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1.
The effect of increasing dialysate magnesium on calciprotein particles, inflammation and bone markers: post hoc analysis from a randomized controlled clinical trial.
Bressendorff, I, Hansen, D, Pasch, A, Holt, SG, Schou, M, Brandi, L, Smith, ER
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2021;(4):713-721
Abstract
BACKGROUND The formation of calciprotein particles (CPPs) may be an important component of the humoral defences against ectopic calcification. Although magnesium (Mg) has been shown to delay the transition of amorphous calcium-/phosphate-containing primary CPP (CPP-1) to crystalline apatite-containing secondary CPP (CPP-2) ex vivo, effects on the endogenous CPP pool are unknown. METHODS We used post hoc analyses from a randomized double-blind parallel-group controlled clinical trial of 28 days treatment with high dialysate Mg of 2.0 mEq/L versus standard dialysate Mg of 1.0 mEq/L in 57 subjects undergoing maintenance hemodialysis for end-stage kidney disease. CPP load, markers of systemic inflammation and bone turnover were measured at baseline and follow-up. RESULTS After 28 days of treatment with high dialysate Mg, serum total CPP (-52%), CPP-1 (-42%) and CPP-2 (-68%) were lower in the high Mg group (all P < 0.001) but were unchanged in the standard dialysate Mg group. Tumour necrosis factor-α (-20%) and interleukin-6 (-22%) were also reduced with high dialysate Mg treatment (both P < 0.01). High dialysate Mg resulted in higher levels of bone-specific alkaline phosphatase (a marker of bone formation) (+17%) but lower levels of tartrate-resistant acid phosphatase 5 b (a marker of bone resorption; -33%) (both P < 0.01). Inflammatory cytokines and bone turnover markers were unchanged in the standard dialysate Mg group over the same period. CONCLUSIONS In this exploratory analysis, increasing dialysate Mg was associated with reduced CPP load and systemic inflammation and divergent changes in markers of bone formation and resorption.
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2.
Sodium toxicity in peritoneal dialysis: mechanisms and "solutions".
Borrelli, S, De Nicola, L, Minutolo, R, Perna, A, Provenzano, M, Argentino, G, Cabiddu, G, Russo, R, La Milia, V, De Stefano, T, et al
Journal of nephrology. 2020;(1):59-68
Abstract
The major trials in peritoneal dialysis (PD) have demonstrated that increasing peritoneal clearance of small solutes is not associated with any advantage on survival, whereas sodium and fluid overload heralds higher risk of death and technique failure. On the other hand, higher sodium and fluid overload due to loss of residual kidney function (RKF) and higher transport membrane is associated with poor patient and technique survival. Recent experimental studies also show that, independently from fluid overload, sodium accumulation in the peritoneal interstitium exerts direct inflammatory and angiogenetic stimuli, with consequent structural and functional changes of peritoneum, while in patients with Chronic Kidney Disease sodium stored in interstitial skin acts as independent determinant of left ventricular hypertrophy. Noteworthy, this tissue pool of sodium is modifiable being removed by dialysis. Therefore, novel PD strategies to optimize sodium removal, including the use of bimodal and/or low-sodium solutions, are actively tested. Nonetheless, a holistic approach aimed at preserving peritoneal function and the kidney may represent the key of therapy success in the hard task of preserving adequate sodium balance in PD patients. In this review, we describe the available evidence on sodium toxicity in PD, either related or unrelated to fluid overload, and we also discuss about possible "solutions" to preserve or restore sodium balance in PD patients.
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3.
The efficacy and safety of low dialysate sodium levels for patients with maintenance haemodialysis: A systematic review and meta-analysis.
