JOURNAL TRANSCRIPT

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Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine S. O’Riordan, E. Ouldred, S. Brice, S. H. D. Jackson & C. G. Swift Clinical Age Research Unit, Department of Healthcare of the Elderly, Guys, Kings and St Thomas’ School of Medicine, Denmark Hill Campus, Kings College London, London SE5 9PJ

Aims To assess whether cystatin C, a new serum marker of renal function, is a better index of creatinine or digoxin clearance than serum creatinine in older people. Methods Twenty-two volunteers over the age of 65 years (mean 73t5) were recruited from a healthy elderly volunteer database. None of the volunteers was taking digoxin or other medication known to interfere with digoxin kinetics or assay. Digoxin was infused at a dose of 7–10 mg kgx1 and blood samples were taken over the following 48 h and assayed for serum digoxin. Serum cystatin C, creatinine and creatinine clearance were measured and a calculated creatinine clearance was estimated using the Cockcroft Gault formula. Digoxin clearance was calculated using a pharmacokinetic software package. All values were log transformed to normalize their distribution. Results Of the 22 volunteers enrolled into the study, 18 completed the study. Serum cystatin C ranged between 0.72 and 1.89 mg lx1 and serum creatinine ranged from 69.6 to 153.9 mmol lx1. Measured creatinine clearance ranged from 38 to 123 ml minx1 and calculated creatinine clearance from 29.5 to 88.0 ml minx1. Digoxin clearance ranged from 51.0 to 103.5 ml minx1. Cystatin C correlated extremely well with creatinine (r=0.93, P50 years=0.84–1.55 mg lx1. Thus, these reference ranges do not agree with each other, especially in the older age groups. Data from the present study was much more in keeping with the ranges published by Norland et al. [19]. Our volunteers showed a threefold variation in creatinine clearance but none had severe renal impairment. In keeping with others, our work has shown the serum cystatin C concentration to be very similar to serum creatinine concentration and creatinine clearance as a marker of renal function. The findings support the hypothesis that creatinine concentration and cystatin C concentration have similar properties as plasma markers of GFR [21]. The Cockcroft and Gault formula [17] consistently produced lower values of creatinine clearance than the measured creatinine clearance. This has been shown previously in this age group and may reflect inaccuracies in the measured creatinine clearances [22]. Neither cystatin C concentration nor creatinine concentration showed a good correlation with digoxin clearance. The latter in the present study was similar to that quoted in young patients by Ewy et al. [15] but lower than that quoted for young patients by Cusack et al. [14]. The digoxin clearances quoted in these two studies for older people were lower than our values. The older patients in the study by Ewy et al. [15] were healthy elderly volunteers living at home but in the study by Cusack et al. [14] they were in-patients receiving digoxin for its positive inotropic effect. Inaccuracies may have been introduced when calculating the AUC for digoxin clearance because of the use of low concentrations of the drug, which were close to or at the limit of quantification. The use of such low concentrations at the end of the sampling period is an inevitable consequence of using single dose methodology. Using AUC(0,48 h) corrected for dose did not, f 2002 Blackwell Science Ltd Br J Clin Pharmacol, 53, 398–402

however, give better correlations with cystatin C concentration, creatinine concentration or creatinine clearance. Cystatin C concentration could not be used to predict steady state digoxin concentration, and nor did it correlate better than creatinine concentration with creatinine clearance. In conclusion, serum cystatin C concentration is no better than serum creatinine concentration at predicting digoxin clearance and it remains to be seen whether the former will have any advantages over the latter as a serum marker of GFR in elderly patients with normal or impaired renal function. This study was funded by a British Geriatrics Society Research Start Up Grant. Cystatin C kits were donated by Dade Behring, Marburg, Germany.

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