Cystatin C and Beta2-microglobulin: Markers of Glomerular Filtration in Critically Ill Children

José David Herrero-Morín; Serafín Málaga; Nuria Fernández; Corsino Rey; María Ángeles Diéguez; Gonzalo Solís; Andrés Concha


Crit Care. 2007;11(3) 

In This Article

Abstract and Introduction


Introduction: Parameters allowing regular evaluation of renal function in a paediatric intensive care unit (PICU) are not optimal. The aim of the present study was to analyse the utility of serum cystatin C and beta2-microglobulin (B2M) in detecting decreased glomerular filtration rate in critically ill children.
Methods: This was a prospective, observational study set in an eight-bed PICU. Twenty-five children were included. The inverses of serum creatinine, cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24-hour urine sample and CrC estimation by Schwartz formula (Schwartz). The diagnostic value of serum creatinine, cystatin C, and B2M to identify a glomerular filtration rate under 80 ml/minute per 1.73 m2 was evaluated using receiver operating characteristic (ROC) curve analysis.
Results: Mean age was 2.9 years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m2 in 14 children, and Schwartz was less than 80 ml/minute per 1.73 m2 in 9 children. Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of B2M and Schwartz (r = 0.697) were better than correlations between inverse of cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r = 0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a Schwartz CrC rate under 80 ml/minute per 1.73 m2 was better than that of creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine).
Conclusion: Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children.


Glomerular filtration rate (GFR) is difficult to measure in clinical practice.[1,2,3,4] The ideal laboratory marker should be of endogen synthesis, regular production rate, eliminated only by glomerular filtration, and without tubular secretion or reabsorption.[4,5,6] Creatinine clearance (CrC) using a 24-hour urine sample and serum creatinine (Cr) are the most commonly used parameters to estimate GFR in clinical practice,[2,4,5,7,8] although not the most accurate. However, there are limitations to their use. Cr could be affected by factors other than renal function (for example, muscle mass, protein intake, inflammatory illness, or hepatic disease).[2,4,9,10,11,12] Moreover, Cr is partially secreted by renal tubules[2,4,10,13] and frequently overestimates GFR.[1,2,4,5,13] On the other hand, CrC requires urine collection over a 24-hour period with a steady-state situation.[1,2,4,11,14] Mathematical formulas using Cr serum levels to estimate GFR (Schwartz formula is the most widely used and is based on Cr, age, and height) have been developed.[15,16]

To overcome the problems of measuring GFR, an extensive search is being conducted to find a serum marker able to detect renal function impairment, especially at the initial phase. Cystatin C and beta2-microglobulin (B2M) are low-molecular-weight proteins freely filtered by the glomerulus.[1,6,11,12] Their serum concentrations, especially that of cystatin C, are less dependent on extra renal factors than in the case of Cr.[1,5,6,10,11,13,14,17,18] Early detection of renal function impairment in paediatric intensive care would be of great value, allowing accurate treatment, adjustment of drug dose, and prevention of more severe renal damage.[3,7,9] Previous studies demonstrated the superiority of serum cystatin C compared with creatinine in the evaluation of GFR,[1,5,8,11,13,17,18,19] especially when there is a minor reduction in GFR.[1,5,6,8,12,13] We have not found any medical literature evaluating these low-molecular-weight proteins in critically ill children. The aim of this study was to evaluate the accuracies of serum Cr, serum cystatin C, and B2M as markers of GFR in critically ill children by comparing their results with CrC and Schwartz.


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