirubin, supporting a preliminary hemolysis-associated endothelial activation signature. - Why It Matters
Sickle cell nephropathy can develop early and progress to chronic kidney disease, but clinically useful biomarkers for early renal injury and disease subphenotyping remain under investigation. The observed relationship between sFLT-1 and hemolysis markers suggests that hemolysis-associated endothelial activation may be detectable even when overt renal abnormalities are limited.
- Evidence Gaps & Limitations
This was a small, monocenter exploratory study, with only 12 adults with HbSS included in the primary HD-versus-VOD analysis. The cohort was clinically stable and did not include patients experiencing recent sickle cell crises, limiting conclusions about biomarker behavior during acute complications. The associations are exploratory and do not establish causality or show that sFLT-1 predicts future kidney disease, vaso-occlusive events, or other clinical outcomes. Larger, multicenter longitudinal studies are needed to validate these findings and determine whether the biomarkers have diagnostic, prognostic, or treatment-monitoring value before clinical implementation can be considered.
Source: Journal of Sickle Cell Disease- “Biomarker profiles in distinct clinical subphenotypes of SCD: an explorative study”
Regulatory & Guideline Watch
The 2019 American Society of Hematology (ASH) guideline suggests angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin II receptor blocker (ARB) therapy for children and adults with SCD and albuminuria, with monitoring of renal function and potassium. The recommendation is based on very-low-certainty evidence. The ASH guideline did not evaluate the evidence for albuminuria screening and refers to the National Heart, Lung, and Blood Institute (NHLBI) recommendation to begin annual screening for proteinuria at age 10. The 2014 NHLBI Expert Panel Report recommends screening all individuals with SCD for proteinuria beginning at age 10 and repeating screening annually if the result is negative. A positive screen should be followed by a first-morning urine albumin-to-creatinine ratio; if the ratio is abnormal, renal specialist consultation or referral should be considered.