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Prevalence and outcomes of proton pump inhibitor associated hypomagnesemia in chronic kidney disease. Hughes John,Y Y Chiu Diana,Kalra Phillip A,Green Darren PloS one BACKGROUND:Proton pump inhibitors (PPIs) are one of the most widely prescribed medications across the world. PPIs have been associated with significant electrolyte abnormalities including hypomagnesaemia. We explored the prevalence of PPI associated hypomagnesaemia (PPIH) in different Chronic Kidney Disease (CKD) stages, in different PPI agents, and the impact of PPIH on survival in CKD. METHODS:This was a subgroup analysis of the Salford Kidney Study, a prospective, observational, longitudinal study of non-dialysis CKD patients. Patients with outpatient magnesium samples obtained between 2002 and 2013 were included in the analysis. The prevalence hypomagnesaemia based on mean values over 12 months as well as 'ever' hypomagnesaemia were investigated. RESULTS:1,230 patients were included in this analysis, mean age 64.3± 32.3 years and mean eGFR 29.2±15.8 ml/min/1.73m2. Mean serum magnesium in those on PPI was significantly lower than those not on PPI overall (0.85±0.10 mmolL-1 versus 0.79±0.12 mmolL-1 respectively, p<0.001). This finding was maintained at all CKD stages. The adjusted odds ratio (OR) for mean hypomagnesaemia in PPI use was 1.12 (95% CI 1.06-1.18) p = <0. 'Ever hypomagnesaemia' had an OR of 1.12 (95% CI 1.07-1.16) p = <0.001. The expected rise in serum magnesium with declining eGFR was not observed in those on a PPI but was seen in those not on PPI. There was no difference in serum magnesium between PPI drugs. Thiazide diuretics were also associated with hypomagnesaemia independent of PPI use. Cox regression analysis demonstrated no reduction in survival in patients with PPI associated hypomagnesaemia. CONCLUSION:No specific PPI drugs show a favourable profile in regards of risk for hypomagnesaemia in CKD. Avoiding concurrent use of PPI and thiazide may be of value in patients with hypomagnesaemia. 10.1371/journal.pone.0197400

Proteinuria-associated renal magnesium wasting leads to hypomagnesemia: a common electrolyte abnormality in chronic kidney disease. Oka Tatsufumi,Hamano Takayuki,Sakaguchi Yusuke,Yamaguchi Satoshi,Kubota Keiichi,Senda Masamitsu,Yonemoto Sayoko,Shimada Karin,Matsumoto Ayumi,Hashimoto Nobuhiro,Mori Daisuke,Monden Chikako,Takahashi Atsushi,Obi Yoshitsugu,Yamamoto Ryohei,Takabatake Yoshitsugu,Kaimori Jun-Ya,Moriyama Toshiki,Horio Masaru,Matsui Isao,Isaka Yoshitaka Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:Hypomagnesemia (Hypo-Mg) predicts mortality and chronic kidney disease (CKD) progression. However, in CKD, its prevalence, kidney-intrinsic risk factors, and the effectiveness of oral magnesium (Mg) therapy on serum Mg levels is uncertain. METHODS:In a cross-sectional study enrolling pre-dialysis outpatients with CKD, the prevalence of electrolyte abnormalities (Mg, sodium, potassium, calcium and phosphorus) was compared. In an open-label randomized controlled trial (RCT), we randomly assigned CKD patients to either the magnesium oxide (MgO) or control arm. The outcome was serum Mg levels at 1 year. RESULTS:In 5126 patients, Hypo-Mg was the most common electrolyte abnormality (14.7%) with similar prevalence across stages of CKD. Positive proteinuria was a risk factor of Hypo-Mg (odds ratio 2.2; 95% confidence interval 1.2-4.0). However, stratifying the analyses by diabetes mellitus (DM), it was not significant in DM (Pinteraction = 0.04). We enrolled 114 patients in the RCT. Baseline analyses showed that higher proteinuria was associated with higher fractional excretion of Mg. This relationship between proteinuria and renal Mg wasting was mediated by urinary tubular markers in mediation analyses. In the MgO arm, higher proteinuria or tubular markers predicted a significantly lower 1-year increase in serum Mg. In patients with a urinary protein-to-creatinine ratio (uPCR) <0.3 g/gCre, serum Mg at 1 year was 2.4 and 2.0 mg/dL in the MgO and control arms, respectively (P < 0.001), with no significant between-group difference in patients whose uPCR was ≥0.3 g/gCre (Pinteraction=0.001). CONCLUSIONS:Proteinuria leads to renal Mg wasting through tubular injuries, which explains the high prevalence of Hypo-Mg in CKD. 10.1093/ndt/gfy119

Routine hemodialysis induces a decline in plasma magnesium concentration in most patients: a prospective observational cohort study. Scientific reports In hemodialysis patients, lower plasma magnesium (Mg) concentrations are associated with a higher overall and cardiovascular mortality. The optimal concentration appears to be above the reference range for the healthy population. Plasma Mg is not routinely measured after hemodialysis. Aim of this study was to determine the effect of routine hemodialysis on plasma Mg. Plasma Mg was measured in duplicate before (Mg) and after (Mg) dialysis in 6 consecutive hemodialysis sessions of 34 patients using a fixed 0.50 mmol/L dialysate Mg concentration. Mean Mg was 0.88 mmol/L (±0.14) and mean Mg was statistically significantly lower: mean intra-dialytic decline 0.10 mmol/L (95%-CI 0.06-0.13). A 0.10 mmol/L higher Mg was associated with a 0.03 mmol/L higher Mg (95%-CI 0.024-0.037). At a Mg of 0.74 mmol/L, Mg equalled Mg. There was an intra-dialytic decline of plasma Mg at higher Mg values and an increase at lower Mg values. In conclusion, in the majority of the hemodialysis patients, Mg concentrations are in the reference range of the healthy population, which may be too low for hemodialysis patients. Routine hemodialysis with the widely used 0.50 mmol/L dialysate Mg concentration, further declines magnesium in the majority of patients. Current dialysate Mg concentrations may be too low. 10.1038/s41598-018-28629-x

