Chronic renal allograft damage: Existing challenges

Transplantation

Volumn 91, Issue 9 SUPPL., 2011, Pages

  Arias, Manuel ^a   Serón, Daniel ^b   Moreso, Francesc ^b   Bestard, Oriol ^c   Praga, Manuel ^d  

^a HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA   (Spain)

^b HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^c HOSPITAL UNIVERSITARI DE BELLVITGE   (Spain)

^d UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ALISKIREN; ANGIOTENSIN RECEPTOR ANTAGONIST; AZATHIOPRINE; BORTEZOMIB; CALCINEURIN INHIBITOR; CREATININE; CYCLOSPORIN A; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ECULIZUMAB; EPLERENONE; HLA ANTIBODY; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PENTOXIFYLLINE; PREDNISOLONE; SPIRONOLACTONE; TACROLIMUS; THIAZIDE DIURETIC AGENT;

ACUTE GRAFT REJECTION; ALLOIMMUNITY; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN SPECIFICITY; ARTERY HYALINOSIS; ARTICLE; CARDIOVASCULAR RISK; CHRONIC ALLOGRAFT NEPHROPATHY; CHRONIC GRAFT REJECTION; COMBINATION CHEMOTHERAPY; COMPLEMENT ACTIVATION; CREATININE BLOOD LEVEL; DIFFERENTIAL DIAGNOSIS; DISEASE COURSE; DONOR SELECTION; DRUG EFFICACY; DRUG EXPOSURE; DRUG MECHANISM; DRUG SAFETY; EFFECTOR CELL; GLOMERULUS FILTRATION RATE; GRAFT FAILURE; GRAFT RECIPIENT; GRAFT SURVIVAL; HUMAN; HUMORAL IMMUNITY; HYALINE DEGENERATION; IMMUNOLOGICAL MONITORING; IMMUNOPATHOGENESIS; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY DISEASE; KIDNEY FIBROSIS; KIDNEY FUNCTION; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; MEMORY CELL; NEPHROTOXICITY; OUTCOME ASSESSMENT; PLASMA CELL; PREOPERATIVE EVALUATION; PRIORITY JOURNAL; PROTEINURIA; REGULATORY T LYMPHOCYTE; RISK FACTOR; SURVIVAL TIME; T LYMPHOCYTE ACTIVATION;

CALCINEURIN; CHRONIC DISEASE; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; KIDNEY; KIDNEY TRANSPLANTATION;

EID: 79955426470     PISSN: 00411337     EISSN: None     Source Type: Journal    
DOI: 10.1097/TP.0b013e31821792fd     Document Type: Article

References (136)