Geng, X, Song, Y, Hou, B, Ma, Y, Wang, Y
International journal of surgery (London, England). 2020;:332-339
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Abstract
BACKGROUND & AIM: Fluid overload and hypertension frequently results in cardiovascular disease, which is one of the leading causes of death in dialysis patients. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing cardiovascular disease morbidity and mortality. This meta-analysis was designed to evaluate the efficacy and safety of using a low (<138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. METHODS We searched the Cochrane Library, PubMed, EMBASE, Web of Science up to August 22, 2019. Randomised controlled trials (RCTs), both parallel and cross-over, of low (<138 mM) versus neutral (138-140 mM) or high (>140 mM) dialysate [Na+] for maintenance HD patients were included. Mean difference (MD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2. RESULTS 12 Randomised controlled trials with 390 patients were included in this meta-analysis. Of these studies, three studies were parallel group, and the remaining nine were crossover. Compared to neutral or high dialysate [Na+], low dialysate [Na+] reduced dialysis mean arterial pressure (MAP) with a pooled MD of -3.38 mmHg (95% CI -4.57 to -2.19; P < 0.00001), reduced interdialytic weight gain with a pooled MD of -0.35 kg (95% CI -0.51 to -0.18; P < 0.0001), reduced predialysis serum [Na+] with a pooled MD of -2.62 mM (95% CI -3.59 to -1.66; P < 0.00001). In contrast, low dialysate [Na+] increased intradialytic hypotension events with a pooled RR of 1.54 (95% CI 1.16 to 2.05; P = 0.003), increased the incidence of intradialytic cramps with a pooled RR of 1.77 (95% CI 1.15 to 2.73; P = 0.01). However, no difference was found between lower and higher dialysate [Na+] in systolic blood pressure and diastolic blood pressure. CONCLUSIONS Though our pooled result indicated that low dialysate [Na+] reduced MAP, interdialytic weight gain and predialysis serum [Na+] significantly, it also indicated that low dialysate [Na+] could increase the incidence of intradialytic hypotension and intradialytic cramps events. Considering the contradiction in efficacy and safety of low dialysate [Na+] in our analysis, future larger and up-to-date definitive studies are needed to evaluate the medium to long-term effects of low sodium levels in dialysis fluid, and better inform clinical practice.
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Evaluation of intradialytic sodium shifts during sodium controlled hemodialysis.
Ponce, P, Pinto, B, Wojke, R, Maierhofer, AP, Gauly, A
The International journal of artificial organs. 2020;(9):620-624
Abstract
Plasma sodium shifts during hemodialysis treatments can be minimized by application of a sodium control algorithm. The present randomized cross-over trial was designed to apply this option on a large patient cohort and to observe the time course of plasma sodium over the treatment. In one study phase, patients received post-dilution online hemodiafiltration treatments with sodium control over the entire treatment. In the other study phase, patients received isolated ultrafiltration during the first 90 min followed by post-dilution online hemodiafiltration with sodium control for the remainder of the session, with the purpose to follow a possible initial equilibration process without the influence of a diffusive solute transfer. Each phase included six treatments and was delivered in randomized order. Eighty-one patients were enrolled, 77 patients could be analyzed as intention-to-treat population. The difference of the mean plasma sodium concentration between start and end of the treatment was -0.60 mmol/L (confidence interval -0.88 to -0.32) and -0.15 mmol/L (confidence interval -0.43 to 0.13), for sodium control and isolated ultrafiltration during the first 90 min followed by post-dilution online hemodiafiltration with sodium control, respectively. The functionality of the sodium control option could be confirmed and further reproduced in a bigger population of dialysis patients, providing the basis to investigate the clinical benefit of individually adjusting dialysate sodium in further clinical studies.
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Total serum and intraerythrocyte magnesium concentrations in hemodialysis patients using different dialysate solutions.
