gms | German Medical Science

Objectives: Despite the clinical relevance of chronic kidney disease in elderly patients few equations for estimating the glomerular filtration rate (GFR) adapted to older age exist. The most frequently used equations are based on serum creatinine levels which may lead to improper estimations in older patients due to the influence of muscle mass, dietary protein intake and the higher prevalence of chronic diseases. The aim of our study is to identify reliable predictors of glomerular filtration in elderly patients using a population pharmacokinetic model of iohexol, a substance which is solely excreted renally and therefore may be used to assess renal function.

Methods: A cross-sectional subsample of 570 participants with an age of at least 70 years (mean 78.5 years, 244 women, 137 with diabetes mellitus, 434 with arterial hypertension, 85 with myocardial infarction, 43 with stroke, 130 with cancer, 298 with a history of smoking) from the Berlin Initiative Study (BIS) was used. For each participant height (1.66 [1.43-1.92] m), weight (77 [47-136] kg), serum creatinine (0.99 [0.46-4.77] mg/dL) and cystatin C (1.15 [0.23-44.20] mg/L) measurements were obtained before intravenous application of 3235 mg iohexol (mean and range). Blood samples were drawn 10, 20, 30, 60, 90, 120, 150, 180, 240, 300 and 1400 minutes after the administration of iohexol. A population pharmacokinetic model was developed using standard approaches in NONMEM 7.3 including the evaluation of covariates by stepwise covariate modeling and visual inspection.

Results: A two-compartment pharmacokinetic model with first order elimination described the data best. The central and peripheral volume of distribution were 11.30 L (10.97 - 11.69 L) and 5.40 L (5.21 - 5.53 L) respectively, the central and intercompartmental clearance were 4.16 L/h (4.07 - 4.23 L/h) and 5.42 L/h (5.10 - 5.83 L/h) (mean population estimates and 95% CI of bootstrap statistics). The elimination clearance was mainly linked to cystatin C and creatinine serum concentrations. With increasing cystatin C and creatinine concentrations the elimination clearance decreased. Minor covariates for the elimination clearance were age, weight and sex with a decrease of -0.0076 L/h per year, an increase of 0.0084 L/h per kg body weight and an 18% higher clearance in male participants. The central volume of distribution was linked to sex, creatinine and weight with a 23% higher volume in male participants, a decreasing volume with higher serum creatinine concentrations and an increase of 0.011 L per kg body weight. The observed residual (unexplained) inter-individual variability could be reduced by 61% for the elimination clearance and 32% for the central volume of distribution.

Conclusion: The clearance of iohexol was linked to a set of laboratory and demographic parameters which may be used to improve the prediction of GFR specifically in elderly patients.