A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy

Introduction: In kidney transplant recipients (KTRs) whose primary disease is IgA nephropathy (IgAN), IgAN recurrence occurs in approximately half of patients by 5 years postoperatively and is associated with graft survival. Although the alternative and lectin pathways are important in the primary pathogenesis of IgAN, the significance of mesangial C1q deposition, which triggers the classical pathway, is unknown. We investigated the clinicopathological significance of mesangial C1q deposition in both recurrent IgAN in KTRs and native IgAN. Methods: Between 2000 and 2021, we conducted a 1:2 matched case-control study of 18 KTRs diagnosed with recurrent IgAN, with a group of native IgAN patients as the control. We evaluated the rate and presence/absence of mesangial C1q deposition in terms of pathological findings and kidney outcomes in each group. Results: The rate of mesangial C1q deposition was significantly higher in the recurrent IgAN patients in KTRs than in native IgAN patients (11/18 [61.1%] vs. 5/36 [13.9%], p = 0.001). In the former group, the incidence of glomerular crescents was relatively higher in C1q-positive patients. There was no significant difference in the annual rate of estimated glomerular filtration rate decline between C1q-positive and C1q-negative patients in either group. Conclusion: Mesangial C1q deposition was more frequent in KTRs with recurrent IgAN than in patients with native IgAN, but we found no difference in kidney outcomes with respect to mesangial C1q deposition. Further large-scale investigations of the importance of mesangial C1q deposition are needed in both KTRs with recurrent IgAN and patients with native IgAN.

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Clinical and Pathological Significance of Mesangial C1q Deposition in Kidney Transplant Recipients with Recurrent IgA Nephropathy and Patients with Native IgA Nephropathy

Hayashi

Kawabe

Yamamoto

et al. 2023

“…There are no studies on C1q deposition of IgAN in DS. On the other hand, the rate of C1q deposition has been reported to be 2–13.54% in native IgAN and 15.7% in transplanted IgAN, respectively [16, 17]. In one recent report, 13.54% of patients with IgAN were C1q positive and the rate of progression to ESKD was significantly higher in these cases than in C1q-negative cases ( p < 0.05).…”

Section: Discussionmentioning

confidence: 99%

“…In one recent report, 13.54% of patients with IgAN were C1q positive and the rate of progression to ESKD was significantly higher in these cases than in C1q-negative cases ( p < 0.05). Moreover, C1q-positive cases showed higher rates of endocapillary hypercellularity, tubular atrophy, interstitial fibrosis, and cellular and fibrocellular crescents compared to C1q-negative cases [17]. Another report demonstrated that mesangial C1q deposition, urinary protein, and the estimated glomerular filtration rate are independent predictors of graft failure in cases of kidney transplantation [18].…”

Section: Discussionmentioning

confidence: 99%

Early Recurrence of Immunoglobulin A Nephropathy after Kidney Transplantation in a Patient with Down Syndrome

Ohki¹,

Kawabe²,

Yamamoto³

et al. 2023

A 39-year-old male kidney transplant recipient with Down syndrome (DS) was admitted to our hospital for biopsy. He had proteinuria at age 9, was diagnosed with immunoglobulin A nephropathy (IgAN) at age 22, had a tonsillectomy at age 35, and underwent ABO-compatible kidney transplantation (from his mother) at age 36. His serum creatinine was stable at 2.21 mg/dL 3 months after the kidney transplant, and his urine protein was 0.11 g/day. A protocol biopsy was performed 7 months after the kidney transplant, and there was suspicion of early recurrence of IgAN. One year after the transplant, urine erythrocytes were elevated and proteinuria was 0.41 g/day; at 3 years and 5 months after the kidney transplant, hematuria was evident along with proteinuria (0.74 g/day). Therefore, an episode biopsy was performed. A total of 23 glomeruli were obtained, four of which exhibited global sclerosis; three others showed intra- and extracapillary proliferative glomerulonephritis compatible with IgAN recurrence. Here, we report a rare case of early recurrence of IgAN with disease progression despite tonsillectomy in a patient with DS.

“…The complement-activation pathway in IgAN is mainly alternative and lectin pathways rather than classical pathway. Of note, several recent studies have emphasized mesangial C1q deposition, which is rare in native IgAN but relatively frequent in recurrent IgAN, and may predict a poor outcome of kidney transplantation in native and recurrent IgAN cases [17][18][19]. Future research is needed to determine the effects of mesangial C1q deposition on recurrence and progression of IgAN.…”

Section: Risk Factors For Recurrence and Progression Of Iganmentioning

confidence: 99%

Current Status and Perspectives on Recurrent IgA Nephropathy after Kidney Transplantation

Kawabe¹,

Yamamoto²

2023

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. IgAN progresses to end-stage kidney disease in 20-40% of patients within 20 years of diagnosis. Kidney transplantation is the most effective option for patients with end-stage kidney disease caused by IgAN, but recurrence can occur in the transplanted kidney. The IgAN recurrence rate varies from 1% to 10% per year, and varies according to the follow-up period, diagnostic modality, and biopsy criteria. Of note, studies based on protocol biopsies have reported a higher incidence of recurrence, which also occurred earlier after transplantation. In addition, recent data show that recurrence of IgAN is a more significant cause of allograft failure than previously believed. Little is known about the pathophysiology of IgAN recurrence, but several potential biomarkers have been investigated. Among them, galactose-deficient IgA1 (Gd-IgA1), IgG anti-Gd-IgA1 antibodies, and soluble CD89 could play a pivotal role in disease activity. This review aims to describe the current status of recurrent IgAN, including the incidence, clinical characteristics, risk factors, and future perspectives, with a focus on the available therapeutic approaches.