B-286 Advancing Renal Biomarker Interpretation in Ghana: Verified Reference Intervals for Serum Cystatin C

Abstract

Cystatin C is increasingly recommended for the assessment of kidney function and is particularly useful for estimating glomerular filtration rate (eGFR) when creatinine-based measurements are unreliable, including in individuals with altered muscle mass or other non–GFR determinants of creatinine. Despite its clinical advantages, cystatin C testing only became commercially available in Ghana in 2025. The absence of locally derived reference intervals (RIs) limits accurate interpretation and clinical adoption. This study aimed to establish and independently verify sex-specific reference intervals for serum cystatin C in apparently healthy Ghanaian adults. Reference intervals were established using 262 remnant serum specimens from adults undergoing routine clinical testing at the University of Ghana Medical Centre. The absence of acute illness and known kidney disease was confirmed through electronic medical record review. Serum cystatin C was measured using a commercially available immunoturbidimetric assay on the Beckman Coulter AU5800 analyzer. Serum creatinine was measured using an IDMS-traceable creatinine sarcosine oxidase assay on the Mindray BS-480 analyzer. RIs were determined non-parametrically using the 2.5th and 97.5th percentiles with corresponding 90% confidence intervals (CIs), in accordance with CLSI EP28-A3c guidelines. Verification was performed in an independent cohort of 130 non-pregnant adults aged 18–70 years prospectively recruited for a longitudinal kidney biomarker study. Participants had no history of kidney disease, hypertension, or diabetes and demonstrated preserved kidney function (eGFR =90 mL/min/1.73 m², or eGFR =60 mL/min/1.73 m² for individuals older than 60 years). Median serum creatinine concentrations and derived creatinine RIs were consistent with previously published Ghanaian data, supporting the appropriateness of the reference population. Males exhibited significantly higher serum creatinine concentrations (median 0.97 mg/dL; 95% CI: 0.94–0.98) compared to females (median 0.70 mg/dL; 95% CI: 0.69–0.72; p < 0.001). Serum cystatin C concentrations were modestly but significantly higher in males. The sex-specific RI for cystatin C in males was 0.67 (90% CI: 0.61–0.70) to 1.11 mg/L (90% CI: 1.01–1.22), and in females was 0.62 (90% CI: 0.55–0.64) to 1.05 mg/L (90% CI: 0.98–1.12) (p < 0.001). Given substantial overlap between sex-specific limits, a combined RI was also derived: 0.63 (90% CI: 0.61–0.65) to 1.02 mg/L (90% CI: 0.98–1.07). In the verification cohort (81 females, 49 males), 97.5% of females and 100% of males fell within their respective sex-specific RIs. Using the combined RI, 97% (126/130) of participants were within the established limits, confirming robustness. This study establishes and verifies the first locally derived reference intervals for serum cystatin C in healthy Ghanaian adults. While statistically significant sex differences were observed, the substantial overlap supports potential clinical use of a combined RI. These findings provide an essential foundation for integrating cystatin C into routine renal assessment in Ghana and support its complementary use alongside creatinine to improve early detection and risk stratification of kidney disease. Further studies evaluating its clinical utility in acute kidney injury and chronic kidney disease management are warranted.