1. Gaston RS, Cecka JM, Kasiske BL, et al. Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure. Transplantation 2010; 90: 68.
2. Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: Have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 2004; 4: 1289.
3. Srinivas TR, Meier-Kriesche H-U. Minimizing immunosuppression, an alternative approach to reducing side effects: Objectives and interim result. Clin J Am Soc Nephrol 2008; 3(suppl2): 101.
4. United States Renal Data System. USRDS 2008 Annual Data Report. Available at: www.usrds.org. Accessed November 8, 2009.
5. Solez K, Colvin RB, Racusen LC, et al. Banff'05 Meeting Report: Dif-ferential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant 2007; 7: 518.
6. Nankivell BJ, Borrows RJ, Fung CL, et al. The naturalhistoryofchronic allograft nephropathy. N Engl J Med 2003; 349: 2326.
7. ElZoghby ZM, Stegall MD, Lager DJ, et al. Identifying specific causes ofkidney allograft loss. Am J Transplant 2009; 9: 527.
8. MeierKriesche HU, Schold JD, Srinivas TR, et al. Lack of improve-ment in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004; 4: 378.
9. Naesens M, Lerut E, Damme BV, et al. Tacrolimus exposure and evo-lution of renal allograft histology in the first year after transplantation. Am J Transplant 2007; 7: 2114.
10. Goldman M, Wood K. European research on cell and organ transplan-tation: Towards novel opportunities? Transpl Int 2007; 20: 1016.
11. Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection: From association to causation. Transplantation 2008; 86:377.
12. El Kossi M, Harmer A, Goodwin J, et al. De novo membranous ne-phropathy associated with donorspecific alloantibody. Clin Trans-plant 2008; 22: 124.
13. Sarwal M, Chua MS, Kambham N, et al. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med 2003; 349: 125.
14. Lerut E, Kuypers DR, Verbeken E, et al. Acute rejection in non-compliant renal allograft recipients: A distinct morphology. Clin Transplant 2007; 21: 344.
15. Jeannet M, Pinn VW, Flax MH, et al. Humoral antibodies in renal allotransplantation in man. N Engl J Med 1970; 282: 111.
16. Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med 1994; 331: 365.
17. Hostetter TH, Olson JL, Rennke HG, et al. Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation. Am JPhysiol 1981; 241: F85.
18. Brent L. A history oftransplantation inmunology. San Diego, CA, Academic Press 1997.
19. Terasaki PI, Kreisler M, Mickey RM. Presensitization and kidney trans-plant failures. Postgrad Med J1971; 47: 89.
20. Malhotra P, Malu S, Kapur S. Immunology of transplant rejection. Emedicine from WebMD [overview]. Available at: http://emedicine. medscape.com/article/432209. Accessed July 28, 2009.
21. Game DS, Lechler RI. Pathways of allorecognition: Implications for transplantation tolerance. Transpl Immunol 2002; 10: 101.
22. Womer KL, Sayegh MH, Auchincloss H Jr. Involvement ofthe direct and indirect pathways of allorecognition in tolerance induction. Philos Trans R Soc Lond B Biol Sci 2001; 356: 639.
23. Terasaki PI, Ozawa M, Castro R. Four-year follow-up of a prospective trial ofHLA and MICA antibodies on kidney graft survival. Am J Trans-plant 2007; 7: 408.
24. Colvin RB. Antibody-mediated renal allograft rejection: Diagnosis and pathogenesis. J Am SocNephrol2007; 18: 1046.
25. Hernandez D, Sanchez Fructuoso A, Seron D, et al. Chronic transplant nephropathy. Nefrologia 2006; 26(suppl 1): 1.
26. Pascual MA, Crespo M, TolkoffRubin N. Progress in understanding humoral rejection in kidney transplantation: Implications for patient management. Nefrologia 2001; 21: 327.
27. Kieran N, Wang X, Perkins J, et al. Combination of peritubularc4d and transplant glomerulopathy predicts late renal allograft failure. JAm Soc Nephrol 2009; 20: 2260.
28. Colvin RB, Smith RN. Antibody-mediated organallograft rejection. Nat Rev Immunol 2005; 5: 807.
29. Nickeleit V, Mihatsch MJ. Kidneytransplants, antibodies and rejection: Is C4d a magic marker? Nephrol Dial Transplant 2003; 18: 2232.
30. Palomar R, Lopez-Hoyos M, Pastor JM, et al. Impact ofHLA antibodies on transplant glomerulopathy. Transplant Proc 2005; 37: 3830.
31. Kinukawa T, Kato M, Terasaki PI, et al. Retrospective antibody analysis ofthirty patients with kidney graft failure. Clin Transpl 2006: 291.
32. Smith RN, Kawai T, Boskovic S, et al. Chronic antibody mediated rejection of renal allografts: Pathological, serological and immuno-logic features in nonhuman primates. Am J Transplant 2006; 6: 1790.
