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Letters |
SW Thames Institute for Renal Research, SW Thames Renal Unit, St. Helier Hospital, Wrythe Lane, Carshalton, Surrey, UK SM5 1AA
To the Editor:
I read with interest the letter by Kos et al. (1) on serum cystatin C during malignant progression. This is the first attempt I have seen to explore the increases in cystatin C found in the serum of patients with progressive malignancy. I quite agree with the authors that previous studies have involved too few patients to allow clear-cut conclusions as to whether cystatin C is affected by malignancy.
The authors have shown that there is a progressive increase in the relative amount of cystatin C (compared with their healthy controls) in patients with primary metastatic melanoma and in patients with colorectal cancer. Unfortunately, interpretation of their data is complex. There are common misunderstandings that a lack of change in serum creatinine implies a lack of change in glomerular filtration rate (GFR) and that it is essential that cystatin C correlate exactly with serum creatinine.
Kos et al. (1) have not presented the creatinine data that go with their cystatin C results, so it is difficult to know whether creatinine was increased in (some of) the patients with increased cystatin C. The most important problem is that they have not used a reference technique to measure GFR to establish whether, in patients with progressively more serious malignancy, there was any change in GFR.
The studies I have been involved in (2)(3), and those of other groups (3)(4), have clearly shown that cystatin C is a more sensitive indicator of changes in GFR than creatinine. Indeed, cystatin C can be increased in situations where there are no apparent changes in serum creatinine. In view of the very small changes in cystatin C reported, less than twofold proportional increases, I feel it is essential that independent assessment of GFR is performed to establish whether the increases in cystatin C are attributable to increased production rate or to decreased elimination by glomerular filtration.
The data showing that in malignancy there are increases in the mRNA for cystatin and cysteine proteinases do provide some evidence that there will be an increased production or increased release of cystatin C into the serum of such patients. When performing a study such as Kos et al. (1) describe that intends to establish whether there is an increased concentration in the serum of patients, it is inappropriate to use serum creatinine as an indicator of a lack of change in GFR. The increase in serum cystatin C in colorectal cancer and metastatic melanoma may indicate the influence of nonrenal factors on the concentration of cystatin C. However, in the absence of a reference GFR procedure to eliminate any changes in clearance, this work acts more as a stimulant to further study rather than as definitive evidence.
References
Department of Biochemistry, and Molecular Biology, Jozef Stefan Institute, 1000 Ljubljana, Slovenia
To the Editor:
There is a clear need for more accurate and efficient markers for the assessment of glomerular filtration rate (GFR). Because the introduction of various new therapies for treating cancer requires reliable assessment of a patient's renal function, the application of new markers in clinical practice is particularly important in oncology. Cystatin C has been proposed as a promising marker of renal functional impairment, having significantly better characteristics than creatinine, a marker commonly used for clinical determination of GFR (1). However, the increasing evidence that overexpression of cysteine proteinases plays an active role in tumor progression (2) raises the possibility that their inhibitors, including cystatin C, may also be up-regulated in cancer patients. Indeed, in melanoma and colorectal cancer patients, we noticed significantly higher serum cystatin C than in controls (3). Because serum creatinine, a rough indicator of GFR, was not changed, we raised the possibility of nonrenal effects on the serum concentration of cystatin C in patients with malignant disease. Of course, for definitive evidence, a reference GFR procedure needs to be used, but for the large number of patients and controls included in our studies (>600) this would have been impracticable.
The aim of our Letter to the Editor in Clinical Chemistry was to highlight the increased cystatin C in serum of patients with two kinds of malignancy, a result that is relevant not only to cancer researchers, but also to clinical chemists. We hope that our work will stimulate further studies to establish definitively the behavior of cystatin C in patients with malignant disease and the potential of cystatin C for assessing GFR.
References
The following articles in journals at HighWire Press have cited this article:
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  O. F. Laterza, C. P. Price, and M. G. Scott Cystatin C: An Improved Estimator of Glomerular Filtration Rate? Clin. Chem., May 1, 2002; 48(5): 699 - 707. [Abstract] [Full Text] [PDF]
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R. P. Woitas, B. Stoffel-Wagner, S. Flommersfeld, U. Poege, P. Schiedermaier, H.-U. Klehr, U. Spengler, F. Bidlingmaier, and T. Sauerbruch Correlation of Serum Concentrations of Cystatin C and Creatinine to Inulin Clearance in Liver Cirrhosis Clin. Chem., May 1, 2000; 46(5): 712 - 715. [Full Text] [PDF]
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