Glomerular diseases最新文献

Introduction: Treating lupus nephritis is vital to reducing morbidity and mortality. In Thailand, comparative data on intravenous cyclophosphamide- and mycophenolate mofetil (MMF)-based induction therapies are limited. This study assessed renal remission outcomes for these regimens.

Methods: We analyzed renal and patient outcomes in 89 individuals with biopsy-proven active lupus nephritis treated at Phramongkutklao Hospital between 2020 and 2023. Among the cohort, 55 patients received a cyclophosphamide regimen, and 34 were treated with an MMF regimen.

Results: Baseline clinical characteristics were comparable between the two groups, except for higher hematuria and renal activity index, as well as lower C3 complement levels and renal chronicity in the cyclophosphamide group. The average doses administered were 0.55 ± 0.12 g/m² per dose for intravenous cyclophosphamide and 2.15 ± 0.31 g/day for MMF. By the 24th week, the overall remission rate (complete and partial remission) was 81.8% (45 patients) in the cyclophosphamide group and 85.3% (29 patients) in the MMF group (relative risk 1.01, 95% CI 0.82-1.23, p = 0.949). Proteinuria reduction from baseline at the 24th week was -54.1 ± 93.3% in the cyclophosphamide group and -69.4 ± 22.2% in the MMF group (relative risk 1.01, 95% CI 0.99-1.01, p = 0.465). Adverse events were similar across the two regimens. However, 1 patient in the cyclophosphamide group died, and three required dialysis.

Conclusion: Induction therapy with cyclophosphamide- and MMF-based regimens demonstrated comparable efficacy and safety in achieving renal remission in patients with active lupus nephritis.

Introduction: Systemic lupus erythematosus (SLE), as an autoimmune disease, and lupus nephritis (LN), are typically diagnosed in women at fertile age. Late-onset SLE is defined as a disease onset over 45-50 years. Our main objective was to analyze the clinical, histological, prognostic, and therapeutic features related to LN in our late-onset SLE population.

Methods: A single-center and retrospective study was performed comparing clinical-demographic, histological, prognostic, and therapeutic features of 45 LN patients from 1994 to 2023. We divided the study population according to the age of onset of LN into classic onset (<45 years) and late onset (≥45 years).

Results: Late-onset LN patients showed a higher association with Sjögren's and antiphospholipid syndrome, more cardiovascular comorbidities at presentation, poorer renal function at diagnosis, and higher Systemic Lupus Damage Index (SDI) score. Histology showed more nonproliferative LN classes (II and V). Late-onset LN responders, compared to those with classic onset, achieved response later. Nonresponsive patients had a higher incidence of acute kidney injury (AKI), more glomerulosclerosis and interstitial fibrosis-tubular atrophy (IFTA) at presentation, and a higher frequency for renal replacement therapy (RRT) at diagnosis and during follow-up. The main independent variables associated with relapse were younger age at SLE diagnosis and initial partial renal response (PRR).

Conclusions: Late-onset LN is often accompanied by other systemic autoimmune diseases such as Sjögren's and antiphospholipid syndrome. These patients have major cardiovascular comorbidities, poor estimated glomerular filtration rate (eGFR) at diagnosis, and increased chronicity index in histology. A tailored approach in this fragile population in order to avoid unnecessary immunosuppression is of critical interest.

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding of its pathogenesis.

Methods: We conducted a retrospective analysis of 18 patients with PGNMID from the Cleveland Clinic Kidney Biopsy Epidemiology Project from January 2015 to March 2023.

Results: PGNMID was more predominant among males (67%), and whites (78%), with median age of 60 years. Over 2/3rd of patients presented with hypertension, renal insufficiency, and hematuria, while 26% of patients had nephrotic syndrome. Mean serum creatinine and proteinuria at biopsy were 3.2 mg/dL and 4.3 g/g, respectively. A detectable monoclonal (M) protein was detected in 28% of cases; however, only 3 patients had underlying hematologic disorders (multiple myeloma, CLL, and B-cell lymphoma). An endocapillary hypercellularity/membranoproliferative pattern (72%), IgG/kappa (83%), and IgG3 (56%) were predominant findings on kidney pathology. Eight patients (44%) progressed to end-stage kidney disease (ESKD), with a median onset of 7.5 months after the initial kidney biopsy. While 6 patients achieved complete remission primarily with clone-directed therapy.

