Urine High and Low Molecular Weight Proteins One-Year Post-Kidney Transplant: Relationship to Histology and Graft Survival

Abstract

Increased urinary protein excretion is common after renal transplantation and portends worse outcome. In this study we assessed the prognostic contribution of several urinary proteins. Urinary total protein, albumin, retinol binding protein (RBP), α-1-microglobulin, IgG and IgM, were measured in banked urine samples from 221 individuals one-year after renal transplantation (age 52 ± 13 years, 55% male, 93 % Caucasian and 82 % living donor). Levels of all proteins measured were higher than in normal non-transplant populations. Patients with glomerular lesions had higher urinary albumin than those with normal histology, while those with Interstitial Fibrosis and Tubular Atrophy plus Inflammation (ci>0, cg=0, i>0) had higher levels of IgG, IgM, α-1-microglobulin and RBP. Concomitant normal levels of urinary albumin, IgM and RBP identified normal histology (specificity 91%, sensitivity 15 %,). Urinary levels of the specific proteins were highly correlated, could not differentiate among the histologic groups, and appeared to result from tubulointerstitial damage. Increased urinary excretion of the low molecular weight protein RBP was a sensitive marker of allografts at risk, predicting long-term graft loss independent of histology and urinary albumin. This study highlights the prognostic importance of tubulointerstitial disease for long-term graft loss.

Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure

“…Protein/creatinine levels in spot urine samples were not available in this study. In addition, we have no data on albuminuria or proteinuria composition, which could discriminate between glomerular and tubular origin of the proteinuria, and could be a better marker in patients with total proteinuria ,0.3 g/24 h. 12,27,28 Finally, the potential benefit of renin-angiotensin system inhibitor use 29 in kidney transplant patients could not be evaluated in our observational cohort study with inherent selection bias, as patients with proteinuria were more likely to receive reninangiotensin system inhibitors compared with patients without proteinuria.…”

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

“…It has been found that urRBP was an independent risk factor of renal outcome in patients with macroalbuminuric diabetic nephropathy [21] and a prognostic marker for various glomerulopathy [22]. urRBP has also been demonstrated to be predictable of normal allograft histology when it and urinary albumin, IgM were within normal range [8]. In an earlier study with 183 kidney transplant recipients, Hosaka et al noticed that urRBP level higher than 0.6 mg/L had the best predictive value for diagnosing allograft dysfunction at 1 year post-transplantation [20].…”

“…Several previous studies have suggested that urinary retinol-binding protein (urRBP), which is a biomarker of renal tubular injury, could potentially serve as a biomarker that predicts allograft survival in TG patients [7][8][9]. The advantage that urRBP is routinely measured in our center enabled us to characterize the relationship between urRBP and allograft survival in a large cohort of TG patients.…”

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“…[36][37][38] Low-grade proteinuria, which we observed in our patients, was associated mostly with interstitial and tubular damage. 36,37,40 It is known that proteinuria itself can injure tubular epithelial cells and stimulate them to synthesize chemokines, which contribute to inflammation in the tubulointerstitium. 40,41 In turn, interstitial inflammation strongly correlates with reduced allograft survival.…”

“…36,37,40 It is known that proteinuria itself can injure tubular epithelial cells and stimulate them to synthesize chemokines, which contribute to inflammation in the tubulointerstitium. 40,41 In turn, interstitial inflammation strongly correlates with reduced allograft survival. The correlations between proteinuria and the full range of tubular enzymes (particularly NAG and AST) point to an association of proteinuria with ongoing injury in the tubulointerstitial compartment of the KAG and lead us to believe that measuring enzymuria enhances the diagnostic significance of proteinuria alone.…”