Aphereseverfahren bei Nierenerkrankungen und Nierentransplantation – Der aktuelle Stand des Wissens

Die Evidenz für den Einsatz von Aphereseverfahren bei nephrologischen Erkrankungen ist stark vom Krankheitsbild und deren Akuität abhängig. Für eine Reihe nephrologischer Erkrankungen ergeben sich damit klare Indikationen für die Anwendung eines Aphereseverfahrens. Hierzu gehören die ANCA–assoziierten Vaskulitiden, bei denen in Fällen der schwerer Nierenbeteiligung (Serum-Kreatinin-Wert > 500 μmol/l bzw. > 5,8 mg/dl) sowie schwerer pulmonaler Beteiligung der therapeutische Plasmaersatz durchgeführt werden sollte. Gleichermaßen ist diese Behandlung bei der Anti-GBM-Erkrankung, der kryoglobulinämischen Vaskulitis und dem Hyperviskositätssyndrom etabliert. Thrombotische Mikroangiopathien sollten bis zur Differenzierung der Pathogenese mittels TPE anbehandelt, bei der Diagnose eines aHUS aber mit Eculizumab weiterbehandelt werden. Im Rahmen der Nierentransplantation spielen Aphereseverfahren für die Vorbereitung AB0–inkompatibler Transplantationen und vermutlich auch bei der Therapie akuter humoraler Abstoßungsreaktionen eine Rolle. Dagegen gibt es für andere Krankheitsbilder wie den SLE mit Lupusnephritis und das nephrotische Syndrom oder die fokal-segmentale Glomerulosklerose (FSGS) Hinweise auf eine Wirksamkeit der Apherese, welche aber letztlich im Rahmen eines individuellen Heilversuchs eingesetzt werden kann. Perspektivisch könnte die Apherese aber auch bei anderen schwer verlaufenden nephrologischen Krankheitsbildern eine Anwendung finden.

Availability of evidence for the application of apheresis for the treatment of renal disorders depends on the type of renal disease and its acuity. Apheresis has a clear indication in a variety of renal disorders. Typically, ANCA-associated vasculitis with severe renal injury (defined as serum creatinine > 500 μmol/l or > 5.8 mg/dl) or severe lung injury should be treated with therapeutic plasma exchange (TPE). Other clear indications represent anti-GBM disease, cryoglobulinemic vasculitis and hyperviscosity syndrome. Thrombotic microangiopathies should undergo TPE until their pathogenesis is further clarified and a decision can be made to either use eculizumab in cases of atypical haemolytic-uremic syndrome (aHUS) or continue TPE. Apheresis techniques are frequently used during recipients' preparation for AB0-incompatible kidney transplantation and might also play a relevant role in the treatment of acute humoral graft rejection. On the other hand, there are diseases like lupus nephritis, some cases of nephrotic syndrome and also focal segmental glomerular sclerosis (FSGS) in which apheresis could be effective, but should only be used for individualized healing approaches. Perspectively, apheresis might also have a role in other severe (and mainly acute) forms of renal disease.

Key words

apheresis - immunoadsorption - kidney disease - glomerulonephritis - kidney transplantation

