LONGITUDINAL ASSESSMENT OF CHRONIC KIDNEY DISEASE IN CHILDREN AND YOUNG ADULTS WITH SICKLE CELL ANEMIA
- 1Gerência de Desenvolvimento Técnico-Científico, Fundação Hemominas, Belo Horizonte, MG, Brazil
- 2Faculdade de Medicina (FM), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
Abstract
Introduction: Sickle cell nephropathy is a major cause of morbidity and premature mortality, but its natural history is poorly understood. Aim: To determine the longitudinal prevalence of chronic kidney disease (CKD) and identify predictors of persistent CKD among children and young adults with sickle cell anemia. Methods: A prospective cohort study was conducted at the Belo Horizonte Sickle Cell Clinic of Fundação Hemominas. Patients with HbSS aged 1.7–21 years were enrolled during routine visits between 2016 and 2021. Baseline clinical and laboratory data were collected at steady state, and urinary biomarkers were measured using multiplex xMAP assays or ELISA. Only participants with kidney assessments at two visits > 3 months apart were included to confirm CKD according to KDIGO criteria. Estimated glomerular filtration rate was calculated using the Bedside Schwartz equation for participants < 18 lt; 18 years and the 2021 CKD Epidemiology Collaboration creatinine equation for adults. Albuminuria was defined as urinary albumin-to-creatinine ≥ 30 mg/g. CKD stage was classified according to KDIGO guidelines using both eGFR and albuminuria at baseline and follow-up visits. Participants with CKD stage ≥ 1 at both study visits were classified as having persistent CKD and compared with those without CKD. Multivariable logistic regression was used to identify baseline predictors independently associated with persistent CKD, adjusting for disease-modifying therapy. Results: A total of 180 participants were included, with a median baseline age of 10.7 years (IQR, 7.5–15.4); 89 (49.4%) were male. The median interval between the baseline and follow-up sample collections was 3.73 years (IQR, 2.60–4.58 years). One hundred twenty-one (71.7%) participants were receiving disease-modifying therapy [hydroxyurea (HU), chronic blood transfusion, or both]. Persistent CKD was identified in 48 participants (26.7%; 95% CI 20.2-33.1%), including 41 (85.4%) at stage 1, 6 (12.5%) at stage 2, and 1 (2.1%) at stage 3 of CKD. During follow-up, 25 of 178 participants (14.0%) progressed to a worse KDIGO category, whereas 153 (86.0%) remained stable. Higher baseline levels of total bilirubin, osteoactivin, and Angiotensin (Ang) II/Ang-(1–7) ratio were associated with persistent CKD in univariable analyses (P < 0.05). In multivariable logistic regression adjusted for disease-modifying therapy, higher baseline total bilirubin (OR 1.40, 95%CI 1.10–1.78; P = 0.006) and baseline Ang II/Ang-(1–7) ratio (OR 8.11, 95%CI 2.00–33.00; P = 0.003) remained independently associated with CKD. Discussion: One-quarter of participants had persistent CKD, reinforcing early screening and treatment. Higher baseline total bilirubin supports the role of chronic hemolysis in kidney injury. Furthermore, a higher Ang II/Ang-(1–7) ratio suggests a predominance of the classical renin–angiotensin system activation, promoting glomerular hypertension, inflammation, and fibrosis. These findings raise the possibility that therapeutic strategies aimed at restoring the balance of the renin–angiotensin system by reducing the Ang II/Ang-(1–7) ratio may help prevent or slow CKD progression in SCA. Conclusions: Persistent CKD was common in children and young adults with SCA. These findings suggest that chronic hemolysis and renin–angiotensin system dysregulation may play complementary roles in the development and persistence of CKD, highlighting potential therapeutic targets to delay kidney disease progression.
