目的:铜代谢紊乱疾病被认为是威尔逊病(WD)肾脏症状的原因。尽管如此,关于威尔逊病患者肾损害的确切特征的知识仍然有限,包括临床表现,生化指标,影像学发现,和肾组织病理学改变。
方法:在本研究中,我院20例诊断为Wilson病和肾脏受累的患者。这些患者符合经验证的欧洲威尔逊病标准,原发性肾脏疾病或由其他基础疾病引起的继发性肾脏损害的患者被排除在外.收集患者的基线资料。监测各种生化和血液学参数。使用自动生化分析仪测量生化检查,通过流式细胞术分析检测血常规,用原子吸收分光光度计测定24小时尿铜。此外,CER用日立7020全自动生化分析仪通过比浊法免疫法测定(板内和板间变异系数分别为2.7%和5.13%)。用盐酸对苯二胺比色法检测铜氧化酶(板内和板间变异系数均<10%)。根据欧洲肝脏研究协会(EASL)和CKD流行病学合作指南,建立了威尔逊病和肾损害的诊断标准。分别。统计学分析采用SPSS22.0软件进行t检验和χ2检验。当P<0.05时考虑显著差异。
结果:在那些患有威尔逊病相关肾损害的患者中,水肿,肉眼血尿,少尿,大多数患者存在腰痛。在19例患者中还观察到显微镜下血尿和蛋白尿。与没有肾脏受累的患者相比,合并肾脏并发症的患者白细胞(WBC)和中性粒细胞计数显着增加(P<0.05)。此外,肾损害患者的舒张压和收缩压均显著升高,血红蛋白水平显著降低(P<0.05)。彩色多普勒超声结果显示12例患者的双肾弥漫性病变,在5例患者中发现肾囊肿,2例患者肾血流信号异常。同时,不同程度的IgA,IgM,基于IgG的免疫球蛋白,免疫荧光法检测肾小球系膜区补体C3和C1q沉积。此外,肾穿刺活检结果揭示了一系列发现,包括1例微小病变肾病,IgA肾病3例,非典型膜性增生性肾病2例,局灶节段性肾小球硬化1例。
结论:本研究全面阐明了与Wilson病相关的肾损害的独特特征,同时还推测威尔逊病的肾功能不全可能与免疫复合物沉积有关。根据潜在的发病机制,与威尔逊病相关的肾损伤可分为原发性或继发性。为了减缓肾功能损害的进展,必须尽早进行肾活检病理检查,以明确损害的类型并采取适当的治疗方法。
OBJECTIVE: Copper metabolism disorder disease is thought to contribute to renal symptoms in Wilson\'s disease (WD). Nonetheless, there remains limited knowledge regarding the precise characteristics of renal damage in individuals with Wilson\'s disease, encompassing clinical presentations, biochemical indicators, imaging findings, and renal histopathological alterations.
METHODS: In this study, 20 patients diagnosed with Wilson\'s disease and renal involvement were enrolled in our hospital. These patients met the validated European criteria for Wilson\'s disease, and those with primary kidney disease or secondary renal damage caused by other underlying conditions were excluded. The baseline data of patients were collected. Various biochemical and hematological parameters were monitored. Biochemical examinations were measured using an automatic biochemistry analyzer, blood routines were tested by flow cytometry analysis, 24-h urine copper was tested by atomic absorption spectrophotometer. Besides, CER was measured by turbidimetric immunoassay with a Hitachi 7020 automatic biochemical analyzer (the intraplate and interplate coefficients of variation were 2.7% and 5.13% respectively). Copper oxidase was tested by colorimetric method using p-phenylenediamine hydrochloride (the intraplate and interplate coefficients of variation were both <10%). Diagnostic criteria for Wilson\'s disease and kidney damage were established based on the European Association for the Study of the Liver (EASL) and CKD Epidemiology Collaboration guidelines, respectively. Statistical analysis was carried out using t-tests and χ2 tests in SPSS 22.0 software. Significant differences were considered when P<0.05.
RESULTS: In those patients with Wilson\'s disease-related renal damage, edema, gross hematuria, oliguria, and lumbar pain were present in most patients. Microscopic haematuria and proteinuria were also observed in 19 patients. Compared to patients without renal involvement, those with renal complications exhibited a significant increase in white blood cell (WBC) and neutrophil counts (P<0.05). Additionally, patients with renal damage showed a noteworthy rise in both diastolic and systolic blood pressure, along with a significant reduction in hemoglobin levels (P<0.05). Color Doppler ultrasound results revealed diffuse lesions in both kidneys in 12 patients, renal cysts were identified in 5 patients, and 2 patients exhibited abnormal renal blood flow signals. Meanwhile, varying degrees of IgA, IgM, IgG-based immunoglobulins, complement C3 and C1q deposition in the glomerular mesangial area were detected by immunofluorescence. Furthermore, renal puncture biopsy results revealed a spectrum of findings, including minimal change nephrosis in 1 case, IgA nephropathy in 3 cases, atypical membranous proliferative nephropathy in 2 cases, and focal segmental glomerulosclerosis in 1 case.
CONCLUSIONS: This study comprehensively elucidates the distinct attributes of renal damage related to Wilson\'s disease, while also speculating that renal dysfunction in Wilson\'s disease could be linked to immune complex deposition. Depending on the underlying pathogenesis, kidney injury associated with Wilson\'s disease can be classified as primary or secondary. To slow down the progression of renal impairment, it is essential to undergo a renal biopsy pathological examination as early as possible to clarify the type of impairment and take the appropriate treatment.