Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. High circulating FGF23 levels are associated with increased mortality in patients with chronic kidney disease and those on dialysis. Current data also suggest higher circulating levels of FGF23 are associated with cardiovascular mortality, vascular calcification, and left ventricular hypertrophy; however, evidence on the role of FGF23 in patients on dialysis is incomplete, and some of the data, especially those on cardiovascular disease (CVD), are controversial. This study aimed to evaluate factors associated with FGF23 in hemodialysis patients with or without CVD. Randomly selected 76 patients on maintenance hemodialysis at a single hemodialysis center were enrolled. After the exclusion of eight patients with extremely outlying FGF23 levels, 68 patients, including 48 males and 46 patients with a CVD history, were included in the study. The mean age was 64.4 ± 12.1 years, and the mean dialysis duration was 12.7 ± 7.1 years. Dialysis duration, time-averaged concentration of urea (TAC-urea), ultrafiltration rate (UFR), blood pressure during hemodialysis session, laboratory data, and echocardiographic parameters including interventricular septum thickness (IVST), left ventricular mass indices (LVMI), and ejection fraction were included in univariate and multivariate analyses. The median lgFGF23 levels in the overall cohort and in those with and without CVD were 2.14 (interquartile range, IQR − 0.43 to − 4.23), 2.01 (− 0.52 to 4.12), and 2.59 (0.07 to 4.32), respectively, and there was no difference between the patients with and without CVD (p = 0.14). The univariate analysis revealed that FGF23 was significantly associated with age (r = − 0.12, p < 0.01), duration of hemodialysis (r = − 0.11, p < 0.01), TAC-urea (r = 0.29, p = 0.01), UFR (r = 0.26, p = 0.04), alkaline phosphatase (ALP; r = − 0.27, p = 0.03), corrected serum calcium (cCa; r = 0.32, p < 0.01), serum phosphate (iP, r = 0.57, p < 0.01), intact parathyroid hormone (iPTH; r = 0.38, p < 0.01), IVST (r = 0.30, p = 0.01), and LVMI (r = 0.26, p = 0.04). In multivariate regression analysis, FGF23 was significantly associated with cCa (F = 25.6, p < 0.01), iP (F = 22.5, p < 0.01), iPTH (F = 19.2, p < 0.01), ALP (F = 5.34, p = 0.03), and UFR (F = 3.94, p = 0.05). In addition, the univariate analysis after the categorization of patients according to CVD indicated that FGF23 was significantly associated with cCa (r = 0.34, p = 0.02), iP (r = 0.41, p < 0.01), iPTH (r = 0.39, p = 0.01), and TAC-urea (r = 0.45, p < 0.01) in patients with CVD, whereas only IVST (r = 0.53, p = 0.04) was associated with FGF23 in those without CVD. FGF23 levels in hemodialysis patients were extremely high and associated not only with mineral bone disease-related factors but also with UFR. Additionally, dialysis efficacy might be associated with lower FGF23 levels in patients with CVD.