Kusic, J, Markovic, R, Andjelkovic Apostolovic, M, Dragovic, G
Magnesium research. 2020;(2):28-36
Abstract
Beside routinely used 0.5 mmol/L dialysate-magnesium, higher dialysate-magnesium (1.0 mmol/L) was recently introduced. The aim of this study was to evaluate the impact of different dialysate-magnesium on serum and intraerythrocyte levels of magnesium (Mg) before and after dialysis. The study included 43 patients receiving chronic hemodialysis, divided into two groups based on dialysate-magnesium (0.5 or 1.0 mmol/L) used prior to study initiation and during 12 months of follow-up. Blood samples were taken at the mid-week dialysis; total serum Mg was measured colorimetrically and intraerythrocyte Mg by atomic absorption spectrophotometry. Hypermagnesiemia-associated complications were observed for 12 months. Total serum Mg was 1.14 ± 0.19 mmol/L before and 0.95 ± 0.16 mmol/L after dialysis in patients using lower dialysate-Mg (p < 0.001), whereas it was 1.47 ± 0.25 mmol/L before and 1.49 ± 0.18 mmol/L after dialysis in patients using higher dialysate-Mg (p = 0.926). Intraerythrocyte Mg was 1.98 ± 0.34 mmol/L before and 1.97 ± 0.28 mmol/L after dialysis in the lower dialysate-Mg group (p = 0.939), while it was 2.09 ± 0.37 mmol/L before and 2.19 ± 0.48 mmol/L after dialysis in the higher dialysate group (p = 0.067). After 12 months total serum Mg decreased in both the groups, remaining lower in 0.5 mmol/L dialysate-Mg group. No hypermagnesiemia-related symptoms occur during 12 months of follow-up in both the groups. In patients using lower dialysate-Mg total serum Mg remains within the reference range and shows postdialytic decline, while in higher dialysate-Mg group it exceeded reference range before and after dialysis without significant intradialytic change. The intraerythrocyte values remain within reference range with both dialysates used. No clinical signs and symptoms of hypermagnesiemia occur during longer administration of higher dialysate-magnesium despite high total serum Mg level.
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High magnesium dialysate does not improve intradialytic hemodynamics or abrogate myocardial stunning.
Jefferies, HJ, Lemoine, S, McIntyre, CW
Hemodialysis international. International Symposium on Home Hemodialysis. 2020;(4):506-515
Abstract
BACKGROUND Hemodialysis (HD) induces myocardial stunning and is associated with adverse cardiovascular outcomes. Intradialytic hypotension is a modifiable determinant of myocardial stunning. Magnesium (Mg) is reported to be valuable in maintaining intradialytic blood pressure, which potentially would protect against demand myocardial ischemia. This study aimed to compare high vs. low dialysate Mg effects on intradialytic hemodynamics and HD-induced myocardial stunning. METHODS Twenty stable prevalent HD patients entered a randomized cross-over trial of low (0.5 mmol/L) vs. high (1.0 mmol/L) dialysate Mg. Patients were studied after 2 weeks of standard HD with each Mg concentration. Serial echocardiography assessed myocardial stunning, measured by left ventricular regional wall motion abnormalities (RWMAs). Continuous intradialytic hemodynamics were measured noninvasively using thoracic bioimpedance. FINDINGS Median predialysis serum Mg was higher with high dialysate Mg (1.45[1.29-1.55] vs. 1.03[0.98-1.1] mmol/L, P < 0.0001). There was no significant difference in maximum intradialytic reduction in systolic BP. There was no significant difference in stroke volume, total peripheral resistance, and cardiac output. Overall ventricular global longitudinal strain (GLS) (as a sensitive marker of contractile function) was higher before dialysis in high Mg group, but there was no difference in GLS at peak stress. However, we showed a significant correlation between Mg changes and GLS changes, r = -0.47, P = 0.02. There was no difference in mean number of peak stress RWMAs per patient (4.0 ± 2.2 vs. 4.3 ± 2.9, P = 0.5). Ultrafiltration volume, a critical determinant of stunning, was not different between high and low dialysate Mg studies (1.35[0-3.3] vs. 1.5[0-2.8], P = 0.49). DISCUSSION Manipulation of magnesium by altering dialysate magnesium concentration does not influence intradialytic hemodynamic response or HD-induced myocardial stunning in the short term. However, decreasing Mg changes appears to decrease GLS changes.
