Comparative study between serum cystatin c and creatinine levels in chronic Kidney disease patients and blood donors

Chronic Kidney Disease (CKD) is a disease spectrum characterized by progressive loss of renal function over a period of time. Chronic kidney disease has reached epidemic proportion with current reported incidence of approximately 14.5% among the adult population in the United States of America. While no data exists on the Kenyan situation, risk factors for CKD such as post-streptococcal glomerulonephritis, hypertension, diabetes mellitus and lately HIV-associated nephropathy (HIVAN) are on the rise. Recent studies show that early diagnosis allows for institution of therapy to either arrest or reverse progression of the CKD. Glomerular filtration rate (GFR) is accepted as the best overall measure of renal function and is determined by the renal clearance of exogenous markers such as inulin, iohexol and chromium-labeled ethylene diamine tetrachloroacetic acid (51Cr-EDTA).Currently, creatinine clearance (CrCI) is the widely used endogenous marker for estimating glomerular filtration rate. While a number of equations based on serum creatinine (SCr) are in use to estimate GFR,case diagnosis and stratification of CKD is poor. Estimated GFRs based on serum cystatin C (cys C) levels have been shown to be more sensitive to early CKDcompared to serum creatinine, hence a suitable alternative. In this study, estimated GFRs for CKD patients at the Kenyatta National Hospital and blood donors at the National Blood Transfusion Centre (Nairobi) were derived from serum cystatin C and serum creatinine. Secondly, the reference ranges for both serum cystatin C and serum creatinine were compared to those from studies done in other parts of the world. Main Objectives: o To compare serum cystatin Cand creatinine levels among CKDpatients and blood donors. Specific Objectives: o To determine the serum cystatin Cand creatinine levels in CKDpatients and blood donors. o To determine reference ranges for serum cystatin Cand creatinine using blood donors as the reference population. o To compare the estimated GFRsbased on the two markers and stratify the CKD patients as per the National Kidney Foundation (NKF) guidelines. 1 Study Design Comparative descriptive study between two assay markers. Study Setting and Population/Subjects 1. Confirmed CKDpatients on follow-up at the renal clinic in KNH. 2. Volunteer blood donors at the blood transfusion unit (BTU) - KNH and those at the various outreach tents organized by the NBTC,Nairobi. Methods A total of 124 blood donors, well above the minimum requirement of 40 by IFCC for establishment of reference range were recruited. One hundred and fifty (150) CKDpatients were also recruited into the study according to the formula for prevalence study. Minimal demographic data was obtained by direct interviews using a study questionnaire. Additional information on CKD patients was obtained by perusal of the treatment files on clinic day followed by a clinical evaluation. Once informed consent was guaranteed,S ml of whole blood was obtained from each study participant for eventual determination of serum cystatin C and creatinine at the KNH main laboratory. Data Management The data obtained from the laboratory was entered into a computer database. Spreadsheets were generated and analyzed using Windows SPSSversion 17. Results Out of the 124 blood donors recruited into the study, 78 (63%) were males while 46 (37%) were females. The age group pattern was: ~20 years were 24%, 48% were in the 21- 25 years; 26% in the 26 - 30 years and 2% were above 30 years. The serum cystatin C levels for blood donors had 0.6mg/L as the lowest and 1.6mg/L as the highest level while it was 65~mo1/L and 120~mo1/L for serum creatinine respectively. The reference ranges for cystatin c and creatinine (irrespective of age and gender) were 0.8- l.4mg/L and 63 -109 urnol/L respectively. Of the 150 CKDpatients, 57% were males and 43% were females. The youngest CKDpatient was 18 years and the oldest was 77 years. The younger CKDstudy participants had glomerulopathies 2 (17%) as the commonest underlying morbidity while hypertension with diabetes co-morbidity was seen in the older CKDpatients. Staging ofthe CKDstudy participants using derived estimated GFRas per serum cystatin Chad 75% in early disease (stages 1-3) with only 2% in ESRD. However, eGRF based on serum creatinine had 64% of participants in early CKD(stages 1-3) and 15.4% had ESRD. Correlation between cystatin C and creatinine levels among CKD study participants had an r value of 0.849 and a p value of 0.00. The correlation between cystatin C and its derived eGFR had an r value of -0.837 and p value of 0.00. The correlation between serum creatinine and eGFR-serum creatinine had an r value of -.678 and p value of 0.00. Conclusions l. The reference ranges for blood donors aged 18 - 34 years for both serum cystatin C and creatinine in this study were 0.8 - 1.4 mg/L and 62 -120 mol/L respectively. 2. There is a difference in the staging for CKDparticipants as per National Kidney Foundation (NKF)guidelines using the estimated GFRderived from the two markers separately 3. There is a difference in the staging for CKDparticipants as per NKFguidelines using the estimated GFRderived from cystatin Cand serum creatinine separately. Crosstabulation of the staging of the CKDparticipants yielded a kappa vaue of 0.359. Recommendations Laboratory input in the management and follow-up is central and at all times staging of known and at risk CKDpatients as per the National Kidney Foundation should be done on every clinical request for renal function tests. A follow-up study involving a larger sample size of blood donors be carried out to capture more variables such as age, gender and race. A comparative study involving a 'gold standard' for measured GFRbe carried out to assessthe sensitivity and specificty of serum cystatin Cand serum creatinine.