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Indian Pediatr 2014;51: 263-264 |
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Estimating Accurate Glomerular Filtration
Rate in Children
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Sidharth Kumar Sethi
Pediatric Nephrology, Kidney and Urology Institute,
Medanta, The Medicity, Gurgaon, India.
Email: [email protected]
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Areliable and accurate assessment of glomerular
filtration rate (GFR) is critical for diagnosing acute and chronic
kidney impairment, intervening early to prevent end-stage renal failure,
prescribing nephrotoxic drugs and drugs cleared by a failing kidney, and
monitoring for side effects of medications. Estimation of GFR using
exogenously administered substances is well established and precise, but
these methods are cumbersome and time consuming [1].
Plasma creatinine is the most commonly used index for
estimating renal function in the clinical practice. Due to its small
size and lack of protein binding, it is freely filtered through the
glomerulus. However, it is also actively secreted by the proximal
tubules at unpredictable rates. Moreover, with decreasing GFR, the
fraction of tubular secretion increases, leading to an over-estimation
of 10-40% when compared to that of inulin clearance [2]. Especially in
children, estimation of creatinine is difficult, as there is a muscle
mass related increase in plasma creatinine in children after 2 years of
life. Moreover, plasma creatinine may change in cases of excessive
dietary intake of meat, malnourished children and anorectic adolescents
[3]. On the other hand, cystatin C is produced endogeneously at a
constant rate, is freely filtered by the glomerulus, and is completely
reabsorbed and catabolised by the renal tubule cells. Blood levels of
cystatin C have been found to be a reliable indicator of renal function.
The levels of cystatin C are independent of age, height, obesity and
malnutrition [3,4]. Recent studies also suggest that serum cystatin-C is
better than serum creatinine in detecting acute kidney injury in
critically ill children [2]. Due to high cost, difficult assay
methodologies and standardization, and non-availability of definite
cut-off values, cystatin C has still not replaced creatinine in the
clinical practice.
To compensate for the increasing muscle mass during
childhood, creatinine based formulae which include height and muscle
mass have been developed. The most commonly used formula is the Schwartz
formula. The low muscle mass in malnourished children, may influence the
value of k, and may affect the GFR estimation, and thus may lead to
over-estimation of GFR in this subset [3]. Moreover, the value of k
should be different based on the method of estimation of serum
creatinine. Schwartz, et al. [5], using the enzymatic method of
creatinine estimation, recently proposed a new k value of 0.413. To
improve the bias and accuracy of the GFR estimation, it is important for
all the pediatricians to understand that the value of k should be
locally derived based on the method of creatinine estimation, reference
GFR estimation and the local population characteristics. Hari, et al.
[6], based on the regression analysis, found the value of k to be 0.42
in Indian children where the creatinine was estimated by kinetic Jaffe
method and 99mTc-DTPA GFR
was the reference GFR.
Cystatin-C based equations have been found to have
better accuracy of predicting GFR, as compared to the creatinine based
equations. The combined equations have generally been found to have
better accuracy in the estimation, than individual equations [2]. In the
current issue of Indian Pediatrics, Hari, et al. [7] prove that
cystatin-C equations have better accuracy [7]. They also found that the
combined cystatin-C and creatinine-based equation was not better than
only cystatin-C or creatinine based equation. The strengths of the study
are testing the equation in the GFR 60-90 mL/min/1.73m 2.
Early detection of chronic kidney disease and monitoring of renal
function deterioration requires an equation which works well in early
stages of chronic kidney disease. Another strength of this study is its
relevance for the pediatricians in India which can help in the current
clinical practice. There is a need to have more studies in children and
adolescents with an early chronic kidney disease, to enhance the use of
these equations.
It is important for pediatricians to understand that
children and adolescents with early chronic kidney disease and a
well-maintained fluid and electrolyte balance, the urinalysis may be
entirely normal. Therefore, a reduced GFR may serve as the only clinical
sign of kidney damage. Early intervention in the course of renal
impairment offers the best chance of preventing end stage renal disease
in children. There currently exists no equation for monitoring acute
changes in GFR [8]. However, the equations developed till now, may be
able to determine longitudinal changes in GFR over time. The parameters
used in the equation may be used on the locally available marker, which
has been standardized according to the local laboratory.
Funding: None; Competing interests: None
stated.
References
1. Schwartz GJ, Brion LP, Spitzer A. The use of
plasma creatinine concentration for estimating glomerular filtration
rate in infants, children, and adolescents. Pediatr Clin North Am.
1987;34:571-90.
2. Andersen TB, Eskild-Jensen A, Frøkiaer J, Brøchner-Mortensen
J. Measuring glomerular filtration rate in children; can cystatin C
replace established methods? A review. Pediatr Nephrol. 2009;24:929-41.
3. Hari P, Bagga A, Mahajan P, Lakshmy R. Effect of
malnutrition on serum creatinine and cystatin C levels. Pediatr Nephrol.
2007;22:1757-61.
4. Bökenkamp A, Domanetzki M, Zinck R, Schumann G,
Byrd D, Brodehl J. Cystatin C — a new marker of glomerular filtration
rate in children independent of age and height. Pediatrics.
1998;101:875-81.
5. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel
F, Warady BA, et al. New equations to estimate GFR in children
with CKD. J Am Soc Nephrol. 2009;20:629-37.
6. Hari P, Biswas B, Pandey R, Kalaivani M, Kumar R,
Bagga A. Updated height- and creatinine-based equation and its
validation for estimation of glomerular filtration rate in children from
developing countries. Clin Exp Nephrol. 2012;16:697-705.
7. Hari P, Ramakrishnan L, Gupta R, Kumar R, Bagga A.
Cystatin-C based glomerular filtration rate estimating equations in
early chronic kidney disease. Indian Pediatr 2014;51:273-77.
8. Schwartz GJ, Work DF. Measurement and estimation
of GFR in children and adolescents. Clin J Am Soc Nephrol.
2009;4:1832-43.
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