Fecal Calprotectin as a Prognostic Biomarker for Mortality and Renal Outcomes in Chronic Kidney Disease

Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut-kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients.

We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed.

Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034-2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046-4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209-3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141-5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455-3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139-6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163-10.554, p < 0.0001) compared to those with low levels of both markers.

FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD.