The validity of pediatric estimated glomerular filtration rate equations (eGFRs) in early stages of CKD including hyperfiltration is unknown. The purpose of this study was to develop an eGFR equation for adolescents with obesity and type 2 diabetes (T2D).
eGFRs were developed from iohexol-derived GFRs (iGFRs) in 26 overweight/obese (BMI > 85th percentile) youth and 100 with T2D from the iCARE (Improving renal Complications in Adolescents with T2D through REsearch) cohort. Twenty percent of the cohort was withheld as a validation dataset. Linear regression analyses were used to develop the best formula based on body size, sex, creatinine, urea, ± cystatin C. Comparable validity of commonly used eGFR equations was assessed.
Mean age 15.4 + 2.4 years, BMI Z-score 2.5 + 1.2, 61% female, and mean iGFR 129.0 + 27.7 ml/min/ 1.73 m2. The best adjusted eGFR formula (ml/min/1.73 m2) was 50.7 × BSA0.816 × (height (cm)/creatinine)0.405 × 0.8994 if sex = female | 1 otherwise. It resulted in 53.8% of eGFRs within 10% of measured iGFR and 96.2% within 30%. Bland–Altman 95% limits of agreement in the external dataset were − 37.6 to 45.5 ml/min/1.73m2 (bias = 3.96), and the correlation was 0.62. This equation performed better than all previously published creatinine-based eGFRs. cystatin C did not significantly improve results; however, some other cystatin C formulas also performed well.
The iCARE equation provides a more accurate creatinine-based eGFR in obese youth with and without T2D. Further studies are warranted to evaluate within-subject variability and applicability to lower GFRs and other populations.
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Pettitt DJ, Talton J, Dabelea D, Divers J, Imperatore G, Lawrence JM, Liese AD, Linder B, Mayer-Davis EJ, Pihoker C, Saydah SH, Standiford DA, Hamman RF, Group SfDiYS (2014) Prevalence of diabetes in U.S. youth in 2009: the SEARCH for diabetes in youth study. Diabetes Care 37:402–408
Demmer RT, Zuk AM, Rosenbaum M (2014) Diabetes prevalence among youth. Jama 312:1153
Dabelea D, Stafford JM, Mayer-Davis EJ, D’Agostino R Jr, Dolan L, Imperatore G, Linder B, Lawrence JM, Marcovina SM, Mottl AK, Black MH, Pop-Busui R, Saydah S, Hamman RF, Pihoker C, Group SfDiYR (2017) Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. Jama 317:825–835
Dart AB, Sellers EA, Martens PJ, Rigatto C, Brownell MD, Dean HJ (2012) High burden of kidney disease in youth-onset type 2 diabetes. Diabetes Care 35:1265–71
Group TS (2013) Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care 36:1735–1741
Kovesdy CP, Furth SL, Zoccali C, World Kidney Day Steering C (2017) Obesity and kidney disease: hidden consequences of the epidemic. Intern Med J 47:134–143
Levey AS, Inker LA, Coresh J (2014) GFR estimation: from physiology to public health. Am J Kidney Dis 63:820–834
Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637
Zappitelli M, Parvex P, Joseph L, Paradis G, Grey V, Lau S, Bell L (2006) Derivation and validation of cystatin C-based prediction equations for GFR in children. Am J Kidney Dis 48:221–230
Filler G, Priem F, Vollmer I, Gellermann J, Jung K (1999) Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate. Pediatr Nephrol 13:501–505
Tonneijck L, Muskiet MH, Smits MM, van Bommel EJ, Heerspink HJ, van Raalte DH, Joles JA (2017) Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol 28:1023–1039
Sochett EB, Cherney DZ, Curtis JR, Dekker MG, Scholey JW, Miller JA (2006) Impact of renin angiotensin system modulation on the hyperfiltration state in type 1 diabetes. J Am Soc Nephrol 17:1703–1709
Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G, Investigators GFRS (2012) Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 35:2061–2068
Jerums G, Premaratne E, Panagiotopoulos S, MacIsaac RJ (2010) The clinical significance of hyperfiltration in diabetes. Diabetologia 53:2093–2104
Bjornstad P, Nehus E, El Ghormli L, Bacha F, Libman IM, McKay S, Willi SM, Laffel L, Arslanian S, Nadeau KJ, Group TS (2018) Insulin sensitivity and diabetic kidney disease in children and adolescents with type 2 diabetes: an observational analysis of data from the TODAY clinical trial. Am J Kidney Dis 71:65–74
Gaspari F, Ruggenenti P, Porrini E, Motterlini N, Cannata A, Carrara F, Jimenez Sosa A, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Trevisan R, Bossi A, Zaletel J, Remuzzi G, Investigators GFRS (2013) The GFR and GFR decline cannot be accurately estimated in type 2 diabetics. Kidney Int 84:164–173
Dart AB, Wicklow BA, Sellers EA, Dean HJ, Malik S, Walker J, Chateau D, Blydt-Hansen TD, McGavock JM (2014) The improving renal complications in adolescents with type 2 Diabetes Through the Research (iCARE) Cohort Study: Rationale and Protocol 38:349–55
Ball BW, Sellers EA, Wicklow BA, Dean HJ, Canadian Task Force on Preventive Health C (2013) Diabetes guidelines. CMAJ 185:237
Haycock GB, Schwartz GJ, Wisotsky DH (1978) Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 93:62–66
