Search Results (7)

Kidney transplantation is the most effective replacement therapy for kidney failure, providing the best outcomes in terms of patient survival and offering a better quality of life. However, despite the progressive improvement in kidney survival, the recurrence of original disease remains one of the most important causes of graft loss and a major challenge that requires clinical vigilance throughout the transplant’s duration. Additionally, the type and severity of recurrence affect both treatment options and graft survival. This is especially true for the recurrence of systemic diseases. In this narrative review, we will discuss the timing, frequency, severity, and treatment of post-transplant recurrence in three systemic diseases: lupus nephritis (LN), Antineutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (ANCA-GN), and Henoch–Schönlein purpura (HSP). The recurrence of lupus nephritis is less common than that of primary focal segmental glomerulosclerosis or C3 glomerulopathy. Its severity can range from mild mesangial to diffuse proliferative forms, with varying prognoses and treatment options, much like the original disease. In some patients with LN, as well as in those with ANCA-GN or HSP, the reactivation of the primary disease can affect other organs besides the kidneys, potentially leading to life-threatening conditions. These cases may require a multidisciplinary approach, making these transplants clinically more challenging. Extrarenal flare-ups often necessitate an increase in immunosuppression, which in turn raises the risk of infections. In these autoimmune diseases, the role of immunological tests in determining the timing of kidney transplants remains a topic of ongoing debate. However, elevated levels of certain immunological markers, such as anti-dsDNA antibodies, ANCA titers, or serum immunoglobulin A may indicate a reactivation of the disease, suggesting the need for more intensive patient monitoring. Full article

Objective: IgA vasculitis (IgAV), previously named as Henoch–Schönlein purpura, is the most frequent systemic vasculitis in children. In adults, IgAV is less common although it is associated with more severe disease. In fact, the frequency of glomerulonephritis (referred to as IgAV nephritis) in adults is higher than in children and tends to present more severely, with around 10–30% of those affected eventually progressing to end-stage renal disease. In this review, we describe the pathophysiology, main clinical features, diagnosis of the disease, and latest clinical data regarding IgAV therapy. Methods: A narrative literature review, primarily based on articles published in PubMed, was conducted. In addition to discussing the main aspects of glucocorticoids and conventional disease-modifying drugs used in the management of IgAV, this review focuses on the latest information reported regarding biologics and potential future therapies. Results: Glucocorticoids are the first-line therapy for IgAV, especially in adults with severe manifestations. Colchicine, dapsone, and methotrexate can be useful for controlling minor manifestations. Several immunomodulatory agents, such as cyclosporine A, tacrolimus, and mycophenolate mofetil, have shown favorable results as glucocorticoid-sparing agents. Leflunomide has shown promising results but requires further study. The use of rituximab has demonstrated efficacy in reducing relapse frequency, lowering the cumulative glucocorticoid burden, and achieving long-term remission of the disease in children and adults with IgAV. Immunoglobulins and plasma exchange therapy can also be useful in difficult and life-threatening situations. Other potential therapies with encouraging results include TRF-budesonide, B-cell-directed therapy, B-cell-depleting agents, sodium–glucose cotransporter-2 inhibitors, endothelin receptor antagonists, and complement pathway inhibitors. Conclusions: Glucocorticoids are the first-line therapy for IgAV, especially in adults with severe manifestations. The role of various immunomodulatory therapies, such as calcineurin inhibitors and mycophenolate mofetil, remains promising, while rituximab reduces the long-term side effects of glucocorticoids and can help achieve disease remission. Other potential therapies with encouraging results require further research. Full article

Purpose of Review: IgA vasculitis (IgAV), formerly Henoch–Schonlein purpura, is the most common systemic vasculitis in childhood. In adults, however, this condition is poorly understood, yet associated with more severe disease and poorer outcomes. This necessitates the need for early diagnosis and management. Scope of Review: We describe the pathophysiology, clinical manifestations, and diagnosis of IgAV in adults. Poor outcomes are often due to the high frequency of glomerulonephritis in IgAV-IgA vasculitis-associated nephritis (IgAVN). We hence also aim to summarize the latest clinical data regarding treatment strategies in IgAVN. The diagnosis and differentiation in histology between IgAVN and IgA nephropathy (IgAN) remain a challenge. Review of treatment therapies: Pathological mechanisms between IgAVN and IgAN appear to be consistent between the two, and data from IgAN are often extrapolated to IgAVN. The role of various immunosuppression therapies remains controversial, and in this review, we will discuss immunosuppression use and highlight evidence surrounding emerging and promising novel therapies in IgAVN/IgAN. Our aim for this review is to guide future treatment strategies and direct future studies. Full article

