Renal glomerular lesions in children with juvenile rheumatoid arthritis (literature review)

The literature review describes the different forms of glomerulonephritis (GN) in children with polyarticular and systemic forms of juvenile rheumatoid arthritis (JRA). In the available literature, there are 21 clinical cases of GN: ANCA-associated GN, mesangial proliferative GN, including IgA- and IgM-nephropathy, membranous nephropathy, focal-segmental glomerulosclerosis, minimal change disease, and extracapillary GN. The mechanism of glomerular lesions in JRA is explained by hyperproduction of pro-inflammatory cytokines and by nephrotoxic action of basal anti-inflammatory medications. The clinical manifestations and the effectiveness of treatment of each variant of GN in children with JRA were analyzed in detail. Most publications are devoted to ANCA-associated GN, which developed in patients with a torpid course and a high activity of polyarticular and systemic forms of JRA. The peculiarity of ANCA-associated GN was the presence of hypercreatininemia and in almost half of cases the development of terminal renal failure, despite conducted immunosuppressive therapy. Single cases of other variants of GN were described more than 10 years ago. Proteinuria and the rare nephrotic syndrome were clinically observed, which was the reason for intravital renal morphological examination. Immunosuppressive therapy was effective in mesangial proliferative GN and minimal change disease. All cases of focal-segmental glomerulosclerosis, extracapillary GN were accompanied by the formation of terminal renal failure. Favorable prognosis appeared in children with drug-induced membranous nephropathy after their withdrawal. There are publications on a positive therapeutic effect of genetically engineered biological drugs in ANCA-associated GN, IgM-nephropathy, and a hormone-resistant variant of MCD in children with JRA.

IgM nephropathy complicated by cerebral venous sinus thrombosis: a case study

Background IgM nephropathy is a rare disease with variable clinical presentations and is an unusual cause of nephrotic syndrome. Histopathological findings typically include mesangial hypercellularity with IgM and complement deposition, though the spectrum may range from normal glomeruli through to focal and segmental glomerulosclerosis. Thromboembolism is a well recognised complication of nephrotic syndrome, but cerebral venous sinus thrombosis is rarely described. Case presentation This is the case of a 23-year-old male presenting with the nephrotic syndrome, whose initial renal biopsy was consistent with minimal change disease. Complete remission was achieved with prednisone, however multiple relapses and steroid dependence prompted re-biopsy, the results of which were more consistent with IgM nephropathy. His last relapse was complicated by cerebral venous sinus thrombosis. He then received rituximab and a weaning course of prednisone to again enter remission. Conclusions This case highlights the need to consider IgM nephropathy in the differential diagnosis of nephrotic syndrome. Additionally, it emphasises the risk of thrombosis in patients with severe nephrosis.

Successful treatment of a rare variant of mesangioproliferative glomerulonephritis with IgM deposits with Cyclosporin A

