No abstract

Background: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in nontransplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. Conclusions: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function. Methods

Proteinuria is constituted by urinary albumin (UAE) and nonalbumin proteins (NAP). UAE was shown to predict ESRD and death. Whether NAP predicts graft or patient outcome is unknown in renal transplantation.We retrospectively analyzed the impact of UAE and NAP respectively on end-stage renal disease (ESRD) and death in 616 renal transplant recipients. In subjects with proteinuria <0.25 g/day, 76% of urine proteins were NAP; in those with >1 g/day, 44% of the urine proteins were NAP. Determinants of UAE and NAP were partly different: fasting glucose, body weight, donor cause of death and cyclosporine were significantly associated with NAP (but not UAE); panel reactive antibodies (PRA) and rapamycine were significantly associated with UAE (but not with NAP). NAP Massive proteinuria has been recognized as a risk factor for long-term graft loss (1,2). A recent study from our group indicated that low-grade proteinuria was a powerful independent predictor of long-term graft loss (3).Total proteinuria is made of various proportions of urine albumin (UAE) and nonalbumin proteinuria (NAP). Nonalbumin proteinuria includes several types of urinary proteins, and some of them were associated with renal damage or outcome in renal transplantation, including alpha-1 microglobulin, beta-2 macroglobulin and IgG (4). Other urinary proteins (cystatin C, transferrin, nephrin, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1,. . .) are biomarkers of renal damage in nontransplanted populations (5-10).Interestingly, it was recently demonstrated that UAE was an independent powerful risk factor for graft loss and death in renal transplant recipients (11). However, it is presently unknown whether NAP has any predictive value on graft loss or death, and therefore whether UAE and NAP provide different information on patient or renal outcome. The question about the respective prognostic value of UAE and NAP is not only academic: if only UAE (but not NAP) is an independent parameter associated to graft loss or death, screening for UAE may be discussed in all renal transplant recipients. Conversely, if NAP in addition to UAE also provides information on renal/patient outcome, then it would be interesting to identify the role of urinary proteins using proteomic analyses.To date, this type of analysis was not reported in the literature. We recently showed that UAE is a strong risk factor for graft loss and death; both UAE and total proteinuria were measured in each 616 patients included in this study (11), which allowed us to calculate NAP values in all patients. In the present analysis, we retrospectively analyzed and compared the respective predictive value of UAE and NAP in this population. Patients and Methods Study populationAs previously published (11), 616 patients were followed at our institution between 1998 and 2005: both total proteinuria and UAE were measured. Most patients received our institution's immunosuppressive regimen: induction therapy with antithymocyte globulin (Thymoglobulin ® , Sangstat, 2775