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Reducing the risk of intradialytic hypotension by altering the composition of the dialysate.
Vareesangthip, K, Davenport, A
Hemodialysis international. International Symposium on Home Hemodialysis. 2020;(3):276-281
Abstract
Hypotension is the most common complication of outpatient hemodialysis sessions, with a reported prevalence of 4% to 31%, depending on which definition has been used and whether patients are symptomatic and nursing interventions were required. Dialysis centers which mix the dialysate in the dialysis machine have the opportunity to individualize the composition of the dialysate for patients. This permits a choice of dialysate sodium, potassium, calcium, magnesium, bicarbonate, acetate, and citrate concentrations and temperature. Studies have reported a higher intradialytic systolic blood pressure and fewer episodes of intradialytic hypotension when using a higher dialysate sodium, calcium, magnesium concentrations and lower temperature, but no clinical advantage for changing the potassium, bicarbonate, or citrate for acetate concentrations. The introduction of newer technology allowing real time measurements of plasma electrolyte concentrations will potentially allow changing the dialysate composition to reduce the risk of intradialytic hypotension without increasing the risk of positive electrolyte balances.
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Hypersensitivity reactions to bicarbonate dialysate containing acetate: a case report with literature review.
Nishiuchi, Y, Shima, H, Fukata, Y, Tao, T, Okamoto, T, Takamatsu, N, Okada, K, Minakuchi, J
CEN case reports. 2020;(3):243-246
Abstract
Although hemodialysis-hypersensitivity reactions have various causes, only a few cases of hypersensitivity to acetate dialysate accompanied by fever have been reported. We present the case of a 69-year-old hemodialysis patient who was admitted due to fever after dialysis. He had undergone online hemodiafiltration using acetate-free citrate-containing dialysate. After admission, we switched to acetate-containing bicarbonate dialysate. He was diagnosed with pneumonia and treated with ceftriaxone. However, fever that occurred post dialysis persisted, displaying a gradual elevation in CRP level and eosinophils (up to 9.7 mg/dL and 3774 cells/μL, respectively). After a series of negative workups for infection and dialysis membrane allergy, we suspected that acetate-containing bicarbonate dialysate to be the cause of the allergic reaction and switched to acetate-free bicarbonate dialysate. Consequently, eosinophil count decreased and the fever abated. The drug-induced lymphocyte stimulation test finding (for acetate dialysate) was positive, and he was diagnosed with acetate dialysate-induced hypersensitivity reactions. The condition was not detected earlier due to the complications associated with pneumonia.
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Short-Term Effects of Branched-Chain Amino Acids-Enriched Dialysis Fluid on Branched-Chain Amino Acids Plasma Level and Mass Balance: A Randomized Cross-Over Study.
Deleaval, P, Luaire, B, Laffay, P, Jambut-Cadon, D, Stauss-Grabo, M, Canaud, B, Chazot, C
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2020;(1):61-68
Abstract
OBJECTIVE(S): The hemodialysis (HD) session per se is a catabolic event contributing to protein-energy wasting via several mechanisms including nutrient losses. Amino acids (AAs) losses in the dialysate are estimated from 6 to 10 g per treatment. The HD patient plasma AA concentration is usually lower than in normal subjects. This is even more marked in patients with long dialysis vintage or malnutrition. METHODS The aim of the study was to evaluate the effect on mass balance of a branched-chain AA (BCAA)-enriched (valine, isoleucine, leucine) dialysis fluid in a group of 6 stable HD anuric patients, fasting since 12 hours. The specific choice of BCAA relied on their key role on protein and muscle anabolism and their usual decreased plasma concentration in HD patients. Each patient was prescribed in a cross-over design and random order, either receiving a standard high-flux HD or