The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality

Abstract

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.

Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

“…[27][28][29] Eight studies reported associations that could not be extracted or reliably expressed as RRs comparing the top versus bottom third of baseline FGF-23 concentration (see Supplemental Table 4 for results from these and the other excluded studies). [30][31][32][33][34][35][36][37] Of 34 studies included in primary analyses, 17 were in predominantly general population cohorts, 22,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] nine were in patients with CKD not on dialysis, 23,[54][55][56][57][58][59][60][61] and eight in patients on dialysis 24,[62][63][64][65][66][67][68] ( Figure 1). For patients on dialysis, a single large trial (EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular ...…”

“…However, the studies excluded because of inability to convert associations showed positive associations between FGF-23 and disease risks that were similar in size to those observed by the included studies (Supplemental Table 4). [30][31][32][33][34][35][36][37] Furthermore, given the lack of trends across the three population types despite a two-fold increase in the absolute difference in FGF-23 concentration, it is unlikely that individual participant data would identify an important log-linear trend missed by our tabular meta-analysis.…”

Association between periodontitis and chronic kidney disease: Systematic review and meta‐analysis

“…It also improves endothelial function (Tonetti et al, 2007) that may contribute to an increased kidney microcirculation and, hence, more effective filtration. Moreover, periodontal treatment was associated with a decrease in asymmetric dimethylarginine (ADMA) level 6 months after periodontal treatment (Almeida et al, 2017), a predictor of progression of renal disease, and of all-cause, and particularly, cardiovascular risk and mortality (Langsford et al, 2017).…”

The Landscape of Diabetic Kidney Disease in the United States

“…Therefore, whether or not moderate levels of albuminuria by itself are an early predictor of DKD and its progression remains controversial [ 17 , 47 , 48 ]. This may be due to multiple pathophysiological factors which are part of the constellation of DKD (interstitial damage, vascular and/or glomerular) [ 49 ] and reinforces the need to search for more sensitive and specific biomarkers [ 50 , 51 ]. Nevertheless, albuminuria, together with eGFR, remains useful for monitoring kidney function [ 38 , 52 ].…”