Immune-inflammatory biomarkers (IIBs) have been shown to be correlated with prognosis in patients undergoing peritoneal dialysis (PD). In this study, we aimed to evaluate the relationship between a...

Objectives. The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods. In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results. Of 1753 patients, the mean age was 51.1±14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29±1.75. During the follow-up period of 31.2±18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P<0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (logrank=22.41, P<0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, P=0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR=1.39, 95% CI 1.10-2.47, P=0.021). Conclusions. Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients.

Background. Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. Methods. From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR≤2.74, 2.74<NLR≤3.96, and NLR>3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. Results. During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR=1.39, 95%CI=1.01‐1.93, P=0.046) and CVD mortality (HR=1.81, 95%CI=1.22‐2.69, P=0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P<0.001) and CVD mortality (P=0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI=1.26−3.23, P=0.003) and CVD mortality was 2.98 (95%CI=1.58−5.62, P=0.001) in the younger group (age<60 years). Conclusions. NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.

Context: The proximal tubular epithelial cells (PTECs) are the primary target of aristolochic acids and especially vulnerable to mitochondrial injury from insults of toxic xenobiotics. Objectives: This study aimed to investigate the possible role of mitochondrial injury in Caulis Aristolochia manshuriensis (CAM)-induced aristolochic acid nephropathy (AAN). Materials and methods: Male Sprague-Dawley rats were gavaged with CAM extract every other week for 1, 4, 8 and 12 weeks, respectively. Results: The rats in the model group showed chronic AAN as evidenced by worsening kidney function evaluated by blood urea nitrogen, creatinine and proteinuria levels, and severe tubulointerstitial injury marked by massive tubular atrophy and interstitial fibrosis in kidney tissues. Moreover, overt apoptosis and impaired regeneration of PTECs were observed in AAN rats. Furthermore, the study revealed that mitochondria in PTECs were fragmented into small, punctuate suborganelles in AAN rats. Two mitochondrial respiratory chain proteins, mitochondrial DNA (mtDNA)-encoded cytochrome c oxidase subunit І (COX-І) and nuclear DNA-encoded nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)-1β subcomplex 8 (NDUFβ8), were both down-regulated after one week of CAM treatment. However, with AAN progression, NDUFβ8 level restored, while COX-І level maintained low. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), master regulator of mitochondrial biogenesis, was significantly down-regulated at week 4 and week 8, but significantly up-regulated at week 12. In addition, mtDNA copy number reduced markedly along with AAN progression. Discussion and conclusion: A rat model of chronic AAN was successfully reproduced by gavage with CAM extract. Dynamic changes of mitochondrial injury induced by CAM might contribute to the AAN progression.

A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurre...