Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
Kidney Int. 2017 Mar;91(3):691-698. doi: 10.1016/j.kint.2016.09.045. Epub 2016 Dec 18.
Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13.7%). Among patients 50 and older, the prevalence of monoclonal gammopathy was 21%, which is approximately five-fold higher than the 4.2% expected rate in this population. Fifteen patients had monoclonal gammopathy of undetermined significance, one had multiple myeloma, one with smoldering myeloma, two had POEMS syndrome, and one had T-cell lymphocytic leukemia. Renal biopsy was performed in 15 cases, of which six showed thrombi, 11 showed mesangiolysis, and all showed double contours along glomerular capillary walls. Acute tubular injury was present in 12 cases. Treatment options were varied and included therapeutic plasma exchange in 11 patients. Ten patients progressed to end-stage renal disease, of which two received kidney transplant. Thus, our study shows an unexpectedly high prevalence of monoclonal gammopathy in patients with TMA, suggesting a potential pathogenetic mechanism. This study underscores the importance of evaluating for a monoclonal gammopathy in patients with TMA as well as the potential for targeting the underlying hematologic disorder as an approach to treating TMA.
血栓性微血管病（TMA）是一种罕见的疾病，由一组不同的疾病组成，这些疾病通过内皮损伤的共同组织学发现联系在一起。单克隆免疫球蛋白可能是 TMA 发病机制中的一个潜在触发因素。为了确定与单克隆免疫球蛋白相关的 TMA 的单克隆丙种球蛋白病的患病率和临床病理特征，我们对 146 例临床诊断为 TMA 的成人（18 岁及以上）进行了回顾性研究。在 146 例 TMA 患者中，我们在 20 例患者（13.7%）中检测到单克隆免疫球蛋白。在 50 岁及以上的患者中，单克隆丙种球蛋白病的患病率为 21%，这大约是该人群预期的 4.2%的五倍。15 例患者患有意义未明的单克隆丙种球蛋白病，1 例患有多发性骨髓瘤，1 例患有冒烟型骨髓瘤，2 例患有 POEMS 综合征，1 例患有 T 细胞淋巴细胞白血病。对 15 例患者进行了肾活检，其中 6 例显示血栓，11 例显示系膜溶解，所有患者均显示肾小球毛细血管壁上的双轮廓。12 例存在急性肾小管损伤。治疗方案各不相同，包括 11 例患者接受了治疗性血浆置换。10 例患者进展为终末期肾病，其中 2 例接受了肾移植。因此，我们的研究表明 TMA 患者中单克隆丙种球蛋白病的患病率出乎意料地高，提示存在潜在的发病机制。这项研究强调了在 TMA 患者中评估单克隆丙种球蛋白病的重要性，以及针对潜在血液学疾病作为治疗 TMA 的一种方法的潜在性。
