Stage-wise variation in serum C-reactive protein and cardiovascular risk in chronic kidney disease of uncertain etiology among Sri Lankans; a preliminary study

BACKGROUND: Chronic kidney disease of uncertain etiology (CKDu) is a progressive nephropathy histologically characterized by tubulointerstitial fibrosis with varying degrees of inflammatory infiltrations. C-reactive protein (CRP) is an acute phase protein that serves as a marker of systemic inflammation and cardiovascular disease (CVD) risk. Therefore, this study aimed to evaluate serum CRP levels in patients with CKDu and to assess their association with renal function and CVD risk. METHODS: A cross-sectional study was conducted on 40 clinically diagnosed CKDu patients at different severity stages (stage 2 (n = 5, 12.5%), stage 3A (n = 8, 20.0%), stage 3B (n = 10, 25.0%), stage 4 (n = 10, 25.0%), and stage 5 (n = 7, 17.5%). As the control group, age and sex matched 16 apparently healthy individuals (mean age 52.19 ± 10.26 years, 56.2% male) were recruited. CRP concentrations were measured using immunoturbidimetry (range 0-150 mg/L), and CVD risk was categorized based on CDC/AHA guideline. Patients with CRP > 10 mg/L were excluded to minimize confounding from potential underlying infections. RESULTS: CRP levels across CKDu stages demonstrated a nonlinear trend with significant peak at stage 3A (1.6 mg/L; IQR: 1.08-2.95), compared to their matched control subjects (0.50 mg/L; IQR 0.30-1.73; p = 0.0045), followed by a decline in later stages. No significant association was observed between CRP and eGFR (r = 0.11, 95% CI -0.21 to 0.41, p = 0.49). After classifying the CKDu patients for CVD risk, Stage 3A patients had higher odds of increased CVD risk than controls (odds ratio = 21.0, p = 0.0236) followed by stage 3B (odds ratio = 13.5, p = 0.0352). Further, CVD risk stratification was not confounded by age, sex, and renal function indicators (eGFR and serum creatinine). CONCLUSION: Elevated CRP levels and associated CVD risk in CKDu patients appear most pronounced in intermediate disease stages (3A-3B), providing a rationale for a large longitudinal study.