currently used creatinine clearance-based equations may require the
introduction of a correction factor for the accurate estimation of the
glomerular filtration rate in the Indian population
- Two equations - The Modification of Diet in Renal
Disease (MDRD) Study equation and the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equation - are commonly used to estimate the
glomerular filtration rate in adults.
- New data suggests that the equations may not give
accurate results in Indians due to the lower muscle mass and predominantly
vegetarian diet as compared to the Americans, for whom they were
- The introduction of a correction can improve the
accuracy of the calculations.
. This was the
conclusion of a pilot study published in the BMC Nephrology.
filtration rate is a measure of kidney function
- the rate at which the
glomeruli which are the filtering units of the kidney remove nitrogenous waste
products like urea and creatinine from the blood. These waste products are
formed following the breakdown of protein in the body and can be toxic if they
are retained in the body in large amounts.
Creatinine is produced naturally at a fairly constant rate by the body
and the amount of creatinine in the body can be measured easily as
a byproduct of muscle metabolism that is excreted unchanged in the kidney.
It is an important indicator of kidney (renal) function.
‘The glomerular filtration rate (eGFR) may be overestimated when calculated using the current creatinine-based equations in the Indian population, given the limited muscle mass and the predominantly vegetarian diet in Indians as compared to the Americans.’
Creatinine gets removed from the
blood primarily through glomerular filtration but is also actively secreted by
the kidney tubules in
very small amounts such that creatinine clearance overestimates actual GFR by
10% to 20%. None of the creatinine is reabsorbed.
filtration rate (eGFR)
measured GFR (mGFR) is estimated by measuring the clearance of a substance
called inulin from the blood
. This process is, however, cumbersome and is
not done in all centers.
the estimated glomerular filtration rate (eGFR) is routinely used for the
diagnosis and estimation of risk in chronic kidney disease as well as for the
selection of live donors for kidney transplantation
. It is
calculated based on formulas that incorporate the creatinine clearance (CrCl,
creatinine levels in the blood and urine) by the kidneys, the age, and sex of
If there is kidney dysfunction and the
filtration is deficient, creatinine blood levels rise and the CrCl rate will overestimate the GFR because
the active secretion will account for a larger fraction of the total creatinine
cleared. Drugs like cimetidine
reduce creatinine tubular secretion
and, therefore, increase the accuracy of the GFR estimate. Hence, in the
absence of secretion, creatinine behaves like inulin.
Pilot study to assess the
existing eGFR calculators in Indians
The Chronic Kidney
Epidemiology Collaboration (CKD-EPI) equation is often
preferred for the calculation. The formula has been developed using details
from the North American Caucasian population with a correction later introduced
for the Black population. To suit the Japanese, Chinese, Thai, Korean and
Pakistani populations, correction factors have been applied or new equations
have been developed. No such modification currently exists for the Indian
In a pilot study, the
scientists assessed the performance of the existing eGFR calculators based on
creatinine or cystatin C clearance in 130 Indians, comprising of 63 healthy
kidney donors and 67 suffering from chronic kidney disease. They compared the
eGFR to the mGFR in individual patients. Around 50% of the individuals were
vegetarians. The scientists found that:
- The creatinine-based eGFR calculations overestimated
the GFR when compared to the mean mGFR
- The cystatin C based calculation of eGFR, which does
not depend on the muscle mass or protein content of the diet, was not
significantly different from the mGFR
The difference between
the creatinine-based eGFR calculation and the mGFR appears to be due to the low
muscle mass in the Indian population as compared to the western society. The
diet also seems to have contributed, since the majority of the Indian
population is vegetarian, or eats meat only infrequently.
The findings of the
study have significant implications for healthy individuals being considered
for kidney donation. If the creatinine-based equation is used, it will give a
better estimation of the kidney function, which may not be as good.
is, therefore, time to either develop a correction factor to the
creatinine-based equations or develop a new equation to estimate the GFR
accurately in the Indian population
. Though the cystatin C
test, which provides more accurate results, is a good alternative, a test that
uses the measurement of creatinine has the advantage of being cheaper and more
The scientists do admit
some shortcomings of the study, which include a small number of subjects, who
were mainly North Indian, and the absence of a formal measurement of the muscle
mass, which could have provided valuable information.
Two equations are
commonly used to estimate the glomerular filtration rate in adults - The Modification of Diet in Renal Disease
(MDRD) Study equation and the Chronic Kidney Disease Epidemiology Collaboration
. The Bedside Schwartz equation is used in individuals
less than 18 years.
The MDRD equation is as
GFR (mL/min/1.73 m2
= 175 × (Scr
× (0.742 if
female) × (1.212 if African American)
is serum creatinine in mg/dL,
CKD-EPI equation is as below:
GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ,
1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if
- Scr is serum creatinine in mg/dL,
- κ is 0.7 for females and 0.9 for males,
- α is -0.329 for females and -0.411 for males,
- min indicates the minimum of Scr /κ or 1,
- max indicates the maximum of Scr /κ or 1.
The CKD-EPI equation is
more accurate for values > 60 mL/min/1.73 m2
than is the MDRD
Study equation. An eGFR of less than 60 mL/min/1.73 m2
reduced kidney function, while a GFR of less than 15 mL/min/1.73 m2
indicates kidney failure.
The equations are not
recommended for use in patients with unstable creatinine concentrations, for
example in acutely ill or hospitalized patients, or in those with extremes in
muscle mass or diet, for instance, in bodybuilders or malnourished individuals. Reference:
- Kumar V et al. Existing creatinine-based equations overestimate glomerular filtration rate in Indians. BMC Nephrology2018;19:22. https:doi.org/10.1186/s12882-018-0813-9
- National Institute of Diabetes and Digestive and Kidney Diseases - (https:www.niddk.nih.gov/)