Symptomatische Therapie bei nephrotischem Syndrom

Zusammenfassung

Glomeruläre Erkrankungen gehören zu den häufigsten renalen Pathologien und führen in vielen Fällen zu terminaler Niereninsuffizienz. Die klinische Manifestation dieser Erkrankungen lässt sich in 5 Gruppen einteilen, wobei der zugrundeliegende pathophysiologische Mechanismus die klinischen Erscheinungen prägt. Eines dieser fünf klinischen Syndrome ist das nephrotische Syndrom, welches durch das gemeinsame Auftreten einer großen Proteinurie (> 3,5 g/Tag) mit Hypalbuminämie, Hyperlipoproteinämie und Ödemen gekennzeichnet ist. Das nephrotische Syndrom kann klinisches Korrelat verschiedener Krankheiten sein. Heute liefert die bis vor wenigen Jahren nur wenig verstandene Pathophysiologie dieses Syndroms wichtige Informationen zur Etablierung neuer Therapiekonzepte. Der Durchbruch im Verständnis der Funktion des glomerulären Filters gelang in den letzten Jahren zunehmend durch genetische und molekularbiologische Untersuchungen, welche die viszeralen Epithelzellen des Glomerulus – Podozyten – in den Fokus der Aufmerksamkeit gerückt haben. Heute kennen wir unterschiedliche Faktoren, die zur Schädigung der Podozyten führen können, hierunter toxische Substanzen, immunologische Phänomene oder systemische Erkrankungen wie Diabetes mellitus.

Abstract

Glomerular diseases are among the most common renal pathologies leading frequently to end-stage renal disease. Clinical disease can be divided into five different groups the features of which are determined by the underlying pathophysiology. One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema. The nephrotic syndrome may be the clinical manifestation of a row of underlying diseases. The pathophysiological basics had remained elusive for decades, yet recently significant progress which allows for establishing new therapeutic strategies has been made. A major breakthrough in understanding the function of the glomerular filter unit has been possible in the last years through both genetic and cell biological studies, which have revealed a crucial role for the visceral epithelial cells of the glomerulus – the podocytes. By now various factors have been found causing podocyte damage, such as toxines, immunological phenomena or systemic disease like diabetes mellitus.