Conclusion: Despite monoclonal protein deposition on kidney biopsy, 28% patients with PGNMID had a detectable monoclonal protein. Unlike other forms of paraproteinemic kidney diseases, renal outcomes for patients with PGNMID are poor, with 44% progressing to ESKD (median time 7.5 months) after kidney biopsy in our cohort. Clone-directed therapy to improve outcomes remains the mainstay of treatment, despite the absence of detectable clone in most cases. Thus, further investigation into the pathogenesis of PGNMID is warranted to guide future treatment discovery and clinical trials.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are FDA-approved for weight loss and are increasingly prescribed for patients with obesity and type 2 diabetes mellitus. Multiple studies have demonstrated desirable renal and cardiovascular benefits from these novel agents. So far, a few case reports of acute tubular injury and acute interstitial nephritis have been reported with GLP-1RA. Podocytopathies in association with semaglutide are rare. In this case report, we present a case of nephrotic syndrome that developed after exposure to semaglutide and propose potential pathophysiological mechanisms underlying this rare renal complication.

Case presentation: Herein, we report a novel case of a 43-year-old female who was evaluated in the nephrology clinic for abrupt onset of bilateral lower extremity edema and foamy urine, a few weeks after exposure to semaglutide. She was diagnosed with nephrotic syndrome and subsequently underwent a kidney biopsy, which revealed features suggestive of minimal change disease, along with coexistent thin basement membrane disease.

Conclusion: GLP-1RAs have been increasingly prescribed due to their proven pleiotropic benefits, including improvements in albuminuria, glycemic control, weight loss, and cardioprotective effects. Despite the considerable benefits of GLP-1RAs, it is essential to recognize novel side effects.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have significantly impacted the management of diabetic kidney disease (DKD) and heart failure (HF), providing benefits beyond glycemic control. This review examines the mechanisms through which SGLT2is provide renal and cardiovascular protection and assesses their clinical efficacy.

Summary: By inducing glucosuria and natriuresis, SGLT2is alleviate multiple complications induced by chronic hyperglycemia. Moreover, SGLT2is reduce albuminuria, improve tubular function, and modulate erythropoiesis. Additionally, they mitigate inflammation and fibrosis by decreasing oxidative stress and downregulating proinflammatory pathways. Clinical trials have demonstrated significant reductions in renal and cardiovascular events among patients with type 2 diabetes mellitus. A comprehensive review of the literature was conducted through PubMed, highlighting the effects of SGLT2is and the results of major clinical trials involving SGLT2is.

Key messages: SGLT2is play a crucial role in the management of DKD and HF by addressing multiple pathogenic pathways. Currently, SGLT2is are included in clinical guidelines for DKD and HF management, and their benefits extend to nondiabetic populations. Further research is needed to explore SGLT2is' multifaceted mechanisms and potential applications across diverse patient populations and different disease etiologies.

Introduction: Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear.

Case presentation: Here, we present 2 patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3, leading to reduced regulatory T cells. Serum could not be obtained from this patient during the active phase of MCD to directly establish the presence of anti-nephrin antibodies. However, this patient demonstrated IgG dusting over podocyte cell bodies by immunofluorescence microscopy, as well as colocalization of IgG with nephrin in confocal microscopy. The second patient developed MCD in the context of immune checkpoint inhibitor treatment for metastatic carcinoma. Anti-nephrin antibodies were detected in this patient during active disease. The patient's kidney biopsy also showed evidence of binding of anti-nephrin antibodies within the glomeruli.

Conclusion: These cases demonstrate that genetic and iatrogenic mechanisms of breakdown in peripheral tolerance can lead to MCD.

Introduction: Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is associated with severe kidney failure and high morbidity and is exceedingly rare in children. The few pediatric studies published about this condition report dependency of kidney replacement therapy at presentation and partial or complete response in kidney function in a minority of cases.

