Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation.

BACKGROUND: Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. METHODS: Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. RESULTS: Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. CONCLUSIONS: C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

Do Natriuretic Peptide Measurements Provide Insights into Management of End-Stage Renal Disease Patients Undergoing Dialysis?

PURPOSE OF REVIEW: Impaired renal function may affect natriuretic peptide levels through a variety of factors and mechanisms, such as high prevalence of concomitant vascular and myocardial diseases, reduced clearance, increased risk of volume overload, and different types and solute removal techniques in the setting of dialysis. Nevertheless, accumulating evidence suggests that natriuretic peptide testing may provide insights into management of patients with chronic kidney disease (CKD) and end-stage kidney disease (ESRD) on dialysis, as they have been shown to be independently associated with morbidity and mortality. RECENT FINDINGS: Rising natriuretic peptide levels over time may identify CKD patients more likely to approach ESRD and requiring dialysis initiation. Moreover, serial natriuretic peptide measurements may also be helpful in guiding fluid management in ESRD patients on dialysis. However, since patients with CKD usually have significantly higher and more variable baseline levels of natriuretic peptides than those without CKD, traditional cut-off values may not be applicable, and individualized trajectories should be applied and interpreted in the clinical context. Routine clinical use natriuretic peptide testing in the CKD and ESRD settings still needs to be refined and individualized, yet their diagnostic and prognostic values can provide valuable insights into clinical trajectories and potential treatment responses.