Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1 Kajigaya, Kawasaki, Kanagawa, 213-8587, Japan.
Department of Pathology, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
CEN Case Rep. 2024 Apr;13(2):110-116. doi: 10.1007/s13730-023-00809-3. Epub 2023 Jul 15.
Poststreptococcal acute kidney glomerulonephritis (PSAGN) has been seen in adults in recent years, especially in patients with type 2 diabetes mellitus, and the renal prognosis has not always been good. There have been cases of PSAGN in which complete remission was not achieved and hematuria and proteinuria persisted, leading to end-stage renal disease. Previous reports showed that the patients subjected to PSAGN have an underlying defect in regulating the alternative pathway of complement, and they identified that antibodies to the C3 convertase, C3 nephritic factors (C3NeF), are involved. C3NeF stabilizes C3 convertase, sustains C3 activation, and causes C3 glomerulonephritis (C3GN). On the other hand, factor H is a glycoprotein that suppresses the overactivation of the alternative pathway by decaying the C3 convertase. Anti-factor H (aFH) antibodies interfere with factor H and cause the same activation of the alternative pathway as C3NeF. However, a limited number of reports describe the clinical course of C3GN with aFH antibodies. We encountered a 49-year-old Japanese man with type 2 diabetes mellitus. He was referred to our hospital because of his elevated serum creatinine, proteinuria, hematuria, and developed edema on both legs. He was diagnosed as PSAGN at the first kidney biopsy, and his renal function improved and edema and hematuria disappeared, but proteinuria persisted after 5 months. He was diagnosed as C3GN at the second kidney biopsy. In our case, no C3NeF was detected. However, a high titer of aFH antibodies was detected in stored serum from the initial presentation, providing a unified diagnosis of aFH antibody-positive C3GN secondary to PSAGN. He progressed to end-stage renal disease (ESRD) and hemodialysis was started. The persistence of high levels of aFH autoantibodies may have caused C3GN secondary to PSAGN due to activating the alternative complement pathway, which eventually worsened the nephropathy and led to ESRD.
近年来，成年人中出现了链球菌后急性肾小球肾炎（PSAGN），尤其是在 2 型糖尿病患者中，其肾脏预后并不总是良好。有一些 PSAGN 病例未完全缓解，血尿和蛋白尿持续存在，导致终末期肾病。以前的报告表明，患有 PSAGN 的患者在调节补体替代途径方面存在潜在缺陷，他们发现与 C3 转化酶、C3 肾炎因子（C3NeF）有关的抗体。C3NeF 稳定 C3 转化酶，维持 C3 激活，并导致 C3 肾小球肾炎（C3GN）。另一方面，因子 H 是一种糖蛋白，通过降解 C3 转化酶来抑制替代途径的过度激活。抗因子 H（aFH）抗体干扰因子 H 并引起与 C3NeF 相同的替代途径激活。然而，只有少数报告描述了具有 aFH 抗体的 C3GN 的临床病程。我们遇到了一位 49 岁的日本男性，患有 2 型糖尿病。他因血清肌酐升高、蛋白尿、血尿和双下肢水肿而被转至我院。首次肾活检诊断为 PSAGN，肾功能改善，水肿和血尿消失，但 5 个月后蛋白尿持续存在。第二次肾活检诊断为 C3GN。在我们的病例中，未检测到 C3NeF。然而，在初次就诊时储存的血清中检测到高滴度的 aFH 抗体，提供了一个统一的诊断，即继发于 PSAGN 的 aFH 抗体阳性 C3GN。他进展为终末期肾病（ESRD），开始血液透析。高水平的 aFH 自身抗体的持续存在可能导致 PSAGN 继发的 C3GN，因为它激活了替代补体途径，最终使肾病恶化并导致 ESRD。
