De La Flor Merino José C, Apaza Jacqueline, Díaz Francisco, Sandoval Edna, Valga Francisco, Villa Daniel, Marschall Alexander, Abascal María Luisa, Rivas Andrea, Cieza Michael
Department of Nephrology, Hospital Central Defense Gomez Ulla, Madrid, Spain.
Department of Nephrology, Hospital Fuensanta, Madrid, Spain.
Glomerular Dis. 2023 Jul 3;3(1):140-147. doi: 10.1159/000531737. eCollection 2023 Jan-Dec.
Cryoglobulinemia refers to the presence of cryoglobulins (CGs) in the serum, encompassing a group of diseases caused by the type of circulating GC. Cryoglobulinemic glomerulonephritis (CryoGN) is the principal manifestation of renal involvement. The diagnosis may be challenging because the hallmark of cryoglobulinemia is the detection of CG in the serum. However, cases of CryoGN without serological evidence of CGs are not uncommon in clinical practice, often diagnosed by anatomopathological findings in the renal biopsy.
We report the case of an 86-year-old male who developed renal impairment, nephritic syndrome, and nephrotic-range proteinuria, without serological evidence of CGs, associated with staphylococcal bacteremia without apparent focus. Renal biopsy and pathological examination showed a membranoproliferative glomerulonephritis pattern with CD61-negative pseudothrombi. Immunofluorescence microscopy showed atypical IgA-dominant deposits. Electron microscopy revealed amorphous subendothelial and mesangial deposits and organized electrodense deposits within capillary loops (pseudothrombi) with microtubular substructure measuring 20-40 nm in thickness. These findings were consistent with seronegative CryoGN and microtubular organized atypical IgA-dominant deposits.
In this report, we discuss the clinical, analytical, and histopathological findings of a rare case of CryoGN without serological evidence of CGs. Regarding the etiology that triggered the glomerular disease in our patient, we conducted an exhaustive study in order to determine the underlying cause of CryoGN. At the time of biopsy, the patient had an active staphylococcal bacteremia. There are reports that postulate that staphylococcal antigens drive activation of immune system and in consequence, could cause this rare form of IgA-dominant glomerulonephritis with cryoglobulinemic features. After ruling out other causes of cryoglobulinemia, we discuss a plausible causal relationship of the staphylococcal infection in the pathogenesis of CryoGN in our patient.
冷球蛋白血症是指血清中存在冷球蛋白（CGs），涵盖了一组由循环中GC类型引起的疾病。冷球蛋白血症性肾小球肾炎（CryoGN）是肾脏受累的主要表现。诊断可能具有挑战性，因为冷球蛋白血症的标志是血清中CG的检测。然而，在临床实践中，无CG血清学证据的CryoGN病例并不少见，通常通过肾活检的解剖病理学发现来诊断。
我们报告了一例86岁男性病例，该患者出现肾功能损害、肾炎综合征和肾病范围蛋白尿，无CG血清学证据，与无明显病灶的葡萄球菌菌血症相关。肾活检和病理检查显示为膜增生性肾小球肾炎模式，伴有CD61阴性假血栓。免疫荧光显微镜检查显示非典型IgA为主的沉积物。电子显微镜显示无定形的内皮下和系膜沉积物，以及毛细血管袢内有组织的电子致密沉积物（假血栓），其微管亚结构厚度为20-40nm。这些发现与血清阴性CryoGN和微管组织化非典型IgA为主的沉积物一致。
在本报告中，我们讨论了一例无CG血清学证据的罕见CryoGN病例的临床、分析和组织病理学发现。关于引发我们患者肾小球疾病的病因，我们进行了详尽研究以确定CryoGN的潜在原因。在活检时，患者存在活动性葡萄球菌菌血症。有报告推测葡萄球菌抗原驱动免疫系统激活，因此可能导致这种具有冷球蛋白血症特征的罕见IgA为主的肾小球肾炎形式。在排除冷球蛋白血症的其他原因后，我们讨论了葡萄球菌感染在我们患者CryoGN发病机制中的合理因果关系。
