Abstract
The role of urinary retinol-binding protein (RBP) as a biomarker of CKD in proximal tubular diseases, glomerulopathies and in transplantation is well established. However, whether urinary RBP is also a biomarker of renal damage and CKD progression in general CKD is not known. In this study, we evaluated the association of urinary RBP with renal function and cardiovascular risk factors in the baseline data of the Progredir Study, a CKD cohort in Sao Paulo, Brazil, comprising 454 participants with stages 3 and 4 CKD. In univariate analysis, urinary RBP was inversely related to estimated glomerular filtration rate (CKD-EPI eGFR) and several cardiovascular risk factors. After adjustments, however, only CKD-EPI eGFR, albuminuria, systolic blood pressure, anemia, acidosis, and left atrium diameter remained significantly related to urinary RBP. The inverse relationship of eGFR to urinary RBP (β-0.02 ± 95CI -0.02; -0.01, p<0.0001 for adjusted model) remained in all strata of albuminuria, even after adjustments: in normoalbuminuria (β-0.008 ± 95CI (-0.02; -0.001, p = 0.03), in microalbuminuria (β-0.02 ± 95CI (-0.03; -0.02, p<0,0001) and in macroalbuminuria (β-0.02 ± 95CI (-0.03; -0.01, p<0,0001). Lastly, urinary RBP was able to significantly increase the accuracy of a logistic regression model (adjusted for sex, age, SBP, diabetes and albuminuria) in diagnosing eGFR<35 ml/min/1.73m2 (AUC 0,77, 95%CI 0,72–0,81 versus AUC 0,71, 95%CI 0,65–0,75, respectively; p = 0,05). Our results suggest that urinary RBP is significantly associated to renal function in CKD in general, a finding that expands the interest in this biomarker beyond the context of proximal tubulopathies, glomerulopathies or transplantation. Urinary RBP should be further explored as a predictive marker of CKD progression.
Highlights
Retinol binding protein (RBP) is a low molecular weight protein belonging to the lipocalin super family [1] and mainly synthesized in the liver
Urinary RBP was inversely associated to renal function and positively associated to diabetes, female gender, systolic blood pressure, albuminuria, glycated hemoglobin, total-cholesterol, HDL-cholesterol, and pulse wave velocity (PWV)
Other parameters related to uremia such as anemia, acidosis and mineral metabolism were associated to urinary RBP
Summary
Retinol binding protein (RBP) is a low molecular weight protein belonging to the lipocalin super family [1] and mainly synthesized in the liver. 4–5% of serum RBPretinol circulates freely, pass the glomerular barrier and is reabsorbed and degraded in the proximal tubule, a process mediated by megalin [3]. Due to these properties, urinary RBP is an established biomarker of proximal tubular dysfunction and is used as a diagnostic tool in proximal tubulopathies, such as Fanconi syndrome, Dent’s disease, cystinosis, or cast nephropathy. Urinary RBP has been positively associated to the risk of CKD [6], and in heart transplantation it has been associated with the risk of cyclosporine toxicity and CKD [7]. One of the most common causes of CKD worldwide, data are scarce, with few small cross-sectional studies in the 80 ́s showing that urinary RBP was associated to surrogate markers of progression such as microalbuminuria, HbA1c, and other parameters of microvascular disease [8,9,10]
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