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The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality
David Langsford1, Mila Tang, Hicham I Cheikh Hassan
1Division of Nephrology, University of British Columbia, Vancouver, Canada.
Insights
Prognosis in chronic kidney disease (CKD) varies by cause. Biomarker profiles differ by CKD etiology and are linked to mortality risk, offering insights for patient outcomes.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Prognosis for adverse outcomes in chronic kidney disease (CKD) is significantly influenced by its underlying cause.
- Understanding these etiological differences is crucial for accurate risk stratification and patient management.
Purpose of the Study:
- To investigate whether biomarker profiles differ based on the specific etiology of CKD.
- To determine the association between these distinct biomarker profiles and mortality risk in CKD patients.
Main Methods:
- A prospective observational study involving 1,157 patients with CKD, categorized into diabetic kidney disease (DKD), glomerulonephritis (GN), and cystic/interstitial disease (PCK/TIN).
- Analysis of a comprehensive biomarker panel including NT-proBNP, troponin I, ADMA, IL-6, FGF23, and cystatin C, among others.
- The primary outcome assessed was mortality prior to initiating dialysis.
Main Results:
- Diabetic kidney disease (DKD) exhibited the highest pre-dialysis mortality rate (20%), predominantly cardiovascular.
- Specific biomarker profiles were significantly associated with mortality risk depending on CKD etiology: DKD with CysC, ADMA, NT-proBNP; GN with FGF23, TnI; and PCK/TIN with ADMA, IL-6.
- Hazard ratios indicated increased mortality risk associated with certain biomarkers within each etiological group.
Conclusions:
- Biomarker profiles are not uniform across different etiologies of CKD.
- Distinct biomarker profiles are significantly associated with mortality risk, highlighting the importance of etiological context in CKD prognosis.
Background:
Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality.
Methods:
Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC).
Results:
The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1).
Conclusions:
Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.
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