Our analysis demonstrated that the multidisciplinary care program provided better health care and reduced renal replacement therapy in patients with advanced chronic kidney disease. By decreasing hospitalizations, emergent start, and the need for renal replacement therapy, the multidisciplinary care program was cost-effective.

The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smooth muscle cells (VSMCs). Increased levels of circulating angiopoietin-2 correlate with markers of CKD progression and angiopoietin-2 regulate inflammatory responses, including intercellular and vascular adhesion and recruitment of VSMCs. Here, we investigate the potential role of angiopoietin-2 in the pathogenesis of arterial stiffness associated with CKD. In a cohort of 416 patients with CKD, the plasma level of angiopoietin-2 correlated independently with the severity of arterial stiffness assessed by pulse wave velocity. In mice subjected to 5/6 subtotal nephrectomy or unilateral ureteral obstruction, plasma levels of angiopoietin-2 also increased. Angiopoietin-2 expression markedly increased in tubular epithelial cells of fibrotic kidneys but decreased in other tissues, including aorta and lung, after 5/6 subtotal nephrectomy. Expression of collagen and profibrotic genes in aortic VSMCs increased in mice after 5/6 subtotal nephrectomy and in mice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6C low macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-b1 in aortic endothelial cells and Ly6C low macrophages. Angiopoietin-2 blockade attenuated expression of monocyte chemokines, profibrotic cytokines, and collagen in aorta of mice after 5/6 subtotal nephrectomy. This study identifies angiopoietin-2 as a link between kidney fibrosis and arterial stiffness. Targeting angiopoietin-2 to attenuate inflammation and collagen expression may provide a novel therapy for cardiovascular disease in CKD. 25: 119825: -120925: , 201425: . doi: 10.1681 Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with CKD. [1][2][3][4] Arteriosclerosis characterized by arterial stiffness is the major vascular complication. 5,6 The independent predictive value of arterial stiffness for CVD has been well demonstrated in different populations. 7,8 Although arterial stiffness is a hallmark of the aging process, many other factors such as endothelial dysfunction, local or systemic inflammation, and genetic factors are also implicated in the pathogenesis of arterial stiffness. [9][10][11] Arterial stiffness in patients with CKD is characterized by arterial intima-media hypertrophy resulting from alterations of the intrinsic properties of the arterial wall. 3,12 Increased arterial stiffness is observed in the early stages of CKD. 6,9 Arterial stiffness is accelerated in patients with CKD compared with age-, sex-, and pressure-matched controls, suggesting unique CKD-related factors leading to such a complication. 6,9,12 Traditional risk factors in patients with CKD, such as hypertension, diabetes, and hyperlipidemia, account for the increased CVD morbidity and mortality in part; however, actual m...

Background/Aims: Experimental studies have demonstrated interleukin-6 and iron load induce expression of hepcidin (an iron regulatory peptide), whereas anemia and erythropoietin (EPO) suppress its expression. We are the first to explore the relationships of plasma prohepcidin (the pro-hormone of hepcidin) in patients undergoing chronic hemodialysis (HD). Methods: We enrolled 71 chronic HD patients. During the preceding 3 months before enrollment, they all had steady weekly levels of haematocrit (Hct) and fixed subcutaneous doses of recombinant human EPO. Plasma levels of prohepcidin, proinflammatory cytokines, and EPO were determined by ELISA kits. Results: Of the patients, prohepcidin levels correlated positively with Hct, and negatively with interleukin-6 and EPO. Examined by a multivariate lineal regression method, we found Hct was the only significant predictor of plasma prohepcidin level. However, prohepcidin had no significant correlation with iron profiles. Conclusion: Our findings suggest prohepcidin expression in chronic HD patients might be positively regulated by Hct.

Background/Aims: To explore the efficacy of oral N-acetylcysteine (NAC) supplementation for anemia and oxidative stress in hemodialysis (HD) patients. Methods: Of the eligible patients (n = 325) in an outpatient HD unit, 49 received NAC 200 mg orally thrice a day during the first 3 months, while the other 276 patients not receiving NAC were observed. Results: During the 4-month study, 11 patients receiving NAC withdrew but had no severe adverse effects, while 49 patients not receiving NAC had negative confounding events. Thus only the data of the remaining patients, 38 taking NAC and 227 not taking NAC, were analyzed for efficacy. The demographic and laboratory data of both groups were similar at baseline. When the erythropoietin dosage was stable throughout, only the NAC group had a significant increase in hematocrit, accompanied with a decrease in plasma levels of 8-isoprostane and oxidized low-density lipoprotein. Analyzed as a nested case-control study, NAC supplementation was also found to be a significant predictor of positive outcomes in uremic anemia. Conclusions: Oral NAC supplementation may be a promising therapy for uremic anemia and oxidative stress in HD patients.

Subjects: To evaluate second-trimester maternal serum inhibin A levels in Asian pregnancies with fetal Down syndrome and other chromosomal abnormalities. Methods: Inhibin A level was measured from the serum samples of 25 chromosomally abnormal pregnancies, including 15 cases of Down syndrome, 4 cases of trisomy 18, 1 case of trisomy 13, and 5 cases of sex chromosome aneuploidies (4 cases of 47,XXY and 1 case of 45,X) and in a cohort of 150 controls during the second trimester of pregnancy. Results: The multiple of median levels of Down syndrome (1.74) and other chromosomally abnormal pregnancies (2.03) are significantly higher than that of normal pregnancies (p = 0.002 and p = 0.024, respectively). Only 3 of 15 (20%) Down syndrome cases had inhibin A levels at or above the 95th centile of the control values. Conclusions: Inhibin A levels are raised in Asian women affected with fetal Down syndrome and sex chromosome abnormality. In spite of the poor discrepancy of inhibin A, it might be a potential marker for Down syndrome screening in Asians.