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2型糖尿病患者血清和尿多克隆游离轻链的定量评估:糖尿病肾病的早期标志物?

Quantitative assessment of serum and urinary polyclonal free light chains in patients with type II diabetes: an early marker of diabetic kidney disease?

作者信息

Hutchison Colin A, Cockwell Paul, Harding Steven, Mead Graham P, Bradwell Arthur R, Barnett Anthony H

机构信息

Queen Elizabeth Hospital, Department of Renal Medicine, QEMC, Birmingham, B15 2TH, UK.

出版信息

Expert Opin Ther Targets. 2008 Jun;12(6):667-76. doi: 10.1517/14728222.12.6.667.

Abstract

OBJECTIVE

Free light chains (FLCs) are bi-products of normal immunoglobulin synthesis and are predominately removed from the circulation by the kidneys. This study assessed polyclonal FLCs as a novel biomarker of early diabetic kidney disease.

RESEARCH DESIGN/METHODS: Serum and urinary FLCs were assessed by the immunoassay Freelite, in white and South-Asian patients with type II diabetes recruited from the United Kingdom Asian Diabetes Study.

RESULTS

The incidence of monoclonal proteins in this diabetic population was 1.9%. Type II diabetic patients had significantly raised concentrations of serum polyclonal FLCs before overt renal impairment developed (p < 0.001). Both kappa and lambda FLCs correlated with all tested markers of renal function; in particular cystatin-C: Spearman's coefficient (R) = 0.55 (p < 0.01) and R = 0.56 (p < 0.01), respectively. The South-Asian diabetic patients had higher serum polyclonal FLCs than Caucasian diabetic patients and this was independent of renal function. Urinary FLCs concentrations were raised in diabetic patients (p < 0.001). The majority (68%) of diabetic patients with normal urinary albumin:creatinine ratios (ACRs) had abnormal urinary FLC:creatinine ratios. Both kappa and lambda FLC concentrations correlated with urinary ACR: R = 0.32, p < 0.01 and R = 0.25, p < 0.01 respectively.

CONCLUSIONS

Type II diabetic patients can have significantly raised concentrations of serum and urinary polyclonal FLCs before overt renal disease occurs. These novel findings provide the basis for future studies to assess whether polyclonal FLCs could provide a useful tool for early diagnosis of diabetic kidney disease.

摘要

目的

游离轻链(FLCs)是正常免疫球蛋白合成的副产物,主要通过肾脏从循环中清除。本研究评估多克隆FLCs作为早期糖尿病肾病的一种新型生物标志物。

研究设计/方法:采用免疫分析法Freelite对从英国亚洲糖尿病研究中招募的白种人和南亚II型糖尿病患者的血清和尿液FLCs进行评估。

结果

该糖尿病患者群体中单克隆蛋白的发生率为1.9%。II型糖尿病患者在明显肾功能损害出现之前血清多克隆FLCs浓度显著升高(p<0.001)。κ和λFLCs均与所有检测的肾功能标志物相关;特别是胱抑素-C:Spearman系数(R)分别为0.55(p<0.01)和0.56(p<0.01)。南亚糖尿病患者的血清多克隆FLCs高于白种人糖尿病患者,且这与肾功能无关。糖尿病患者尿液FLCs浓度升高(p<0.001)。大多数(68%)尿白蛋白:肌酐比值(ACRs)正常的糖尿病患者尿FLC:肌酐比值异常。κ和λFLC浓度均与尿ACR相关:R分别为0.32,p<0.01和0.25,p<0.01。

结论

II型糖尿病患者在明显肾脏疾病发生之前血清和尿液多克隆FLCs浓度可显著升高。这些新发现为未来研究评估多克隆FLCs是否可为糖尿病肾病的早期诊断提供有用工具奠定了基础。

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