Case presentation: We describe the case of a 14-year-old girl with crescentic glomerulonephritis based on double positive anti-GBM and myeloperoxidase-antineutrophil cytoplasmic antibodies with a mitigated clinical course presenting with fatigue, anemia, and an estimated glomerular filtration rate range between 34 and 42 mL/min/1.73 m². Response to treatment with daily therapeutic plasma exchanges, corticosteroids, and oral cyclophosphamide was prompt.

Conclusion: This ultrarare presentation highlights the need to consider determining anti-GBM antibodies and/or obtaining a kidney biopsy even in children with less severe presentations of unexplained glomerulonephritis and underlines the clinical treatment dilemma in this disease for children due to the potential long-term sequelae.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can be a life-threatening condition, characterized by necrotizing inflammation of small blood vessels. Major organ involvement, most commonly kidney and lung disease, is associated with significant morbidity and mortality. Intensive early immunosuppressive therapy is the cornerstone of management and has transformed ANCA-associated vasculitis (AAV) into a chronic relapsing condition. Remission induction with tapering glucocorticoids in combination with cyclophosphamide or rituximab is the standard of care for severe disease. Avacopan, an oral C5aR1 antagonist, has been approved for remission induction and helps minimize glucocorticoid exposure. Plasma exchange should be considered for severe kidney or life-threatening disease. Lower dose glucocorticoid induction regimens can be used without compromising remission rates. Remission maintenance therapy is recommended, and rituximab is usually first line over azathioprine. Mycophenolate mofetil (MMF) or methotrexate with low-dose glucocorticoids are third-line options. Immunosuppression-associated infection risk remains a concern, both during acute presentations and in the long term, highlighted by the impact of rituximab on humoral immunity and vaccine response during the COVID-19 pandemic. There remains an ongoing need for therapies that induce rapid remission and optimize kidney recovery while minimizing infection risk. Clinical trials are evaluating newer therapeutic options. Due to increasing treatment options, management should be individualized, balancing effective immunosuppression against comorbidities and frailty.

Summary: This review focuses on the treatment decision pathways for clinicians and patients in the management of severe AAV (granulomatosis with polyangiitis and microscopic polyangiitis). Key clinical trials, predictors of outcome, novel therapeutics, and practical steps to mitigate infection risk are discussed.

Key messages: Immunosuppression regimens have been refined due to emerging evidence from clinical trials. Rituximab, avacopan, and reduced-dose glucocorticoid schedules have been the focus of recent studies. Infections and immunosuppression-induced immunodeficiency must be considered when determining individualized treatment.

Background: IgA nephropathy is the most common primary glomerular disease worldwide, and it is an important cause of end-stage kidney disease. Until recently, there were not any treatments of proven benefit, and care of patients with IgAN primarily involved supportive measures. Within the past few years, however, multiple new drugs have shown promise in clinical trials.

Summary: Among the new drugs, several complement inhibitory drugs have demonstrated efficacy at reducing proteinuria, and there is a strong rationale for expecting that these agents will be effective at slowing progression of the disease. Furthermore, anticomplement drugs target a part of the immune system that is not directly blocked by other classes of immunosuppressive agents. One of the new drugs, iptacopan, is a selective inhibitor of the alternative pathway. Preliminary results from a phase 3 study of iptacopan in IgA nephropathy demonstrated that treatment is associated with a rapid reduction in proteinuria, and the drug recently received accelerated approval from the Food and Drug Administration. Additional drugs that have been tested in IgA nephropathy include agents that block the complement cascade at the levels of C3 and C5. Complement activation in the kidneys of IgA nephropathy patients generates biomarkers that can be detected in the blood, urine, and kidney biopsies. If multiple complement inhibitory drugs receive approval for IgA nephropathy, these biomarkers may be useful for selecting the most appropriate drug for an individual patient. Complement biomarkers may also be useful for monitoring a patient's response to treatment.

Key messages: Several complement inhibitors are currently in clinical trials for IgAN. Iptacopan recently received accelerated approval for the indication and complement inhibitory drugs will likely become an integral part of the treatment for this disease in the near future. As these drugs become available in the clinic, it will be important to develop biomarkers that can guide clinicians to the best drug for an individual patient.