Ahmed M S, Wong C F, Shawki H, Kapoor N, Pandya B K
Department of Nephrology, Aintree University Hospital Foundation Trust, Liverpool, UK.
Clin Nephrol. 2008 Apr;69(4):298-301. doi: 10.5414/cnp69298.
The hepatitis C virus (HCV) infection is associated with several renal diseases including mixed essential cryoglobulinemia, membranoproliferative glomerulonephritis (MPGN) and less frequently membranous nephropathy and crescentic glomerulonephritis. We present a case of HCV-associated cryoglobulin-negative, MPGN Type 1 with features of early crescents and rapidly deteriorating renal function requiring urgent treatment.
A 35-year-old male was admitted with history of arthralgia and erythematous rash. His past medical history included being an intravenous drug abuser. Biochemistry test showed raised serum creatinine of 150 micromol/l. He had nephrotic range proteinuria of 6 g/day and a serum albumin of 23 g/l. Viral serology for hepatitis B and HIV was negative but confirmed evidence of HCV infection with genotype 3A and viral load of 151,014 copies. He had a renal biopsy and histology demonstrated features of crescentic MPGN Type 1. His renal function deteriorated rapidly with his serum creatinine rising to 300 micromol/l over 2 days. We commenced treatment with intravenous methylprednisolone, 500 mg once daily (o.d.) for 3 days, followed by oral prednisolone 40 mg o.d. Concurrently, pegylated Interferon- (IFN) I+/- was commenced. After a 2-week treatment, his renal function showed remarkable recovery with creatinine reduced to 140 micromol/l. After 3 months, ribavirin was added when his renal function remained stable. He had tolerated his treatment without any major side effects. At 6 months follow-up clinic, his renal function was normal with serum creatinine of 69 micromol/l, 24-h urinary protein had dropped to 0.35 g/day, serum albumin increased to 38 g/l and HCV PCR was negative.
The current treatment strategy of HCV-associated renal diseases includes targeting viral trigger HCV with interferon and ribavirin. Both IFN-I+/- and ribavirin have their limitation and adverse effects. In a clinical scenario where there is evidence of rapidly deteriorating renal function with crescentic glomerulonephritis, cautious use of immunosuppressive therapy may well be essential in the acute stage to halt the progression of kidney damage. Literature review of the treatment strategy for MPGN Type 1, cryoglobulin-negative with early features of crescents associated with HCV showed that there was no report or guideline available.
To our knowledge, this is the first case in the literature of rapidly progressing MPGN Type 1 associated with HCV and nephrotic syndrome treated successfully with antiviral drugs and steroids concurrently. Our case highlights an important treatment strategy and may be beneficial to nephrologists facing this clinical scenario in the future. However, a randomized controlled trial is required to evaluate the efficacy of this treatment combination before it can be a standard treatment.
丙型肝炎病毒（HCV）感染与多种肾脏疾病相关，包括混合性冷球蛋白血症、膜增生性肾小球肾炎（MPGN），较少见的有膜性肾病和新月体性肾小球肾炎。我们报告一例HCV相关性冷球蛋白阴性的Ⅰ型MPGN病例，具有早期新月体特征且肾功能迅速恶化，需要紧急治疗。
一名35岁男性因关节痛和红斑皮疹入院。他既往有静脉吸毒史。生化检查显示血清肌酐升高至150微摩尔/升。他有肾病范围的蛋白尿，每天6克，血清白蛋白为23克/升。乙肝和艾滋病毒的病毒血清学检查为阴性，但确诊为HCV感染，基因型为3A，病毒载量为151,014拷贝。他接受了肾活检，组织学显示为新月体性Ⅰ型MPGN特征。他的肾功能迅速恶化，血清肌酐在2天内升至300微摩尔/升。我们开始静脉注射甲泼尼龙治疗，每日一次，500毫克，共3天，随后口服泼尼松龙，每日40毫克。同时，开始使用聚乙二醇干扰素-α 联合或不联合利巴韦林治疗。经过2周治疗，他的肾功能显著恢复，肌酐降至140微摩尔/升。3个月后，当他的肾功能保持稳定时，加用了利巴韦林。他耐受了治疗，没有出现任何严重副作用。在6个月的随访门诊中，他的肾功能正常，血清肌酐为69微摩尔/升，24小时尿蛋白降至0.35克/天，血清白蛋白升至38克/升，HCV PCR检测为阴性。
目前HCV相关性肾脏疾病的治疗策略包括用干扰素和利巴韦林靶向病毒触发因素HCV。干扰素-α联合或不联合利巴韦林都有其局限性和不良反应。在有新月体性肾小球肾炎且肾功能迅速恶化证据的临床情况下，在急性期谨慎使用免疫抑制治疗对于阻止肾脏损害进展可能至关重要。对具有HCV相关早期新月体特征的冷球蛋白阴性的Ⅰ型MPGN治疗策略的文献综述显示，没有相关报告或指南。
据我们所知，这是文献中首例与HCV相关的快速进展性Ⅰ型MPGN合并肾病综合征患者，同时成功接受抗病毒药物和类固醇治疗的病例。我们的病例突出了一种重要的治疗策略，可能对未来面临这种临床情况的肾科医生有益。然而，在这种治疗组合成为标准治疗之前，需要进行随机对照试验来评估其疗效。