Schwartz GJWH, Erway B, Nordin G, Seedmiller J, Lieske JC, Back S-E, Miller G, Eckfeldt JH (2018) Multicenter laboratory comparison of iohexol measurment. The Journal of Applied Laboratory Medicine: An AACC Publication, pp 1–14
de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J (2007) Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ 85:660–667
Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Munoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453
Pottel H, Hoste L, Martens F (2012) A simple height-independent equation for estimating glomerular filtration rate in children. Pediatr Nephrol 27:973–979
Pottel H, Hoste L, Dubourg L, Ebert N, Schaeffner E, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Mariat C, Martens F, Delanaye P (2016) An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant 31:798–806
Pottel H, Delanaye P, Schaeffner E, Dubourg L, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Goffin K, Pauwels S, Mariat C, Flamant M, Ebert N (2017) Estimating glomerular filtration rate for the full age spectrum from serum creatinine and cystatin C. Nephrol Dial Transplant 32:497–507
Counahan R, Chantler C, Ghazali S, Kirkwood B, Rose F, Barratt TM (1976) Estimation of glomerular filtration rate from plasma creatinine concentration in children. Arch Dis Child 51:875–878
Leger F, Bouissou F, Coulais Y, Tafani M, Chatelut E (2002) Estimation of glomerular filtration rate in children. Pediatr Nephrol 17:903–907
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470
Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD 3rd, Zhang YL, Greene T, Levey AS (2008) Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51:395–406
Ng DK, Jacobson LP, Brown TT, Palella FJ Jr, Martinson JJ, Bolan R, Miller ER 3rd, Schwartz GJ, Abraham AG, Estrella MM (2014) HIV therapy, metabolic and cardiovascular health are associated with glomerular hyperfiltration among men with and without HIV infection. AIDS 28:377–386
Bjornstad P, Cherney DZ (2018) Renal hyperfiltration in adolescents with type 2 diabetes: physiology, sex differences, and implications for diabetic kidney disease. Curr Diab Rep 18:22
Dart AB, Sharma A, McGavock J, Schwartz G, Chateau D, Blydt-Hansen T (2015) A new formula to estimate gfr in obese youth; the iCARE study equation
Thomas MC, Moran JL, Harjutsalo V, Thorn L, Waden J, Saraheimo M, Tolonen N, Leiviska J, Jula A, Forsblom C, Groop PH, FinnDiane Study G (2012) Hyperfiltration in type 1 diabetes: does it exist and does it matter for nephropathy? Diabetologia 55:1505–1513
Nelson RG, Bennett PH, Beck GJ, Tan M, Knowler WC, Mitch WE, Hirschman GH, Myers BD (1996) Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic renal disease Study group. N Engl J Med 335:1636–1642
Cachat F, Combescure C, Cauderay M, Girardin E, Chehade H (2015) A systematic review of glomerular hyperfiltration assessment and definition in the medical literature. Clin J Am Soc Nephrol 10:382–389
Har R, Scholey JW, Daneman D, Mahmud FH, Dekker R, Lai V, Elia Y, Fritzler ML, Sochett EB, Reich HN, Cherney DZ (2013) The effect of renal hyperfiltration on urinary inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Diabetologia 56:1166–1173
Kidney Disease Improving Global Outcomes CKDWG (2013) KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. 3:1
Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310
Hoste L, Dubourg L, Selistre L, De Souza VC, Ranchin B, Hadj-Aissa A, Cochat P, Martens F, Pottel H (2014) A new equation to estimate the glomerular filtration rate in children, adolescents and young adults. Nephrol Dial Transplant 29:1082–1091
De Souza V, Pottel H, Hoste L, Dolomanova O, Cartier R, Selistre L, Ranchin B, Hadj-Aissa A, Lemoine S, Cochat P, Dubourg L (2015) Can the height-independent Pottel eGFR equation be used as a screening tool for chronic kidney disease in children? Eur J Pediatr 174:1225–1235
Maahs DM, Bushman L, Kerr B, Ellis SL, Pyle L, McFann K, Bouffard A, Bishop FK, Nguyen N, Anderson PL (2014) A practical method to measure GFR in people with type 1 diabetes. J Diabetes Complicat 28:667–673
Ms. Paula Maier of the GFR Lab and the Toxicology lab at the University of Rochester Medical Center for the assay of iohexol and calculations of GFR.
This study was funded by the Canadian Diabetes Association #OG-3-11-3354-AD (Diabetes Canada) and the Manitoba Health Research Council #1475 (Research Manitoba). Dr. Schwartz also has funding from the NIH NIDDK U24 DK082194.
Conflict of interest
The iohexol (Omnipaque 300) was provided at no charge by GE Healthcare, Amersham Division (Princeton, NJ) for the purposes of this study following approval from Health Canada for this off-label use. The authors declare that they have no conflicts of interest.
All procedures performed in this study were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Dart, A.B., McGavock, J., Sharma, A. et al. Estimating glomerular filtration rate in youth with obesity and type 2 diabetes: the iCARE study equation. Pediatr Nephrol 34, 1565–1574 (2019). https://doi.org/10.1007/s00467-019-04250-6
- Type 2 diabetes