60 CHAPTER 5
61 might also be responsible for development of co-morbidities. Moreover, these subjects have a mean BMI result similar to the subjects with obesity. Obesity might also be responsible for the decline in renal function observed in these subjects since it is an identified risk factor for the development of CKD11.
The observed difference between creatinine eGFR and cystatin C eGFR is based on the fact that cystatin C is sensitive to small variation in GFR and has a better discriminatory capabilities than serum creatinine especially when a risk factor for developing CKD is present.76,81,92.
Similarly, there is a lower Cystatin C eGFR in the diabetic subjects, this might be due to the high prevalence of chronic kidney disease (CKD) and end stage renal disease in type 2 diabetic patients.94
Hypertensive subjects have a higher eGFR-cystatin C when compared to the subjects in subgroup B and C. This might be due to minimal involvement of the kidneys in hypertension and perhaps, due to tubular secretion of cystatin C in hypertensive patients giving a falsely lower serum cystatin C.69,70 This finding might probably be due to use of diuretics that is recommended for treatment of hypertension in blacks.
Among the obesed subjects, the difference in eGFR-Cr and eGFR-Cystatin C might be because these subjects are relatively younger. The observation might also be due to the fact that obesity has a lesser degree of injury on the renal function.
The Receiver Operator Curve (ROC) showed different areas under the curve (AUC) for creatinine eGFR and Cystatin C eGFR. The area under the curve (AUC) for cystatin C is higher than that of creatinine and they are both comparable. Although, many studies
62 reported that serum Cystatin C is more sensitive to decline in renal function76,92-95, the observed results of AUC in this study did not show that Cystatin C is more sensitive than Creatinine. The observation in this study is supported by earlier reports90-91. This varying degree of sensitivity might probably be due to genetic influence in blacks. The AUC findings in this study are slightly lower than those reported82. This might be because of the different analytical methods used to assay serum creatinine and cystatin C. This study used immunoturbidimetric method to assay cystatin C and Jaffe’s method for Creatinine as against immunonephelometric method for cystatin C and enzymatic method for Creatinine in a previous study82. However, the results of AUC in this study are in keeping with those reported in a similar study in India.110
From this study, it is observed that diabetes mellitus is a strong risk factor for developing chronic kidney disease and that additional co-morbidity such as hypertension place a lethal effect on the kidneys. Obesity is a low risk factor for chronic kidney disease especially when there is no comorbidity. Cystatin C appears to be a better predictor of early renal impairment as observed in the subjects. Estimated GFR-Cysttain C is lower than eGFR-Cr in the subjects. This suggests that, serum Creatinine level and eGFR-Cr are not sufficient for assessment of renal function in subjects with risk factors for CKD
From this study, there is no correlation between Cystatin C and age, gender or BMI.
This is similar to previous reports that cystatin C is not affected by extra-renal factors limiting serum creatinine. 74-75.
Conversely, this study shows that serum creatinine positively correlates with age, and BMI in the subjects and control. The subjects included in this study are older and this
63 might explain the level of relationship between creatinine and age. This study shows that serum creatinine is influenced by gender, this is supported by earlier studies documenting the effect of gender on serum creatinine concentration 18-20.
Cystatin C correlates positively with serum creatinine in the subjects and negatively correlate with creatinine in the controls. This might be due to the fact that cystatin C starts to rise early in renal impairment and serum cystatin C can be implemented as a surrogate renal marker.76
According to NKF-KDOQI classification of chronic kidney disease, subgroups A, B and C will be placed in stage 2 CKD and D in stage 1 based on eGFR-cr. Conversely, Subgroups A and D will be in stage 2 CKD while Subgroup B and C in stage 3 CKD based on eGFR-cyst. C. However, the controls will be placed in stage 1 CKD by both eGFR. These findings further buttress the fact that cystatin C is sensitive to changes in GFR and has a better discriminatory capabilities.94 Furthermore, creatinine is unable to classify those in stage 3.50
Conclusively, Cystatin C is superior to serum creatinine for detection of decreased GFR in those with risks for CKD especially diabetes mellitus. However, this difference in eGFR-Cr and eGFR-cystatin C is not preserved in normal individuals. Cystatin C appears to be a more robust marker and tends to reflect GFR more accurately than Serum creatinine.
64 5.2 LIMITATIONS OF THE STUDY
The study did not include a reference exogenous renal marker such as inulin for comparison, this was due to cost and inconvenience for patients.
A clearance was not done due to cost and inconvenience of collecting timed urine
Patients were not followed up for a repeat serum creatinine and cystatin C, three (3) months after the initial assay due to time and cost.