Comparison between the 0- and 30-s balloon dilation time in percutaneous transluminal angioplasty for restenosed arteriovenous fistula among hemodialysis patients: a multicenter, prospective, randomized trial (CARP study).

BACKGROUND: This study aims to compare patency rates of the 0- and 30-s (sec) balloon dilation time in hemodialysis (HD) patients with restenosis after percutaneous transluminal angioplasty (PTA). METHODS: The patients who underwent PTA within 6 months for failed arteriovenous fistula at the forearm were randomly assigned the 0-s or 30-s dilation time group. Effect of dilation time on the 3- and 6-month patency rates after PTA was examined. RESULTS: Fifty patients were enrolled in this study. The 3-month patency rate in the 30-s dilation group was better than that in the 0-s dilation group (P = 0.0050), while the 6-month patency rates did not show a significant difference between the two groups (P = 0.28). Cox's proportional hazard model revealed that 30-s of inflation time (hazard ratio 0.027; P = 0.0072), diameter of the proximal (hazard ratio 0.32; P = 0.031), and dilation pressure (hazard ratio 0.63; P = 0.014) were associated with better 3-month patency. Dilation pressure between previous and present PTA did not differ in the 0-s (P = 0.15) and 30-s dilation groups (P = 0.16). The 6-month patency rate of the present PTA in the 30-s dilation group was higher than that of the previous PTA (P = 0.015). The visual analog scale did not differ between the two groups (P = 0.51). CONCLUSION: The presenting data suggest that 30-s dilation potentially results in a better 3-month patency rate than 0-s dilation in HD patients with restenosis after PTA.

Different risk factors are associated with vascular access patency after construction and percutaneous transluminal angioplasty in patients starting hemodialysis.

BACKGROUND: The objective of this multicenter, prospective observational study was to determine the factors related to patency rates after construction of vascular access (VA) and the first percutaneous transluminal angioplasty (PTA). METHODS: The 24-month primary and secondary patency rates after construction of a radiocephalic arteriovenous fistula (RC-AVF) and arteriovenous graft (AVG) were evaluated using the Kaplan-Meier method and log-rank test. The 12-month post-PTA patency rate was also investigated. A Cox proportional hazard model was used to identify clinical parameters associated with the primary patency rate and the post-PTA patency rate. RESULTS: A total of 611 patients were enrolled in the study. The primary patency rate after VA construction was lower in hemodialysis (HD) patients with an AVG than in those with an AVF. Aging (hazard ratio [HR], 1.02 per 1 year; p < 0.001), female sex (HR, 1.41; p = 0.03), diabetes mellitus (HR, 1.37; p = 0.03), low serum albumin (HR, 0.76 per 1-g/dL decrease; p = 0.02), and use of an erythropoietin-stimulating agent (HR, 1.62; p = 0.02) were risk factors for VA problems. The post-PTA patency rate was associated with aging (HR, 1.02; p < 0.001), diabetes mellitus (HR, 1.49; p = 0.02), polycystic kidney disease (HR, 2.14; p = 0.01), temporary catheter use for initiation of HD (HR, 1.60; p = 0.02), and period from VA construction to use (HR, 0.99; p = 0.04). CONCLUSION: Although a poor patency rate is commonly associated with advanced age and diabetes, different risk factors affect patency between VA construction and the first PTA.

Valproic acid attenuates renal fibrosis through the induction of autophagy.

BACKGROUND: Renal fibrosis is a common pathological feature of the progression of chronic kidney disease. Although valproic acid (VPA) has been recently shown to induce autophagy, the effect of VPA-induced autophagy on renal fibrosis remains unknown. We, therefore, investigated whether VPA-induced autophagy suppresses renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO). METHODS: Male C57BL/6 mice were divided into five groups (n = 8 per group): (1) sham group; (2) vehicle group; (3) VPA-treated group; (4) 3-methyladenine (3-MA; autophagy inhibitor)-treated group; and (5) VPA plus 3-MA-treated group. Mice underwent UUO and the kidneys were studied after 5 days. We also investigated the effect of VPA-induced autophagy on α-smooth muscle actin (α-SMA) in transforming growth factor (TGF)-ß1-stimulated rat kidney fibroblasts and epithelial cells. RESULTS: VPA attenuated renal fibrosis and induced autophagy in UUO mice, while 3-MA increased renal fibrosis and suppressed autophagy. In addition, the anti-fibrotic effect of VPA was diminished by 3-MA in UUO mice. In rat kidney fibroblasts and epithelial cells, VPA suppressed TGF-ß1-stimulated α-SMA expression and induced autophagy. In contrast, 3-MA enhanced α-SMA expression while inhibiting autophagy. Furthermore, the combined use of VPA and 3-MA treatments increased the expression of α-SMA compared with VPA treatment alone in TGF-ß1-stimulated rat kidney fibroblasts and epithelial cells, which was accompanied by the inhibition of autophagy. CONCLUSION: These findings suggest that VPA may be a candidate drug for the treatment of renal fibrosis through the induction of autophagy.

Expression of age-related factors during the development of renal damage in patients with IgA nephropathy.

BACKGROUND: Chronic kidney disease patients share clinical and pathological features with the general aging population. Increased oxidative DNA damage, accumulation of cell cycle-arrested cells and decreased Klotho expression are assumed to be age-related factors that are reportedly linked to kidney disease. This study sought to determine the association between these age-related factors and renal damage in patients with IgA nephropathy (IgAN). METHODS: We performed a cross-sectional analysis of 71 patients who were diagnosed with IgAN by renal biopsy. Expression of 8-hydroxydeoxyguanosine (8-OHdG, a marker of oxidative DNA damage), p16 (a marker of cell cycle-arrest) and Klotho (an anti-aging protein) were evaluated by immunohistochemical staining of renal biopsy samples. We correlated the changes in expression of these markers with Lee's pathologic grades and the Oxford classification. We also investigated the independent association between these markers and interstitial fibrosis using multiple linear regression analysis. RESULTS: 8-OHdG and p16 increased but Klotho decreased with progression of pathologic grade. Expression of 8-OHdG and p16 increased with the deterioration of mesangial hypercellularity and segmental glomerulosclerosis. In addition, p16 increased but Klotho decreased with progression of tubular atrophy/interstitial fibrosis. In univariate regression analysis, age, body mass index, systolic blood pressure, urinary protein excretion and expression of 8-OHdG, p16 and Klotho showed significant correlations with interstitial fibrosis. Multivariable regression analyses revealed that aging, increased renal expression of p16 and decreased expression of Klotho were independently correlated with interstitial fibrosis. CONCLUSIONS: The age-related factors might play important roles in the development of IgAN.