Hutchison Colin A, Harding Stephen, Hewins Pete, Mead Graham P, Townsend John, Bradwell Arthur R, Cockwell Paul
Renal Unit, University Hospital Birmingham, Birmingham, UK.
Clin J Am Soc Nephrol. 2008 Nov;3(6):1684-90. doi: 10.2215/CJN.02290508.
Monoclonal free light chains (FLC) frequently cause kidney disease in patients with plasma cell dyscrasias. Polyclonal FLC, however, have not been assessed in patients with chronic kidney disease (CKD) yet could potentially play an important pathologic role. This study describes for the first time polyclonal FLC in patients with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A sensitive, quantitative immunoassay was used to analyze serum and urinary polyclonal FLC in 688 patients with CKD of various causes.
Serum kappa and lambda FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (kappa: R = 0.8, P < 0.01; and lambda: R = 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (kappa: P < 0.001; lambda: P < 0.005) and also rose significantly with increasing CKD stage (both FLC P < 0.0001). Urinary FLC concentrations were positively correlated with their corresponding serum concentration (kappa: R = 0.63; lambda: R = 0.65; both P < 0.001) and urinary albumin creatinine ratio (kappa: R = 0.58; lambda: R = 0.65; both P < 0.001). The proportion of patients with abnormally high urinary FLC concentrations rose with both the CKD stage and the severity of albuminuria.
This study demonstrates significant abnormalities of serum and urinary polyclonal FLC in patients with CKD. These data provide the basis for studies that assess the contribution of polyclonal FLC to progressive renal injury and systemic inflammation in patients with kidney disease.
单克隆游离轻链(FLC)常导致浆细胞发育异常患者发生肾脏疾病。然而,多克隆FLC在慢性肾脏病(CKD)患者中尚未得到评估,但可能发挥重要的病理作用。本研究首次描述了CKD患者中的多克隆FLC。
设计、地点、参与者及测量方法:采用一种灵敏的定量免疫分析法,对688例各种病因的CKD患者的血清和尿液多克隆FLC进行分析。
血清κ和λFLC浓度随CKD分期逐渐升高(P均<0.001),且与肾功能指标,包括胱抑素C显著相关(κ:R = 0.8,P < 0.01;λ:R = 0.79,P < 0.01)。不同疾病组间尿FLC浓度差异显著(κ:P < 0.001;λ:P < 0.005),且也随CKD分期的增加而显著升高(两种FLC的P均<0.0001)。尿FLC浓度与其相应的血清浓度呈正相关(κ:R = 0.63;λ:R = 0.65;P均<0.001),与尿白蛋白肌酐比值也呈正相关(κ:R = 0.58;λ:R = 0.65;P均<0.001)。尿FLC浓度异常升高的患者比例随CKD分期和蛋白尿严重程度的增加而升高。
本研究表明CKD患者血清和尿液多克隆FLC存在显著异常。这些数据为评估多克隆FLC对肾病患者进行性肾损伤和全身炎症的作用的研究提供了基础。