Proteinuria in Kidney Transplant Recipients: Prevalence, Prognosis, and Evidence-Based Management

American Journal of Kidney Diseases

Volumn 54, Issue 6, 2009, Pages 1131-1144

  Knoll, Greg A ^a  

^a OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

Author keywords

ACE inhibitor; albuminuria; Kidney transplant; proteinuria

Indexed keywords

ALBUMIN; ALPHA 1 MICROGLOBULIN; ANGIOTENSIN RECEPTOR ANTAGONIST; AZATHIOPRINE; BETA 2 MICROGLOBULIN; CALCINEURIN INHIBITOR; CREATININE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; LOSARTAN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PREDNISONE; RAPAMYCIN; RETINOL BINDING PROTEIN;

ACUTE GRAFT REJECTION; ALBUMINURIA; ALLOGRAFT; CARDIOVASCULAR RISK; CLINICAL ASSESSMENT; DIASTOLIC BLOOD PRESSURE; DRUG SUBSTITUTION; EVIDENCE BASED MEDICINE; EVIDENCE BASED PRACTICE; GLOMERULONEPHRITIS; GLOMERULOPATHY; GRAFT RECIPIENT; GRAFT SURVIVAL; HUMAN; KIDNEY DISEASE; KIDNEY FUNCTION; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; MICROALBUMINURIA; OUTCOME ASSESSMENT; PREDICTION; PREVALENCE; PROGNOSIS; PROTEIN RESTRICTION; PROTEINURIA; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK FACTOR; SAMPLE SIZE; SYSTOLIC BLOOD PRESSURE; TREATMENT DURATION; URINE VOLUME;

EVIDENCE-BASED MEDICINE; GRAFT SURVIVAL; HUMANS; KIDNEY TRANSPLANTATION; PREVALENCE; PROGNOSIS; PROTEINURIA; RISK FACTORS; TRANSPLANTATION;

EID: 70449625145     PISSN: 02726386     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.ajkd.2009.06.031     Document Type: Review

References (80)