We investigated the polarisation of CD68+ macrophages and perforin and granulysin distributions in kidney lymphocyte subsets of children with IgA vasculitis nephritis (IgAVN). Pro-inflammatory macrophage (M)1 (CD68/iNOS) or regulatory M2 (CD68/arginase-1) polarisation; spatial arrangement of macrophages and lymphocytes; and perforin and granulysin distribution in CD3+ and CD56+ cells were visulaised using double-labelled immunofluorescence. In contrast to the tubules, iNOS+ cells were more abundant than the arginase-1+ cells in the glomeruli. CD68+ macrophage numbers fluctuated in the glomeruli and were mostly labelled with iNOS. CD68+/arginase-1+ cells are abundant in the tubules. CD56+ cells, enclosed by CD68+ cells, were more abundant in the glomeruli than in the tubuli, and co-expressed NKp44. The glomerular and interstitial/intratubular CD56+ cells express perforin and granulysin, respectively. The CD3+ cells did not express perforin, while a minority expressed granulysin. Innate immunity, represented by M1 macrophages and CD56+ cells rich in perforin and granulysin, plays a pivotal role in the acute phase of IgAVN. Full article

Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient’s response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review’s findings. Full article

Background: Henoch-Schönlein purpura (HSP) is a common systemic vasculitis in children, involving the skin, musculoskeletal system, gastrointestinal tract and kidneys. Some studies in children have shown possible risk factors linked with the development and severity of HSP Nephritis (HSPN). The aim of this study was to research predicting factors for the development of HSPN. Methods: We retrospectively evaluated 132 pediatric patients with HSP, according to EULAR/PRINTO/PRESS criteria. All patients were screened for HSPN by urinalysis. Finally, we compared demographic, clinical and laboratory data in HSP patients with and without nephritis. Results: The median age at HSP diagnosis [6.2 (2.6–17.5) vs. 5.5 (0.8–15.4) years, p = 0.03] and the incidence of abdominal pain (48 vs. 27%, p = 0.01) were significantly higher in HSPN patients. No differences were evidenced regarding gender, allergic diseases, skin recurrences, gastrointestinal involvement, musculoskeletal involvement, scrotal involvement, and laboratory data (white blood cell count, neutrophil count, lymphocyte count, platelet count, C-reactive protein, erythrocyte sedimentation rate, and blood concentration of IgA). Conclusions: The age at diagnosis and abdominal pain were independent risk factors for renal involvement in HSP patients. However, due to the retrospective nature of this study, further long-term and prospective studies will be necessary. Full article

Chronic kidney disease is a recognised complication of immunoglobulin A vasculitis, (IgAV; formerly Henoch–Schonlein purpura—HSP). The pathophysiology of IgAV and why some patients develop significant renal involvement remains largely unknown. Identifying urinary inflammatory markers could direct targets for earlier intervention. The aim of this cross-sectional exploratory study was to perform a large protein array analysis to identify urinary markers to provide insight into the mechanisms of kidney inflammation in children with established IgAV nephritis (IgAVN). Determination of the relative levels of 124 key proteins was performed using commercially available proteome profiler array kits. Twelve children were recruited: IgAVN, n = 4; IgAV without nephritis (IgAVwoN), n = 4; healthy controls (HCs), n = 4. The urinary concentrations of twenty proteins were significantly different in IgAVN compared to IgAVwoN. The largest fold changes were reported for B-cell activating factor (BAFF), Cripto-1, sex-hormone-binding globulin and angiotensinogen. The urinary levels of complement components C5/C5a and factor D were also significantly elevated in patients with IgAVN. A total of 69 urinary proteins significantly raised levels in comparisons made between IgAVN vs. HCs and nine proteins in IgAVwoN vs. HCs, respectively. This study identified key urinary proteins potentially involved in IgAVN providing new insight into the pathophysiology. Further longitudinal studies with larger cohorts are needed to quantitatively analyse these biomarkers. Full article