Characterization of IgA Deposition in the Kidney of Patients with IgA Nephropathy and Minimal Change Disease

Abstract

Approximately 5% of patients with IgA nephropathy (IgAN) exhibit mild mesangial lesions with acute onset nephrotic syndrome and diffuse foot process effacement representative of minimal change disease (MCD). It is not clear whether these unusual cases of IgAN with MCD (IgAN-MCD) are variant types of IgAN or coincidental deposition of IgA in patients with MCD. In a retrospective multicenter cohort study of 18 hospitals in Korea, we analyzed 46 patients with IgAN-MCD. Patients with endocapillary proliferation, segmental sclerosis, and crescent were excluded, and the clinical features and prognosis of IgAN-MCD were compared with those of pure MCD. In addition, we performed galactose-deficient IgA1 (KM55) staining to characterize IgAN-MCD. Among the 21,697 patients with glomerulonephritis enrolled in the database, 46 patients (0.21%) were diagnosed with IgAN-MCD, and 1610 patients (7.4%) with pure MCD. The 46 patients with IgAN-MCD accounted for 0.6% of primary IgAN patients (n = 7584). There was no difference in prognosis between patients with IgAN-MCD and those with only MCD. IgA and KM55 showed double positivity in all patients with IgAN-MCD (n = 4) or primary IgAN (n = 5) under double immunofluorescent staining. However, in four patients with lupus nephritis, mesangial IgA was deposited, but galactose-deficient-IgA1 (Gd-IgA1) was not. These findings suggest that IgAN-MCD is a dual glomerulopathy in which MCD was superimposed on possibly indolent IgAN. We confirmed by KM55 staining that IgAN-MCD is true IgAN, enabling better characterizations of the disease. Furthermore, IgAN-MCD shows a good prognosis when treated according to the usual MCD treatment modality.

Immune Characteristics of IgA Nephropathy With Minimal Change Disease

“…Whether MCD-IgAN is a variant form of IgAN or simply MCD superimposed on mild underlying IgAN or even with quiescent IgA deposition coincidence of MCD has not been established yet. Although several published studies have described the clinical and pathological features of MCD-IgAN and suggested it as a dual glomerulopathy ( Qin et al, 2013 ; Wang et al, 2013 ; Woo et al, 2013 ; Herlitz et al, 2014 ; Li et al, 2016 ; Cho et al, 2020 ), advanced studies on the pathogenesis of MCD-IgAN are rare. In the present study, we explored the comprehensive immune characteristics of MCD-IgAN patients.…”

“…However, with respect to MCD-IgAN, whether it shares the same immunopathogenesis of the four-hit processes as IgAN still needs to be investigated. Until now, only one published study from Cho et al confirmed positive Gd-IgA1 deposition in the glomeruli of IgAN-MCD patients and inferred that Gd-IgA1 played a role in the pathogenesis of MCD-IgAN and IgAN ( Cho et al, 2020 ). However, this information should be interpreted carefully.…”

Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis

“…These observations may be a result of AP system dysregulation. Some previous studies have documented a decrease in renal function in C3G patients at diagnosis [ 20 , 21 ]. Considering these findings together with our current results, we hypothesize that a similar clinical pattern would be present as a result of AP dysregulation—that is, renal injury and inflammation would be attributed to damage caused by the already advanced CP activation as well as additional damage due to AP dysregulation.…”

Effect of pulsed intravenous methylprednisolone with alternative low-dose prednisone on high-risk IgA nephropathy: a 18-month prospective clinical trial

“…However, this study still has some limitations: single-center enrolled Asian patients; a short follow-up period; insufficient patient cases for some subgroups of Oxford MEST-C kidney pathology classification. Additionally, a specific podocytopathic variant of IgAN or the existence of features of minimal change disease (MCD) with diffuse podocyte foot process effacement in IgAN patients were recently reported 33 , 34 , steroid therapy was indicated an appropriate therapeutic strategy in those patients, which was also recommended by the newly-released KDIGO 2021 guidelines for the management of glomerular diseases 10 , 11 . A multicenter, double-blind, broader inclusion criteria and long-term follow-up trial are needed in the future.…”