Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease

Abstract

Background Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. Methods Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. Results Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070–3.455, P = 0.029). Conclusions Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Review on Inflammation Markers in Chronic Kidney Disease

“…Another chemokine named CXCL16, a scavenger receptor for oxidized low-density lipoprotein (LDL), was reported by Lin et al to be independently associated with a change in renal function in all-stage CKD [ 113 ]. Additionally, it appears to be a marker of renal injury in patients with type 2 DM, where it is independently predictive of microalbuminuria [ 114 , 115 ] and its urinary levels could reflect the degree of interstitial fibrosis and tubular atrophy in patients with advanced diabetic kidney disease [ 116 ]. It appears to also play a role in the etiopathogenesis of preeclampsia, where its blockade could pave the way to the discovery of new treatments of preeclampsia [ 117 ].…”

The Role of Chemokines and Chemokine Receptors in Diabetic Nephropathy

“…In patients with type 2 diabetes enrolled in the ROADMAP (Randomized Olmesartan and Diabetes Micro-Albuminuria Prevention) and observational follow-up studies, enhanced plasma CXCL16 levels, angiopoietin-2, and TGF-β1 were shown to be independently predictive of microalbuminuria [88]. Urinary CXCL16 and endostatin can reflect the degree of interstitial fibrosis and tubular atrophy, which is a risk factor for poor renal outcome in DN patients, and act as biomarkers among these patients [89].…”

Gait speed and handgrip strength as predictors of all-cause mortality and cardiovascular events in hemodialysis patient

“…Multiple plasma inflammatory markers were simultaneously measured by multiplex enzyme-linked immunosorbent assay as previously described [32]. We reviewed the previous literature and selected the following candidate inflammatory markers: a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF), CXCL16, endocan, endostatin, follistatin, IL-6, IL-25, IL-18, monocyte chemoattractant protein-1 (MCP-1), MCP-2, MCP-4, matrix metalloproteinase-7 (MMP-7), MMP-8, osteoprotegerin, PCSK9, receptor activator of nuclear factor-κΒ ligand (RANKL), and tumor necrosis factor-α (TNF-α).…”