Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We ...determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, -4.3% to 37.1%;
=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%;
=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.
SGLT2 inhibitors in non-diabetic kidney disease Tesař, Vladimír
Advances in clinical and experimental medicine : official organ Wroclaw Medical University,
02/2022, Letnik:
31, Številka:
2
Journal Article
Recenzirano
Odprti dostop
There is an accumulating evidence demonstrating renoprotective and cardioprotective role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in early to advanced diabetic kidney disease. Data from ...recently published Dapagliflozin and Prevention of Adverse Outcomes in the Chronic Kidney Disease (DAPA-CKD) trial clearly show that dapagliflozin is similarly renoprotective in non-diabetic chronic kidney disease in a wide range of estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 (0.42-1.25 mL/s/1.73 m2) and albumin/creatinine ratio 200-5000 mg/g (approx. 20-500 mg/mmol). Patients with type 1 diabetes, autosomal dominant polycystic kidney disease, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and lupus nephritis were excluded from the study, but, on the other hand, prespecified subanalysis demonstrated that dapagliflozin should be renoprotective also in patients with immunoglobulin A (IgA) nephropathy. The renoprotective effect of SGLT2 inhibitors is additive to the renoprotection conferred with blockers of renin-angiotensin system, including both inhibitors of angiotensin converting enzyme (ACEI), or angiotensin receptor blocker (ARB). These promising data will be hopefully confirmed by the ongoing the Study of Heart and Kidney Protection With Empagliflozin (EMPA-KIDNEY) trial, the results of which are expected later in 2022.
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians ...caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti–glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the “Grading of Recommendations Assessment, Development and Evaluation” (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.
IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which ...might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treatment options for patients with IgA nephropathy including the drugs currently under evaluation in randomized control trials. An early initiation of immunosupressive regimens in patients with IgA nephropathy at risk of progression should result in the slowing down of the progression of renal function to end stage renal disease.
The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Evaluation of serum levels of ...anti-podocyte antibodies paved the way for non-invasive diagnosis and helped distinguish between primary and secondary MN although the relationship between anti-podocyte antibodies and cancer remains to be elucidated. Serum levels of anti-PLA2R antibodies directed against the major podocyte autoantigen are related to MN activity and the decrease in serum levels of anti-PLA2R antibodies in response to treatment (immunologic remission) also serves as an early indicator of the later putative proteinuric remission, enabling personalization of the treatment. The serum levels of anti-podocyte antibodies also enable the prediction of renal outcomes in terms of both remission and the risk of progression to end-stage renal disease. The positivity of anti-PLA2R antibodies before renal transplantation is associated with the risk of recurrence of MN. It remains to be established if all these relations observed in patients with anti-PLA2R antibodies are also valid for expanding spectrum of antibodies directed against recently discovered minor antigens (e.g., THSD7A, NELL-1, semaphorin 3B).
Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review ...(01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
Efficacy of immunosuppressive treatment of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by its toxicity. With the replacement of cyclophosphamide with ...rituximab, serious adverse events seem to be associated especially with high-dose corticosteroids. Activation of alternative complement pathway plays an important role in the pathogenesis of AAV. Avacopan (C5a receptor inhibitor) was demonstrated to have at least similar efficacy and better safety (in terms of corticosteroid-related adverse events) compared with high-dose corticosteroids in the induction treatment of AAV. Other modes of the inhibition of alternative complement pathway are currently tested in AAV or could be considered on the basis of the experience in other glomerular diseases.
Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease (CKD) and immune-mediated kidney ...disease management ....
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