Hypomagnesemia is not an independent risk factor for mortality in Japanese maintenance hemodialysis patients. Mizuiri Sonoo,Nishizawa Yoshiko,Yamashita Kazuomi,Naito Takayuki,Ono Kyoka,Tanji Chie,Usui Koji,Doi Shigehiro,Masaki Takao,Shigemoto Kenichiro International urology and nephrology PURPOSE:It is unclear whether hypomagnesemia is an independent risk factor or innocent bystander for mortality in maintenance hemodialysis (MHD) patients. Thus, we studied associations between hypomagnesemia and all-cause as well as cardiovascular (CV) mortality in MHD patients. METHODS:Baseline clinical characteristics and coronary artery calcium score (CACS) of 353 Japanese MHD patients were reviewed. Three-year survival rate and mortality risk factors were assessed. RESULTS:Median (interquartile range) age, dialysis vintage, serum magnesium (Mg), serum albumin and CACS of the subjects were 68 (60-78) years, 75 (32-151) months, 2.4 (2.2-2.7) mg/dl, 3.6 (3.3-3.8) g/dl, and 1181 (278-3190), respectively. During the 3-year period, 91 patients died. Kaplan-Meier overall 3-year survival rates were 59.0% in in patients with Mg < 2.4 mg/dl (n = 136) and 82.3% in patients with Mg ≥ 2.4 mg/dl (n = 217), (P < 0.0001). In Cox regression models not incorporating serum albumin, Mg < 2.4 mg/dl was significantly associated with 3-year all-cause death, independent of age, dialysis vintage, average ultrafiltration, Log (CACS + 1), warfarin use, serum potassium, high-sensitivity C-reactive protein (hsCRP), phosphate, uric acid, and intact parathyroid hormone [Hazard ratio (HR) 95% confidence interval (CI): 2.82 (1.31-6.29), P = 0.0078], and CV death, independent of age, dialysis vintage, Log (CACS + 1), warfarin use, serum hsCRP, and uric acid [HR (95% CI): 4.47 (1.45-16.76), P = 0.0086]. Nevertheless, associations of Mg < 2.4 mg/dl with all-cause and CV mortality were all absent in models that included serum albumin. CONCLUSIONS:Hypomagnesemia is not an independent risk factor for mortality but is associated with malnutrition in MHD patients. 10.1007/s11255-019-02073-w

High serum magnesium levels are associated with favorable prognoses in diabetic hemodialysis patients, retrospective observational study. Ogawa Chie,Tsuchiya Ken,Maeda Kunimi PloS one BACKGROUND:Recent studies have found hypomagnesemia is linked to a heightened risk of cardiovascular events and mortality in hemodialysis (HD) patients; however, the level of serum magnesium (s-Mg) necessary for promoting overall health in these patients and the effects of s-Mg in diabetes HD patients remains to be clarified. METHODS:HD outpatients (n = 148 under, age ≤ 70 y) were followed over a 6-y period. They were divided into four groups according to their average s-Mg during the first year (L; low level, H; high level) and if they had DM or not (non-DM). The endpoint was mortality and hospitalization for decline of Activities of Daily Living (death/hospitalization). A receiver operating characteristics curve was used in diagnostic tests to identify s-Mg associated with this endpoint. Kaplan-Meier, log-rank test, and a Cox proportional hazards model were used to evaluate prognoses. Fisher's exact test and multiple regressions examined the causes of the endpoints between the four groups and the factors predictive of s-Mg. RESULTS:s-Mg at 2.7 mg/dL was associated with death/hospitalization. The 5-y survival rate was 38.1%, 86.7%, 73.2% and 87.5%, in the DM/Mg(L), DM/Mg(H), non-DM/Mg(L) and non-DM/Mg(H) groups, respectively (P < 0.001). The Cox proportional hazards model showed significantly lower risk in other groups compared with that in the DM/Mg(L) group [DM/Mg(H); hazard ratio (HR): 0.22, 95% confidence interval (CI): 0.05-0.97, P = 0.046, non-DM/Mg(L); HR: 0.32, 95% CI: 0.15-0.68, P = 0.003, non-DM/Mg(H); HR: 0.17, 95% CI: 0.06-0.44, P < 0.001]. The frequency of the different causes of the endpoints for each group was not significant; s-Mg only associated with age in the DM group. CONCLUSIONS:s-Mg greater than 2.7 mg/dL associated with a favorable prognosis in HD patients with DM, suggesting that s-Mg is a factor independent of diabetes. 10.1371/journal.pone.0238763

