Long-term kidney transplant outcomes in Chinese patients with primary glomerulonephritis: A multicenter study in China

To the Editor: The primary cause of end-stage kidney disease (ESKD) in China is chronic glomerulonephritis (GN), which accounts for 45% of ESKD patients.1 There is currently no nationwide large-scale study on the long-term prognosis of kidney transplantation in patients with chronic GN in China. Over the past decade, however, few landmark studies from populations in Europe2,3 and the United States4 have provided important reference data for this issue. Therefore, we propose to conduct a nationwide multicenter retrospective study, which was launched by the National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, from 2017 to 2020, to retrospectively analyze and collect the clinical prognosis characteristics of different chronic GN patients in China after kidney transplantation, laying the foundation for describing disease outcomes, exploring relevant risk factors, guiding clinical decision-making, and improving the long-term prognosis of kidney transplant patients in China. This research project was reviewed and approved by the Institutional Research Ethics Committee of Jinling Hospital, Nanjing University School of Medicine (No. 2017NZKYKS-002-01) and was conducted according to the principles of the Declaration of Helsinki. Informed written consent was obtained from all participants. We screened 28,709 patients and ultimately enrolled 698 cases between January 1, 1994 and June 30, 2017, aged >18 years with primary renal diagnosis of GN or autosomal dominant polycystic kidney disease (ADPKD) from 10 Chinese kidney transplantation centers. In total, 550 patients were diagnosed with chronic GN, including IgA nephropathy (IgAN, n = 425), lupus nephritis (LN, n = 64), focal segmental glomerulosclerosis (FSGS, n = 27), ANCA-associated vasculitis (AAV, n = 16), membranous nephropathy (MN, n = 11), and membranoproliferative glomerulonephritis (MPGN, n = 7). Meanwhile, 148 patients were diagnosed with ADPKD and were selected as the control group. The assembly of the final study cohort of patients was shown in Supplementary Figure 1, https://links.lww.com/CM9/B979. Baseline demographic, socioeconomic, comorbidity, and transplant-related characteristics differed considerably by cause of ESKD Supplementary Table 1, https://links.lww.com/CM9/B979. There were two primary outcomes: death-censored graft loss, which was defined as return to dialysis or re-transplantation, and all-cause patient death. First of all, after a median follow-up of 72.5 (interquartile range IQR, 49.0–116.0) months, among the GN subtypes, none of the patients with MN, MPGN, or AAV died. However, the mortality ranged from 4.7% (3/64) in LN to 7.4% (2/27) in FSGS. Mortality was lower for patients with IgAN (0.5 deaths per 100 person-years), which was lower than for patients with ADPKD (0.8 deaths per 100 person-years). Among the GN subtypes, the 5-, 10-, and 15-year cumulative human survival rates were 98.3%, 98.0%, and 92.8%, respectively. Compared with the GN subtypes, the human survival rates were similar in ADPKD patients at 99.3%, 96.0%, and 89.0%, respectively. However, the survival rate both in the GN subtypes and ADPKD patients declined dramatically after 15 years. The 20-year cumulative human survival rate was 81.1% in patients with GN subtypes and 76.4% in patients with ADPKD Figure 1A.Figure 1: Human and allograft survival rates in patients with ESKD in China. (A) Cumulative human survival rate in patients with ESKD due to GN or ADPKD. There was no significant difference between the GN group and the ADPKD group during the follow-up duration in the cumulative human survival rate. (B) Cumulative allograft survival rate in patients with ESKD due to GN or ADPKD. (C) Allograft survival curve and cumulative survival rate of patients with ESKD due to GN subtypes or ADPKD. AAV: ANCA associated vasculitis; ADPKD: Autosomal dominant polycystic kidney disease; ESKD: End-stage kidney disease; FSGS: Focal segmental glomerulosclerosis; GN: Glomerulonephritis; IgAN: IgA nephropathy; LN: Lupus nephritis; MN: Membranous nephropathy; MPGN: Membranoproliferative glomerulonephritis.Secondly, after excluding death as a cause, allograft failure due to any cause was observed in 69 (9.9%) patients after a median follow-up of 72.5 (IQR, 49.0–116.0) months. The graft survival rate of GN patients was 98.0% at 1 year, 96.0% at 3 years, 93.3% at 5 years, 84.6% at 10 years, and 75.8% at 15 years Figure 1B. The rate of all-cause allograft failure was the lowest in AAV (6.3%, 0.75 events per 100 person-years) and the highest in MPGN (71.4%, 10.45 events per 100 person-years) Figure 1C. The rates of death, all-cause allograft failure, and allograft failure excluding death as a cause are shown in Supplementary Table 2, https://links.lww.com/CM9/B979. The rates of allograft failure were higher for all GN subtypes except AAV when compared with ADPKD (1.07 events per 100 person-years). However, this rate was lower for IgAN than for other GN subtypes except AAV. The allograft survival rate was the worst in MN, with a 1-year survival rate of 90.9% and a 5-year survival rate of 63.6%. The 5-year survival rate in MPGN was 71.4%, followed by FSGS, which was 85.2% at 5 years. However, the 5-year graft survival rate was above 90.0% for IgAN, LN, and AAV patients. Ten years post transplantation, patients with AAV still had a survival rate over 90%, while in the IgAN and LN groups, the survival rate was approximately 85.0%. Fifteen years post transplantation, the allograft survival rates for patients with LN, FSGS, and IgAN were reduced to 65.6%, 63.0%, and 82.8%, respectively. The frequencies of secondary outcomes, including acute rejection, chronic rejection, recurrent GN, BKVAN, de novo GN, malignancy, de novo diabetes, cardiovascular events, and cerebrovascular events differed by GN subtype, are shown in Supplementary Table 3, https://links.lww.com/CM9/B979. Taken together, this multicenter study combined large sample size, long follow-up time, and large variety of disease subtypes to examine renal transplantation prognosis in patients with chronic GN in China. The main results of this study are consistent with those of our previous single-center study,5 but are based on representativeness and clinical significance. There was no significant difference in the cumulative human survival rate between ESRD patients due to GN and ADPKD. In comparison to outcomes in ADPKD, graft survival is significantly lower in most GNs. Acknowledgments The authors are thankful to all the patients, nurses, and physicians who took part in this study. We also thank Dr. Dongrui Cheng, Dr. Xuefeng Ni, and Dr. Xue Li for the clinical care assistance. Funding This work is supported by grants from the Special Funds of the National Natural Science Foundation of China (No. 32141004) and Natural Science Foundation of Jiangsu Province (No. BK20210150). Conflicts of interest None.