Behandlung der chronischen Nierenkrankheit bei IgA-Nephropathie

Die Immunglobulin-A-Nephropathie galt in der Vergangenheit als hauptsächlich gutartig, doch inzwischen weiß man, dass viele Patienten im Verlauf dialysepflichtig werden. Traditionelle Behandlungen mit Renin-Angiotensin-Aldosteron-System (RAAS)-Hemmern und neuere Therapien wie z.B. SGLT2-Inhibitoren werden hinsichtlich ihrer Rolle bei der Verringerung der Proteinurie und dem Erhalt der Nierenfunktion diskutiert.

Abstract

This article provides an overview of treatment approaches for chronic kidney disease (CKD) in patients with IgA nephropathy (IgAN). IgAN is the most common primary glomerulonephritis and results from an autoimmune reaction to aberrantly glycosylated immunoglobulin A (IgA) antibodies. Although historically considered largely benign, it is now recognized that a significant percentage of patients develop dialysis-dependent kidney disease over the years. Traditional treatments with RAAS inhibitors and newer therapies such as SGLT2 inhibitors, endothelin receptor antagonists, and delayed release, primarily locally acting enteric corticosteroids regarding their role in reducing proteinuria and preserving kidney function are also discussed. Additionally, non-immunosuppressive options and lifestyle modifications are examined for their potential to slow disease progression. Further promising medications are currently in clinical trials, including complement inhibitors and immunomodulators. These emerging therapies offer hope for significantly improving the prognosis of IgAN in the future. By presenting a comprehensive overview of current and potential future treatment strategies, this review aims to provide clinicians with up-to-date information to optimize the management of CKD in patients with IgAN.

Kernaussagen

• Die Behandlung der IgA-Nephropathie entwickelt sich dank eines besseren Verständnisses ihrer Pathogenese aktuell rasch weiter.

• Mehrere neue Behandlungsstrategien befinden sich in der klinischen Entwicklung; viele davon sind spezifisch auf die pathogenetischen Prozesse der Krankheit zugeschnitten.

• Die Behandlung der IgA-Nephropathie wird zukünftig wahrscheinlich zum einen immunologische Mechanismen und zum anderen die CKD-Progression adressieren.

• Die Behandlung von Patienten mit IgA-Nephropathie sollte sich auf eine optimale unterstützende Therapie und sekundäre Prophylaxe konzentrieren, bei der Lebensstil-Modifikationen, blutdrucksenkende Maßnahmen und die Reduktion der Proteinurie im Mittelpunkt stehen.

Schlüsselwörter

IgA-Nephropathie - chronische Nierenerkrankung - Glomerulonephritis - Renin-Angiotensin-Aldosteron-System - Proteinurie - Komplementinhibitoren - Immunmodulatoren

Keywords

IgA nephropathy - chronic kidney disease - glomerulonephritis - renin-angiotensin-aldosterone system - proteinuria - complement inhibitors - immunomodulators

Publication History

Article published online:
14 January 2025

• Literatur

• 1 Levin A, Ahmed SB, Carrero JJ. et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int 2024; 105 (04) 684-701
• 2 Pattrapornpisut P, Avila-Casado C, Reich HN. IgA Nephropathy: Core Curriculum 2021. Am J Kidney Dis 2021; 78 (03) 429-441
• 3 Pitcher D, Braddon F, Hendry B. et al. Long-Term Outcomes in IgA Nephropathy. Clin J Am Soc Nephrol 2023; 18 (06) 727-738
• 4 Kunter U, Floege J. The longer the better: follow-up in seemingly ‘benign’ immunoglobulin a nephropathy. Nephrol Dial Transplant 2017; 32 (11) 1777-1779
• 5 Gleeson PJ, O’Shaughnessy MM, Barratt J. IgA nephropathy in adults-treatment standard. Nephrol Dial Transplant 2023; 38 (11) 2464-2473
• 6 El Karoui K, Fervenza FC, De Vriese AS. Treatment of IgA Nephropathy: A Rapidly Evolving Field. J Am Soc Nephrol 2024; 35 (01) 103-116
• 7 Thompson A, Carroll K, Inker LA. et al. Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy. Clin J Am Soc Nephrol 2019; 14 (03) 469-481
• 8 Ebbestad R, Sanaei Nurmi M, Lundberg S. Long-Term Outcomes of Patients with IgA Nephropathy Categorized by the International IgAN Risk Prediction Tool and by the Degree of Hematuria at Diagnosis. Nephron 2022; 146 (06) 573-583
• 9 Rovin BH, Adler SG, Barratt J. et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100 (04) 753-779
• 10 Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of Diabetes on The Effects Of Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors on Kidney Outcomes: Collaborative Meta-Analysis of Large Placebo-Controlled Trials. Lancet 2022; 400: 1788-1801
• 11 Rovin BH, Barratt J, Heerspink HJL. et al. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet 2023; 402: 2077-2090
• 12 Schanz M, Seikrit C, Hohenstein B. et al. First Real-World Evidence of Sparsentan Efficacy in Patients with IgA Nephropathy Treated with SGLT2 Inhibitors. Clinical Kidney Journal 2024; in press
• 13 Agarwal R, Filippatos G, Pitt B. et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J 2022; 43 (06) 474-484
• 14 Del Vecchio L, Allinovi M, Comolli S. et al. Drugs in Development to Treat IgA Nephropathy. Drugs 2024; 84 (05) 503-525
• 15 Rauen T, Eitner F, Fitzner C. et al. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med 2015; 373 (23) 2225-2236
• 16 Lv J, Wong MG, Hladunewich MA. et al. Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA 2022; 327 (19) 1888-1898
• 17 Lee M, Suzuki H, Nihei Y. et al. Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis. Clin Kidney J 2023; 16 (Suppl. 02) ii1-ii8
• 18 Lafayette R, Kristensen J, Stone A. et al. Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial. Lancet 2023; 402: 859-870
• 19 Perkovic V, Kollins D, Renfurm R. et al. WCN24–1506 Efficacy and Safety of Iptacopan in Patients with IgA Nephropathy: Interim Results from the Phase 3 APPLAUSE-IgAN Study. Kidney Int Rep 2024; 9 (04) S506
• 20 Stamellou E, Nadal J, Hendry B. et al. Long-term outcomes of patients with IgA nephropathy in the German CKD cohort. Clin Kidney J 2024; 17 (08) sfae230
• 21 The KDIGO 2024 Clinical Practice Guideline for the Management of IgA Nephropathy (IgAN) and IgA Vasculitis (IgAV) Public draft 30.09.2024.
• 22 Caravaca-Fontán F, del Vecchio L, Praga M. et al. Sodium glucose co-transporter 2 inhibitors in the treatment of glomerular diseases: a CKJ controversy. Clinical Kidney Journal 2024; 17 (09) sfae237
• 23 Caravaca-Fontán F, Stevens K, Padrón M. et al. Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis. Nephrol Dial Transplant 2024; 39 (02) 328-340