Background. Quality of life (QOL) may be associated with morbidity and survival in end-stage renal disease (ESRD), and is considered to be an important outcome measure for patients with chronic kidney disease (CKD). However, the prognostic role of QOL for survival in CKD remains unclear. We studied the relationship between QOL and risks of ESRD and mortality in CKD patients. Methods. From 1 January 2007 to 31 December 2007, we prospectively used the Taiwan version of World Health Organization Quality-of-Life Questionnaire (Taiwan version) (WHOQOL-BREF(TW)) with 568 CKD patients at a medical centre in southern Taiwan, and patients were followed up for 1–2 years after enrollment. The primary outcome was the time to dialysis or death. We used Kaplan–Meier curve and Cox proportional hazard model for survival analyses. Results. Of the 568 patients enrolled, 423 were able to complete the questionnaires, and their data were analysed. The median follow-up time was 410 days. Progressive decreases in scores of QOL in all domains were noted with decrease in eGFR. In unadjusted analysis, dialysis and death were associated with lower scores of total and all four domains of WHOQOL-BREF(TW). In adjusted analysis, the total scores and scores of both physical and psychological domains predicted dialysis and mortality (every 1-point decrease hazard ratio (HR): 1.050, 95% CI: 1.008–1.095, P = 0.020; HR: 1.179, CI: 1.033–1.346, P = 0.014; HR: 1.167, CI: 1.016–1.339, P = 0.028, respectively). The adjusted risks of ESRD and mortality also increased in patients in the lowest tertile of psychological domain (P < 0.01), and physical domain and total scores (P < 0.05). Conclusions. Physical, psychological and total scores of QOL are significantly correlated with increased risks of ESRD and death in CKD patients. QOL should be considered as an independent predictor of risks of ESRD and mortality.

Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults. This cross-sectional study compared the Taiwanese eGFR equations, the MDRD study, and the CKD-EPI equations with inulin clearance (C_in). A total of 695 adults including 259 healthy volunteers and 436 CKD patients were recruited. Participants from the Kaohsiung Medical University Hospital were used as the development set (N = 556) to develop the Taiwanese eGFR equations, whereas participants from the National Taiwan University Hospital were used as the validation set (N = 139) for external validation. The Taiwanese eGFR equations were developed by using the extended Bland-Altman plot in the development set. The Taiwanese MDRD equation was 1.309×MDRD^0.912, Taiwanese CKD-EPI was 1.262×CKD-EPI^0.914 and Taiwanese four-level CKD-EPI was 1.205×four-level CKD-EPI^0.914. In the validation set, the Taiwanese equations had the lowest bias, the Taiwanese equations and the Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the Japanese equations had the best precision and the highest P₃₀ among all equations. However, the Taiwanese MDRD equation had higher concordance correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and the Japanese equations. Moreover, only the Taiwanese equations had no proportional bias among all of the equations. Finally, the Taiwanese MDRD equation had the best diagnostic performance in terms of ordinal logistic regression among all of the equations. The Taiwanese MDRD equation is better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and Taiwanese four-level CKD-EPI equations for Taiwanese adults.

Mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and its derivative, everolimus, are potent immunosuppressive and antiproliferative drugs. Inflammatory diseases are characterized by immunological dysfunction, and monocyte recruitment underlies the mechanism of cell damage. Chemokines attract inflammatory cells to sites of inflammation. Interleukin-8 (IL-8/CXCL8); the monocyte chemoattractant protein-1 (MCP-1/CCL2); the regulated on activation, normal T cell expressed, presumably secreted protein (RANTES/CCL5); the macrophage inflammatory protein (MIP)-1α (CCL3); and MIP-1β (CCL4) are involved in the pathogenesis of inflammation. However, whether mTOR inhibitors moderate the production of chemokines in monocytes remains unclear. A human monocyte cell line, THP-1, and primary monocytes obtained from human volunteers, were stimulated using lipopolysaccharide (LPS), and then treated with sirolimus. The expression of the MCP-1, RANTES, IL-8, MIP-1α, MIP-1β, and TNF-α proteins was measured using enzyme-linked immunosorbent assays, and intracellular signalling was examined using western blotting. Sirolimus significantly suppressed the LPS-induced expression of MCP-1, IL-8, RANTES, MIP-1α, and MIP-1β in the THP-1 cells and human primary monocytes. The mitogen-activated protein kinase (MAPK) inhibitors that were examined suppressed the LPS-induced expression of MCP-1, IL-8, RANTES, MIP-1α, and MIP-1β. In addition, sirolimus suppressed the LPS-induced phosphorylation of p38 and p65 in the THP-1 and human primary monocytes. Sirolimus downregulates the expression of chemokines in monocytes, including MCP-1, RANTES, IL-8, MIP-1α, and MIP-1β, by inhibiting the NF-κB-p65 and MAPK-p38 signalling pathways.

In the chronic kidney disease (CKD) population, the impact of serum potassium (sK) on renal outcomes has been controversial. Moreover, the reasons for the potential prognostic value of hypokalemia have not been elucidated. 2500 participants with CKD stage 1–4 in the Integrated CKD care program Kaohsiung for delaying Dialysis (ICKD) prospective observational study were analyzed and followed up for 2.7 years. Generalized additive model was fitted to determine the cutpoints and the U-shape association between sK and end-stage renal disease (ESRD). sK was classified into five groups with the cutpoints of 3.5, 4, 4.5 and 5 mEq/L. Cox proportional hazard regression models predicting the outcomes were used. The mean age was 62.4 years, mean sK level was 4.2±0.5 mEq/L and average eGFR was 40.6 ml/min per 1.73 m². Female vs male, diuretic use vs. non-use, hypertension, higher eGFR, bicarbonate, CRP and hemoglobin levels significantly correlated with hypokalemia. In patients with lower sK, nephrotic range proteinuria, and hypoalbuminemia were more prevalent but the use of RAS (renin-angiotensin system) inhibitors was less frequent. Hypokalemia was significantly associated with ESRD with hazard ratios (HRs) of 1.82 (95% CI, 1.03–3.22) in sK 5 mEq/L conferred 1.6-fold (95% CI,1.09–2.34) increased risk of ESRD compared with sK = 4.5–5 mEq/L. Hypokalemia was also associated with rapid decline of renal function defined as eGFR slope below 20% of the distribution range. In conclusion, both hypokalemia and hyperkalemia are associated with increased risk of ESRD in CKD population. Hypokalemia is related to increased use of diuretics, decreased use of RAS blockade and malnutrition, all of which may impose additive deleterious effects on renal outcomes.