1. Palmer B.F. Proteinuria as a therapeutic target in patients with chronic kidney disease. Am J Nephrol 27 (2007) 287-293
2. Sarafidis P.A., and Bakris G.L. Microalbuminuria and chronic kidney disease as risk factors for cardiovascular disease. Nephrol Dial Transplant 21 (2006) 2366-2374
3. Vassalotti J.A., Stevens L.A., and Levey A.S. Testing for chronic kidney disease: A position statement from the National Kidney Foundation. Am J Kidney Dis 50 (2007) 169-180
4. Sarafidis P.A., Khosla N., and Bakris G.L. Antihypertensive therapy in the presence of proteinuria. Am J Kidney Dis 49 (2007) 12-26
5. Fernandez-Fresnedo G., Escallada R., Rodrigo E., et al. The risk of cardiovascular disease associated with proteinuria in renal transplant patients. Transplantation 73 (2002) 1345-1348
6. Rose B.D., and Post T.W. Measurement of urinary protein excretion. UpToDate 17.1. http://www.utdol.com Accessed January 13, 2009
7. Schaub S., Mayr M., Honger G., et al. Detection of subclinical tubular injury after renal transplantation: Comparison of urine protein analysis with allograft histopathology. Transplantation 84 (2007) 104-112
8. Schaub S., Rush D., Wilkins J., et al. Proteomic-based detection of urine proteins associated with acute renal allograft rejection. J Am Soc Nephrol 15 (2004) 219-227
9. Garg A.X., Muirhead N., Knoll G., et al. Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression. Kidney Int 70 (2006) 1801-1810
10. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification and stratification. Am J Kidney Dis 39 suppl 1 (2003) S1-S266
11. Levey A.S., Eckardt K.U., Tsukamoto Y., et al. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 67 (2005) 2089-2100
12. Steinhauslin F., and Wauters J.P. Quantitation of proteinuria in kidney transplant patients: Accuracy of the urinary protein/creatinine ratio. Clin Nephrol 43 (1995) 110-115
13. Rodrigo E., Pinera C., Ruiz J.C., et al. Quantitation of 24-hour urine protein excretion in kidney transplant patients by the use of protein to creatinine ratio. Transplant Proc 35 (2003) 702
14. Torng S., Rigatto C., Rush D.N., Nickerson P., and Jeffery J.R. The urine protein to creatinine ratio (P/C) as a predictor of 24-hour urine protein excretion in renal transplant patients. Transplantation 72 (2001) 1453-1456
15. Ginsberg J.M., Chang B.S., Matarese R.A., and Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 309 (1983) 1543-1546
16. First M.R., Vaidya P.N., Maryniak R.K., et al. Proteinuria following transplantation. Correlation with histopathology and outcome. Transplantation 38 (1984) 607-612
17. Yakupoglu U., Baranowska-Daca E., Rosen D., Barrios R., Suki W.N., and Truong L.D. Post-transplant nephrotic syndrome: A comprehensive clinicopathologic study. Kidney Int 65 (2004) 2360-2370
18. Chung J., Park S.K., Park J.S., Kim S.C., Han D.J., and Yu E. Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: Histopathologic findings of renal allografts with proteinuria. Clin Transplant 14 (2000) 499-504
19. Fernandez-Fresnedo G., Plaza J.J., Sanchez-Plumed J., Sanz-Guajardo A., Palomar-Fontanet R., and Arias M. Proteinuria: A new marker of long-term graft and patient survival in kidney transplantation. Nephrol Dial Transplant 19 (2004) 47-51
20. Halimi J.M., Laouad I., Buchler M., et al. Early low-grade proteinuria: Causes, short-term evolution and long-term consequences in renal transplantation. Am J Transplant 5 (2005) 2281-2288
21. Karthikeyan V., Karpinski J., Nair R.C., and Knoll G. The burden of chronic kidney disease in renal transplant recipients. Am J Transplant 4 (2004) 262-269
22. Kim H.C., Park S.B., Lee S.H., Park K.K., Park C.H., and Cho W.H. Proteinuria in renal transplant recipients: Incidence, cause, and prognostic importance. Transplant Proc 26 (1994) 2134-2135
23. Park J.H., Park J.H., Bok H.J., et al. Persistent proteinuria as a prognostic factor for determining long-term graft survival in renal transplant recipients. Transplant Proc 32 (2000) 1924
24. Vathsala A., Verani R., Schoenberg L., et al. Proteinuria in cyclosporine-treated renal transplant recipients. Transplantation 49 (1990) 35-41
25. Amer H., Fidler M.E., Myslak M., et al. Proteinuria after kidney transplantation, relationship to allograft histology and survival. Am J Transplant 7 (2007) 2748-2756
26. Sancho A., Gavela E., Avila A., et al. Risk factors and prognosis for proteinuria in renal transplant recipients. Transplant Proc 39 (2007) 2145-2147
27. Ibis A., Altunoglu A., Akgul A., et al. Early onset proteinuria after renal transplantation: A marker for allograft dysfunction. Transplant Proc 39 (2007) 938-940