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

P0478CLINICOPATHOLOGICAL CHARACTERISTICS AND TREATMENT OUTCOMES OF IGM NEPHROPATHY

Background and Aims IgM nephropathy (IgMN) is a controversial clinicopathological entity that is characterized by the presence of dominant diffuse mesangial IgM deposits, with diverse clinical presentations and varying response to supportive or immunosuppressive treatment. The aim of our study was to determine the clinical features, histopathological characteristics and treatment outcomes in patients with IgMN. Method We conducted a multicenter retrospective observational study that included patients that had undergone a kidney biopsy between January 1990 and December 2018. We identified 40 patients with mesangial proliferative glomerulopathy with dominant IgM deposits. Patients with the presence of systemic diseases (systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus or paraproteinemia) were excluded, as well as those with incomplete histological or follow-up data. Demographic, clinical, analytical, and histological data were collected, and the different treatment regimens were compared for achieving clinical remission and prevention of kidney disease progression. Results 33 patients were identified with primary mesangial IgM nephropathy, with a median post-biopsy follow-up of 7.3 (2.8-11.1) years. Mean age of presentation was 34.9±19.0 years, 51.5% were females. The most frequent initial manifestation was nephrotic syndrome in 54.5% of cases, followed by proteinuria with microscopic hematuria in 21.2%, proteinuria in 19.1%, and isolated microhematuria in 3% of patients. On presentation, mean eGFR measured by CKD-EPI was 102.9±38.9 ml/min, median proteinuria was 3.3 g/24h (IQR 1.13-4.88), 69.7% had microscopic hematuria and 27.3% presented with hypertension. Light microscopy revealed mesangial hypercellularity and expansion in 81.8% and 78.8% respectively, 6.6% showed extracapillary proliferation, 33.3% showed segmental sclerosis, 39.4% had mild to moderate interstitial fibrosis, and 46.9% had vascular hyaline deposits. On immunofluorescence all patients showed diffuse mesangial IgM deposits, along with subdominant mesangial deposits of IgG (6.1%), IgA (6%), C3 (39.4%), C1q (27.3%) and Lambda (3%). In nephrotic patients, 16.7% were steroid-resistant, whereas 40% of steroid-sensitive patients were steroid-dependent. 41.7% of steroid-sensitive and nondependent IgMN patients developed a median 3.5 relapses during follow-up. 12 nephrotic patients (3 steroid-resistant and 9 steroid-dependent) received immunosuppressive treatment; 5 patients were initially treated with oral cyclophosphamide, 5 with a calcineurin inhibitor (CNI) and 2 with chlorambucil. All steroid-dependent or resistant patients treated with cyclophosphamide or chlorambucil achieved partial or complete clinical remission. Out of the five patients treated with a CNI, 3 attained remission whereas the other two were switched to cyclophosphamide and chlorambucil respectively after which remission was obtained. No patients progressed to end-stage kidney disease. Conclusion IgMN is a rare mesangial proliferative glomerulopathy with a varying clinical and morphological spectrum. It commonly presents as nephrotic syndrome, and is frequently associated with microscopic hematuria. Clinical course is variable, with frequent relapses and a high prevalence of steroid dependence. Complete remission can be achieved with immunosuppressive therapy in cases of steroid-dependent or resistant IgMN, particularly with cytotoxic agents.

IgM nephropathy in children: clinical, immunological, pathomorphological features

BACKGROUND. Studies on the problem of IgM nephropathy in children in the world literature are few. Data on the disease in adults and children In Belarus have not previously been presented.THE AIM: to analyze the clinical, immunological, morphological characteristics, treatment regimen and prognostic factors of IgM nephropathy in children.PATIENTS AND METHODS. The study included 153 patients during the 6 years observed in the Republican Center for Pediatric Nephrology, among whom 21 were diagnosed with IgM nephropathy.RESULTS. Analysis of clinical, morphological features, the participation of markers of activation of T- and B-lymphocytes, pro-inflammatory and profibrotic molecules was performed.CONCLUSIONS. In most cases, IgM nephropathy is characterized by steroid dependence or resistance, or frequent relapses, which dictates the need to join cytostatic agent. In childhood is characterized by a benign course with no signs of progression.

Other primary glomerular diseases

This chapter covers the other primary glomerular diseases, including their pathologies, treatment options for their management, and risk factors. Some of these primary glomerular diseases are quite rare. This chapter covers fibrillary glomerulonephritis (FGN), collagenofibrotic glomerulopathy, thin basement membrane nephropathy (TBMN), lipoprotein glomerulopathy (LPG), ‘pure’ mesangial proliferative glomerulonephritis (MesPGN), IgM nephropathy, C1q nephropathy, idiopathic nodular glomerulosclerosis, and C4 glomerulopathy. It describes the use of light microscopy, immunofluorescence, electron microscopy, and immunochemistry where applicable. For each disease, the natural history, clinical presentation, pathogenesis, and pathology are described, and, where applicable, specific studies are discussed. Any specific treatments are outlined for each.