Menè Paolo, Stoppacciaro Antonella, Lai Silvia, Festuccia Francescaromana
Division of Nephrology, Department of Clinical and Molecular Medicine, "Sapienza" University, Rome, Italy.
Division of Pathology, Department of Clinical and Molecular Medicine, "Sapienza" University, Rome, Italy.
Int J Nephrol Renovasc Dis. 2022 May 13;15:173-183. doi: 10.2147/IJNRD.S280179. eCollection 2022.
"Cast nephropathy" (CN) is a pathological feature of myeloma kidney, also seen to a lesser extent in the context of severe nephrotic syndrome from non-haematological diseases. The name relates to obstruction of distal tubules by "casts" of luminal proteins concentrated by intensive water reabsorption resulting from dehydration or high-dose diuretics. Filtered proteins form complexes with endogenous tubular Tamm-Horsfall glycoprotein. The resulting gel further slows or stops luminal flow upon complete obstruction of distal convoluted tubules and collecting ducts. Thus, a tubular obstructive form of acute kidney injury (AKI) is a common consequence of CN. The pathogenesis of CN will be reviewed in light of recent advances in the understanding of monoclonal disorders of B lymphocytes, leading to the release of immunoglobulin components (free light chains, FLC) into the bloodstream and their filtration across the glomerular basement membrane. Treatment aiming at reduction of the circulating burden of FLC may help recovery of renal function in a fraction of these patients, besides filling the void between the onset of AKI, histopathological diagnosis, and full response to pharmacologic treatment.
“管型肾病”(CN)是骨髓瘤肾病的一种病理特征,在非血液系统疾病所致的严重肾病综合征中也较少见。该名称与因脱水或大剂量利尿剂导致的大量水重吸收使管腔蛋白“管型”阻塞远端肾小管有关。滤过的蛋白质与内源性肾小管Tamm-Horsfall糖蛋白形成复合物。当远端曲管和集合管完全阻塞时,所形成的凝胶会进一步减缓或停止管腔流动。因此,肾小管阻塞型急性肾损伤(AKI)是CN的常见后果。鉴于对B淋巴细胞单克隆疾病认识的最新进展,将对CN的发病机制进行综述,这导致免疫球蛋白成分(游离轻链,FLC)释放到血液中并通过肾小球基底膜滤过。除了填补急性肾损伤发作、组织病理学诊断和对药物治疗的完全反应之间的空白外,旨在降低FLC循环负荷的治疗可能有助于部分此类患者肾功能的恢复。