Serum magnesium and cardiovascular mortality in peritoneal dialysis patients: a 5-year prospective cohort study. Ye Hongjian,Cao Peiyi,Zhang Xiaodan,Lin Jianxiong,Guo Qunying,Mao Haiping,Yu Xueqing,Yang Xiao The British journal of nutrition The aim of this study was to explore the association between serum Mg and cardiovascular mortality in the peritoneal dialysis (PD) population. This prospective cohort study included prevalent PD patients from a single centre. The primary outcome of this study was cardiovascular mortality. Serum Mg was assessed at baseline. A total of 402 patients (57 % male; mean age 49·3±14·9 years) were included. After a median of 49·9 months (interquartile range: 25·9-68·3) of follow-up, sixty-two patients (25·4 %) died of CVD. After adjustment for conventional confounders in multivariate Cox regression models, being in the lower quartile for serum Mg level was independently associated with a higher risk of cardiovascular mortality, with hazards ratios of 2·28 (95 % CI 1·04, 5·01), 1·41 (95 % CI 0·63, 3·16) and 1·62 (95 % CI 0·75, 3·51) for the lowest, second and third quartiles, respectively. A similar trend was observed when all-cause mortality was used as the study endpoint. Further analysis showed that the relationships between lower serum Mg and higher risk of cardiovascular and all-cause mortality were present only in the female subgroup, and not among male patients. The test for interaction indicated that the associations between lower serum Mg and cardiovascular and all-cause mortality differed by sex (P=0·008 and P=0·011, respectively). In conclusion, lower serum Mg was associated with a higher risk of cardiovascular and all-cause mortality in the PD population, especially among female patients. 10.1017/S0007114518001599

Serum Magnesium Abnormality and Influencing Factors of Serum Magnesium Level in Peritoneal Dialysis Patients: A Single-Center Study in Northern China. Tsai Shihming,Zhao Huiping,Wu Bei,Zuo Li,Wang Mei Blood purification BACKGROUND/AIMS:Both hypomagnesemia and hypermagnesemia have been associated with cardiovascular diseases, bone diseases, and mortality in dialysis patients. We aimed to investigate the prevalence of and influencing factors for abnormal serum Mg levels in patients on peritoneal dialysis (PD). METHODS:A cross-sectional study in Peking University People's Hospital recorded the demographic information, clinical characteristics, and laboratory data. Data were assessed and compared with the results from 2 other studies in China. RESULTS:Of 180 enrolled PD patients, the primary diseases were glomerulonephritis (38.3%) and diabetic nephropathy (38.3%). Mean serum Mg concentration was 1.02 ± 0.16 mmol/L; 67% had normal serum Mg concentrations, and 33% had hypermagnesemia. CONCLUSIONS:Hypermagnesemia is likely to occur in patients with higher serum phosphate, lower intact parathyroid hormone, and lower high-sensitivity C-reactive protein levels. Serum Mg level distributions in PD patients vary throughout China, may have different potential causes (such as geographical location and dietary habits) and should be further studied. 10.1159/000485315

Hypomagnesemia Is a Risk Factor for Cardiovascular Disease- and Noncardiovascular Disease-Related Mortality in Peritoneal Dialysis Patients. Zhang Fengping,Wu Xianfeng,Wen Yueqiang,Zhan Xiaojiang,Peng Fen Fen,Wang Xiaoyang,Qian Zhou,Feng Xiaoran Blood purification PURPOSE:Recent research has shown that hypomagnesemia is associated with increased all-cause mortality in hemodialysis patients. However, the relationship between the long-term prognosis of peritoneal dialysis (PD) and the study is not yet clear. This study will analyze the effects of hypomagnesemia on all-cause, cardiovascular diseases (CVD), and non-CVD mortality in PD patients. METHOD:In a retrospective cohort study, 1,004 samples were selected from 7 PD centers in China. Based on the baseline blood magnesium level at the beginning of stable dialysis, all patients were classified into blood magnesium <0.7 mmol/L group, 0.7-1.2 mmol/L group, and >1.2 mmol/L group (the end event was death). The Kaplan-Meier method was used to calculate the difference in cumulative survival rate; the Cox proportional hazard model was used to analyze the risk factors of all-cause, CVD, and non-CVD death causes. RESULTS:Cox multiple regression analysis results (reference comparison of 0.7-1.2 mmol/L group): patients with serum magnesium <0.7 mmol/L have a higher risk ratio of all-cause mortality (HR = 1.580, 95% CI: 1.222-2.042, p = 0.001), and it is also obvious after correction by multiple models (HR = 1.578, 95% CI: 1.196-2.083, p = 0.001). Subgroup analysis of the causes of death was as follows: CVD risk (HR = 1.628, 95% CI: 1.114-2.379, p = 0.012) and non-CVD risk (HR = 1.521, 95% CI: 1.011-2.288, p = 0.044). Further analysis of the causes of infection-related death in non-CVD is also significant (HR = 1.919, 95% CI: 1.131-3.1257, p = 0.016). On the other hand, the serum magnesium>1.2 mmol/L group had lower all-cause mortality after correction (HR = 0.687, 95% CI: 0.480-0.985, p = 0.041), and subgroup analysis of the cause of death had no statistical significance (p > 0.05). CONCLUSIONS:Hypomagnesemia (serum magnesium <0.7 mmol/L) during stable dialysis in PD patients is a risk factor for CVD- and non-CVD-related mortality, especially infection-related death causes. 10.1159/000514148