28. Roodnat J.I., Mulder P.G., Rischen-Vos J., et al. Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation 72 (2001) 438-444
29. Boulware L.E., Jaar B.G., Tarver-Carr M.E., Brancati F.L., and Powe N.R. Screening for proteinuria in US adults: A cost-effectiveness analysis. JAMA 290 (2003) 3101-3114
30. Akbari A., Hussain N., Karpinski J., and Knoll G.A. Chronic kidney disease management: Comparison between renal transplant recipients and nontransplant patients with chronic kidney disease. Nephron 107 (2007) c7-c13
31. Myslak M., Amer H., Morales P., et al. Interpreting post-transplant proteinuria in patients with proteinuria pre-transplant. Am J Transplant 6 (2006) 1660-1665
32. D'Cunha P.T., Parasuraman R., and Venkat K.K. Rapid resolution of proteinuria of native kidney origin following live donor renal transplantation. Am J Transplant 5 (2005) 351-355
33. Laplante L., Beaudry C., and Houde M. Early disappearance of proteinuria attributed to the original kidneys after kidney transplantation. Union Med Canada 104 (1975) 246-248
34. Solez K., Colvin R.B., Racusen L.C., et al. Banff '05 meeting report: Differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN'). Am J Transplant 7 (2007) 518-526
35. Jafar T.H., Schmid C.H., Landa M., et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: A meta-analysis of patient-level data. Ann Intern Med 135 (2001) 73-87
36. Lewis E.J., Hunsicker L.G., Clarke W.R., et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345 (2001) 851-860
37. Fellstrom B., Holdaas H., Jardine A.G., et al. Risk factors for reaching renal endpoints in the Assessment of Lescol in Renal Transplantation Trial. Transplantation 79 (2005) 205-212
38. Fontan M.P., Rodriguez-Carmona A., Garcia F.T., and Valdes F. Early proteinuria in renal transplant recipients treated with cyclosporin. Transplantation 67 (1999) 561-568
39. Letavernier E., and Legendre C. mToR inhibitors-induced proteinuria: Mechanisms, significance, and management. Transplant Rev 22 (2008) 125-130
40. Ruiz J.C., Campistol J.M., Sanchez-Fructuoso A., et al. Increase of proteinuria after conversion from calcineurin inhibitor to sirolimus-based treatment in kidney transplant patients with chronic allograft dysfunction. Nephrol Dial Transplant 21 (2006) 3252-3257
41. Boratynska M., Banasik M., Watorek E., et al. Conversion to sirolimus from cyclosporine may induce nephrotic proteinuria and progressive deterioration of renal function in chronic allograft nephropathy patients. Transplant Proc 38 (2006) 101-104
42. Saurina A., Campistol J.M., Piera C., et al. Conversion from calcineurin inhibitors to sirolimus in chronic allograft dysfunction: Changes in glomerular haemodynamics and proteinuria. Nephrol Dial Transplant 21 (2006) 488-493
43. Bumbea V., Kamar N., Ribes D., et al. Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant 20 (2005) 2517-2523
44. Letavernier E., Pe'raldi M.N., Pariente A., Morelon E., and Legendre C. Proteinuria following a switch from calcineurin inhibitors to sirolimus. Transplantation 80 (2005) 1198-1203
45. Myers B.D., Sibley R., Newton L., et al. The long-term course of cyclosporine-associated chronic nephropathy. Kidney Int 33 (1988) 590-600
46. Ducloux D., Motte G., Billerey C., et al. Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: A 2-year follow-up. Transplant Int 15 (2002) 387-392
47. van den Akker J.M., Wetzels J.F., and Hoitsma A.J. Proteinuria following conversion from azathioprine to sirolimus in renal transplant recipients. Kidney Int 70 (2006) 1355-1357
48. Diekmann F., Gutierrez-Dalmau A., Lopez S., et al. Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: Comparison of two CNI-free protocols. Nephrol Dial Transplant 22 (2007) 2316-2321
49. Stephany B.R., Augustine J.J., Krishnamurthi V., et al. Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation. Transplantation 82 (2006) 368-374
50. Straathof-Galema L., Wetzels J.F., Dijkman H.B., Steenbergen E.J., and Hilbrands L.B. Sirolimus-associated heavy proteinuria in a renal transplant recipient: Evidence for a tubular mechanism. Am J Transplant 6 (2006) 429-433
51. Mreich E., Coombes J.D., and Rangan G.K. Sirolimus does not reduce receptor-mediated endocytosis of albumin in proximal tubule cells. Transplantation 83 (2007) 105-107
52. Letavernier E., Bruneval P., Mandet C., et al. High sirolimus levels may induce focal segmental glomerulosclerosis de novo. Clin J Am Soc Nephrol 2 (2007) 326-333
53. Dittrich E., Schmaldienst S., Soleiman A., Horl W.H., and Pohanka E. Rapamycin-associated post-transplantation glomerulonephritis and its remission after reintroduction of calcineurin-inhibitor therapy. Transplant Int 17 (2004) 215-220