33. Rahimi S, Qian Z, Layton J, et al. Non-complement-and complement-activating antibodies synergize to cause rejection of cardiac allografts. Am J Transplant 2004; 4: 326.
34. Wahrmann M, Exner M, Schillinger M, et al. Pivotal role of comple-ment-fixing HLA alloantibodies in presensitized kidney allograft recip-ients. Am J Transplant 2006; 6(5 pt 1): 1033.
35. Gao ZH, McAlister VC, Wright JR Jr, et al. ImmunoglobulinG sub-class antidonor reactivity in transplant recipients. Liver Transpl 2004; 10: 1055.
36. Cruzado JM, Bestard O, Grinyo JM. Control of antidonor antibody production post-transplantation: Conventional and novel immuno-suppressive therapies. Contrib Nephrol2009; 162: 117.
37. Nickeleit V, Andreoni K. The classification and treatment of antibody-mediated renal allograft injury: Where do we stand? Kidney Int 2007; 71: 7.
38. Steele DJ, Laufer TM, Smiley ST, et al. Two levels of help for B cell alloantibodyproduction. J Exp Med 1996; 183: 699.
39. Bestard O, Nickel P, Cruzado JM, et al. Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipi-ents. J Am Soc Nephrol 2008; 19: 1419.
40. Sun Q, Liu ZH, Cheng Z, et al. Treatment of early mixed cellular and humoral renal allograft rejection with tacrolimus and mycophenolate mofetil. Kidney Int2007; 71: 24.
41. Bock HA. Steroidresistant kidney transplant rejection: Diagnosis and treatment. J Am Soc Nephrol 2001; 12(suppl 17): S48.
42. Sun Q, Liu ZH, Yin G, et al. Tacrolimus combined with mycophenolate mofetil can effectively reverse C4d-positive steroid-resistant acute re-jection in Chinese renal allograft recipients. Nephrol Dial Transplant 2006; 21: 510.
43. Pascual M, Saidman S, TolkoffRubin N, et al. Plasma exchange and tacrolimus-mycophenolate rescue for acute humoral rejection in kid-ney transplantation. Transplantation 1998; 66: 1460.
44. Andree H, Nickel P, Nasiadko C, et al. Identification ofdialysis patients with panelreactive memory T cells before kidney transplantation us-ing an allogeneic cell bank. J Am Soc Nephrol 2006; 17: 573.
45. Sureshkumar KK, Hussain SM, Carpenter BJ, et al. Antibody-mediated rejection following renal transplantation. Expert Opin Pharmacother 2007; 8: 913.
46. Singh N, Pirsch J, Samaniego M. Antibody-mediated rejection: Treatment alternatives and outcomes. Transplant Rev (Orlando) 2009; 23: 34.
47. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care ofkidney transplant recipients. Am J Transplant 2009; 9(suppl 3): S1.
48. Birnbaum LM, Lipman M, Paraskevas S, et al. Management ofchronic allograft nephropathy: A systematic review. Clin J Am Soc Nephrol 2009; 4: 860.
49. Theruvath TP, Saidman SL, Mauiyyedi S, et al. Control of antidonor antibody production with tacrolimus and mycophenolate mofetil in renal allograft recipients with chronic rejection. Transplantation 2001; 72: 77.
50. Srinivas TR, Schold JD, Guerra G, et al. Mycophenolate mofetil/siroli-mus compared to other common immunosuppressive regimens in kid-ney transplantation. Am J Transplant 2007; 7: 586.
51. Pilat N, Baranyi U, Klaus C, et al. Treg-therapy allows mixed chimerism and transplantation tolerance without cytoreductive conditioning. Am J Transplant 2010; 10: 751.
52. Stegall MD, Gloor JM. Deciphering antibody-mediated rejection: New insights into mechanisms and treatment. Curr Opin Organ Transplant 2010; 15: 8.
53. Everly JJ, Walsh RC, Alloway RR, et al. Proteasome inhibition for antibody-mediated rejection. Curr Opin Organ Transplant 2009; 14: 662.
54. Burdick JF, Beschorner WE, Smith WJ, et al. Characteristics of early routine renal allograft biopsies. Transplantation 1984; 38: 679.
55. Seron D, Alexopoulos E, Raftery MJ, et al. Diagnosis of rejection in renal allograft biopsies using the presence of activated and proliferating cells. Transplantation 1989; 47: 811.
56. Rush DN, Henry SF, Jeffery JR, et al. Histological findings in early routine biopsies of stable renal allograft recipients. Transplantation 1994; 57: 208.
57. Solez K, Axelsen RA, Benediktsson H, et al. International standardiza-tion ofcriteria for the histologic diagnosis of renal allograft rejection: The Banff working classification ofkidneytransplant pathology. Kid¬ney Int 1993; 44: 411.
58. Nankivell BJ, Borrows RJ, Fung CL, et al. Natural history, risk factors, and impact of subclinical rejection in kidney transplantation. Trans-plantation 2004; 78: 242.