BACKGROUND AND AIMS Oxalate is an organic acid found in abundance in plants and can also be synthesized as a terminal metabolite by the organic acid metabolism systems in humans. As a major excretion pathway of oxalate is urine, serum oxalate (SOx) concentration elevates in end-stage renal disease (ESRD) patients and causes calcium oxalate deposition to tissues. We previously reported that calcium oxalate might be one of the major components of coronary artery calcification (CAC) in ESRD patients; however, the association between SOx and CAC is unknown. This study aimed to demonstrate the relationship between SOx and CAC in haemodialysis patients. METHOD A total of 77 patients undergoing maintenance haemodialysis at a single facility who underwent an atherosclerosis check-up from 2011 to 2012 were enrolled and measured SOx retrospectively in 2021. Of those, 17 extremely outlying SOx patients were excluded, and 60 patients including 42 males were analysed. The median age was 64 (35–85) years, and median dialysis duration was 87.5 (17.1–410) months. Gender, Agastston's CAC score, major artery calcification volume, laboratory data and medications around the atherosclerosis check-up date and new-onset cardiovascular disease (CVD) events and deaths during the 10-year observation period were recorded. A CVD event is defined as an admission due to non-fatal myocardial infarction, coronary artery disease or heart failure. SOx level was measured by the commercial colorimetric oxalate assay kit, and the normal SOx level was 181 µmol/L. RESULTS The median SOx was 267 (221–563) µmol/L and new-onset CVD events, all-cause deaths occurred in 28 (47%) and 22 (37%) patients, respectively. In univariate analysis, SOx was associated with males (r = 0.27, P = 0.03), serum albumin (r = –0.25, P = 0.05), uric acid (r = 0.29, P = 0.02), phosphate (r = 0.26, P = 0.04), alkaline phosphatase (r = –0.28, P = 0.03), lanthanum carbonate (r = 0.32, P = 0.01), major artery calcification volume (r = 0.28, P = 0.03) and CAC score (r = 0.29, P = 0.02). In multivariate regression analysis, SOx was associated with lanthanum carbonate (F = 5.96, P = 0.02) and CAC score (F = 4.47, P = 0.03, Table 1). Receiver operating characteristic curve showed SOx = 269.5 µmol/L was the best cut-off for predicting CVD events. We divided subjects into two groups by this cut-off SOx value and revealed SOx was associated with new-onset CVD events (N = 60, P = 0.01) even after adjusted by age under 75 years (N = 52, P = 0.03) or both age under 75 years and CAC score under 1000 (N = 28, P = 0.04) by the Kaplan–Meier method (Fig. 1). CONCLUSION SOx was associated with CAC score, lanthanum carbonate and CVD events in ESRD patients undergoing haemodialysis.
Background and Aims In dialysis patients, many literatures have shown the association between predialytic hypotension and poor prognosis. Particularly, decrease in diastolic blood pressure (DBP) will be involved myocardial injury because of reduced coronary blood-flow. Such myocardial damage would also be caused by decreased oxygen-supply capacity. Mean corpuscuar hemoglobin-concentration (MCHC) is a hemoglobin concentration per 1% hematocrit (Ht) and could be considered as an indicator of peripheral oxygen-supply. In several literatures, low MCHC had been associated with increased all-cause mortality in non-dialysis patients with congestive heart-failure. In dialysis patients with low Ht between 32 to 35%, low DBP and low MCHC could additively act on myocardial damage. In this study, we examined the relation between the stratified groups by DBP and MCHC and cardiovascular mortality using Yoshikawa clinic dialysis-database (YCD). Method A total of 407 dialysis patients registered in YCD enrolled in this study from April 2006 and on. The cut-off values (COVs) of predialytic DBP and MCHC on cardiovascular death (CVD) were determined from the Receiver Operating Characteristic (ROC) curve. According to these COVs, the whole cohort was divided into 4 groups, group HH (high DBP and high MCHC), group HL (high DBP and low MCHC), group LH (low DBP and high MCHC), and group LL (low DBP and low MCHC). Their survival analysis was estimated by the Kaplan–Meier method, and a log-rank test was used to examine the differences between the survival curves. The prognostic factors for CVD were extracted from background factors, including predialytic DBP, MCHC and above-mentioned grouping, using Cox-regression model. Results In 407 patients, mean predialytic DBP and time-averaged MCHC were 73.3 mmHg and 31.5 % respectively. During observation period of 5.1 years 163 patients died, among that 94 were CVD. The COVs of DBP and MCHC were 79 mmHg and 31.16 %, respectively. According to these COVs, 407 patients were divided into 64 of group HH, 65 of group HL, 171 of group LH and 107 patients of group LL. On the survival curve, the group LL had the highest mortality rate, followed by the group HL. The group HH showed the lowest mortality rate. In multivariate analysis, category variables LL and HL were extracted as prognostic factors for CVD. Their Hazard ratio were 1.960 and 3.863, respectively. Age, intradialytic hypotension, DBP, Kt/V, serum sodium, CRP and blood glucose were extracted as the other prognostic factors. Conclusion These results suggest that low MCHC level would deteriorate prognosis on dialysis patients with predialytic low-DBP. MCHC level could become a new treatment-target in the low DBP group in the future.
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