Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure

Abstract

Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for $7 years posttransplantation. Compared with proteinuria ,0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3-1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P,0.001), for proteinuria 1.0-3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P,0.001), for proteinuria .3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P,0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P,0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained .3 months after transplant (AUC 0.73, P,0.001) than in those obtained earlier (AUC 0.56, P,0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria .1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.

Variability of the Estimated Glomerular Filtration Rate in the First Year after Kidney Transplantation Is an Independent Risk Factor for Poor Renal Allograft Outcomes: A Retrospective Cohort Study

“…Although the graft attrition rate at 1 year after transplantation has improved, it has not translated into a proportionate improvement in long-term renal graft survival [14, 15]. In recent years, specific diseases, such as antibody-mediated rejection and de novo/recurrent glomerular diseases, have been identified as the primary causes of renal graft failure [15–18].…”

“…In recent years, specific diseases, such as antibody-mediated rejection and de novo/recurrent glomerular diseases, have been identified as the primary causes of renal graft failure [15–18]. The inability to prevent or treat these specific diseases is likely associated with the insufficient improvement in long-term renal graft survival.…”

“…The inability to prevent or treat these specific diseases is likely associated with the insufficient improvement in long-term renal graft survival. One of the challenges for research in organ transplantation is the identification of markers that can sufficiently diagnose these specific diseases and that can be used as endpoints in clinical studies [15]. Additionally, many previous studies have attempted to identify markers of renal graft injury that can be used to improve long-term graft survival [15, 19–21].…”

Proteinuria, Estimated Glomerular Filtration Rate and Urinary Retinol-Binding Protein as Clinical Predictors of Long-Term Allograft Outcomes in Transplant Glomerulopathy

“…In a study involving 33 patients, Kotanko et al found that paradoxically lower urNAG excretion is associated with reduced graft survival [24]. In a subsequent investigation, Ferdau et al demonstrate that urNAG level is positively associated with graft failure [13][14][15]. However, this predictive value disappeared when adjusted for albuminuria which had been demonstrated to be the best predictor of allograft failure.…”

“…Proteinuria has been established as a risk factor that confers poor outcome for a variety of kidney diseases both in the native kidneys and renal allografts [13][14][15]. Chronic endothelial injury and remodeling account for the main mechanism for proteinuria in TG, the severity of which as assessed by histologic score of cg does not necessarily correlated with proteinuria degree clinically, though.…”