#4385 RELEVANCE OF REPEATED ALBUMINURIA AND GLOMERULAR FILTRATION RATE IN A LARGE COHORT OF SICKLE CELL ANEMIA CHILDREN LIVING IN A RESOURCE-LIMITED AREA
Authors: Nkoy Agathe , Mumaka Floreen , Ngonde Ange , Kitenge Robert , Tshilolo Leon , Van den Heuvel Lambertus P , Labarque Veerle , Ekulu Pepe , Levtchenko Elena 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is associated with significant morbidity and mortality among patients with sickle cell anemia (SCA). Glomerular hyperfiltration (GHF) and albuminuria are known as early manifestations of kidney disease occurring in early childhood and can predict the progression to CKD in these patients. Studies reported the prevalence of these kidney abnormalities in SCA children using a single measure and their association with genetic risk factors, especially the co-inheritance of APOL1 risk variants (RVs). However, data on the prevalence of persistent kidney abnormalities (based on the KDIGO CKD definition) and their association with APOL1 RVs are limited in SCA children, particularly those living in sub-Saharan Africa. This study aimed: (i) to determine the prevalence of persistent kidney abnormalities (albuminuria and/or GHF) in SCA children living in the Democratic Republic of Congo (DRC); and (ii) to assess the association between persistent kidney abnormalities with clinical and genetic risk factors.

Method
From March 2021 to December 2022, we prospectively enrolled 585 steady state SCA children aged 2 to 18 years (male gender 278/585; 47.5%). The SCA status was confirmed through the molecular sequencing of beta-globin gene. Clinical and biological parameters were obtained. All participants were genotyped for apolipoprotein-L1 (APOL1) G1 (rs73885319, rs60910145) and G2 (rs71785313) variants. APOL1 high-risk genotype (HRG) was defined by the presence of 2 risk variants (G1/G1, G2/G2, and G1/G2), and low-risk genotype (LRG) by the presence of 0 or 1 risk variant. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) ≥ 30mg/g. The estimated glomerular filtration rate (eGFRcr) was calculated using the original Schwartz formula and GHF was defined as eGFRcr ≥ 180 ml/min/1.73 m2 for children between 2-10 years of age and &gt; 140 ml/min/1.73 m2 for children more than 10 years of age. All measurements were repeated at least three months later in participants who presented with kidney abnormalities at the first screening. The main outcome parameter was persistent albuminuria or persistent GHF for more than three months.

Results
At enrollment, 234/585 (40.0%) participants presented with kidney abnormalities, among which 80/585 (13.7%) with albuminuria and 171/585 (29.2%) with hyperfiltration. From participants found with kidney abnormalities at the first screening, 176/234 (75.2%) were available for repeated screening: 56/176 (31.8%) presented with persistent kidney abnormalities and 120/176 (68.2%) had a regression of kidney abnormalities without any treatment. Out of 176 participants who benefited from repeated screening, 57 had baseline albuminuria and 130 had baseline GHF. Persistent albuminuria and persistent GHF were found in 38.6% (22/57) and 28.5% (37/130), respectively. Multivariate logistic regression revealed that APOL1 HRG was significantly associated with persistent albuminuria (OR 3.4, 95CI 1.1-10.7, p = 0.037), while male gender was significantly associated with persistent GHF (OR 2.1, 95CI 1.0-4.2, p = 0.042).

Conclusion
A significant proportion (almost 70.0%) of SCA children who had kidney abnormalities at the first measure, presented regression of these abnormalities without any reno-protective drugs. This result emphasizes the importance of repeating screening at least three months later to confirm CKD, as recommended by the KDIGO Guidelines. This strategy will reduce the need for unnecessary treatment, which represents a high financial burden in a resource-limited area.