To date, only a few large-scale studies have measured the effect of dialysis modality on mortality in Asian populations. Here, we sought to compare survival between incident hemodialysis (HD) and peritoneal dialysis (PD) patients using the Korean Health Insurance Review & Assessment Service database. This enabled us to perform a population-based complete survey that included 32,280 incident dialysis patients and followed them for a median of 26.5 months. To reduce biases due to nonrandomization, we first matched 7049 patient pairs with similar propensity scores. Using the log-rank test, we found the mortality rate in PD patients was significantly higher than that in HD patients. Subsequent subgroup analyses indicated that in older patients (55 years and older), with the exception of the subgroup of patients with no comorbidities and the subgroup of patients with malignancy, PD was consistently associated with a higher mortality rate. In younger patients (under 55 years), regardless of the covariates, the survival rate of PD patients was comparable to that of HD patients. Thus, while the overall mortality rate was higher in incident PD patients, mortality rates of some incident PD and HD patients were comparable in Korea.

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Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial-to-mesenchymal transition (EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species via the activation of membranous NADPH oxidase (from 15 min) and mitochondria (from 6 h) along with glycocalyx shedding (from 6 h), which were blocked by probenecid. GM6001, an inhibitor of matrix metalloproteinase, alleviated UA-induced glycocalyx shedding and EndoMT. Antioxidants including N-acetyl cysteine, apocynin, and mitotempo ameliorated EndoMT; however, they did not change glycocalyx shedding in HUVECs. In the kidney of hyperuricemic rats, endothelial staining in peritubular capillaries (PTCs) was substantially decreased with a de novo expression of a-smooth muscle actin in PTCs. Plasma level of syndecan-1 was increased in hyperuricemic rats, which was ameliorated by allopurinol. UA caused a phenotypic transition of endothelial cells via induction of oxidative stress with glycocalyx shedding, which could be one of the mechanisms of UA-induced endothelial dysfunction and kidney disease.

Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.Regardless of the type of initial injury to the kidney, renal hypoxia is the common final pathway of renal fibrosis 1 , which is regarded a prime target for preventing the progression of chronic kidney disease (CKD) to end-stage renal disease.Hypoxia-inducible factor (HIF) is a key transcriptional factor in the regulation of the adaptive response to hypoxia. HIF is a heterodimeric complex that has three forms (HIF-1, HIF-2, and HIF-3), which differ in their α-subunit. If the α-subunit is not hydroxylated by prolyl hydroxylase under hypoxic conditions, it cannot be recognized by von Hippel-Lindau tumor suppressor protein (pVHL), which is part of an E3-ubiquitin ligase complex that targets HIF-α for proteosomal degradation 2 . Then, α-subunit combines with a constitutively expressed β-subunit in the nucleus. Finally, HIF regulates the expression of salient target genes that are involved in numerous biological processes, including energy metabolism, angiogenesis, erythropoiesis, iron metabolism, cell proliferation, and apoptosis 2 . HIF activation ameliorates tissue hypoxia and eventually helps the hypoxic cells survive. Even though the effect of HIF activation in CKD has been widely evaluated, the results have been inconsistent. Reduced renal fibrosis by genetic ablation of tubular HIF-1 suggested a profibrotic role of HIF 3 , while contrary results demonstrated that an HIF stabilizer exerted a beneficial effect on renal fibrosis in an animal model of CKD 4 . Accumulating evidence suggests that HIFs exert beneficial effects in diabetic nephropathy. Activation of HIFs by cobalt chloride, a non-specific pan-HIF activator, attenuated diabetes-induced alteration in oxygen m...

PurposeThe aim of this study was to investigate whether the survival rate among Korean dialysis patients changed during the period between 2005 and 2008 in Korea.Materials and MethodsA total of 32357 patients who began dialysis between January 1, 2005 and December 31, 2008 were eligible for analysis. Baseline demographics, comorbidities, and mortality data were obtained from the database of the Health Insurance Review & Assessment Service.ResultsKaplan-Meier curves according to the year of dialysis initiation showed that the survival rate was significantly different (log-rank test, p=0.005), most notably among peritoneal dialysis (PD) patients (p<0.001), although not among hemodialysis (HD) patients (p=0.497). In multivariate analysis, however, patients initiating either HD or PD in 2008 also had a significantly lower risk of mortality compared to those who began dialysis in 2005. Subgroup survival analysis among patients initiating dialysis in 2008 revealed that the survival rate of PD patients was significantly higher than that of HD patients (p=0.001), and the survival benefit of PD over HD remained in non-diabetic patients aged less than 65 years after adjustment of covariates.ConclusionSurvival of Korean patients initiating dialysis from 2005 to 2008 has improved over time, particularly in PD patients. In addition, survival rates among patients initiating dialysis in 2008 were different according to patients' age and diabetes, thus we need to consider these factors when dialysis modality should be chosen.