Hypomagnesaemia in haemodialysis is associated with increased mortality risk: its relationship with dialysis fluid. Pérez-García Rafael,Jaldo María Teresa,Puerta Marta,Ortega Mayra,Corchete Elena,de Sequera Patricia,Martín-Navarro Juan Antonio,Albalate Marta,Alcázar Roberto Nefrologia Hypomagnesaemia in haemodialysis (HD) is associated with increased mortality risk: its relationship with dialysis fluid (DF). INTRODUCTION:Low concentrations of magnesium (Mg) in blood have been linked to the development of diabetes, hypertension, arrhythmias, vascular calcifications and an increased risk of death in the general population and in haemodialysis patients. The composition of the dialysis fluid in terms of its magnesium concentration is one of the main determinants of magnesium in haemodialysis patients. OBJECTIVE:To study magnesium concentrations in haemodialysis patients, their predictive mortality rate and what factors are associated with hypomagnesaemia and mortality in haemodialysis. METHODS:Retrospective study of a cohort of prevalent haemodialysis patients followed up for two years. Serum magnesium was measured every six months. The analysis used the initial and average magnesium values for each patient, comparing patients with magnesium below the mean (2.1mg/dl) with those with magnesium above the mean. During the follow-up, three types of dialysis fluid were used: type 1, magnesium 0.5 mmol/l; type 3, magnesium 0.37 mmol/l (both with acetate); and type 2, magnesium 0.5 mmol/l with citrate. RESULTS:We included 137 haemodialysis patients in the study, of which 72 were male and 65 were female, with a mean age of 67 (15) [26-95] years old. Of this group, 57 patients were diabetic, 70 were on online haemodiafiltration (OL-HDF) and 67 were on high-flow haemodialysis (HF-HD). The mean magnesium of the 93 patients with dialysis fluid type 1 was 2.18 (0.37) mg/dl. In the 27 patients with dialysis fluid type 3 it was 2.02 (0.42) mg/dl. And in the 17 with dialysis fluid type 2 it was 1.84 (0.24) mg/dl (p=.01). There was a pronounced direct relationship between Mg and P and albumin. After a mean follow-up of 16.6 (8.9) [3-24] months, 77 remained active, 24 had died and 36 had been transplanted or transferred. Patients with magnesium above than 2.1mg/dl had a longer survival (p=.008). The survival of patients with the three types of dialysis fluid did not differ significantly (Log-Rank, p=.424). Corrected for blood magnesium, patients with dialysis fluid with citrate have better survival (p=.009). The COX regression analysis shows how age, serum albumin, magnesium, dialysis technique and type of dialysis fluid have an independent predictive mortality rate. CONCLUSIONS:Low serum magnesium levels have a greater association with an increased risk of mortality compared to high levels. The type of dialysis fluid affects the magnesium concentration and the risk of death. 10.1016/j.nefro.2020.04.013

Serum magnesium, mortality, and cardiovascular disease in chronic kidney disease and end-stage renal disease patients: a systematic review and meta-analysis. Xiong Jiachuan,He Ting,Wang Min,Nie Ling,Zhang Ying,Wang Yiqin,Huang Yunjian,Feng Bing,Zhang Jingbo,Zhao Jinghong Journal of nephrology BACKGROUND:Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. METHODS:Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. RESULTS:Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19-1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79-0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053-0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12-1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). CONCLUSIONS:Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed. 10.1007/s40620-019-00601-6

Hypomagnesemia and cause-specific mortality in hemodialysis patients: 5-year follow-up analysis. Selim Gjulsen N,Spasovski Goce,Tozija Liljana,Georgievska-Ismail Ljubica,Zafirova-Ivanovska Beti,Masin-Spasovska Jelka,Rambabova-Busletic Irena,Petronijevic Zvezdana,Dzekova-Vidimliski Pavlina,Ristovska Vesna,Pusevski Vladimir,Stojceva-Taneva Olivera The International journal of artificial organs INTRODUCTION:The aim of this prospective study was to evaluate the association between serum magnesium (Mg) and mortality, in particular the cause-specific mortality of Mg and other risk factors in hemodialysis (HD) patients. METHODS:We studied a cohort of 185 HD patients receiving thrice-weekly HD treatment, on a dialysate Mg concentration of 0.5 mmol/L. We stratified 3 patient groups according to the level of Mg: lower (<1.1 mmol/L), intermediate-reference (1.1 to <1.3 mmol/L), and higher (Mg >1.3 mm/L). RESULTS:During the 5-year follow-up, 60 patients died, with cardiovascular (CV) disease as the predominant cause (73.3%). Hazard ratio (HR) for all-cause and CV mortality were 2.55 and 2.67 in the lower versus intermediate Mg group, but there was no significant association between the higher and intermediate Mg group. Univariate Cox regression analysis showed that Mg <1.1 versus 1.1-1.30 mml/L with HR 2.34, was a significant univariate predictor for increased mortality in addition to the Hb <110 g/L, Alb <40 g/L, C-reactive protein (CRP) ≥10 mg/L and brain natriuretic peptide >1,200 pg/mL. However, in the multivariate analysis only CRP ≥10 mg/L with HR 3.89 was a significant predictor of mortality. Subgroup analyses showed that among patients with CRP >10 mg/L, HR for all-cause and CV mortality of the lower versus intermediate Mg group were 1.96 and 2.39, respectively, not reaching significance for the higher versus intermediate Mg group. Conversely, there was no association between Mg level and all-cause and CV mortality within these 3 groups among patients with CRP <10 mg/L. CONCLUSIONS:Lower serum Mg level was significantly associated with an increased all-cause and cardiovascular mortality in HD patients, especially in inflamed patients. 10.5301/ijao.5000611

