Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease

Abstract Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the important factors associated with chronic kidney disease (CKD), and there are many similarities between the two in adverse outcomes. N-terminal propeptide of collagen type 3 (PRO-C3), as a biomarker of advanced fibrosis in MAFLD, may also predict the risk of future MAFLD with chronic kidney disease (MLKD) development. Methods: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. PRO-C3 concentration was measured and regression analyses were used to determine associations with MLKD. A derivative algorithm for MLKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. Results: The study included two Asian cohorts (MLKD: n=180; mean eGFR: 94.93 ml/min/1.73m 2 ; median ACR: 6.58 mg/mmol). PRO-C3 was associated with the severity of MLKD and independently correlated to MLKD (adjusted odds ratio =1.16, 95% confidence interval [CI]: 1.08-1.23, P<0.001). A new non-invasive score (named PERIOD) that included PRO-C3 predicted MLKD (AUROC of 0.842, 95% CI: 0.805-0.875); its accuracy, specificity, and negative predictive values were 80.2%, 85.1%, and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC=0.807, 95% CI: 0.691-0.893) with similar results in all subgroups. In the MLKD subgroup, the accuracy for identifying advanced liver fibrosis was further improved by combining the PRO-C3-based ADAPT score with the Agile 3+ score (AUROC=0.90, 95% CI: 0.836-0.964, PPV=0.97). Conclusions: PRO-C3 and the PERIOD score is useful for accurately predicting the risk of MLKD. PRO-C3 can also be used as a marker for assessing liver fibrosis in MLKD patients.