59. Alperovich G, Maldonado R, Moreso F, et al. Glomerular enlargement assessed by paired donor and early protocol renal allograft biopsies. Am J Transplant 2004; 4: 650.
60. Ibernon M, Goma M, Moreso F, et al. Subclinical rejection impairs glomerular adaptation after renal transplantation. KidneyInt2006; 70: 557.
61. Choi BS, Shin MJ, Shin SJ, et al. Clinical significance of an early proto-col biopsy in living-donor renal transplantation: Ten-year experience at a single center. Am J Transplant 2005; 5: 1354.
62. Shishido S, Asanuma H, Nakai H, et al. The impact of repeated subclin-ical acute rejection on the progression ofchronic allograft nephropa-thy. JAm SocNephrol2003; 14: 1046.
63. Cosio FG, Grande JP, Wadei H, et al. Predicting subsequent decline in kidney allograft function from early surveillance biopsies. Am J Trans-plant 2005; 5: 2464.
64. Moreso F, Ibernon M, Gomà M, et al. Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss. Am J Transplant 2006; 6: 747.
65. Moreso F, Seron D, O'Valle F, et al. Immunephenotype ofglomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis. Am J Transplant 2007; 7: 2739.
66. Hueso M, Navarro E, Moreso F, et al. Intragraft expression of the IL10 gene is upregulated in renal protocol biopsies with early interstitial fibrosis, tubular atrophy, and subclinical rejection. Am J Pathol 2010; 176: 1696.
67. + regulatoryT cells predicts outcome ofsubclinical rejection of renal allografts. J Am SocNephrol2008; 19:2020.
68. Rush D, Nickerson P, Gough J, et al. Beneficial effects of treatment of early subclinical rejection: A randomized study. JAm SocNephrol 1998; 9: 2129.
69. Miyagi M, IshikawaY, Mizuiri S, et al. Significance ofsubclinical rejec-tion in early renal allograft biopsies for chronic allograft dysfunction. Clin Transplant 2005; 19: 456.
70. Gloor JM, Cohen AJ, Lager DJ, et al. Subclinical rejection in tacrolimus-treated renal transplant recipients. Transplantation 2002; 73: 1965.
71. Moreso F, Seron D, Carrera M, et al. Baseline immunosuppression is associated with histological findings in early protocol biopsies. Trans-plantation 2004; 78: 1064.
72. Seron D, OValle F, Moreso F, et al. Immunophenotype of infiltrating cells in protocol renal allograft biopsies from tacrolimus-versus cyclosporine-treated patients. Transplantation 2007; 83:649.
73. Rowshani AT, Scholten EM, Bemelman F, et al. No difference in degree of interstitial Sirius redstained area in serial biopsies from area under concentration-over-time curves-guided cyclosporine versus tacrolimus-treated renal transplant recipients at one year. J Am Soc Nephrol 2006; 17: 305.
74. Rush D, Arlen D, Boucher A, et al. Lack of benefit of early protocol biopsies in renal transplant patients receiving TAC and MMF: A ran-domized study. Am J Transplant 2007; 7: 2538.
75. Liptak P, Ivanyi B. Primer: Histopathology of calcineurin-inhibitor toxicity in renal allografts. Nat Clin Pract Nephrol 2006; 2: 398; quiz following.
76. Naesens M, Kuypers DRJ, Sarwal M. Calcineurin inhibitor nephrotox-icity. Clin JAm Soc Nephrol 2009; 4: 481.
77. Nankivell BJ, Borrows RJ, Fung CL, et al. Calcineurin inhibitor neph-rotoxicity: Longitudinal assessment by protocol histology. Transplan-tation 2004; 78: 557.
78. Mota A, Arias M, Taskinen EI, et al. Sirolimus based the rapy following early cyclosporine withdrawal provides significantly improved renal histology and function at 3 years. Am J Transplant 2004; 4: 953.
79. Flechner SM, Kurian SM, Solez K, et al. De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years. Am J Transplant 2004; 4: 1776.
80. Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005; 353: 770.
81. Larson TS, Dean PG, Stegall MD, et al. Complete avoidance of cal-cineurin inhibitors in renal transplantation: A randomized trial com-paring sirolimus and tacrolimus. Am J Transplant 2006; 6: 514.
82. Servais A, Meas-Yedid V, Toupance O, et al. Interstitial fibrosis quan-tification in renal transplant recipients randomized to continue cyclo-sporine or convert to sirolimus. Am J Transplant 2009; 9: 2552.
83. Serón D, Moreso F, Bover J, et al. Early protocol renal allograft biopsies and graft outcome. Kidney Int 1997; 51: 310.
84. Serón D, Moreso F, Fulladosa X, et al. Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsies. Kidney Int 2002; 61: 727.