Comparison of Sevelamer and Calcium Carbonate in Prevention of Hypomagnesemia in Hemodialysis Patients. International journal of preventive medicine BACKGROUND:Chronic kidney disease (CKD) is a life-threatening disease with numerous complications. Hemodialysis (HD) patients are prone to magnesium deficiency due to malnutrition, which can cause cardiovascular complications and increase mortality. The present study aimed to investigate the effects of sevelamer and calcium carbonate, as phosphate binders, on serum levels of magnesium, calcium, and phosphorus in HD patients. METHODS:A parallel clinical trial was conducted on 54 patients undergoing HD at Kosar Hospital of Semnan. The inclusion criteria were end-stage renal disease (ESRD), alternative HD treatment for at least 3 months 3 times a week, and serum phosphate levels greater than 4.5 mg/dL. The participants were randomly assigned to two groups of sevelamer (n = 27) and calcium carbonate (n = 27). If the participants were taking a phosphate binder, they were asked to stop it for 3 weeks. Participants in the sevelamer group received 800 mg of sevelamer at most three times a day and those in the calcium carbonate group were treated with 500 mg of calcium carbonate at most 3 times a day. Before and 3 months after the intervention, the serum levels of calcium, magnesium, and phosphorus were measured through the Arsenazo method using the Pars Azmun kit in the Selectra auto-analyzer. Twenty-one patients in the sevelamer group and 22 patients in the calcium carbonate group finished the study. RESULTS:The results showed that calcium carbonate and sevelamer increased serum magnesium level by 0.20 ( = 0.028) and 0.26 ( = 0.002), on average, which were statistically significant. The administration of calcium carbonate did not significantly change serum calcium levels ( = 0.53), whereas sevelamer reduced serum calcium levels by 0.23 ( = 0.017), on average. This reduction was statistically significant. The results also indicated that none of the calcium carbonate ( = 0.099) and sevelamer ( = 0.543) caused significant changes in serum phosphorus levels. The study findings showed no significant difference between the two groups in terms of changes in the serum levels of magnesium (0.590), calcium (0.116), and phosphorus (0.113). CONCLUSIONS:Both drugs (Sevelamer and calcium carbonate) prevented hypomagnesemia and increased serum magnesium levels, but no significant differences were found in blood levels of calcium, phosphorus, and magnesium compared to the two drugs. Considering the effect of magnesium on cardiovascular diseases, increasing the serum magnesium levels through the administration of calcium carbonate and sevelamer can prevent the likelihood of cardiovascular diseases. However, none of the studied drugs was superior to the other in this regard. 10.4103/ijpvm.IJPVM_464_19

The association between circulating magnesium and clinically relevant outcomes in patients with chronic kidney disease: A systematic review and meta-analysis. Leenders Nicoline H J,Vermeulen Emma A,van Ballegooijen Adriana J,Hoekstra Tiny,de Vries Ralph,Beulens Joline W,Vervloet Marc G Clinical nutrition (Edinburgh, Scotland) BACKGROUND & AIMS:Despite modern treatment, risk for cardiovascular disease and mortality in patients with chronic kidney disease (CKD) is unacceptably high. Observational studies have shown associations of magnesium with risk for several clinical outcomes in CKD of variable magnitude. The aim of this review is to provide a systematic overview and meta-analysis of longitudinal studies assessing the association of plasma magnesium concentration with clinically relevant outcomes in adult patients with chronic kidney disease, with a minimal follow-up of 6 months. Primary outcomes of interest were all-cause mortality, cardiovascular mortality, cardiovascular events, sudden death and hospitalisation. METHODS:The electronic databases PubMed, Embase and The Cochrane Library were searched using terms relating to plasma magnesium and CKD patients, and two authors independently selected eligible studies. Study quality was assessed according to the Newcastle-Ottawa Scale. Results of studies with a comparable magnesium exposure and outcome measure, were pooled using a random-effects meta-regression analysis. RESULTS:The search yielded 6156 records of which 33 studies, involving 348,059 patients, met the eligibility criteria. Finally, 22 studies could be included in the meta-analysis. Higher magnesium was associated with a lower risk for all-cause mortality (HR 0.90 [0.87-0.94] per 0.1 mmol/L increase of magnesium) and cardiovascular mortality and events (HR 0.85 [0.77-0.94] per 0.1 mmol/L). CONCLUSIONS:Magnesium concentration is inversely associated with all-cause mortality and cardiovascular mortality and events. Therefore, increasing magnesium may improve risk in patients with chronic kidney disease. This meta-analysis forms a firm base for future prospective trials to test whether increasing plasma magnesium, indeed has beneficial effects on clinical outcomes. 10.1016/j.clnu.2020.12.015

Baseline Serum Magnesium Level and Its Variability in Maintenance Hemodialysis Patients: Associations with Mortality. Wu Lingping,Cai Kedan,Luo Qun,Wang Lailiang,Hong Yue Kidney & blood pressure research BACKGROUND/AIMS:The study aimed at investigating the impact of serum magnesium (Mg) baseline level and its variability on mortality in maintenance hemodialysis (MHD) patients. METHODS:Eligible patients receiving regular MHD at Ningbo No. 2 Hospital between January 2009 and August 2016 were enrolled and follow-ups were conducted afterwards until death or transplantation. General information, laboratory results, and outcomes of subjects were collected. The relationship between baseline serum Mg level, its coefficient of variation (CV), and all-cause mortality and cardiovascular disease mortality were assessed, respectively. Subjects were divided into groups in 2 manners: by serum Mg level (lower Mg group: serum Mg <1.00 mmol/L, higher Mg group: serum Mg ≥1.00 mmol/L) and by serum Mg CV (high variation group: CV ≥0.149 mmol/L, middle variation group: 0.114 mmol/L ≤ CV < 0.149 mmol/L, and low variation group: CV <0.114 mmol/L). RESULTS:169 MHD patients were recruited in the study, with mean serum Mg 1.00 ± 0.18 mmol/L, average age 60.20 ± 15.64 years, and median dialysis duration 37.00 (18.30, 77.97) months. During the follow-up, 69 (40.83%) patients died, 24 (34.78%) of which died due to cardiovascular disease. Comparing the two groups, patients in the lower Mg group had a higher all-cause mortality (50.00 vs. 29.33%, p = 0.007). The multivariate Cox regression analysis suggested that lower Mg level was an independent factor for all-cause mortality as well as cardiovascular mortality (HR = 13.268, 95% CI 6.234-28.237, p < 0.001; HR = 12.702, 95% CI 3.737-43.174, p < 0.001, respectively). However, there were no significant statistical differences of all-cause and cardiovascular mortality among these three groups concerning Mg variation. And in the univariate and multivariate Cox regression analysis, serum magnesium CV was not the independent factor for all-cause mortality and cardiovascular mortality. CONCLUSIONS:The lower baseline serum magnesium level was associated with all-cause and cardiovascular mortality in MHD patients. However, the variability of magnesium level was not independently associated with the risk of death and further studies need to be conducted. 10.1159/000498957

