ObjectiveWe conducted this cross-sectional study to investigate the relationship between stage of diabetic nephropathy and likelihood or severity of depression in patients with diabetes.Research design and methodsWe studied 2212 patients with diabetes (mean age 60.9 years; 928 women; 1838 patients with type 2 diabetes). Presence and severity of depression was examined using the Patient Health Questionnaire-9 (PHQ-9). Patients were classified into 5 stages of nephropathy, according to albuminuria and estimated glomerular filtration rate (eGFR); patients in stage 5 undergoing dialysis and kidney transplantation were analyzed separately (stages 5D and 5T). The relationship between stage of nephropathy and depression was examined using analysis of covariance and multivariate logistic regression analysis.ResultsBoth least square mean PHQ-9 scores and prevalence of patients with PHQ-9 scores ≥5 points (mild depression) and ≥10 points (moderate or severe depression) increased from stage 1 to 5D, and then declined in stage 5T. Multivariate ORs for mild or greater depression increased in patients in stages 3, 4, and 5D in reference to those in stage 1, which declined in patients in stage 5T. Albuminuria was significantly, but eGFR was not, associated with higher PHQ-9 scores and the PHQ-9 scores ≥5 or ≥10 after adjustment for clinical findings.ConclusionsIn patients with diabetes, progression of nephropathy is likely to be associated with increased risk and severity of depression, which may be reduced after successful kidney transplantation. Albuminuria may be more strongly associated with depression than eGFR.
Mimicking the biological function of the extracellular matrix is an approach to developing cell adhesive biomaterials. The RGD peptide, derived from fibronectin (Fn), mainly binds to integrin αvβ3 and has been widely used as a cell adhesive peptide on various biomaterials. However, cell adhesion to Fn is thought to be mediated by several integrin subtypes and syndecans. In this study, we synthesized an RGD-containing peptide (FIB1) and four integrin α4β1-binding-related motif-containing peptides (LDV, IDAPS, KLDAPT, and PRARI) and constructed peptide-chitosan matrices. The FIB1-chitosan matrix promoted human dermal fibroblast (HDF) attachment, and the C-terminal elongated PRARI (ePRARI-C)-conjugated chitosan matrix significantly promoted HDF attachment through integrin α4β1 and syndecan binding. Next, we constructed a mixed ePRARI-C- and FIB1-chitosan matrix to develop a Fn mimetic biomaterial. The mixed ePRARI-C/FIB1-chitosan matrix promoted significantly better cell attachment and neurite outgrowth compared to those of either ePRARI-C- or FIB1-chitosan matrices. HDF adhesion to the ePRARI-C/FIB1-chitosan matrix was mediated by integrin, α4β1, α5β1, and αvβ3, similar to HDF adhesion to Fn. These data suggest that an ePRARI-C/FIB1-chitosan matrix can be used as a tool to analyze the multiple functions of Fn and can serve as a Fn-mimetic biomaterial.
Aims/Introduction: This study aimed to determine the effect of depression on the progression to end-stage renal disease (ESRD) and pre-ESRD death in patients with advanced diabetic nephropathy. Materials and Methods: This single-center prospective cohort study enrolled Japanese patients with type 2 diabetes and advanced diabetic nephropathy. The total Patient Health Questionnaire-9 score was used to evaluate depression at baseline and classified patients into: no, mild and severe depression groups. The outcomes were ESRD, defined as initiation of renal replacement therapy, and pre-ESRD death. The relationship between the severity of depression and these outcomes was analyzed using a competing risks model, defining each outcome as the competing risk of the other outcome. Results: Of the 486 patients with a mean estimated glomerular filtration rate of 37.1 -21.1 mL/min/1.73 m 2 , 345 were men. During the median follow up of 4.4 years, 164 patients progressed to ESRD and 50 died. The cumulative incidence function of ESRD was significantly higher in the severe depression group (Gray's test, P = 0.003). The ESRD risk increased by 12.4% and 45.1% in patients with mild and severe depression, respectively, compared with those without depression, although these differences did not reach statistical significance in the multivariate subdistribution hazard model (P = 0.450 and 0.161, respectively). The cumulative incidence of death was similar for the study groups. Conclusion: Depression potentially has a weak impact on progression to ESRD, however, the presence of comorbidities might have the possibility to reduce the effect of depression on the renal outcome in patients with advanced diabetic nephropathy.
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