A report from the Dialysis and Transplantation Registration Group of the Chinese Society of Nephrology revealed that in 1999, the population undergoing maintenance dialysis numbered 41,755.21
Liu and his colleagues found that, in China, about 14.82% of the 13,383 hospitalized patients investigated were diagnosed as having CKD.22
They also found that the prevalence of CKD increases dramatically in older people. Therefore, in the elderly population, the evaluation of renal function is critically important in clinical practice, since it has a great impact on diagnosis and medical treatment requiring adjustment in drug dosages in the elderly. The changes in renal function that accompany aging present a decrease in GFR – more than 1 mL/min/1.73 m2
/year in those over the age of 40 years.23
However, this change can vary. Gault and Cockcroft24
found that the variability of creatinine clearance also increased with increasing age. This was accordant with a recent report from the Baltimore Longitudinal Study of Aging, which demonstrated that variability, such as decrease, increase, or no change, in creatinine clearance emerged in 254 healthy individuals followed up for as long as 23 years.23
This variability causes additional difficulties in the estimation of GFR. The American Diabetes Association recommended estimation of GFR using prediction equations based on SC determinations.25
However, this has still not been validated in elderly populations.
Application of SC-based GFR prediction equations to elderly patients with CKD is limited. Bevc et al26
found that both the MDRD equations and the CKD-EPI equation lacked precision, and the accuracy within 30% of estimated 51Cr EDTA clearance values differs according to the stage of CKD. Burkhardt et al27
demonstrated that the accuracies and precisions of the CG equation and the MDRD equations were low, and that there was an underestimation of actual GFR. A cross-sectional study in a French hospital with mostly Caucasian patients28
also found that the CG equation seemed to be the most accurate and appropriate formula. The present study revealed that none of the equations had acceptable accuracy to exactly predict GFR in an elderly population. A new equation is still needed to provide a more accurate estimation of GFR in elderly patients.
Age and body mass are important sources of bias in the prediction. All the equations in our study are based on the SC value. The generation of creatinine is determined primarily by muscle mass and dietary intake. Muscle mass is considered a constant part of total body weight. However, elderly people often have decreased lean body mass and suffer from many chronic diseases associated with decreased muscle mass and SC levels.7
Additionally, elderly patients are often malnourished and Compan et al found that patients classified as malnourished account for 25% of the hospitalized elderly.29
Older and malnourished patients are particularly at risk of having decreased GFR even with normal SC levels.30
All of these factors could influence the accuracy of application of the equations. Recent research finds that applying the CG equation corrected by BSA may be more precise than the MDRD equations in patients with malnutrition or inflammation. In the present study, the CG equation had higher accuracy than the other equations; however, it still did not provide acceptable accuracy.
In these prediction equations, the subjects enrolled did not adequately represent subjects older than 70 years of age. The MDRD equation had not been initially validated in older people, and the mean age was 50.6 ± 12.7 years.16
The CG equation was originally established with 249 patients aged 18 to 92 years. Among the patients, only 59 (23%) were over the age of 70 years and women accounted for only 4% of the patients,14
yet when a study was applied in an elderly population to calculate creatinine clearance, most of the subjects were female. A correction factor of 0.85 was proposed for females, according to data from earlier studies, but in Cockcroft and Gault’s own study, data on females were extremely limited, so this figure must be considered pure speculation.32
Special attention must be given to the application of equations extended to populations not represented in the original study.
The large percentage of diabetic patients in the present study is also a source of bias. Related investigations found that many of the diabetic patients had a supernormal GFR before the onset of overt clinical diabetic nephropathy and progressive renal insufficiency.33
A surrogate marker based on SC cannot effectively detect emerging hyperfiltration in the early phase of diabetic nephropathies.27
In our study, diabetic patients make up 35.7% of the patients, so the remarkable underestimation of actual GFR by formula estimators is, in part, on account of an undetectable hyperfiltration in patients with diabetes; this is consistent with previous results.35
Considering the number of elderly patients with diabetes, it is understandable that our results underestimated the actual GFRs.
The methods used to measure SC were different in each study. In the original MDRD study, SC was measured by the CX3 Beckman method.15
In the CKD-EPI equation,17
SC was determined by the enzymatic method. The other equations in our study were published long ago, and the methods used for SC measurement have not been available until now.36
In our study, SC was measured using the enzymatic method, different from that in the MDRD study. Several studies have proven that calibration of SC assays can influence the accuracy of MDRD.37
Variability among clinical laboratories in the calibration of SC assays results in bias in the estimation of GFR.
In conclusion, our data indicated that when SC was measured by the enzymatic method, none of the equations considered were suitable for use in the elderly Chinese population invested in our study. Further improved formulae are needed to assess GFR in elderly Chinese CKD patients. At present, based on both overall performance and performance in different CKD stages, the CG equation may be the most accurate for use in elderly Chinese patients with CKD.