External validation of the Berlin equations for estimation ...
External validation of the Berlin equations for estimation of GFR in the elderlyAlshaer IM, 1 Kilbride HS,1 Stevens PE,1 Eaglestone G,1 Knight S,1 Carter JL,3 Delaney MP,1 Farmer CKT,1 Irving J,1 O’Riordan SE,2 Dalton RN,4 Lamb EJ.3 The Kent Kidney Care Centre,1 Health Care of the Older Person2 and Clinical Biochemistry,3 East Kent Hospitals University NHS Foundation Trust, Canterbury, Kent, UK and The Wellchild Laboratory,4 Evelina Childrens Hospital, London, UKBackground: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated (eGFR) using equations that adjust serum creatinine concentration for age, race and gender. The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPIcr) equation is recommended for populations of Northern European descent. Newer equations have been reported using cystatin C either alone (CKD-EPIcys) or in combination with creatinine (CKD-EPIcr-cys). Recently two equations derived from the Berlin Initiative Study (BIS1 and BIS2) have been reported and claim low bias and misclassification rates amongst older people. We have independently validated the BIS equations in a prospective cohort of people aged 74 years and over.Methods: Participants (n=394, median [range] age 80 [74-97] years; 48% male; exclusively white; 19% diabetic; 55% hypertensive; 38% albuminuric [>3 mg/mmol]) were recruited from nephrology clinics and the community. GFR was measured using an iohexol plasma clearance method (median [range] measured GFR 53.4 [7.2-100.9] mL/min/1.73 m2) and estimated using BIS1, BIS2, CKD-EPIcr, CKD-EPIcys and CKD-EPIcr-cys equations. Creatinine and cystatin C assays were calibrated against international standards.Results: The BIS1 and BIS2 equations underestimated (P<0.001) and the CKD-EPIcr and the CKD-EPIcr-cys eGFRs overestimated (P<0.001) measured GFR: the CKD-EPIcys equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P30]) of the BIS1 and BIS2 equations was superior (P=0.01 and P<0.001 respectively) to the CKD-EPIcr and CKD-EPIcr-cys equations respectively. Overall misclassification errors were similar amongst the equations.Bias (estimated minus measured GFR, mL/min/1.73 m2), median difference (95% CI)Accuracy, P30 (95% CI)Total misclassified (using GFR threshold of < or >60 mL/min/1.73 m2), n (%)BIS1-3.6 (-4.5 to -2.7)88 (84, 91)69 (17.5)BIS2-2.7 (-3.3 to -2.0)94 (91, 96)52 (13.2)CKD-EPIcr2.3 (1.3 to 3.4)83 (79, 87)59 (14.5)CKD-EPIcys-0.1 (-1.1 to 1.0)86 (82, 89)49 (12.4)CKD-EPIcr-cys1.2 (0.2 to 2.2)86 (82, 90)50 (12.7)Conclusions: The BIS equations provide reliable estimates of GFR in older white people. The BIS2 equation in particular is more accurate than previously published estimating equations in this population. The equations require testing in younger and other ethnic populations. ................
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