Potential Role and Expression Level of Urinary CXCL8 in Different Stages of Incipient Diabetic Nephropathy with Undiminished Creatinine Clearance: A Pilot Study

尿CXCL8在不同阶段伴肌酐清除率未降低的早期糖尿病肾病中的潜在作用及表达水平:一项初步研究

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Abstract

BACKGROUND: Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, with a high prevalence and poor prognosis. Early intervention is crucial to improve the outcomes of DN. CXCL8 is related to podocyte damage in incipient DN; however, the role and expression level of CXCL8 have never been elucidated, especially in those with undiminished creatinine clearance. METHODS: Consecutive inpatients with type 2 diabetes were included in this study. Patients were assigned into four groups based on the Mogensen stage, reflecting pathological features through clinical manifestations: non-DN group, hyperfiltration group, microalbuminuria group and overt DN group. Clinical and laboratory data were retrospectively collected and analyzed. Urinary CXCL8 (uCXCL8) was measured using an enzyme-linked immunosorbent assay (ELISA) method and adjusted for urinary creatinine (Cr) from the same urine sample. RESULTS: In total, 88 eligible consecutive inpatients with type 2 diabetes were included in this study. uCXCL8 was differentially expressed in different stages of incipient DN; it decreased in the hyperfiltration phase of incipient DN (1.40±1.01 pg/μmol Cr) and was highly expressed in patients in the microalbuminuria stage (5.01±4.01 pg/μmol Cr). uCXCL8 was positively correlated with age, diabetes course, cystatin C and urinary albuminuria-to-creatinine ratio, but negatively correlated with estimated glomerular filtration rate (P<0.05). uCXCL8 was a risk factor for classic DN after adjusting for age, diabetes course and cystatin C (OR=1.17, 95% CI 0.98-1.4, P=0.045). CONCLUSION: CXCL8 played an important role in the progression of incipient DN. The unique expression profile of uCXCL8 may provide a reference for understanding the prognosis and mechanisms of incipient DN progression. uCXCL8 was an independent risk factor for the development of classic DN.

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