Improvements in Inflammation and Calcium Balance of Citrate versus Acetate as Dialysate Buffer in Maintenance Hemodialysis: A Unicentric, Cross-Over, Prospective Study

Abstract

<b><i>Introduction:</i></b> The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. <b><i>Methods:</i></b> This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients’ treatment remained unchanged during the study period. <b><i>Results:</i></b> When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. <b><i>Conclusions:</i></b> The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes.

Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism—A Targeted Metabolomics Approach

“…Metabolomics opens the door to studying human metabolism in response to dialysis-induced changes in intermediary metabolism. This study, performed by a targeted metabolomic approach, found noteworthy differences between dialysates that raise new hypotheses that should be further investigated to explain the deleterious acetate effects on dialysis patients [ 9 , 10 , 11 , 12 , 13 ]. Acetyl-CoA levels exceeded by 20–70 times the physiological level despite the apparently small concentrations of acetate in the AD [ 8 , 22 , 23 , 24 ].…”

“…In that sense, and to make the treatment parameters as similar as possible, bicarbonate and sodium concentration in both dialysates were adjusted in the monitor to 32 and 138 mmol/L, respectively. More details on the parameters of the dialysis treatments have been published previously [ 9 ].…”

“…Among the several compounds proposed as alternatives to acetate, citrate is important [ 7 ], as it has been associated with improved hemodynamic tolerance and inflammatory biomarkers in DD-CKD patients [ 9 , 10 , 11 , 12 , 13 ]. Even though the concentration in the dialysate is five times lower than that needed for anticoagulation, citrate also allows patients to receive a reduced heparin dose without increasing the risk of filter coagulation [ 14 , 15 , 16 , 17 ].…”

Effect of Citrate-Acidified Dialysate on Intact Parathyroid Hormone in Prevalent Hemodialysis Patients: A Matched Retrospective Cohort Study

“…In contrast, a crossover, prospective study of 21 hemodialysis patients found that dialysis with citrate dialysate (containing 3.0 mEq/L of calcium) resulted in stable ionized calcium levels, a neutral-to-negative effect on calcium balance, and reductions in inflammatory biomarkers relative to those effects observed with acetate dialysate (containing 3.0 mEq/L of calcium). 28 …”

The metabolomic differential plasma profile between dialysates. Pursuing to understand the mechanisms of citrate dialysate clinical benefits

“…Data processing was done using an in-house R (v.3.6.1) processing script with XCMS and CAMERA packages for peak detection, noise filtering, alignment and normalization. Parameters selected were: CentWave method (noise = 1,000; Adapted from (Broseta et al, 2021) Frontiers in Physiology frontiersin.org ppm = 50; k = 5; I = 300; snthresh = 10; min = 6; max = 25; integrate = 2; nS = 4); matching peaks across samples (grouping): Density method (mzwid = 0.05; bw = 1; mF = 0.5; mS = 1); retention time correction (m = 0; e = 0); integration of samples: FillPeaks method; median fold change normalisation: medFC technique; and CAMERA isotopes: FindIsotopes. The data matrix finally obtained was composed of molecular features consisting of two values: accurate mass (m/z) and retention time (min).…”