Schlüsselwörter

nephrotisches Syndrom - Proteinurie - symptomatische Therapie

Keywords

nephrotic syndrome - proteinuria - symptomatical therapy

Literatur

• 1 Agodoa L Y, Appel L, Bakris G L. et al . Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.  JAMA. 2001;  285 2719-2728
• 2 Bakris G L, Weir M R, Secic M, Campbell B, Weis-McNulty A. Differential effects of calcium antagonist subclasses on markers of nephropathy progression.  Kidney Int. 2004;  65 1991-2002
• 3 Bakris G L, Williams M, Dworkin L. et al . Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.  Am J Kidney Dis. 2000;  36 646-661
• 4 Brenner B M, Cooper M E, de Zeeuw D. et al . Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.  N Engl J Med. 2001;  345 861-869
• 5 Burgess E, Muirhead N, de Cotret P R. et al . Supramaximal dose of candesartan in proteinuric renal disease.  J Am Soc Nephrol. 2009;  20 893-900
• 6 de Brito-Ashurst I, Varagunam M, Raftery M J, Yaqoob M M. Bicarbonate supplementation slows progression of CKD and improves nutritional status.  J Am Soc Nephrol. 2009;  20 2075-2084
• 7 Dear J W, Yuen P ST. Setting the stage for acute-on-chronic kidney injury.  Kidney Int. 2008;  74 7-9
• 8 Dluhy R G, McMahon G T. Intensive glycemic control in the ACCORD and ADVANCE Trials.  N Engl J Med. 2008;  358 2630-2633
• 9 Dogra G K, Watts G F, Herrmann S, Thomas M AB, Irish A B. Statin therapy improves brachial artery endothelial function in nephrotic syndrome.  Kidney Int. 2002;  62 550-557
• 10 Esnault V LM, Ekhlas A, Delcroix C, Moutel M -G, Nguyen J -M. Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents.  J Am Soc Nephrol. 2005;  16 474-481
• 11 Gerstein H C, Mann J FE, Yi Q. et al . Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.  JAMA. 2001;  286 421-426
• 12 Hemmelgarn B R, Manns B J, Lloyd A. et al . Relation between kidney function, proteinuria, and adverse outcomes.  JAMA. 2010;  303 423-429
• 13 Ikizler T A. Dietary protein restriction in CKD: the debate continues.  Am J Kidney Dis. 2009;  53 189-191
• 14 Jafar T H, Stark P C, Schmid C H. et al . Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis.  Ann Intern Med. 2003;  139 244-252
• 15 Kestila M. Positionally cloned gene for a novel glomerular protein nephrin is mutated in congenital nephrotic syndrome.  Molecular Cell. 1998;  1 575-582
• 16 Krikken J A, Laverman G D, Navis G. Benefits of dietary sodium restriction in the management of chronic kidney disease.  Curr Opin Nephrol Hypertens. 2009;  18 531-538
• 17 Kunz R, Friedrich C, Wolbers M, Mann J FE. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin-angiotensin system on proteinuria in renal disease.  Ann Intern Med. 2008;  148 30-48
• 18 Machuca E, Benoit G, Antignac C. Genetics of nephrotic syndrome: connecting molecular genetics to podocyte physiology.  Hum Mol Genet. 2009;  18 R185-194
• 19 Mann J FE, Schmieder R E, Dyal L. et al . Effect of telmisartan on renal outcomes.  Ann Intern Med. 2009;  151 1-10
• 20 Mann J FE, Schmieder R E, McQueen M. et al . Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.  Lancet. 2008;  372 547-553
• 21 Muller D N, Luft F C. Direct renin inhibition with aliskiren in hypertension and target organ damage.  Clin J Am Soc Nephrol. 2006;  1 221-228
• 22 Parving H -H, Persson F, Lewis J B. et al . Aliskiren combined with losartan in type 2 diabetes and nephropathy.  N Engl J Med. 2008;  358 2433-2446
• 23 Pavenstadt H, Kriz W, Kretzler M. Cell Biology of the glomerular podocyte.  Physiol Rev. 2003;  83 253-307
• 24 Perna A, Ruggenenti P, Testa A. et al . ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1.  Kidney Int. 2000;  57 274-281
• 25 Peterson J C, Adler S, Burkart J M. et al . Blood pressure control, proteinuria, and the progression of renal disease.  Ann Intern Med. 1995;  123 754-762
• 26 Rabelink A J, Erkelens D W, Hené R J, Joles J A, Koomans H A. Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidemia of nephrotic syndrome.  Lancet. 1988;  332 1335-1338
• 27 Remuzzi G. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy.  Lancet. 1997;  349 1857-1863
• 28 Ronco P, Debiec H. Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy.  J Am Soc Nephrol. 2010;  21 564-569
• 29 Ruggenenti P, Perna A, Gherardi G. et al . Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria.  Lancet. 1999;  354 359-364
• 30 Ruggenenti P, Perticucci E, Cravedi P. et al . Role of remission clinics in the longitudinal treatment of CKD.  J Am Soc Nephrol. 2008;  19 1213-1224
• 31 Ruggenenti P, Remuzzi G. Proteinuria: Is the ONTARGET renal substudy actually off target?.  Nature Reviews Nephrology. 2009;  5 436-437
• 32 Sarafidis P, Khosla N, Bakris G. Antihypertensive Therapy in the Presence of Proteinuria.  Am J Kidney Dis. 2007;  49 12-26
• 33 Shepherd J, Kastelein J JP, Bittner V. et al . Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: The Treating to New Targets (TNT) Study.  Clin J Am Soc Nephrol. 2007;  2 1131-1139
• 34 Sokol S I, Portnay E L, Curtis J P. et al . Modulation of the renin-angiotensin-aldosterone system for the secondary prevention of stroke.  Neurology. 2004;  63 208-213
• 35 Swift P A, Markandu N D, Sagnella G A, He F J, MacGregor G A. Modest salt reduction reduces blood pressure and urine protein excretion in black hypertensives: a randomized control trial.  Hypertension. 2005;  46 308-312
• 36 Teo K K, Mitchell L B, Pogue J. et al . Effect of ramipril in reducing sudden deaths and nonfatal cardiac arrests in high-risk individuals without heart failure or left ventricular dysfunction.  Circulation. 2004;  110 1413-1417
• 37 Vijan S, Hayward R A. Treatment of hypertension in type 2 diabetes mellitus: Blood pressure goals, choice of agents, and setting priorities in diabetes care.  Ann Intern Med. 2003;  138 593-602
• 38 Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan.  J Am Soc Nephrol. 2008;  19 999-1007
• 39 Weiner D E, Tighiouart H, Levey A S. et al . Lowest systolic blood pressure is associated with stroke in stages 3 to 4 chronic kidney disease.  J Am Soc Nephrol. 2007;  18 960-966
• 40 Wilmer W A, Rovin B H, Hebert C J. et al . Management of glomerular proteinuria: a commentary.  J Am Soc Nephrol. 2003;  14 3217-3232