Existing Creatinine-based Equations Overestimate Glomerular Filtration Rate in Indians

A study published in BioMed Central Nephrology shows that the existing creatinine based eGFR equations significantly overestimate GFR in the predominantly vegetarian Indian population. The study was conducted at Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India under the agis of Dr Vivek Kumar and Dr Vivekanand Jha and Indian and Japanese researchers collaborated for the study.

This study was supported in part by grants from the Department of Biotechnology, Govt of India, International Society of Nephrology Clinical Research Program, and Ministry of Education, Culture, Sports, Science and Technology, Japan.

Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors.

Since measuring GFR is impractical, equations that rely upon the serum concentration of filtration markers (i.e., molecules generated in the body at a fixed rate and eliminated almost exclusively by glomerular filtration) have been developed for estimating GFR (eGFR). Creatinine is the best known of these markers, and was the basis for the development of Modification of Diet in Renal Disease (MDRD) GFR estimating equation. Recognizing that serum creatinine concentration was dependent upon muscle mass, demographic parameters that acted as surrogates for muscle mass, i.e. age, gender and ethnicity, are included in the equation. The MDRD equation was found to be biased and imprecise for values above 60 ml/min, and has been superseded by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, developed in more diverse populations.

Based on the concern that the ethnicity coefficient did not address nonwhite, non-African-American groups, investigations in Chinese and Japanese populations led to development of correction factors and Thai, Korean and Pakistani populations also have correction factors. This study was a precursor to  larger study to develop an ethnicity coefficient for GFR estimation in Indians and evaluated the performance of the existing eGFR equations for assessment of GFR in Indians.

A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: −3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to −0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90–134.50) ml/min/1.73m2.

The study shows that the existing creatinine based eGFR equations significantly overestimate GFR in the predominantly vegetarian Indian population. Better performance of CKD-EPIcys equation and lower creatinine excretion suggest that this overestimation is likely linked to the lower muscle mass. These findings support the need of an appropriately powered study to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

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