[en] [en] BACKGROUND: Serum creatinine (SCr), the most used biomarker to evaluate glomerular filtration rate (GFR), might be inaccurate in children with sickle cell anemia (SCA). In this context, cystatin C (SCys) could be of interest. This study evaluated the performance of commonly used SCr- and SCys-based estimated GFR (eGFR) equations in African children with SCA.
METHODS: This cross-sectional study included 109 steady-state children with SCA aged 3-18 years, from the Democratic Republic of Congo. Measured GFR (mGFR) was obtained using iohexol plasma clearance. eGFR was calculated using commonly used SCr- and SCys-based equations in children. The performance of these equations was evaluated by calculating the bias, precision, and accuracy within 30% (P30) of mGFR.
RESULTS: The mean age of participants was 9.9 ± 4.2 years, and 48.6% were female. The median mGFR was 142 (IQR 119-169) mL/min/1.73 m2. Of the equations studied, the FAS-Age SCr had the lowest bias (0.9 mL/min/1.73 m2). However, the 95% limit of agreement was very wide (-80.3 to + 81.6). SCr failed to rise in an age-dependent manner, reflecting a progressive loss of muscle mass or increased tubular secretion. All SCys-based equations underestimated GFR and failed to detect hyperfiltration, but there was no age-related change in bias.
CONCLUSION: These data show that all common eGFR equations using SCr or SCys poorly predict mGFR in African children with SCA. SCr-based equations potentially miss a decline in kidney function, which suggests that SCys could be the preferred marker in this population.
Disciplines :
Urology & nephrology
Author, co-author :
Nkoy, Agathe Bikupe ; Division of Nephrology, Department of Pediatrics, University Hospital of Kinshasa, University of Kinshasa, Kinshasa, Democratic Republic of Congo. agath.nkoy@gmail.com ; Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium. agath.nkoy@gmail.com
Mumaka, Floreen Maluwenze; Division of Nephrology, Department of Pediatrics, University Hospital of Kinshasa, University of Kinshasa, Kinshasa, Democratic Republic of Congo
Matoka, Therance Tobo; Division of Nephrology, Department of Pediatrics, University Hospital of Kinshasa, University of Kinshasa, Kinshasa, Democratic Republic of Congo
Ngonde, Ange; REZODREPANO SS, Kinshasa, Democratic Republic of Congo
Sumaili, Ernest Kiswaya ; Division of Nephrology, Department of Internal Medicine, University Hospital of Kinshasa, University of Kinshasa, Kinshasa, Democratic Republic of Congo
Bukabau, Justine Busanga ; Division of Nephrology, Department of Internal Medicine, University Hospital of Kinshasa, University of Kinshasa, Kinshasa, Democratic Republic of Congo
Labarque, Veerle ; Department of Pediatric Hematology, University Hospital Leuven, Leuven, Belgium ; Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
van den Heuvel, Lambertus P ; Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium ; Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
Bökenkamp, Arend ; Department of Pediatric Nephrology, Amsterdam University Medical Center, Amsterdam, The Netherlands
Cavalier, Etienne ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Levtchenko, Elena ; Department of Pediatric Nephrology, Amsterdam University Medical Center, Amsterdam, The Netherlands
Delanaye, Pierre ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie ; Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
Pottel, Hans ; Université de Liège - ULiège > Département des sciences cliniques ; Department of Public Health and Primary Care, KU Leuven Campus Kulak, Kortrijk, Belgium
Ekulu, Pépé Mfutu ; Division of Nephrology, Department of Pediatrics, University Hospital of Kinshasa, University of Kinshasa, Kinshasa, Democratic Republic of Congo
VLIR-UOS - Flemish Interuniversity Council. Bureau UOS ULiège - Université de Liège
Funding text :
A.B.N. was supported by the Global Minds Scholarship of VLIR-UOS and DGD (Belgium partner in development). Iohexol, enzymatic serum creatinine, and serum cystatin C measurements were supported by funding from the University of Li\u00E8ge.
