Glomerulonephritis

Zusammenfassung

Glomerulonephritiden sind eine Gruppe von Erkrankungen, die durch entzündliche Prozesse in der Niere charakterisiert sind und sich klinisch mit einem nephritischen oder nephrotischen Syndrom und einem Verlust der Nierenfunktion präsentieren. Oft sind Glomerulonephritiden von einer arteriellen Hypertonie oder Ödemen begleitet. Bei vielen Patienten sind die klinischen Symptome in der Frühphase der Erkrankung sehr mild oder fehlen ganz. So wird die Diagnose oft erst dann gestellt wenn schon ein beträchtlicher Verlust der Nierenfunktion vorliegt. Urinuntersuchungen zeigen bei Patienten mit Glomerulonephritiden in jeder Phase der Erkrankung pathologische Veränderungen. Urinuntersuchungen (Urinstix, Urinsediment) sollten deshalb bei jedem Patienten durchgeführt, sobald der Verdacht auf eine Nierenerkrankung vorliegt. Glomerulonephritiden können ausschließlich auf Glomeruli beschränkt sein, oder sich als begleitende Schäden bei systemischen Erkrankungen, meist Vaskulitiden, auftreten. Bei einigen Patienten reicht eine symptomatische Behandlung, während andere Patienten sich als medizinischer Notfall präsentieren. Bei diesen Patienten ist eine schnelle und intensive Behandlung erforderlich um den Verlust der Nierenfunktion zu verhindern. In dieser Übersichtsarbeit stellen wir die wichtigsten Glomerulonephritiden dar, fokusieren auf die Pathogenese, die diagnostischen Möglichkeiten und die Therapie. Das primäre Ziel ist die frühe Diagnose und eine an der Pathogense orientierte Therapie dieser Patienten.

Abstract

Glomerulonephritis encompasses a group of diseases that are characterized by inflammatory glomerular processes and clinically usually present with a nephritic and / or a nephrotic syndrome, as well as a deterioration of the renal function. Often, the diseases are accompanied by arterial hypertension and severe edema. In many cases however, the clinical symptoms are very mild or missing in the early phase of disease and therefore lead to a delayed diagnosis only after an impairment of renal function has developed. Urinalysis shows abnormalities in the very early phases of glomerulonephritis and should be performed in all patients, as soon as any evidence of renal involvement is present. Glomerulonephritis may occur primarily in the glomeruli, or present as renal involvement in the context of systemic diseases, most often vasculitis. In some cases, a symptomatic therapy is sufficient, while in other patients, a glomerulonephritis may represent as a medical emergency, which should be immediately and aggressively treated in order to prevent loss of renal function. Here we summarize the most important entities of glomerulonephritis, focusing on the pathogenesis, diagnostic tools and treatment options. The primary goal is the early diagnosis and a targeted, effective treatment of these patients.

