Urinary transforming growth factor-beta 1 in chronic kidney disease.

摘要

Background. Transforming growth factors-beta 1 (TGF-beta1) is a multifunctional growth and immunomodulatory chemokine that plays a key role in tissue repair and fibrosis. The renal production and urinary clearance of TGF-beta1 allows it to be a candidate biomarker in chronic kidney disease (CKD).;Objective. To characterize the clinical and genetic factors associated with urinary TGF-beta1 excretion. To explore both urinary TGF-beta1 and TGF-beta1 gene single nucleotide polymorphisms (SNPs) as biomarkers of CKD severity and progression in a CKD population.;Methods. As part of an ongoing cohort study of patients with CKD, urinary levels of TGF-beta1 were measured in 144 subjects. The clinical and genetic factors associated with urine TGF-beta1 were explored using multivariable linear regression. A candidate gene approach was used with the selection of five TGF-beta1 gene polymorphisms: two non-synonomous and three tagging SNPs. All SNPs were examined for deviation from Hardy-Weinberg equilibrium and analyzed using additive or dominant genetic models. The association of TGF-beta1 urine levels and gene polymorphisms with estimated GFR was examined using multivariable linear regression, and adjusted Cox proportional hazard models was used to predict time to CKD progression.;Results. Kidney function was not a determinant of urine TGF-beta1, but albuminuria was positively associated, and platelet count, black race and diabetic medication use were inversely related to its urine excretion. The TGF-beta1 SNPs were not associated with urinary TGF-beta1 levels. The C-allele at +896 T/C was associated with a 6.4 ml/min higher estimated GFR (p = 0.01) at enrollment, while the presence of the rs8179181 SNP T-allele was associated with an 11.7 ml/min decrease (p = 0.002). The rs8179181 SNP was also associated with faster time to CKD progression (hazard ratio 2.7, 95% CI 1.2-6.3). Urine TGF-beta1 levels did not predict time to progression, but there was insufficient power to find an association.;Conclusions. Urine TGF-beta1 levels are not associated with baseline GFR in a cohort of referred patients with CKD. The rs8179181 SNP did show a relationship with CKD severity and time to progression. This genetic effect did not appear to be mediated by urinary TGF-beta1 excretion. The role of TGF-beta1 as a biomarker of CKD progression will need to be further explored in this cohort and in others.