Chowdhury Lynda, Alobaidi Ahmed, Lytvak Irina
Department of Internal Medicine, Methodist Dallas Medical Center, Dallas, USA.
Department of Pathology, Methodist Dallas Medical Center, Dallas, USA.
Cureus. 2022 Aug 4;14(8):e27675. doi: 10.7759/cureus.27675. eCollection 2022 Aug.
Infective endocarditis (IE) is still seen globally with acute kidney injuries remaining a common complication of the disease. Histological specimens often display either diffuse or focal endocapillary proliferation as well as neutrophilic infiltration in endocarditis-related renal disease. C3-dominant glomerulonephritis (C3GN) utilizes mechanisms of complement activation unique from IE-associated glomerulonephritis. In C3GN, micrographic review may reveal scattered accumulation of C3 fragments with subepithelial hump formation and mesangial electron-dense deposits that help solidify the diagnosis of this recently discovered pathological phenomenon. Herein, we summarize a clinical case of likely IE-related C3GN without hypocomplementemia in a patient with a single kidney to help compare and contrast the key elements of each process. A 27-year-old Hispanic man with a past medical history of nephrectomy for renal donation presented to a community hospital with a high fever and altered sensorium. A serum creatinine of 6.98 mg/dL with unknown baselines, nephrotic-range proteinuria, and severe rhabdomyolysis plus methicillin-sensitive bacteremia were quickly discovered after admission. A later transesophageal echocardiogram showed a hypermobile vegetation along the anterior mitral valve leaflet confirming suspected IE. The patient's serum C3 and C4 complement levels and antinuclear, myeloperoxidase, and proteinase-3 antibody titers were all within normal limits. A renal biopsy pursued in the etiological investigation of this non-oliguric acute kidney injury revealed a single subepithelial electron-dense deposit and granular immunofluorescent C3 staining in peripheral mesangial segments. Dominant C3 deposition without associated immunoglobulins can result from in situ localization of bacterial antigens promoting plasmin activation to recruit neutrophils and monocytes to initiate leukocyte-mediated damage. Immunosuppressive therapies for C3GN triggering antibody-independent activation of the alternative or lectin complement pathways may be merited where disease remission becomes difficulty to achieve.
感染性心内膜炎（IE）在全球范围内仍有发生，急性肾损伤仍是该疾病的常见并发症。组织学标本在感染性心内膜炎相关肾病中常表现为弥漫性或局灶性毛细血管内增生以及中性粒细胞浸润。C3 主导的肾小球肾炎（C3GN）利用的补体激活机制与 IE 相关肾小球肾炎不同。在 C3GN 中，显微镜检查可能会发现 C3 片段的散在积聚，伴有上皮下驼峰形成和系膜区电子致密沉积物，这有助于确诊这一最近发现的病理现象。在此，我们总结了一例单肾患者可能与 IE 相关的无补体血症的 C3GN 临床病例，以帮助比较和对比每个过程的关键要素。一名 27 岁有肾移植肾切除术病史的西班牙裔男性因高热和意识改变入住一家社区医院。入院后很快发现血清肌酐为 6.98 mg/dL（基线未知）、肾病范围蛋白尿、严重横纹肌溶解以及甲氧西林敏感菌血症。随后的经食管超声心动图显示二尖瓣前叶有一个活动度高的赘生物，证实了疑似 IE。患者的血清 C3 和 C4 补体水平以及抗核抗体、髓过氧化物酶和蛋白酶 3 抗体滴度均在正常范围内。在对这种非少尿性急性肾损伤进行病因调查时进行的肾活检显示，在外周系膜区有单个上皮下电子致密沉积物和颗粒状免疫荧光 C3 染色。细菌抗原的原位定位可促进纤溶酶激活，从而募集中性粒细胞和单核细胞引发白细胞介导的损伤，进而导致无相关免疫球蛋白的 C3 为主的沉积。对于难以实现疾病缓解的 C3GN，触发替代或凝集素补体途径抗体非依赖性激活的免疫抑制疗法可能是值得的。