Schlüsselwörter

Glomerulonephritis - Pathogenese - Diagnostik - Therapie

Keywords

glomerulonephritis - pathogenesis - diagnostic tools - treatment

• Literatur

• 1 Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol 2008; 19: 1855-1864
• 2 Couser WG. Basic and translational concepts of immune–mediated glomerular diseases. J Am Soc Nephrol 2012; 23: 381-399
• 3 Couser WG, Johnson RJ. The etiology of glomerulonephritis: roles of infection and autoimmunity. Kidney Int 2014; 86: 905-914
• 4 McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant 2011; 26: 414-430
• 5 Kiryluk K, Li Y, Scolari F et al. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 2014; 46: 1187-1196
• 6 Suzuki H, Fan R, Zhang Z et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity. J Clin Invest 2009; 119: 1668-1677
• 7 Gutierrez E, Zamora I, Ballarin JA et al. Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol 2012; 23: 1753-1760
• 8 Floege J. The pathogenesis of IgA nephropathy: what is new and how does it change therapeutic approaches?. Am J Kidney Dis 2011; 58: 992-1004
• 9 Rauen T, Eitner F, Fitzner C et al. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med 2015; 373: 2225-2236
• 10 Beck Jr LH, Bonegio RG, Lambeau G et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361: 11-21
• 11 Hoxha E, Thiele I, Zahner G et al. Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy. J Am Soc Nephrol 2014; 25: 1357-1366
• 12 Hoxha E, Harendza S, Pinnschmidt H et al. M-type phospholipase A2 receptor autoantibodies and renal function in patients with primary membranous nephropathy. Clin J Am Soc Nephrol 2014; 9: 1883-1890
• 13 Polanco N, Gutiérrez E, Covarsí A et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol 2010; 21: 697-704
• 14 Hoxha E, Harendza S, Pinnschmidt HO et al. Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy. Nephrol Dial Transplant 2015; 30: 1862-1869
• 15 Hladunewich MA, Troyanov S, Calafati J et al. The natural history of the non-nephrotic membranous nephropathy patient. Clin J Am Soc Nephrol 2009; 4: 1417-1422
• 16 Ruggenenti P, Cravedi P, Chianca A et al. Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol 2012; 23: 1416-1425
• 17 Ponticelli C, Altieri P, Scolari F et al. A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy. J Am Soc Nephrol 1998; 9: 444-450
• 18 Cattran DC, Appel GB, Hebert LA et al. Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial. Kidney Int. 2001; 59: 1484-1490
• 19 Leeaphorn N, Kue APP, Thamcharoen N et al. Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies. Am J Nephrol 2014; 40: 29-35
• 20 Tomas NM, Beck Jr LH, Meyer-Schwesinger C et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 2014; 371: 2277-2287
• 21 Chugh SS, Clement LC, Mace C. New insights into human minimal change disease: lessons from animal models. Am J Kidney Dis 2012; 59: 284-292
• 22 Hogan J, Radhakrishnan J. The treatment of minimal change disease in adults. J Am Soc Nephrol 2013; 24: 702-711
• 23 McCarthy ET, Sharma M, Savin VJ. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2010; 5: 2115-2121
• 24 Clement LC, Avila-Casado C, Mace C et al. Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med 2011; 17: 117-122
• 25 Wei C, El Hindi S, Li J et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 2011; 17: 952-960
• 26 Meijers B, Maas RJ, Sprangers B et al. The soluble urokinase receptor is not a clinical marker for focal segmental glomerulosclerosis. Kidney Int 2014; 85: 636-640
• 27 Sinha A, Bajpai J, Saini S et al. Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children. Kidney Int 2014; 85: 649-658
• 28 Cathelin D, Placier S, Ploug M et al. Administration of recombinant soluble urokinase receptor per se is not sufficient to induce podocyte alterations and proteinuria in mice. J Am Soc Nephrol 2014; 25: 1662-1668
• 29 Maas RJ, Deegens JK, Wetzels JF. Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future. Nephrol Dial Transplant 2014; 29: 2207-2216
• 30 Sadowski CE, Lovric S, Ashraf S et al. A single-gene cause in 29. 5 % of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2015; 26: 1279-1289
• 31 Cunningham EE, Zielezny MA, Venuto RC. Heroin-associated nephropathy. A nationwide problem. JAMA 1983; 250: 2935-2936
• 32 Praga M, Hernández E, Morales E et al. Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol Dial Transplant 2001; 16: 1790-1798
• 33 Rao TK, Filippone EJ, Nicastri AD et al. Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med 1984; 310: 669-673
• 34 Sethi S, Zand L, Leung N et al. Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy. Clin J Am Soc Nephrol 2010; 5: 770-782
• 35 Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol 2011; 31: 341-348
• 36 Sethi S, Nester CM, Smith RJ. Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int 2012; 81: 434-441
• 37 Pedchenko V, Bondar O, Fogo AB et al. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med 2010; 363: 343-354
• 38 Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol. 2014; 10: 463-473
• 39 Stone JH, Merkel PA, Spiera R et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010; 363: 221-232
• 40 Jones RB, Tervaert JW, Hauser T et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010; 363: 211-220
• 41 Brix SR, Stege G, Disteldorf E et al. CC Chemokine ligand 18 in ANCA-associated crescentic GN. J Am Soc Nephrol 2015; 26: 2105-2117
• 42 Fussner LA, Hummel AM, Schroeder DR et al. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheumatol 2016;
• 43 Ortega LM, Schultz DR, Lenz O et al. Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions. Lupus 2010; 19: 557-574
• 44 Ronco P, Debiec H. Pathophysiological advances in membranous nephropathy: time for a shift in patient’s care. Lancet 2015; 385: 1983-1992