54. Mainra R., Mulay A., Bell R., et al. Sirolimus use and de novo minimal change nephropathy following renal transplantation. Transplantation 80 (2005) 1816
55. Izzedine H., Brocheriou I., and Frances C. Post-transplantation proteinuria and sirolimus. N Engl J Med 353 (2005) 2088-2089
56. Abramowicz D., Hadaya K., Hazzan M., et al. Conversion to sirolimus for chronic renal allograft dysfunction: Risk factors for graft loss and severe side effects. Nephrol Dial Transplant 23 (2008) 3727-3729
57. Franco A.F., Martini D., Abensur H., and Noronha I.L. Proteinuria in transplant patients associated with sirolimus. Transplant Proc 39 (2007) 449-452
58. Lorber M.I., Mulgaonkar S., Butt K.M., et al. Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: A 3-year randomized, multicenter, phase III study. Transplantation 80 (2005) 244-252
59. Hor T., and Baldwin D. Urinary albumin excretion in patients with diabetes after renal transplantation. Transplant Proc 38 (2006) 2879-2882
60. Halimi J.M., Buchler M., Al Najjar A., et al. Urinary albumin excretion and the risk of graft loss and death in proteinuric and non-proteinuric renal transplant recipients. Am J Transplant 7 (2007) 618-625
61. De Zeeuw D., Remuzzi G., Parving H.H., et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: Lessons from RENAAL. Kidney Int 65 (2004) 2309-2320
62. Ruggenenti P., Perna A., Remuzzi G., and GISEN Group. Retarding progression of chronic renal disease: The neglected issue of residual proteinuria. Kidney Int 63 (2003) 2254-2261
63. Lewis E.J., Hunsicker L.G., Bain R.P., Rohde R.D., and Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 329 (1993) 1456-1462
64. 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 139 (2003) 244-252
65. Vogt L., Waanders F., Boomsma F., De Zeeuw D., and Navis G. Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol 19 (2008) 999-1007
66. Bianchi S., Bigazzi R., and Campese V.M. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int 70 (2006) 2116-2223
67. Bakris G.L., Mangrum A., Copley J.B., Vicknair N., and Sadler R. Effect of calcium channel or beta-blockade on the progression of diabetic nephropathy in African Americans. Hypertension 29 (1997) 744-750
68. McCormick B.B., Sydor A., Akbari A., Fergusson D., Doucette S., and Knoll G. The effect of pentoxifylline on proteinuria in diabetic kidney disease: A meta-analysis. Am J Kidney Dis 52 (2008) 454-463
69. Parving H.H., Persson F., Lewis J.B., Lewis E.J., Hollenberg N.K., and Avoid S.I. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 358 (2008) 2433-2446
70. Kunz R., Friedrich C., Wolbers M., and Mann J.F. Meta-analysis: Effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med 148 (2008) 30-48
71. Heinze G., Mitterbauer C., Regele H., et al. Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation. J Am Soc Nephrol 17 (2006) 889-899
72. Opelz G., Zeier M., Lau G., Morath C., and Dohler B. No improvement of patient or graft survival in transplant recipients treated with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers: A Collaborative Transplant Study Report. J Am Soc Nephrol 17 (2006) 3257-3262
73. Hiremath S., Fergusson D., Doucette S., Mulay A.V., and Knoll G.A. Renin angiotensin system blockade in kidney transplantation: A systematic review of the evidence. Am J Transplant 7 (2007) 2350-2360
74. Philipp T., Legendre C., Geiger H., et al. Study on the Evaluation of Candesartan Cilexetil after Renal Transplantation (SECRET-Study). Kidney Blood Press Res 27 (2004) 331-332
75. A Double-Blind, Randomized Placebo-Controlled Study to Evaluate the Renal Protective Effects of Losartan in Patients with Renal Transplants. ClinicalStudyResults.org. http://www.clinicalstudyresults.org/home/ Accessed May 14, 2009
76. Campistol JM, Garcia dM, Alarcon A, et al: Angiotensin II receptor blockage in kidney transplantation: Design and Progress of the AALLOGRAFT study. World Transplant Congress Meeting, Boston, MA, July 22-27, 2006 (abstr 510)
77. Rigatto C., Parfrey P., Foley R., Negrijn C., Tribula C., and Jeffery J. Congestive heart failure in renal transplant recipients: Risk factors, outcomes, and relationship with ischemic heart disease. J Am Soc Nephrol 13 (2002) 1084-1090
78. Knoll G.A., 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 23 (2008) 354-358
79. Biesenbach G., Zazgornik J., Janko O., Hubmann R., and Syre G. Effect of mild dietary protein restriction on urinary protein excretion in patients with renal transplant fibrosis. Wien Med Wochenschr 146 (1996) 75-78
80. Salahudeen A.K., Hostetter T.H., Raatz S.K., and Rosenberg M.E. Effects of dietary protein in patients with chronic renal transplant rejection. Kidney Int 41 (1992) 183-190