Oyindamola Christiana Adebayo,1,2, DieuMerci Kabasele Betukumesu,3 Agathe Bikupe Nkoy,2,3 ,Oluyomi Modupe Adesoji,4 Pepe Mfutu Ekulu,3 Lambertus P. Van den Heuvel,2,5 Elena N. Levtchenko2,6,* and Veerle Labarque1,7,*
1Centre for Molecular and Vascular
Biology, Department of Cardiovascular
Sciences, Katholieke Universiteit Leuven,
Leuven, 2Department of Development and
Regeneration, Katholieke Universiteit
Leuven, Leuven, Belgium, 3Division of
Nephrology, Department of Paediatrics,
Faculty of Medicine, University Hospital of
Kinshasa, University of Kinshasa,
Kinshasa, Democratic Republic of Congo,
4Cologne Centre for Genomics, University
of Cologne, Cologne, Germany,
5Department of Paediatric Nephrology,
Radboud University Medical Centre,
Nijmegen, the Netherlands, 6Department of
Paediatric Nephrology, University Hospitals
Leuven, Leuven, and 7Department of
Paediatric Haemato-Oncology, University
Hospitals Leuven, Leuven, Belgium
Summary
Clinical and genetic factors have been reported as influencing the development
of sickle cell nephropathy (SCN). However, such data remain limited
in the paediatric population. In this cross-sectional study, we enrolled 361
sickle cell disease children from the Democratic Republic of Congo. Participants
were genotyped for the beta (b)-globin gene, apolipoprotein L1
(APOL1) risk variants, and haem oxygenase-1 (HMOX1) GT-dinucleotide
repeats. As markers of kidney damage, albuminuria, hyperfiltration and
decreased estimated glomerular filtration with creatinine (eGFRcr) were
measured. An association of independent clinical and genetic factors with
these markers of kidney damage were assessed via regression analysis.
Genetic sequencing confirmed sickle cell anaemia in 326 participants. Albuminuria,
hyperfiltration and decreased eGFRcr were present in 65 (20%),
52 (16%) and 18 (55%) patients, respectively. Regression analysis revealed
frequent blood transfusions, indirect bilirubin and male gender as clinical
predictors of SCN. APOL1 high-risk genotype (G1/G1, G2/G2 and G1/G2)
was significantly associated with albuminuria (P = 004) and hyperfiltration
(P = 0001). HMOX1 GT-dinucleotide long repeats were significantly associated
with lower eGFRcr. The study revealed a high burden of kidney
damage among Congolese children and provided evidence of the possible
role of APOL1 and HMOX1 in making children more susceptible to kidney
complications.
Keywords: apolipoprotein L1, children, haem oxygenase-1, kidney disease,
sickle cell anaemia.
First published online 20 September 2021
doi: 10.1111/bjh.17832
2021 British Society for Haematology and John Wiley & Sons Ltd
British Journal of Haematology, 2022, 196, 204–214