85. Servais A, MeasYedid V, Buchler M, et al. Quantification of interstitial fibrosis by image analysis on routine renal biopsy in patients receiving cyclosporine. Transplantation 2007; 84: 1595.
86. Cosio FG, Am H, Grande JP, et al. Comparison of low versus high tacrolimus levels in kidney transplantation: Assessment of efficacy by protocol biopsies. Transplantation 2007; 83: 411.
87. Marcussen N, Olsen TS, Benediktsson H, et al. Reproducibility ofthe Banff classification of renal allograft pathology. Inter-and intraob-server variation. Transplantation 1995; 60: 1083.
88. Furness PN, Taub N. International variation in the interpretation of renal transplant biopsies: Report of the CERTPAP Project. Kidney Int 2001; 60: 1998.
89. Sis B, Dadras F, Khoshjou F, et al. Reproducibility studies on arteriolar hyaline thickening scoring in calcineurin inhibitortreated renal allo-graft recipients. Am J Transplant 2006; 6: 1444.
90. Kambham N, Nagarajan S, Shah S, et al. A novel, semiquantitative, clinically correlated calcineurin inhibitor toxicity score for renal allo-graftbiopsies. ClinJAm SocNephrol2007; 2: 135.
91. Krejci K, Tichy T, Hruby M, et al. Subclinical toxicity ofcalcineurin inhibitors in repeated protocol biopsies: An independent risk factor for chronic kidney allograft damage. Transpl Int 2010; 23: 364.
92. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med2000; 342: 605.
93. Opelz G; Collaborative Transplant Study. NonHLA transplantation im-munity revealed by lymphocytotoxic antibodies. Lancet 2005; 365:1570.
94. Lachmann N, Terasaki PI, Budde K, et al. Antihuman leukocyte anti-gen and donorspecific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts. Transplan-tation 2009; 87: 1505.
95. Kowalski RJ, Post DR, Mannon RB, et al. Assessing relative risks of infection and rejection: A metaanalysis using an immune function assay. Transplantation 2006; 82: 663.
96. Iacomini J, Sayegh MH. Measuring T cell alloreactivity to predict kid-ney transplant outcomes: Are we there yet? JAm Soc Nephrol 2006; 17: 328.
97. Hricik DE, Rodriguez V, Riley J, et al. Enzyme linked immunosorbent spot (ELISPOT) assay for interferongamma independently predicts renal function in kidney transplant recipients. Am J Transplant 2003; 3: 878.
98. Nickel P, Presber F, Bold G, et al. Enzymelinked immunosorbent spot assay for donorreactive interferongammaproducing cells identifies T-cell presensitization and correlates with graft function at 6 and 12 months in renaltransplant recipients. Transplantation 2004; 78: 1640.
99. + regulatory T cell recruit-ment in human renal allograft infiltrates. J Immunol 2007; 179: 4901.
100. Kim SH, Oh EJ, Kim MJ, et al. Pretrans plant donor specificinterferon- gamma ELISPOT assay predicts acute rejection episodes in renal trans-plant recipients. Transplant Proc 2007; 39: 3057.
101. Poggio ED, Clemente M, Hricik DE, et al. Panel of reactive T cells as a measurement of primed cellular alloimmunity in kidney transplant candidates. J Am Soc Nephrol 2006; 17: 564.
102. de Zeeuw D, Remuzzi G, Parving HH, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: Lessons from RENAAL. KidneyInt2004; 65: 2309.
103. Reich HN, Troyanov S, Scholey JW, et al. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol 2007; 18: 3177.
104. Praga M. Therapeuticmeasures inproteinuric nephropathy. KidneyInt Suppl 2005; 68: S137.
105. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collabor-ative Study Group. N Engl J Med 1993; 329: 1456.
106. Randomised placebo-controlled trial ofeffect oframipril on decline in glomerular filtration rate and risk ofterminal renal failure in protein-uric, nondiabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici inNefrologia). Lancet 1997; 349: 1857.
107. Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development ofdiabetic nephropathy in patients with type 2 diabetes. NEngl JMed 2001; 345: 870.
108. Levey AS, Cattran D, Friedman A, et al. Proteinuria as a surrogate outcome in CKD: Report of a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administra-tion. Am J Kidney Dis 2009; 54: 205.
109. Hillege HL, Fidler V, Diercks GF, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106: 1777.
110. Tonelli M, Jose P, Curhan G, et al. Proteinuria, impaired kidney func-tion, and adverse outcomes in people with coronary disease: Analysis of a previously conducted randomised trial. BMJ2006; 332: 1426.
