Cystatin C has recently been introduced as an excellent marker of glomerular filtration rate11
that is not influenced by several physiological and pathophysiological conditions. While patients with severely impaired renal function exhibit increased serum creatinine concentrations, detection of slightly or moderately decreased glomerular filtration rate by serum parameters is rather difficult.8
Creatinine clearance, widely used in inhospital patients for estimation of glomerular filtration rate, requires 24 hour urine collection and lacks sufficient reliability in outpatients. Early diagnosis of impaired renal function is particularly important in patients with cirrhosis of the liver. We therefore investigated the diagnostic value of serum cystatin C concentrations in patients with cirrhosis. The following main results were found.
- Serum cystatin C concentrations are significantly increased in patients with cirrhosis and moderately impaired renal function (creatinine clearance 40–69 ml/min) compared with those with creatinine clearance ≥70 ml/min. The difference between these groups is less pronounced for serum creatinine and not significant for serum urea concentrations.
- ROC curves support an advantage of cystatin C over serum concentrations of urea and creatinine.
- In the subgroups of female patients and Child-Pugh C patients, cystatin C was found to be particularly useful for detection of impaired renal function.
Obviously, there was an overlap for concentrations of the renal function parameters between the two groups investigated in our study. This overlap however was smallest for serum cystatin C concentrations. Consequently, as was demonstrated by ROC curves, cystatin C tended to be more sensitive and specific than creatinine throughout almost the whole range of possible cut off values. Urea was even less diagnostically efficient than creatinine. This was further analysed by calculation of sensitivity, specificity, positive and negative predictive values, and efficiency for the most suitable cut off values. Analysis of the 97 patients showed that the sensitivity of cystatin C was superior to that of creatinine and urea. Specificity of cystatin C tended to be lower, but this was not significant. Efficiency however was comparable with the other parameters.
The advantage of cystatin C determination in patients with normal serum creatinine is also supported by the following analysis: 20 of 53 patients with a normal serum creatinine concentration had a decreased creatinine clearance below 70 ml/min. This was the case only in 12 of 45 patients with a normal serum concentration of cystatin C. In addition, 11 of 20 patients with impaired renal function missed by serum creatinine were correctly analysed by cystatin C.
One may argue that renal function in our study was evaluated by 24 hour creatinine clearance rather than by clearance of exogenously administrated substances (for example, inulin clearance). Inulin clearance can reflect glomerular filtration rate more precisely. However, its determination is more cumbersome, requiring a continuous intravenous infusion and urine sampling with a bladder catheter. Thus the majority of clinical investigations of renal function in cirrhosis are based on determination of creatinine clearance. Moreover, recently a correlation between serum cystatin C concentrations and inulin clearance was demonstrated in patients with cirrhosis.23
Furthermore, creatinine clearance can be as precise as inulin clearance in patients with compensated cirrhosis.24
A clear advantage of cystatin C over creatinine or urea determination was found for Child-Pugh C patients. For this subgroup, ROC curves showed a more marked superiority of cystatin C than for the total population. This reflects a trend towards increased diagnostic sensitivity of cystatin C in Child-Pugh C patients at the same specificity levels achieved by the other two parameters. Therefore, in Child-Pugh C patients, cystatin C determinations seem to be of clinical benefit and should be further investigated. In female patients, the differences in areas under the ROC curves were close to statistical significance. Sensitivity of cystatin C however was significantly higher than that of creatinine and urea at equal specificity. The clear advantage of cystatin C compared with creatinine and urea in these patients may be due to the fact that this parameter is not dependent on muscle mass, activity, or nutritional status.
In summary, in patients with cirrhosis, particularly in patients with Child-Pugh class C, cystatin C determination is a valuable tool for the early diagnosis of moderately impaired renal function.