Are prediction equations for glomerular filtration rate useful for the long-term monitoring of type 2 diabetic patients?

N estor Fontsere 2 3 Isabel Salinas 1 2 Jordi Bonal 2 3 Beatriz Bay es 2 3 Joaquim Riba 0 2 Ferran Torres 2 4 Jose Rios 2 4 Ana Sanmart 1 2 Ramo n Romero 2 3 0 Department of Nuclear Medicine, University Hospital Germans Trias i Pujol , Badalona 1 Department of Endocrinology 2 Department of Nephrology, Hospital de Terrassa , Ctra Torrebonica s/n, 08227, Terrassa, Barcelona, Spain 3 Department of Nephrology 4 Biostatistics and Epidemiology Laboratory, Universidad Auto noma de Barcelona , Barcelona, Spain Background. The aim of this study was to compare the accuracy of prediction equations [modification of diet in renal disease (MDRD), simplified MDRD, Cockcroft-Gault (CG), reciprocal of creatinine and creatinine clearance] in a cohort of patients with type 2 diabetes. Methods. A total of 525 glomerular filtration rates (GFRs) using 125I-iothalamate were carried out over 10 years in 87 type 2 diabetic patients. Accuracy was evaluated at three levels of renal function according to the baseline values obtained with the isotopic 2 method: hyperfiltration (GFR: >140 ml/min/1.73 m ; 140 isotopic determinations in 27 patients), normal renal function (GFR: 140-90 ml/min/1.73 m2; 294 isotopic determinations in 47 patients) and chronic kidney disease (CKD) stages 2-3 (GFR: 30-89 ml/min/ 1.73 m2; 87 isotopic determinations in 13 patients). The annual slope for GFR (change in GFR expressed as ml/min/year) was considered to ascertain the variability in the equations compared with the isotopic method during follow-up. Student's t-test was used to determine the existence of significant differences between prediction equations and the isotopic method (P < 0.05 with Bonferroni adjusted for five contrast tests). Results. In the subgroup of patients with hyperfiltration, a GFR slope calculated with 125I-iothalamate 4.8 4.7 ml/min/year was obtained. GFR slope in patients with normal renal function was 3.0 2.3 ml/ min/year. In both situations, all equations presented a significant underestimation compared with the isotopic GFR (P < 0.01; P < 0.05). In the subgroup of CKD stages 2-3, the slope for GFR with 125I-iothalamate was 1.4 1.8 ml/min/year. The best prediction The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: - equation compared with the isotopic method proved to be MDRD with a slope for GFR of 1.4 1.3 ml/ min/year (P: NS) compared with the CG formula 1.0 0.9 ml/min/year (P: NS). Creatinine clearance presented the greatest variability in estimation (P < 0.001). Conclusions. In the normal renal function and hyperfiltration groups, none of the prediction equations demonstrated acceptable accuracy owing to excessive underestimation of renal function. In CKD stages 23, with mean serum creatinine 133 mmol/l (1.5 mg/dl), the MDRD equation can be used to estimate GFR during the monitoring and follow-up of patients with type 2 diabetes receiving insulin, anti-diabetic drugs or both. Introduction Data from the US Renal Data System predict that the number of patients registered with end-stage renal disease (ESRD) in 1997 will have doubled by 2010, leading to approximately 700 000 patients with ESRD and 2.2 million patients in 2030 [1]. According to the current epidemiological data, type 2 diabetes is considered to be one of the most frequent causes of terminal chronic renal insufficiency and inclusion in renal substitution programmes. Simple, purified monitoring of renal function is of vital importance in this subgroup of patients for therapeutic measures aimed at reducing associated comorbidity factors to be applied early. Isotopic determination of the glomerular filtration rate (GFR) would be the gold standard method for determining renal function; however, it is an expensive option and not often used in clinical practice. The CockcroftGault formula (CG) is probably one of the most widely used prediction equations for the follow-up of renal function and for the dose adjustment of potentially nephrotoxic drugs [2]. The CG formula is an estimate of creatinine clearance originally developed in a population of 236 Canadian patients (209 males) with normal renal function and chronic kidney disease (CKD) stages 23 (creatinine clearance: 114.937.4 ml/min). The modification of diet in renal disease (MDRD) equation is the newest equation, used in demographic, biochemical and nutritional studies [3]. The MDRD formula was developed as an estimation of 125I-iothalamate renal clearance-based GFR measurement in a population of 1628 patients, with CKD stages 34 (mean GFR: 39.8 21.2 ml/min/ 1.73 m2). Both equations have been validated and analysed in large patient populations with chronic renal insufficiency, although their predictive capacity has been analysed little in other levels of renal function during the long-term follow-up of type 2 diabetes mellitus (DM) patients [3]. The aim of our study was to compare renal function and annual slope for GFR determined with the isotopic method and the different prediction equations [MDRD, simplified MDRD (sMDRD), CG and reciprocal of creatinine] and with the measurement of creatinine clearance using 24 h urine collection during the follow-up in a cohort of patients with type 2 diabetes. Subjects and methods Study population A total of 525 isotopic determinations of GFR were carried out between October 1989 and November 2003 in 87 patients with type 2 DM (53 women/34 men). All patients included in the study fulfilled the American Diabetes Association diagnostic criteria for type 2 DM, and were followed at the out-patient clinic of a third-level hospital. Mean initial age of the study group was 54 8.5 years (range: 3169) and mean known years of type 2 DM evolution 10.7 7.2 years (range: 131). Initially, 40.7% were under insulin treatment and 60% in the final period. The control mean using the isotopic technique was 10.2 2.2 years (range: 715). Renal function was monitored in each patient using isotopic GFR determination calculated by 125I-iothalamate during the ambulatory follow-up period. Simultaneously with each isotopic determination, demographic (age and sex), anthropometric (weight, height and body surface) and biochemical (serum and urinary creatinine, urea nitrogen and albumin) data were collected during the follow-up period with the aim of establishing the estimation and calculation of renal function using each of the prediction equations of different levels. Data of all diabetic patients at baseline and the last observation during the follow-up period are summarized in Table 1. According to the baseline values obtained with the isotopic GFR, patients were divided into three study subgroups: normal renal function [GFR between 140 and 90 ml/min/ 1.73 m2 (294 isotopic determinations during the follow-up period in 47 type 2 DM patients)]; hyperfiltration [GFR >140 ml/min/1.73 m2 (144 isotopic determinations during the follow-up period in 27 type 2 DM patients)] defined a (...truncated)