an HD treatment using a BCAA-enriched acid concentrate designed to achieve a physiological plasma concentration of BCAAs. HD prescription remained unchanged during the 2 phases of study. Dialysate electrolytes prescription was kept constant for each individual patient, as well as dialysate glucose concentration (5.5 mmol/L). Pre- and post-dialysis BCAAs concentrations were measured by Ion-Exchange Liquid Chromatography. Postdialysis concentrations were corrected for hemoconcentration, and net mass transfer was calculated. RESULTS Six stable prevalent end-stage kidney disease patients were studied. They consisted of 5 men and 1 woman, aged 69.9 years, with body mass index of 25.2 kg/m2. Treatment schedule consisted of treatment time 4 hours, high-flux polysulfone membrane (1.8 m2), blood flow 350 mL/minute, and dialysate/blood flow ratio at 1.5. The average BCAAs concentration in dialysate was targeted to physiological levels and assessed in 6 different samples, respectively for plasma valine, isoleucine, and leucine at 271, 78, and 145 μmol/L. With standard dialysate, plasma valine decreased from 204.5 to 130.8 (P = .0014). Plasma isoleucine and leucine changes were not significant, respectively from 65.7 to 59.3 μmol/L and 110.3 to 113.4 μmol/L. When using the BCAA-enriched dialysis fluid, plasma valine increased from 197.2 to 269.2 μmol/L (P = .0001), plasma isoleucine and leucine respectively from 63.2 to 84.7 (P = .0022) and from 107.2 to 161.6 μmoles/L (P = .0002). Dialysis dose estimated from KT/V did not differ between the sessions. The mass transfer with BCAA-enriched dialysate was +115, +16, and + 83 μmol per session for leucine, isoleucine, and valine, respectively. CONCLUSION(S): In conclusion, the addition of BCAAs at physiological concentration in the dialysis fluid contributes to restore physiological plasma concentrations for valine, isoleucine, and leucine at the end of a dialysis session. As BCAAs are essential to muscle balance, this could help to limit losses of BCAAs, restore physiological BCAAs concentrations, and decrease muscle catabolism observed during the HD treatment. Further outcome-based studies are needed to confirm this hypothesis on a larger scale and longer treatment time.
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Flexitrate regional citrate anticoagulation in continuous venovenous hemodiafiltration: a retrospective analysis.
Lenga, I, Hopman, WM, O'Connell, AJ, Hume, F, Wei, CCY
BMC nephrology. 2019;(1):452
Abstract
BACKGROUND Flexitrate, an innovative regional citrate anticoagulation (RCA) protocol, was compared to traditional RCA (tRCA) and Heparin anticoagulation protocols in intensive care patients treated with continuous renal replacement therapy (CRRT). METHODS A single-center, retrospective, cohort study, was done in a 26-bed intensive care unit in a large community hospital. Eighty dialysis sessions (Flexitrate = 2852 h, tRCA = 3580 h and Heparin = 2026 h), performed in 53 patients, were evaluated for filter life, RCA control, and metabolic control. RESULTS In the Flexitrate cohort, 3.8% of filters clotted, compared to 16.9% with tRCA and 28.3% with Heparin (p < 0.001 for Flexitrate compared to either tRCA or Heparin). Filter survival was significantly improved with Flexitrate compared to tRCA (HR 0.24, p = 0.018) or Heparin (HR 0.14, p = 0.004). Anticoagulation control was superior with Flexitrate with Patient Ionized Calcium out of target a median of 16% of the time, compared to 27% for tRCA (p < 0.001). Filter Ionized Calcium was out of target a median of 6.8% of the time, compared to 23% for tRCA (p = 0.03). Flexitrate produced significantly less alkalosis, hypernatremia, and hypocalcemia than tRCA, and overall metabolic control was comparable to Heparin anticoagulation. The only adverse metabolic outcome with Flexitrate was increased hypomagnesemia. CONCLUSIONS The Flexitrate protocol extended filter life, delivered more consistent anticoagulation, and provided superior metabolic control compared to a tRCA protocol. Filter life was superior to Heparin anticoagulation, with similar metabolic control. A randomized control trial comparing these protocols is recommended.