Adebayo O Nkoy A Cheng C et al. Sickle cell disease: a neglected haemoglobinopathy disorder with a huge global burden Belg J Hematol 2023 14 41 58
Thomson AM McHugh TA Oron AP et al. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021 Lancet Haematol 2023 10 e585 e599 10.1016/S2352-3026(23)00118-7
Ataga KI Saraf SL Derebail VK The nephropathy of sickle cell trait and sickle cell disease Nat Rev Nephrol 2022 18 361 377 10.1038/s41581-022-00540-9 35190716 9832386
Adebayo OC Van den Heuvel LP Olowu WA et al. Sickle cell nephropathy: insights into the pediatric population Pediatr Nephrol 2022 37 1231 1243 10.1007/s00467-021-05126-4 34050806
Zahr RS Saraf SL Sickle cell disease and CKD: an update Am J Nephrol 2024 55 56 71 10.1159/000534865 37899028
Adebayo OC Nkoy AB van den Heuvel LP et al. Glomerular hyperfiltration: part 2—clinical significance in children Pediatr Nephrol 2023 38 2529 2547 10.1007/s00467-022-05826-5 36472656
Inusa BPD Liguoro I Tayo B et al. Reliability of different estimated glomerular filtration rate as measures of renal function in children with sickle cell disease Blood Cells Mol Dis 2021 91 10.1016/j.bcmd.2021.102590 34256313 102590
Ezegbogu M Abdulsalam K Creatinine assay methods in resource-limited settings: a review BJMLS 2018 3 37 47
Delanaye P Ebert N Melsom T et al. Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: how to measure glomerular filtration rate with iohexol? Clin Kidney J 2016 9 682 699 10.1093/ckj/sfw070 27679715 5036902
Delanaye P Melsom T Ebert N et al. Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: why to measure glomerular filtration rate with iohexol? Clin Kidney J 2016 9 700 704 10.1093/ckj/sfw071 27679716 5036903
Pottel H Measuring and estimating glomerular filtration rate in children Pediatr Nephrol 2017 32 249 263 10.1007/s00467-016-3373-x 27115887
Schwartz GJ Work DF Measurement and estimation of GFR in children and adolescents Clin J Am Soc Nephrol 2009 4 1832 1843 10.2215/CJN.01640309 19820136
Nkoy AB Mumaka FM Ngonde A et al. Relevance of repeated analyses of albuminuria and glomerular filtration rate in African children with sickle cell anaemia Br J Haematol 2024 205 1137 1146 10.1111/bjh.19603 38934404
Nkoy AB Matoka TT Bukabau JB et al. Estimated glomerular filtration rate: applicability of creatinine-based equations in African children Pediatr Nephrol 2024 39 3013 3022 10.1007/s00467-024-06349-x 38546762
Pottel H Adebayo OC Nkoy AB Delanaye P Glomerular hyperfiltration: part 1 — defining the threshold — is the sky the limit? Pediatr Nephrol 2023 38 2523 2527 10.1007/s00467-022-05827-4 36459244
Lebensburger JD Aban I Pernell B et al. Hyperfiltration during early childhood precedes albuminuria in pediatric sickle cell nephropathy Am J Hematol 2019 94 4 417 423 10.1002/ajh.25390 30592084 6408275
Fu EL Levey AS Coresh J et al. Accuracy of GFR-estimating equations based on creatinine, cystatin c or both in routine care Nephrol Dial Transplant 2023 16 518 524 10.1093/ndt/gfad219
Delanaye P Pottel H Botev R Con: should we abandon the use of the MDRD equation in favour of the CKD-EPI equation? Nephrol Dial Transplant 2013 28 1396 1403 10.1093/ndt/gft006 23780677
National Kidney Foundation K/DOQI Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Am J Kidney Dis 2002 39 S1 S266
Hoste L Dubourg L Selistre L et al. A new equation to estimate the glomerular filtration rate in children, adolescents and young adults Nephrol Dial Transplant 2014 29 1082 1091 10.1093/ndt/gft277 24046193
Pottel H Björk J Courbebaisse M Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate Ann Intern Med 2021 174 183 191 10.7326/M20-4366 33166224
Schwartz GJ Munoz A Schneider MF et al. New equations to estimate GFR in children with CKD J Am Soc Nephrol 2009 20 629 637 10.1681/ASN.2008030287 19158356 2653687
