Department of Histopathology, Beaumont Hospital, Dublin, Ireland.
Department of Medicine, Beaumont Hospital, Dublin, Ireland.
Nephron. 2018;139(1):63-69. doi: 10.1159/000486018. Epub 2018 Jan 19.
IgA nephropathy is the most common primary glomerulonephritis worldwide and a significant cause of end-stage renal disease (ESRD). While most cases of IgA nephropathy are considered sporadic, familial cases have been reported.
We performed a national audit of 1,809 patients attending renal clinics and dialysis units to identify a family history among patients with kidney disease. We reviewed all renal biopsies performed at our institution spanning a 30-year period. Paediatric cases were not included.
We identified 14 families involving 41 affected individuals with biopsy-proven IgA nephropathy and at least one other member with either biopsy-proven IgA nephropathy or ESRD. Detailed family histories were obtained, medical records reviewed and family pedigrees constructed. Retrospective application of the MESTC criteria to all familial IgA biopsies was performed. Seven families had 2 or more members with biopsy-proven IgA nephropathy, equating to 23 (1.8%) of 1,283 biopsies with IgA nephropathy over the last 30 years. A complex inheritance pattern was observed, with autosomal dominant and autosomal recessive families identified with varying penetrance. There was a male preponderance (68%), and a complex heterogeneity in the clinical and histopathological features of familial IgA patients (age range 16-60 years; creatinine range 60-350 μmol/L). We observed a high rate (66%) of progression to ESRD, with a mean time to progression of 5.13 years (SD 1.8 years; range 2-8 years). Among those patients who had undergone transplantation, recurrence of disease was reported in 5 (50%) cases.
These data suggests familial aggregation of IgA nephropathy, confirm the clinical and histopathological heterogeneity and raise the possibility of monogenic inheritance.
IgA 肾病是全球最常见的原发性肾小球肾炎，也是终末期肾病（ESRD）的重要原因。虽然大多数 IgA 肾病病例被认为是散发性的，但也有家族性病例的报道。
我们对 1809 名在肾脏诊所和透析单位就诊的患者进行了全国性审计，以确定患有肾脏疾病的患者是否有家族史。我们回顾了我们机构在 30 年期间进行的所有肾脏活检。不包括儿科病例。
我们确定了 14 个家族，涉及 41 名经活检证实的 IgA 肾病患者，以及至少一名其他成员患有经活检证实的 IgA 肾病或 ESRD。我们获得了详细的家族史，审查了医疗记录并构建了家族系谱。对所有家族性 IgA 活检应用了 MESTC 标准。7 个家族有 2 个或更多成员经活检证实患有 IgA 肾病，相当于过去 30 年中 1283 例 IgA 肾病活检中有 23 例（1.8%）。观察到一种复杂的遗传模式，确定了常染色体显性和常染色体隐性家族，其外显率不同。存在男性优势（68%），家族性 IgA 患者的临床和组织病理学特征存在复杂的异质性（年龄范围 16-60 岁；肌酐范围 60-350μmol/L）。我们观察到进展为 ESRD 的比率很高（66%），平均进展时间为 5.13 年（SD 1.8 年；范围 2-8 年）。在那些接受过移植的患者中，有 5 例（50%）报告疾病复发。
这些数据表明 IgA 肾病存在家族聚集，证实了其临床和组织病理学的异质性，并提出了单基因遗传的可能性。
