Increased Lifetime Risk of ESRD in Familial IgA Nephropathy

Manman Shi; Shuwen Yu; Yan Ouyang; Yuanmeng Jin; Zijin Chen; Wenjie Wei; Zhengying Fang; Wen Du; Zhaohui Wang; Qinjie Weng; Jun Tong; Xiaoxia Pan; Weiming Wang; Kiryluk Krzysztof; Nan Chen; Jingyuan Xie

doi:10.1016/j.ekir.2020.10.015

Increased Lifetime Risk of ESRD in Familial IgA Nephropathy

Kidney Int Rep. 2020 Oct 20;6(1):91-100. doi: 10.1016/j.ekir.2020.10.015. eCollection 2021 Jan.

Authors

Manman Shi^{1

2}, Shuwen Yu¹, Yan Ouyang¹, Yuanmeng Jin¹, Zijin Chen¹, Wenjie Wei¹, Zhengying Fang¹, Wen Du¹, Zhaohui Wang¹, Qinjie Weng¹, Jun Tong¹, Xiaoxia Pan¹, Weiming Wang¹, Kiryluk Krzysztof³, Nan Chen¹, Jingyuan Xie¹

Affiliations

¹ Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Nephrology, Traditional Chinese Medicine Hospital of Kunshan, Nanjing University of Chinese Medicine, Kunshan, Jiangsu, China.
³ Division of Nephrology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA.

Abstract

Introduction: Familial IgA nephropathy (IgAN) has been widely reported. However, its clinicohistologic characteristics and long-term prognosis are not clear.

Methods: A total of 348 familial IgAN cases from 167 independent families were recruited and their clinicohistologic characteristics as well as lifetime risk of end-stage renal disease (ESRD) were compared to 1116 sporadic IgAN patients from the same geographic region.

Results: Of all familial IgAN patients, 60 (17%) came from 32 single-generation (SG; all affected individuals are siblings) families, whereas 286 (82%) came from 134 multiple-generation (MG; affected individuals were present in at least 2 consecutive generations) families. The lifetime ESRD risk was significantly higher in familial patients than sporadic ones after adjusting by gender (hazard ratio [HR]=1.40, 95% confidence interval [CI]: 1.12-1.74, P = 0.004), with 5 years younger in median ESRD age (60 years vs. 65 years in familial and sporadic cases separately). Interestingly, among familial patients, we found cases from SG families (vs. MG families: HR = 2.62, 95% CI: 1.59-4.31, P < 0.001) or with early onset (onset age <30 years) (vs. late onset: HR = 4.79, 95% CI: 3.16-7.26, P < 0.001) had higher lifetime ESRD risk. Furthermore, among sporadic patients, men had lower estimated glomerular filtration rate (eGFR), higher urine protein, higher Oxford T score, and higher risk for life span ESRD compared with women (male vs. female, 25% vs. 17%, P = 0.003) whereas these gender differences were not seen in familial patients.

Conclusion: Familial IgAN cases had poorer renal outcomes and less gender differences compared with sporadic cases. These findings provide evidence that familial disease represent a distinct subtype of more progressive IgAN. Early diagnosis could improve the prognosis of cases with familial IgAN.

Keywords: end-stage renal disease; familial IgA nephropathy; gender; lifetime risk; multiple-generation; single-generation.