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BibTeX
@article{belisario2026longitudinal,
title = {{LONGITUDINAL ASSESSMENT OF CHRONIC KIDNEY DISEASE IN CHILDREN AND YOUNG ADULTS WITH SICKLE CELL ANEMIA}},
author = {André Rolim BELISÁRIO and Marcos Borato VIANA and Ana Cristina SIMÕES E SILVA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.108368},
url = {https://doi.org/10.1016/j.htct.2026.108368},
note = {CC BY},
}
RIS
TY - JOUR
TI - LONGITUDINAL ASSESSMENT OF CHRONIC KIDNEY DISEASE IN CHILDREN AND YOUNG ADULTS WITH SICKLE CELL ANEMIA
AU - André Rolim BELISÁRIO
AU - Marcos Borato VIANA
AU - Ana Cristina SIMÕES E SILVA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.108368
UR - https://doi.org/10.1016/j.htct.2026.108368
AB - Introduction: Sickle cell nephropathy is a major cause of morbidity and premature mortality, but its natural history is poorly understood. Aim: To determine the longitudinal prevalence of chronic kidney disease (CKD) and identify predictors of persistent CKD among children and young adults with sickle cell anemia. Methods: A prospective cohort study was conducted at the Belo Horizonte Sickle Cell Clinic of Fundação Hemominas. Patients with HbSS aged 1.7–21 years were enrolled during routine visits between 2016 and 2021. Baseline clinical and laboratory data were collected at steady state, and urinary biomarkers were measured using multiplex xMAP assays or ELISA. Only participants with kidney assessments at two visits > 3 months apart were included to confirm CKD according to KDIGO criteria. Estimated glomerular filtration rate was calculated using the Bedside Schwartz equation for participants < 18 lt; 18 years and the 2021 CKD Epidemiology Collaboration creatinine equation for adults. Albuminuria was defined as urinary albumin-to-creatinine ≥ 30 mg/g. CKD stage was classified according to KDIGO guidelines using both eGFR and albuminuria at baseline and follow-up visits. Participants with CKD stage ≥ 1 at both study visits were classified as having persistent CKD and compared with those without CKD. Multivariable logistic regression was used to identify baseline predictors independently associated with persistent CKD, adjusting for disease-modifying therapy. Results: A total of 180 participants were included, with a median baseline age of 10.7 years (IQR, 7.5–15.4); 89 (49.4%) were male. The median interval between the baseline and follow-up sample collections was 3.73 years (IQR, 2.60–4.58 years). One hundred twenty-one (71.7%) participants were receiving disease-modifying therapy [hydroxyurea (HU), chronic blood transfusion, or both]. Persistent CKD was identified in 48 participants (26.7%; 95% CI 20.2-33.1%), including 41 (85.4%) at stage 1, 6 (12.5%) at stage 2, and 1 (2.1%) at stage 3 of CKD. During follow-up, 25 of 178 participants (14.0%) progressed to a worse KDIGO category, whereas 153 (86.0%) remained stable. Higher baseline levels of total bilirubin, osteoactivin, and Angiotensin (Ang) II/Ang-(1–7) ratio were associated with persistent CKD in univariable analyses (P < 0.05). In multivariable logistic regression adjusted for disease-modifying therapy, higher baseline total bilirubin (OR 1.40, 95%CI 1.10–1.78; P = 0.006) and baseline Ang II/Ang-(1–7) ratio (OR 8.11, 95%CI 2.00–33.00; P = 0.003) remained independently associated with CKD. Discussion: One-quarter of participants had persistent CKD, reinforcing early screening and treatment. Higher baseline total bilirubin supports the role of chronic hemolysis in kidney injury. Furthermore, a higher Ang II/Ang-(1–7) ratio suggests a predominance of the classical renin–angiotensin system activation, promoting glomerular hypertension, inflammation, and fibrosis. These findings raise the possibility that therapeutic strategies aimed at restoring the balance of the renin–angiotensin system by reducing the Ang II/Ang-(1–7) ratio may help prevent or slow CKD progression in SCA. Conclusions: Persistent CKD was common in children and young adults with SCA. These findings suggest that chronic hemolysis and renin–angiotensin system dysregulation may play complementary roles in the development and persistence of CKD, highlighting potential therapeutic targets to delay kidney disease progression.
SN - 2531-1379
SN - 2531-1387
ER -