The relationship between serum magnesium levels and mortality in non-diabetic hemodialysis patients: A 10-year follow-up study. Shimohata Homare,Yamashita Marina,Ohgi Kentaro,Tsujimoto Ryuji,Maruyama Hiroshi,Takayasu Mamiko,Hirayama Kouichi,Kobayashi Masaki Hemodialysis international. International Symposium on Home Hemodialysis Introduction Recently, although there are many reports showing that serum magnesium concentration is a predictor of mortality in dialysis patients, the observation periods of those reports were of short duration, typically around 12 months. Thus, we investigated this relationship over a longer follow-up period. Methods This retrospective, observational study included a total of 83 non-diabetic hemodialysis patients. The follow-up period was 120 months. Patients were divided into two groups, those with serum magnesium ≥2.5 mg/dL (Mg ≥2.5 mg/dL group) and serum magnesium <2.5 mg/dL (Mg <2.5 mg/dL group), and Kaplan-Meier analysis and Cox proportional hazards analysis were conducted. In addition to the above analysis, single and multiple regression analysis were performed at baseline to reveal the relationship between serum magnesium and clinical parameters. Findings During the follow-up period, 31 out of 83 patients died. Kaplan-Meier analysis showed a significantly higher incidence of death in the Mg <2.5 mg/dL group (log-rank test 4.951, P = 0.026). Multivariate Cox proportional hazards analysis showed a 62% decreased risk of mortality in the Mg ≥2.5 mg/dL group compared to the Mg <2.5 mg/dL group after adjustment for several confounding factors. Simple correlation coefficient analysis showed positive correlations of serum magnesium levels with serum creatinine, phosphorus, high-density lipoprotein, ankle-brachial index and KT/V, and a negative correlation with age. Multiple linear regression analysis showed that the ankle-brachial index was the only parameter that had a positive and significant correlation with the serum magnesium level. Conclusion Our study demonstrated that higher serum magnesium levels were associated with improved survival in non-diabetic hemodialysis patients. 10.1111/hdi.12759

Influencing factors of serum magnesium in CKD5 patients: A multicenter study in southern China. Frontiers in public health Introduction:Magnesium (Mg) disturbances are related to cardiac, bone, and renal patient mortality. In this study, we compared biochemical markers in hemodialysis (HD) and peritoneal dialysis (PD) patients and explored the influencing factors of serum Mg in stage 5 chronic kidney disease (CKD5) patients. Material and methods:All 598 patients with CKD5 from three medical centers in South China were recruited into this prospective cohort study from March 1, 2018, to January 31, 2021. Our study recorded the clinical characteristics and laboratory data of the patients. Results:Hemodialysis patients (0.99 ± 0.19 mmol/L) had a higher mean serum Mg level than PD patients (0.86 ± 0.20 mmol/L; < 0.01). Regression analysis showed that only corrected calcium (Ca), phosphate (P), Ca/Mg, Ca × P, albumin (Alb), total protein and creatine (Cr) predicted Mg levels in CKD5 patients ( < 0.01). Ca/Mg predicts hypomagnesemia with 78% sensitivity and 85% specificity in CKD5 patients. The AUC value corresponding to Ca/Mg was 0.88. Conclusions:This multicenter study in southern China showed that for all CKD5 patients, corrected Ca and Alb had a significant positive effect on serum Mg, while Ca/Mg had a significant negative effect on serum Mg. In 123 HD patients, Ca × P was positively associated with Mg while Ca/Mg and P were negatively associated with Mg. In 398 PD patients, Ca × P, Alb, and total protein were positively associated with Mg while Ca/Mg and P were negatively associated with Mg. In 77 non-dialysis patients, corrected Ca, Cr, and total protein were positively associated with Mg while Ca/Mg was negatively associated with Mg. Furthermore, Ca/Mg might be another useful technique to monitor blood Mg levels in CKD5 patients. Clinical trial registration:ChiCTR1800014557. 10.3389/fpubh.2022.1047602

Magnesium in chronic kidney disease: unanswered questions. Spiegel David M Blood purification BACKGROUND:Magnesium ion is critical for life and is integrally involved in cellular function and a key component of normal bone mineral. In health, the kidneys, gastrointestinal tract and bone are responsible for maintaining serum magnesium concentrations in the normal range and magnesium balance. Most clinical disorders involving magnesium, other than chronic kidney disease (CKD), result in hypomagnesemia, either from gastrointestinal or kidney losses. CKD and particularly end-stage kidney disease is the only clinical condition where sustained hypermagnesemia may occur and net magnesium balance may be positive. METHODS:This review will focus on normal magnesium homeostasis and review the literature in CKD with a particular focus on end-stage kidney disease and the potential role of magnesium as a phosphate binder and in cardiovascular and bone health. RESULTS:A number of small to medium-size interventional trials have shown that magnesium-based compounds can serve as effective phosphate binders. Observational studies suggest that higher serum magnesium concentrations in dialysis patients may improve survival and may slow the progression of vascular calcification. While a few small prospective trials support these findings, no large or long-term studies are available. CONCLUSIONS:Magnesium balance remains poorly understood in patients with end-stage kidney disease. While observational and small randomized trials suggest that exogenous administration may be useful as a phosphate binder and may have protective cardiovascular effects in terms of both arrhythmias and vascular calcification, large randomized trials are needed to test these hypotheses. 10.1159/000321837

