However, the ROC plots for the diagnostic accuracy of plasma cystatin C and plasma creatinine to detect estimated GFR at less than 73.5 ml/min showed that plasma cystatin C was more specific than plasma creatinine. Even though they were equally sensitive at 100%, plasma cystatin C had a specificity of 71.3% while plasma creatinine had a specificity of 58.6%. The AUC of plasma cystatin C (0.727) was also more (P<0.05) than the AUC of plasma creatinine (0.539}. This is similar to findings of other workers who found that the AUC for the cystatin curve (0.967) was significantly (P=0.04) greater than the AUC of the creatinine curve (0.761) for the detection of GFR less than 78ml/min54, 57. The cut off of 73.5ml/min was used because it is the mean of the mildly reduced GFR. If a decline in GFR is detected at this point, its progression may be reversible.
The superiority of the diagnostic accuracy of plasma cystatin C to plasma creatinine was further supported by the likelihood ratio of both at the cut-off point. While the likelihood ratio of plasma cystatin C was 1.70, that of plasma creatinine was 1.17, confirming that plasma cystatin C was a more accurate marker of mild reduction in GFR.
This means that even though plasma creatinine and plasma cystatin C were correlated and were significant predictors of the GFR in both the diseased (hypertensives and diabetics) and control groups, the cut off cystatin C concentration of 1.21/mg/L (mean of mild renal impairment group) seemed to be a better judge estimate of the estimated
GFR at 73.5ml/min (mean of mild renal impairment group), compared with plasma creatinine of 101.4umol/L at the same GFR level showing that plasma cystatin C could predict the GFR better at that level.
. Thus, the high sensitivity and specificity of cystatin C as well as its independence of other factors age appear to make it equivalent to the estimated GFR for detection of early impairment in renal function.
In this study, it was also found that plasma cystatin C levels predicted the estimated GFR better in the groups with normal and mild renal impairment (mean estimated GFR=102.8ml/min and 73.5ml/min respectively). In the group that had moderate renal impairment (mean estimated GFR=39.3ml/min), plasma creatinine was a better predictor of the estimated GFR. This suggests plasma cystatin C is most informative in the early stages of renal dysfunction, and should be used together with plasma creatinine when managing patients with well established renal dysfunction.
In the group with normal GFR, for every appreciable shift in estimated GFR, there was a 1.4 shift in plasma cystatin C and only 0.53 in plasma creatinine. Also in the group with mild GFR reduction, for every appreciable drop in estimated GFR, there was a 0.96-drop in plasma cystatin C, and only 0.19 in plasma creatinine. These findings make it clear that cystatin C is not only useful in the prediction of early decline in GFR, but that it can reveal the degree of fall in the GFR. A report by Elizabeth Coll and colleagues add support to this view. They
measured cystatin C in patients with renal failure and found that its concentrations started to increase beyond what they considered the normal range at GFRs below 88ml/min, whereas creatinine crossed its upper reference limit only when GFR fell to 75ml/min. The investigators concluded that cystatin C would be especially useful for detecting subtle impairment of kidney function during follow-up53. This is in agreement with the findings of Bruce et al55 that serial measures of serum cystatin C accurately detect trends in renal function in patients with normal GFR and provides means for studying early renal decline in diabetics. Some workers have also found that cystatin C was better for discriminating type 2 diabetics with reduced GFR from those with normal GFR56. It also confirms the findings of others that conclude that cystatin C is a more accurate marker of subtle changes in GFR58.
Studies revealed that in elderly persons without chronic kidney disease (who have GFR ≥60mL/min), elevated cystatin C had a four-fold risk for progressing to chronic kidney disease58. In this study it was also found that in individuals with normal or mildly reduced renal function, the plasma concentration of cystatin C was more informative than plasma creatinine in the prediction of abnormal GFR. But in the moderately impaired renal function (mean estimated GFR = 39.3ml/min) plasma creatinine remained the only informative predictor of the abnormal estimated GFR. This is also consistent with the findings in other studies25, 54,56.
Based on the findings in this study, plasma cystatin C appears a very promising GFR marker, especially when a baseline concentration is measured at patient’s first presentation.
The noble role of plasma cystatin C in the assessment of GFR over plasma creatinine may be attributable to the fact that plasma cystatin C concentrations are not affected by physiological factors like sex, age, and muscle bulk as compared to plasma creatinine. Studies confirm that serum cystatin C is able to predict GFR better than serum creatinine in adult and paediatric populations28, 29,50,51. Cystatin C –based GFR predictions are said to be useful in both children and adults while creatinine-based GRF predictors consider factors like age and obesity59. Also, studies suggest that cystatin C assays are more precise than assays available for serum creatinine2.
Thus, the high sensitivity and specificity of cystatin C as well as its independence of other factors, age; appear to make it equivalent to the estimated GFR for detection of early impairment in renal function.