Chronic renal allograft damage after transplantation:  what are the reasons, what can we do?
OBJECTIVE
Chronic renal allograft damage is one of the main problems after kidney transplantation. This review enumerates causes, describes available therapeutic options, and discusses options of the future.


RESULTS
Alloantigen-dependent and alloantigen-independent factors are responsible for allograft damage. Prevention of renal allograft damage starts with interventions that occur surrounding the explantation in cadaveric organs. These include the use of dopamine or machine perfusion systems.Followed by the critical phase of ischemia/reperfusion injury, the LCN2/lipocalin-2, HAVCR1, and p38 MAPK pathway are new players involved in that process. Innate immunity plays a part, too. Cold ischemia time is associated with genes of apoptosis. Nondonor-specific antibodies like antihuman leukocyte antibodies-Ia or angiotensin type 1 receptor may also play a role. Recent research indicates that genetic polymorphism like the Ficolin-2 Ala258Ser polymorphism and the mannose-binding lectin-2 polymorphism are involved in that process. New therapeutic options are rare and in the future. However, there is some evidence that drugs interfering with metalloproteinases, sexual hormones like dihydroandrosterone, and mesenchymal stem cell therapy may be of importance.


CONCLUSIONS
Taken together, although the understanding of chronic rejection has improved, the available therapeutic options remain scarce.
Department of Nephrology, Technical University of Munic, Munic, Germany. Lutz.Renders@lrz.tum.de
Lutz
L
Renders
Uwe
U
Heemann
D000209:Acute-Phase Proteins / Q000276:immunology; D050377:Cold Ischemia; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007519:Isoantigens / Q000276:immunology*; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000276:immunology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000276:immunology; D011991:Receptors, Virus / Q000276:immunology; D015427:Reperfusion Injury / Q000150:complications; D015398:Signal Transduction / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology; D000097604:Ficolins
D000209:Acute-Phase Proteins; D000072596:Hepatitis A Virus Cellular Receptor 1; D007166:Immunosuppressive Agents; D007519:Isoantigens; D037102:Lectins; D000071068:Lipocalin-2; D054834:Lipocalins; D037601:Mannose-Binding Lectin; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D048051:p38 Mitogen-Activated Protein Kinases; D000097604:Ficolins; C491143:HAVCR1 protein, human; C489506:LCN2 protein, human; C445619:MBL2 protein, human