Magnesium Replacement to Protect Cardiovascular and Kidney Damage? Lack of Prospective Clinical Trials. International journal of molecular sciences Patients with advanced chronic kidney disease exhibit an increase in cardiovascular mortality. Recent works have shown that low levels of magnesium are associated with increased cardiovascular and all-cause mortality in hemodialysis patients. Epidemiological studies suggest an influence of low levels of magnesium on the occurrence of cardiovascular disease, which is also observed in the normal population. Magnesium is involved in critical cellular events such as apoptosis and oxidative stress. It also participates in a number of enzymatic reactions. In animal models of uremia, dietary supplementation of magnesium reduces vascular calcifications and mortality; in vitro, an increase of magnesium concentration decreases osteogenic transdifferentiation of vascular smooth muscle cells. Therefore, it may be appropriate to evaluate whether magnesium replacement should be administered in an attempt to reduce vascular damage and mortality in the uremic population In the present manuscript, we will review the magnesium homeostasis, the involvement of magnesium in enzymatic reactions, apoptosis and oxidative stress and the clinical association between magnesium and cardiovascular disease in the general population and in the context of chronic kidney disease. We will also analyze the role of magnesium on kidney function. Finally, the experimental evidence of the beneficial effects of magnesium replacement in chronic kidney disease will be thoroughly described. 10.3390/ijms19030664

Magnesium and Vascular Calcification in Chronic Kidney Disease: Current Insights. International journal of molecular sciences Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead to adverse effects, the consequences associated with hypomagnesemia are often more severe and lasting. Importantly, observational studies have shown that CKD patients with hypomagnesemia have greater vascular calcification. Vascular calcification is accelerated and contributes to a high mortality rate in the CKD population. Both in vitro and animal studies have demonstrated that Mg protects against vascular calcification via several potential mechanisms, such as inhibiting the formation of both hydroxyapatite and pathogenic calciprotein particles as well as limiting osteogenic differentiation, a process in which vascular smooth muscle cells in the media layer of the arteries transform into bone-like cells. These preclinical findings have led to several important clinical trials that have investigated the effects of Mg supplementation on vascular calcification in people with CKD. Interestingly, two major clinical studies produced contradictory findings, resulting in a state of equipoise. This narrative review provides an overview of our current knowledge in the renal handling of Mg in health and CKD and the underlying mechanisms by which Mg may protect against vascular calcification. Lastly, we evaluate the strength of evidence from clinical studies on the efficacy of Mg supplementation and discuss future research directions. 10.3390/ijms25021155

Serum Magnesium Levels and Mortality in Japanese Maintenance Hemodialysis Patients. Tamura Tomomi,Unagami Kohei,Okazaki Masayuki,Komatsu Mizuki,Nitta Kosaku Blood purification BACKGROUND/AIMS:Although hypomagnesemia was found to be a risk for cardiovascular diseases in the general population, the relationship between serum magnesium (Mg) levels and prognosis of patients on maintenance hemodialysis (MHD) has not been extensively studied. This study sought to determine the relationship of serum Mg levels with aortic arch calcification (AoAC) and mortality in Japanese MHD patients. METHODS:We measured serum Mg levels in a cohort of 392 patients on MHD, classified the patients into 3 groups according to these levels, and followed their course for 4 years. AoAC was assessed using chest-X-rays. RESULTS:During follow-up, there were 117 deaths. Kaplan-Meier analyses showed that the high serum Mg group tended to have better survival rates than the low and middle serum Mg groups but this did not reach statistical significance. We also found that patients in the high serum Mg group had better nutritional status associated with higher serum albumin, triglyceride, and phosphate levels and had a significantly lower serum C-reactive protein level. In total, 83 patients (59.3%) in the high serum Mg group had been prescribed Mg oxide (MgO). CONCLUSIONS:Hypermagnesemia tended to be associated with better survival and a higher prescription rate of MgO. Interventional studies are needed to clarify whether Mg supplementation is beneficial for improving patient prognosis. 10.1159/000496659