111. Ibsen H, Olsen MH, Wachtell K, et al. Reduction in albuminuria trans-lates to reduction in cardiovascular events in hypertensive patients: Losartan intervention for endpoint reduction in hypertension study. Hypertension 2005; 45: 198.
112. Asselbergs FW, Diercks GF, Hillege HL, et al. Effects offosinopril and pravastatin on cardiovascular events in subjects with microalbumin-uria. Circulation 2004; 110: 2809.
113. de Zeeuw D, Remuzzi G, Parving HH, et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004; 110: 921.
114. Knoll GA. Proteinuria in kidney transplant recipients: Prevalence, prognosis, and evidence-based management. Am JKidney Dis 2009; 54: 1131.
115. Amer H, Fidler ME, Myslak M, et al. Proteinuria after kidney transplantation, relationship to allograft histology and survival. Am J Transplant 2007; 7: 2748.
116. Am H, Cosio FG. Significance and management ofproteinuria in kid-ney transplant recipients. JAm Soc Nephrol 2009; 20: 2490.
117. Fernandez-Fresnedo G, Plaza JJ, Sanchez-Plumed J, et al. Proteinuria: A new marker oflong-term graft and patient survival in kidney trans-plantation. NephrolDial Transplant 2004; 19(suppl 3): 47.
118. Halimi J-M, Laouad I, Buchler M, et al. Early lowgrade proteinuria: Causes, short-term evolution and longterm consequences in renal transplantation. Am J Transplant 2005; 5: 2281.
119. Cattran DC, Reich HN, Beanlands HJ, et al. The impact of sex in pri-mary glomerulonephritis. Nephrol Dial Transplant 2008; 23: 2247.
120. Roodnat JI, Mulder PG, Rischen-Vos J, et al. Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation 2001; 72: 438.
121. Cattran DC, Alexopoulos E, HeeringP, et al. Cyclosporininidiopathic glomerular disease associated with the nephrotic syndrome: Workshop recommendations. Kidney Int 2007; 72: 1429.
122. Cattran DC, Appel GB, Hebert LA, et al. A randomized trial of cyclo-sporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int 1999; 56: 2220.
123. Praga M, Barrio V, Fernández-Juárez G, et al; Grupo español de estudio de la nefropatía membranosa. Tacrolimus monotherapy in membranous ne-phropathy: Arandomized controlled trial. KidneyInt2007; 71: 924.
124. Szeto CC, Kwan BC, Lai FM, et al. Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis. Rheumatol-ogy (Oxford) 2008; 47: 1678.
125. Faul C, Donnelly M, Merscher Gomez S, et al. The actincytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008; 14: 931.
126. Tumlin JA, Miller D, Near M, et al. A prospective, openlabel trial of sirolimus in the treatment offocal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2006; 1: 109.
127. Cho ME, Hurley JK, Kopp JB. Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am J Kidney Dis 2007; 49: 310.
128. Letavernier E, Pe'raldi M-N, Pariente A, et al. Proteinuria following a switch from calcineurin inhibitors to sirolimus. Transplantation 2005; 80: 1198.
129. Gutierrez MJ, Gonzalez E, Andres A, et al. Clinical implications of proteinuria in renal transplant recipients switching to rapamycin for chronic allograft dysfunction. Transplant Proc 2009; 41: 2348.
130. van den Akker JM, Wetzels JF, Hoitsma AJ. Proteinuria following con-version from azathioprine to sirolimus in renal transplant recipients. Kidney Int 2006; 70: 1355.
131. StraathofGalema L, Wetzels JF, Dijkman HB, et al. Sirolimusassociated heavy proteinuria in a renal transplant recipient: Evidence for a tubular mechanism. Am J Transplant 2006; 6: 429.
132. Letavernier E, Bruneval P, Vandermeersch S, et al. Sirolimus interacts with pathways essential for podocyte integrity. NephrolDial Transplant 2009; 24: 630.
133. Heinze G, Mitterbauer C, Regele H, et al. Angiotensinconverting en-zyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal trans-plantation. JAm Soc Nephrol 2006; 17: 889.
134. Opelz G, Zeier M, Laux G, et al. No improvement of patient or graft sur-vival in transplant recipients treated with angiotensinconverting enzyme inhibitors or angiotensin II type 1 receptor blockers: A collaborative trans-plant study report. JAm Soc Nephrol 2006; 17: 3257.
135. Hiremath S, Fergusson D, Doucette S, et al. Renin angiotensin system blockade in kidney transplantation: A systematic review of the evi-dence. Am J Transplant 2007; 7: 2350.
136. Knoll GA, Cantarovitch M, Cole E, et al. The Canadian ACE-inhibitor trial to improve renal outcomes and patient survival in kidney transplantation\Study design. Nephrol Dial Transplant 2008; 23: 354.