The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality.
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.
Division of Nephrology, University of British Columbia, Vancouver, Canada.
David
D
Langsford
Mila
M
Tang
Hicham I
HI
Cheikh Hassan
Ognjenka
O
Djurdjev
Manish M
MM
Sood
Adeera
A
Levin
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003928:Diabetic Nephropathies / Q000453:epidemiology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000453:epidemiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D015415:Biomarkers; C000717427:FGF23 protein, human; D010455:Peptides; D000089703:Fibroblast Growth Factor-23