Relationship of serum magnesium level with body composition and survival in hemodialysis patients. Mizuiri Sonoo,Nishizawa Yoshiko,Yamashita Kazuomi,Ono Kyoka,Usui Koji,Arita Michiko,Naito Takayuki,Doi Shigehiro,Masaki Takao,Shigemoto Kenichiro Hemodialysis international. International Symposium on Home Hemodialysis INTRODUCTION:A relationship between serum magnesium (Mg) and body composition parameters has not been reported in hemodialysis (HD) patients. We aimed to clarify whether serum Mg has any association with body composition parameters, or survival in HD patients. METHODS:This study included 215 consecutive maintenance HD patients. Laboratory data collection and postdialysis body composition analysis were performed at baseline. The patients were divided based on baseline serum Mg level tertiles (low, medium, and high Mg groups). Kaplan-Meier survival, logistic regression analyses and Cox proportional hazard analyses were conducted. FINDINGS:Among all patients, the median age and dialysis vintage were 73 (65-81) years and 44 (8-96) months, respectively. The serum Mg levels were < 2.3, 2.3-2.5, and > 2.5 mg/dL for the low (n = 67), middle (n = 76), and high (n = 72) Mg groups, respectively. Compared to other groups, low Mg group showed significantly higher age and C-reactive protein levels, but lower serum albumin, normalized protein catabolic rates and frequency of on-line hemodiafiltration. The low, middle, and high Mg groups differed significantly regarding body cell mass (fat-free mass without bone mineral mass and extracellular water) index (BCMI): [5.6 (4.2-6.8), 6.0 (4.8-8.1), 6.7 (4.9-7.5) kg/m , respectively] and overhydration/extracellular water ratio (OH/ECW) [11.7 (4.5-21.9), 4.8 (1.0-14.1), 8.5 (-0.5-15.0) %, respectively] but not regarding body mass index, lean tissue index, fat tissue index. Hypomagnesemia was significantly associated with BCMI [odds ratio (OR) [95% confidence interval (CI)]: 0.85 [0.73-1.00] and OH/ECW (OR [95% CI]: 1.03 [1.01-1.05]), respectively. Kaplan-Meyer 3-year survival rates were 53.6%, 69.7%, and 71.7% in low, middle, and high Mg groups, respectively. However, hypomagnesemia was not significantly associated with 3-year all-cause mortality independent of age, serum albumin and C-reactive protein. DISCUSSION:Hypomagnesemia was associated with lower BCMI, more pronounced OH/ECW and poorer Kaplan-Meier 3-year cumulative survival, but was not an independent risk factor for mortality in HD patients. 10.1111/hdi.12797

Serum Magnesium and Mortality in Maintenance Hemodialysis Patients. Yu Ling,Li Han,Wang Shi-Xiang Blood purification BACKGROUND AND AIM:The study aimed to investigate the potential contributing effect of serum magnesium on mortality in maintenance hemodialysis (MHD) patients. METHODS:The patients receiving regular MHD in March 2013 were involved. Baseline data including clinical data, anthropometrics and biochemical measurement were collected. After being followed for 36 months, the time of death and reason were recorded. RESULTS:One hundred and thirty-five MHD patients were enrolled in the study and analyzed, with mean serum magnesium of 1.11 ± 0.15 mmol/l. The level of serum magnesium in 64 patients was normal (47.4%), and it was elevated in 71 of the 135 patients (52.6%). And none of MHD patients had hypomagnesemia. The levels of serum albumin (Alb), urea nitrogen, creatinine (Cr), uric acid and phosphorus were significantly higher, but high-sensitivity C-reactive protein (Hs-CRP) and lipoprotein A were significantly lower in hypermagnesemia group compared to the normal serum magnesium group (p < 0.05). Serum Alb, serum Cr, serum phosphorus and Hs-CRP were related factors of hypermagnesemia by multivariate logistic regression analysis (p < 0.05). During the 36 months of follow-up, 27 patients died (20.0%), of whom 55.6% died of cardiovascular (CV) events. Kaplan-Meier curves showed that cumulative incidence of CV mortality were significantly higher in the normal serum magnesium group than in the hypermagnesemia group (p = 0.027); however, there was no significant difference in all-cause mortality (p > 0.05). CONCLUSIONS:Serum magnesium was elevated, which was related with nutrition and inflammation markers including serum Alb, serum Cr, serum phosphorus and Hs-CRP. Lower serum magnesium is a risk factor of CV mortality in MHD patients. Intervention studies are needed to clarify whether magnesium supplementation is beneficial for improving patient prognosis, when MHD patients had inflammatory and malnutrition. 10.1159/000451052

Higher Serum Magnesium Is a Survival Advantage in Maintenance Hemodialysis Patients. Blood purification INTRODUCTION:Elevated serum magnesium is common and associated with survival in maintenance hemodialysis (MHD) patients by observational studies. However, the results of these studies were underpowered and inconclusive. This work was designed to explore the predictive value of serum magnesium on the mortality of patients with MHD. METHODS:We retrospectively analyzed mortality rates in 267 patients with MHD. The collected parameters included anthropometrics and laboratory parameters. Serum magnesium included baseline serum magnesium (BS-Mg) and average serum magnesium (AS-Mg). Receiver operator characteristic (ROC) curves were drawn, and multivariate Cox proportional hazards models were applied to identify the predictive value of serum magnesium on patient mortality. RESULTS:During the 64-month follow-up period, 121 (45.3%) all-cause and 75 (28.1%) cardiovascular disease (CVD) deaths were recorded. The predictability of death of AS-Mg yielded results similar to those of serum albumin, secondary only to age, and superior to those of the high-sensitivity C-reactive protein (Hs-CRP), BS-Mg, by ROC curves. There were significant differences in all-cause and CVD mortality between the four groups (by quartile). Kaplan-Meier survival analyses revealed that the lowest 25th percentile had the poorest prognosis for both all-cause mortality (p < 0.001) and CVD mortality (p = 0.011). Finally, multivariate Cox proportional hazards models showed that increased age, increased Hs-CRP, decreased serum albumin, and AS-Mg were independent predictors of all-cause and CVD mortality. The hazard ratios of AS-Mg (per 0.01 mmol/L) were 0.925 (95% confidence interval, 0.884-0.968, p = 0.001) for all-cause mortality and 0.976 (95% confidence interval, 0.954-0.999, p = 0.040) for CVD mortality. CONCLUSION:AS-Mg was a good indicator for assessing all-cause and CVD mortality in patients with MHD in China. Higher serum magnesium had a survival advantage. Further studies with larger sample sizes should be needed to clarify the best reference value for maximizing the beneficial effects of magnesium. 10.1159/000528383

Dialysate Potassium, Dialysate Magnesium, and Hemodialysis Risk. Pun Patrick H,Middleton John P Journal of the American Society of Nephrology : JASN One of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams. 10.1681/ASN.2017060640