Terpos Evangelos, Katodritou Eirini, Tsiftsakis Evangelos, Kastritis Efstathios, Christoulas Dimitrios, Pouli Anastasia, Michalis Eurydiki, Verrou Evgenia, Anargyrou Konstantinos, Tsionos Konstantinos, Dimopoulos Meletios A, Zervas Konstantinos
Department of Hematology and Medical Research, 251 General Air Force Hospital, 3 Kanellopoulou street, Athens, 11525, Greece.
Haematologica. 2009 Mar;94(3):372-9. doi: 10.3324/haematol.2008.000638.
Renal impairment is a common complication of multiple myeloma. Cystatin-C is considered an accurate marker of glomerular filtration rate in several renal disorders. Microarray analysis has revealed that cystatin-C is one of the most highly up-regulated genes in multiple myeloma. The aim of this study was to evaluate the serum levels of cystatin-C in myeloma patients, explore possible correlations with clinical data, including survival, and assess the effect of bortezomib on cystatin-C in relapsed multiple myeloma.
We measured serum cystatin-C in 157 newly diagnosed, previously untreated myeloma patients, in 28 patients with relapsed disease pre- and post-bortezomib therapy and in 52 healthy controls, using a latex particle-enhanced nephelometric immunoassay.
In newly diagnosed patients, cystatin-C was elevated and showed strong correlations with advanced ISS stage, extensive bone disease, high beta(2)-microglobulin, high serum creatinine, and low creatinine clearance. Multivariate analysis revealed that only cystatin-C and lactate dehydrogenase had an independent prognostic impact on patients' survival. The combination of cystatin-C and lactate dehydrogenase revealed three prognostic groups of patients: a high-risk group (both elevated cystatin-C and lactate dehydrogenase) with a median survival of 24 months, an intermediate-risk group (elevated cystatin-C or elevated lactate dehydrogenase) with a median survival of 48 months and a low-risk group (both low cystatin-C and lactate dehydrogenase) in which median survival has not yet been reached (p<0.001). Cystatin-C could also identify a subset of ISS-II patients with worse outcome. Relapsed patients had higher cystatin-C levels even compared to newly diagnosed patients. Treatment with bortezomib produced a significant reduction of cystatin-C, mainly in responders.
Serum cystatin-C is not only a sensitive marker of renal impairment but also reflects tumor burden and is of prognostic value in myeloma. Its reduction after treatment with bortezomib reflects bortezomib's anti-myeloma activity and possibly bortezomib's direct effect on renal function.
肾功能损害是多发性骨髓瘤的常见并发症。胱抑素-C被认为是几种肾脏疾病中肾小球滤过率的准确标志物。基因芯片分析显示，胱抑素-C是多发性骨髓瘤中上调程度最高的基因之一。本研究的目的是评估骨髓瘤患者血清胱抑素-C水平，探讨其与包括生存在内的临床数据的可能相关性，并评估硼替佐米对复发多发性骨髓瘤患者胱抑素-C的影响。
我们采用乳胶颗粒增强散射比浊免疫分析法，检测了157例新诊断、未经治疗的骨髓瘤患者、28例复发疾病患者在硼替佐米治疗前后以及52例健康对照者的血清胱抑素-C水平。
在新诊断患者中，胱抑素-C升高，且与国际分期系统（ISS）晚期、广泛骨病、高β2微球蛋白、高血清肌酐和低肌酐清除率密切相关。多因素分析显示，只有胱抑素-C和乳酸脱氢酶对患者生存有独立的预后影响。胱抑素-C和乳酸脱氢酶的联合分析确定了三组预后不同的患者：高危组（胱抑素-C和乳酸脱氢酶均升高），中位生存期为24个月；中危组（胱抑素-C或乳酸脱氢酶升高），中位生存期为48个月；低危组（胱抑素-C和乳酸脱氢酶均低），中位生存期尚未达到（p<0.001）。胱抑素-C还可识别ISS-II期患者中预后较差的亚组。复发患者的胱抑素-C水平甚至高于新诊断患者。硼替佐米治疗使胱抑素-C显著降低，主要见于有反应者。
血清胱抑素-C不仅是肾功能损害的敏感标志物，还反映肿瘤负荷，对骨髓瘤具有预后价值。硼替佐米治疗后其降低反映了硼替佐米的抗骨髓瘤活性以及可能对肾功能的直接作用。