Schwartz J, Edelmann CM Jr, Edelmann J, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263
Schwartz GJ Gauthier B A simple estimate of glomerular filtration rate in adolescent boys J Pediatr 1985 106 522 526 10.1016/S0022-3476(85)80697-1 3973793
Pierce CB Muñoz A Ng DK et al. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease Kidney Int 2021 99 948 956 10.1016/j.kint.2020.10.047 33301749
Selistre L De Souza V Cochat P Gfr estimation in adolescents and young adults J Am Soc Nephrol 2012 23 989 996 10.1681/ASN.2011070705 22499586
Björk J Nyman U Delanaye P et al. A novel method for creatinine adjustment makes the revised Lund-Malmö GFR estimating equation applicable in children Scand J Clin Lab Invest 2020 80 456 463 10.1080/00365513.2020.1774641 32628043
Pottel H Delanaye P Schaeffner E et al. Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin c Nephrol Dial Transplant 2017 32 10.1093/ndt/gfw425 gfw425
Pottel H Nyman U Björk J et al. Extending the cystatin C based EKFC-equation to children – validation results from Europe Pediatr Nephrol 2024 39 1177 1183 10.1007/s00467-023-06192-6 37875730
Huang S-HS Sharma AP Yasin A et al. Hyperfiltration affects accuracy of creatinine eGFR measurement Clin J Am Soc Nephrol 2011 6 274 280 10.2215/CJN.02760310 20966120 3052216
Sharma AP Yasin A Garg AX Filler G Diagnostic accuracy of cystatin C–based eGFR equations at different GFR levels in children Clin J Am Soc Nephrol 2011 6 1599 1608 10.2215/CJN.10161110 21700821
Gaspari F Ruggenenti P Porrini E et al. The GFR and GFR decline cannot be accurately estimated in type 2 diabetics Kidney Int 2013 84 164 173 10.1038/ki.2013.47 23447062
Bassiony AI Nassar MK Shiha O et al. Renal changes and estimation of glomerular filtration rate using different equations in morbidly obese Egyptian patients Diabetes & Metabolic Syndrome: Clinical Research & Reviews 2020 14 1187 1193 10.1016/j.dsx.2020.06.046
Zemel BS Kawchak DA Ohene-Frempong K et al. Effects of delayed pubertal development, nutritional status, and disease severity on longitudinal patterns of growth failure in children with sickle cell disease Pediatr Res 2007 61 607 613 10.1203/pdr.0b013e318045bdca 17413865
Esezobor CI Akintan P Akinsulie A et al. Wasting and stunting are still prevalent in children with sickle cell anaemia in Lagos, Nigeria Ital J Pediatr 2016 42 10.1186/s13052-016-0257-4 27146866 4857256 45
Charlotte EE Ritha Carole MB Calixthe IP et al. Describing the growth and nutritional status of sickle cell disease children and adolescents with reference to WHO growth standards in Cameroon BMC Nutr 2022 8 154 10.1186/s40795-022-00650-4 36575492 9793582
Lebensburger JD Gossett J Zahr R et al. High bias and low precision for estimated versus measured glomerular filtration rate in pediatric sickle cell anemia Haematologica 2020 106 295 298 10.3324/haematol.2019.242156 7776243
Ware RE Rees RC Sarnaik SA et al. Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial J Pediatr 2010 156 66 70.e1 10.1016/j.jpeds.2009.06.060 19880138 4755353
Aygun B Mortier NA Smeltzer MP et al. Glomerular hyperfiltration and albuminuria in children with sickle cell anemia Pediatr Nephrol 2011 26 1285 1290 10.1007/s00467-011-1857-2 21559933 3187922
Alvarez O Miller ST Wang WC et al. Effect of hydroxyurea treatment on renal function parameters: results from the multi-center placebo-controlled BABY HUG clinical trial for infants with sickle cell anemia Pediatr Blood Cancer 2012 59 668 674 10.1002/pbc.24100 22294512 3396762
den Bakker E Gemke RJBJ Bökenkamp A Endogenous markers for kidney function in children: a review Crit Rev Clin Lab Sci 2018 55 163 183 10.1080/10408363.2018.1427041
Stevens PE Ahmed SB Carrero JJ KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease Kidney Int 2024 105 S117 S314 10.1016/j.kint.2023.10.018