• Literatur

• 1 Jennette JC, Falk RJ, Hu P, Xiao H. Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Annu Rev Pathol 2013; 8: 139-160
• 2 Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol 2014; 10: 463-473
• 3 Luqmani RA. State of the art in the treatment of systemic vasculitides. Front Immunol 2014; 5: 471-471
• 4 Stone JH, Merkel PA, Spiera R et al. RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363: 221-232
• 5 Casian A, Jayne D. Plasma exchange in the treatment of Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and renal limited vasculitis. Curr Opin Rheumatol 2011; 23: 12-17
• 6 Jayne DR, Gaskin G, Rasmussen N. European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007; 18: 2180-2188
• 7 Pusey CD, Lockwood CM, Peters DK. Plasma exchange and immunosuppressive drugs in the treatment of glomerulonephritis due to antibodies to the glomerular basement membrane. Int J Artif Organs 1983; 6 (Suppl. 01) 15-18
• 8 Biesenbach P, Kain R, Derfler K et al. Long-term outcome of anti-glomerular basement membrane antibody disease treated with immunoadsorption. PLoS One 2014; 9
• 9 Zhang YY, Tang Z, Chen DM et al. Comparison of double filtration plasmapheresis with immunoadsorption therapy in patients with anti-glomerular basement membrane nephritis. BMC Nephrol 2014; 15: 128-128
• 10 Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet 2012; 379: 348-360
• 11 Bacon BR, Gordon SC, Lawitz E et al. HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207-1017
• 12 Poordad F, McCone Jr J, Bacon BR et al. SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-1206
• 13 Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al. AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370: 211-221
• 14 Gragnani L, Fabbrizzi A, Triboli E et al. Triple antiviral therapy in hepatitis C virus infection with or without mixed cryoglobulinaemia: a prospective, controlled pilot study. Dig Liver Dis 2014; 46: 833-837
• 15 Nakajima H, Kaneko S, Takano T et al. Analysis of protein removal properties during cryofiltration apheresis using the evaflux-5A plasma fractionator in a patient with hepatitis C virus-associated cryoglobulinemic glomerulonephritis. Ther Apher Dial 2014; 18: 258-264
• 16 Mahr A, Chaigne-Delalande S, De Menthon M. Therapeutic plasma exchange in systemic vasculitis: an update on indications and results. Curr Opin Rheumatol 2012; 24: 261-266
• 17 Stefanutti C, Di Giacomo S, Mareri M et al. Immunoadsorption apheresis (Selesorb) in the treatment of chronic hepatitis C virus-related type 2 mixed cryoglobulinemia. Transfus Apher Sci 2003; 28: 207-214
• 18 Tsai HM. Deficiency of ADAMTS-13 in thrombotic and thrombocytopenic purpura. J Thromb Haemost 2003; 1
• 19 Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339: 1585-1594
• 20 George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014; 371: 654-666
• 21 Legendre CM, Licht C, Muus P et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013; 368: 2169-2181
• 22 Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA et al. French Society of Pediatric Nephrology. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2007; 18: 2392-2400
• 23 Noris M, Caprioli J, Bresin E et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5: 1844-1859
• 24 Menne J, Kielstein JT, Wenzel U, Stahl RA. [Treatment of typical hemolytic-uremic syndrome. Knowledge gained from analyses of the 2011 E. coli outbreak]. [Article in German]. Internist (Berl) 2012; 53: 1420-1430
• 25 Tyden G, Kumlien G, Genberg H et al. ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab. Am J Transplant 2005; 5: 145-148
• 26 Lawrence C, Galliford JW, Willicombe MK et al. Antibody removal before ABO-incompatible renal transplantation: how much plasma exchange is therapeutic?. Transplantation 2011; 92: 1129-1133
• 27 Saliba F, Ichaï P, Azoulay D et al. Successful long-term outcome of ABO-incompatible liver transplantation using antigen-specific immunoadsorption columns. Ther Apher Dial 2010; 14: 116-123
• 28 Hickstein H, Koball S, Lehmann R et al. AB0 incompatible kidney transplantation using unspecific immunoadsorption. Transfus Apher Sci 2014; 50: 263-266
• 29 Morath C, Becker LE, Leo A et al. ABO-incompatible kidney transplantation enabled by non-antigen-specific immunoadsorption. Transplantation 2012; 93: 827-834
• 30 Eskandary F, Wahrmann M, Biesenbach P et al. ABO antibody and complement depletion by immunoadsorption combined with membrane filtration – a randomized, controlled, cross-over trial. Nephrol Dial Transplant 2014; 29: 706-714
• 31 Lefaucheur C, Nochy D, Andrade J et al. Comparison of combination plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transplant 2009; 9: 1099-1107
• 32 Bohmig GA, Wahrmann M, Regele H et al. Immunoadsorption in severe C4d-positive acute kidney allograft rejection: a randomized controlled trial. Am J Transplant 2007; 7: 117-121
• 33 Hohenstein B, Bornstein SR, Aringer M. Immunoadsorption for connective tissue disease. Atheroscler Suppl 2013; 14: 185-189
• 34 Chapter 12: Lupus nephritis. Kidney Int Suppl (2011) 2012; 2: 221-232
• 35 Fogo AB. Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol 2015; 11: 76-87
• 36 Ulinski T, Davourie-Salandre A, Brocheriou I, Aoun B. Immunoadsorption: a new strategy to induce remission in membranous lupus nephritis. Case Rep Nephrol Urol 2014; 4: 37-41
• 37 Esnault VL, Besnier D, Testa A et al. Effect of protein A immunoadsorption in nephrotic syndrome of various etiologies. J Am Soc Nephrol 1999; 10: 2014-2017
• 38 Torretta L, Perotti C, Costamagna L. Usefulness of plasma exchange in recurrent nephrotic syndrome following renal transplant. Artif Organs 1995; 19: 96-98
• 39 Oto J, Suga K, Matsuura S et al. Low-density lipoprotein apheresis in a pediatric patient with refractory nephrotic syndrome due to focal segmental glomerulosclerosis. J Anesth 2009; 23: 284-287
• 40 Miyazono M, Tomiyoshi Y, Kishi T et al. A case report of nephrotic syndrome due to collapsing focal segmental glomerulosclerosis treated with low-density lipoprotein apheresis. Ther Apher Dial 2008; 12: 333-336
• 41 Ponticelli C. Recurrence of focal segmental glomerular sclerosis (FSGS) after renal transplantation. Nephrol Dial Transplant 2010; 25: 25-31
• 42 Masutani K, Katafuchi R, Ikeda H et al. Recurrent nephrotic syndrome after living-related renal transplantation resistant to plasma exchange: report of two cases. Clin Transplant 2005; 19 (Suppl. 14) 59-64
• 43 Delville M, Sigdel TK, Wei C et al. A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation. Sci Transl Med 2014; 6
• 44 Wei C, Trachtman H, Li J et al. PodoNet and FSGS CT Study Consortia. Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol 2012; 23: 2051-2059
• 45 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
• 46 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
• 47 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
• 48 Wen M, Küchle C, Sarkar O et al. Plasmapheresis combined with rituximab for refractory idiopathic membranous nephropathy. Int Urol Nephrol 2014; 46: 847-848
• 49 Pickering MC et al. C3 glomerulopathy: consensus report. Kidney Int 2013; 84: 1079-1089
• 50 Oberkircher OR, Enama M, West JC et al. Regression of recurrent membranoproliferative glomerulonephritis type II in a transplanted kidney after plasmapheresis therapy. Transplant Proc 1988; 20 (Suppl. 01) 418-423
• 51 McGinley E, Watkins R, McLay A, Boulton-Jones JM. Plasma exchange in the treatment of mesangiocapillary glomerulonephritis. Nephron 1985; 40: 385-390
• 52 Hutchison CA, Cockwell P, Stringer S et al. Early reduction of serum-free light chains associates with renal recovery in myeloma kidney. J Am Soc Nephrol 2011; 22: 1129-1136
• 53 Hutchison CA, Cockwell P, Reid S et al. Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol 2007; 18: 886-895