1 - Paediatric Nephrology Unit, Department of Paediatrics, Hospital Dona Estefania, Centro Hospitalar Universitario De Lisboa Central, Lisbon, Portugal
2 - Laboratório de Genética e Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
3 - Department Of Paediatrics, Hospital Dona Estefania, Centro Hospitalar Universitario de Lisboa Central, Lisbon, Portugal
4 - Paediatric Haematology Unit, Department of Paediatrics, Hospital Dona Estefania, Centro Hospitalar Universitario de Lisboa Central, Lisbon, Portugal,
5 - Department of Paediatrics, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal
6 - Department of Paediatrics, Hospital Beatriz Angelo, Loures, Portugal
7 - Centro Cardiovascular da Universidade de Lisboa (ccul), Centro Académico Médico de Lisboa (caml), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
- 54th ESPN Annual Meeting, Ljubljana, Slovenia, 22-25/06/2022, pitch poster
Introduction: Sickle cell nephropathy (SCN) affects 30-50% of SCD patients and may lead to premature death. Glomerular filtration ratio (GFR) and urine albumin-to-creatinine ratio (uACR) become altered only in advanced SCN. The main goal of the BIODREPA study is to assess non-invasive biomarkers of kidney injury as a tool to detect SCN in children.
Material and methods: Multicentre prospective cohort study of paediatric patients with SCD. The primary outcome was a composite of decreased GFR (30 mg/g), or abnormal findings in kidney ultrasound. Urinary levels of alpha-glutathione S-transferase (a-GST), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were compared between groups defined according to the primary outcome.
Results: We report data from the 65 patients included in the initial cross-sectional analysis of the BIODREPA study. The median age was 8.4 years (IQR 5.5-12.5) and 57% were male. Median GFR was 149 mL/ min/1,73 m2 (IQR 124-164). The primary outcome was met by 59.7% of the cohort (low GFR in 0%; albuminuria in 6.2%; and abnormal kidney ultrasound in 57.1%). The median (IQR) urinary levels of a-GST, NGAL, and KIM-1 normalized to urinary creatinine in ng/mg were: 20.8 (11.1- 53.6), 3.2 (1.4-7.9), and 1.7 (0.7-3.3), respectively. In a comparison between groups according to the primary outcome, a-GST urinary levels were significantly higher in patients with albuminuria (52.1 versus 19.1 ng/dL, p-value 0.014). Despite that, none of the biomarkers was a significant predictor of the primary renal outcome in the logistic regression model adjusted for age and sex.
Conclusions: In the preliminary results of the BIODREPA study, the prevalence of renal involvement among children with SCD was about 60%. The urinary a-GST may be the most promising of the biomarkers studied for early detection of SCN. Future research should prospectively assess consecutive patients with sickle cell disease to identify early predictors of kidney injury.
Keywords: a-GST, KIM-1, NGAL, sickle cell nephropathy