Publications by authors named "Jack F M Wetzels"
Introduction: Standard treatment with cyclophosphamide (CP) or rituximab (RTX) is suboptimal. We adapted and used the low-dose regimen used in vasculitis (RTX 2 × 1000 mg, CP 1.5 mg/kg/d × 8 weeks, and prednisone [i.
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- The haemolytic uraemic syndromes (HUS) include various conditions, with some linked to complement activation (CaHUS).
- The 2023 International Society of Nephrology HUS Forum featured experts discussing the latest knowledge, uncertainties, and proposed solutions in diagnosing and managing HUS.
- Key areas needing research include naming conventions, complement testing, identifying biomarkers, genetic factors for aHUS, treatment strategies for C5 inhibitors, and improving access to care for patients.
Article Synopsis
- The study compares the effectiveness and safety of eculizumab prophylaxis versus rescue therapy for kidney transplant recipients with atypical hemolytic uremic syndrome (aHUS), analyzing data from Dutch and UK patient cohorts.
- Results indicated similar graft survival rates between Dutch patients receiving rescue therapy and UK patients on prophylaxis, with Dutch patients showing slightly better outcomes but not significantly different.
- The findings suggest that in patients with lower genetic risk for recurrence, eculizumab rescue therapy may be as effective as prophylaxis without compromising graft survival.
Introduction: In 2014, a complement assay, which evaluates C5b-9 deposition on endothelial cells, was proposed as a biomarker for atypical hemolytic uremic syndrome (aHUS). Early diagnosis and/or prediction of aHUS (relapse) is pivotal in aHUS kidney transplant recipients who do not receive eculizumab prophylaxis.
Methods: In this pilot study, serum samples of transplanted patients with aHUS in remission without eculizumab and patients with other primary kidney diseases (controls) were blinded and evaluated in the complement assay.
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease caused by dysregulation of the complement alternative pathway. The complement dysregulation specifically leads to damage to the glomerular endothelium. To further understand aHUS pathophysiology, we validated an model for measuring complement deposition on both control and patient human glomerular microvascular endothelial cells (GMVECs).
View Article and Find Full Text PDFMembranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.
View Article and Find Full Text PDFMembranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.
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- A 39-year-old woman diagnosed with relapsing nephrotic syndrome was found to have cryofibrinogen and a monoclonal immunoglobulin (M-protein) in her blood, indicating monoclonal gammopathy related to kidney issues.
- Initial immunosuppressive treatment led to temporary improvement, but after her condition relapsed, she underwent more intensive therapy, including stem cell transplantation, which again provided temporary relief.
- Subsequent experiments revealed that the cryoactivity was dependent on the M-protein, suggesting that cryofibrinogenemia is linked to this protein and should be associated with monoclonal gammopathy of renal significance.
Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min per 1.
View Article and Find Full Text PDFIntroduction: Since 2016, kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) in the Netherlands is performed without eculizumab prophylaxis. Eculizumab is given in case of posttransplant aHUS recurrence. Eculizumab therapy is monitored in the CUREiHUS study.
View Article and Find Full Text PDFIntroduction: A 6-month course of cyclophosphamide (CP) and steroids is effective in primary membranous nephropathy (MN), but unappealing because of long-term side effects. We evaluated efficacy of an "antibody-guided" treatment schedule.
Methods: Patients with phospholipase A2 receptor (PLA2R)-related MN and high risk of progression were treated with CP 1.
Article Synopsis
- - The study focuses on how proteinuria (high levels of protein in urine) affects the pharmacokinetics of eculizumab, a treatment for atypical hemolytic uremic syndrome (aHUS), as kidney damage can lead to proteinuria.
- - Researchers analyzed urine protein-creatinine ratios to see how they influenced the clearance of eculizumab, finding that higher proteinuria levels resulted in a statistically significant reduction in eculizumab effectiveness for some patients.
- - Results indicated that adults with severe proteinuria were more likely to have inadequate response to eculizumab treatment compared to those without proteinuria, highlighting the need for careful monitoring and potential dose adjustments in these patients.
Introduction: The introduction of eculizumab has improved the outcome in patients with atypical hemolytic uremic syndrome (aHUS). The optimal treatment strategy is debated. Here, we report the results of the CUREiHUS study, a 4-year prospective, observational study monitoring unbiased eculizumab discontinuation in Dutch patients with aHUS after 3 months of therapy.
View Article and Find Full Text PDFMany patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s).
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- Monoclonal gammopathy of renal significance (MGRS) involves kidney damage caused by abnormal proteins from certain immune cells, even if they don't qualify for traditional treatment.
- MGRS can lead to various kidney diseases and potentially end-stage kidney failure, and the standard approach is to treat the underlying disease before considering kidney transplants.
- However, the decision for kidney transplantation in MGRS patients should be personalized based on factors like the specific kidney disease type, the patient's age and health, and their treatment history, allowing for transplants even before starting blood condition treatment.
Introduction: COVID-19 vaccination has been associated with rare but severe complications characterized by thrombosis and thrombocytopenia.
Methods And Results: Here we present three patients who developed or relapse atypical hemolytic uremic syndrome (aHUS) in native kidneys, a median of 3 days (range 2-15) after mRNA-based (Pfizer/BioNTech's, BNT162b2) or adenoviral (AstraZeneca, ChAdOx1 nCoV-19) COVID-19 vaccination. All three patients presented with evident hematological signs of TMA and AKI, and other aHUS triggering or explanatory events were absent.
Article Synopsis
- * Two phase 2 clinical studies were conducted on the orally active factor D inhibitor danicopan, aiming to assess its impact on C3G and related conditions.
- * Although danicopan was found to be safe, it failed to provide consistent treatment benefits or sufficiently inhibit the alternative pathway, indicating that stronger and sustained action is needed for effective patient outcomes.
Article Synopsis
- C3 glomerulopathy (C3G) is a rare kidney disease caused by issues in the complement system, specifically the alternative pathway, and the study aimed to analyze biomarkers in patients participating in phase 2 trials of danicopan, a factor D inhibitor.
- Twenty-nine patients were evaluated, revealing systemic activation of the complement pathway with significant correlations between various complement biomarkers and kidney health metrics, such as eGFR and proteinuria.
- The findings highlight strong relationships between complement biomarkers and kidney function/histology, potentially enhancing the understanding and classification of C3G patients.