Letter to the Editor
Calcium mass balance with citrate dialysate is lower than with acetate
El balance de calcio es menor con un líquido de diálisis con citrato que con acetato
Rafael Pérez-García
, Marta Albalate, Patricia De Sequera, Mayra Ortega
Corresponding author
Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, Spain
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El calcio iónico más el unido a citrato y bicarbonato forman el calcio difusible en la sangre; todo el calcio del LD es difusible. 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Ionized calcium plus that bound to citrate and bicarbonate form the diffusible calcium in blood; all DF calcium is diffusible. Note that the concentration of blood-diffusible calcium is greater than that of the DF leaving the dialyser.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The topic of what is the ideal calcium concentration in dialysis fluid (DF) is currently on the agenda of most scientific dialysis meetings. With a calcium concentrations of 1.25<span class="elsevierStyleHsp" style=""></span>mmol/L, haemodialysis tolerance worsens, and with calcium levels of 1.5<span class="elsevierStyleHsp" style=""></span>mmol/L, positive calcium balance together with the development of alkalemia at the end of the hemodialysis session may favour vascular calcification. Dealing with this issue is not easy because the concept of “balance” (concentration measured before and after the haemodialysis session) is interpreted as the theoretical “gradient” that is not measured nor calculated. The reason for this letter is to try to clarify these concepts and to provide some data.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Calcemia usually increases significantly during the haemodialysis session using acetate DF with a calcium concentration of 1.5<span class="elsevierStyleHsp" style=""></span>mmol/L, this is more evident if the initial serum calcium concentration is low.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a> If the acetate of the DF is replaced by citrate, the increase in the concentration of both total and ionic serum calcium after hemodialysis or online haemodiafiltration (OL-HDF) is less or or even null.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3–5</span></a> It could be thought that by using a DF with 1.5<span class="elsevierStyleHsp" style=""></span>mmol/L of calcium, the smaller increase in calcaemia at the end of the citrate session generate a positive calcium gradient from the DF to the blood, which would induce a positive balance for the patient, which would cause the patient's calcification; or, it could be interpreted that the smaller increase in calcemia observed with citrate is the result of a lower, or even negative, calcium balance.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The work of Steckiph<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> compares the calcium balance in OL-HDF using a DF with citrate vs acetate, both with the same calcium concentration. It was a cross-sectional, randomized study in 18 patients; calcium and citrate balance were measured in the entire collection of DF. The calcium concentration in DF during the 2 periods was the same: 1.5<span class="elsevierStyleHsp" style=""></span>mmol/L. The result was that the mean calcium balance at the end of OL-HDF was −274 (260) mg with DF containing citrate and +125 (174) mg with acetate DF.</p><p id="par0020" class="elsevierStylePara elsevierViewall">So what is the true calcium gradient in the dialyser? The gradient is not the same across all capillaries of the dialyser and changes during the dialysis session. Further, the gradient is established as a function of diffusible calcium, which includes the ionized calcium and the bound calcium, which is essentially bound to bicarbonate and citrate present in both DF and blood.</p><p id="par0025" class="elsevierStylePara elsevierViewall">With DF containing citrate, the blood entering a dialyser capillar at the beginning of the session has a low concentration of both citrate and calcium-citrate complexes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). At the end of the capillar, the citrate concentration increased from 0.1 to 1<span class="elsevierStyleHsp" style=""></span>mmol/L and the calcium -citrate complexes are up to 0.3–0.4<span class="elsevierStyleHsp" style=""></span>mmol/L<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> since citrate is being transferred from the DF. This calcium that is now bound to the citrate comes mainly from that bound to albumin, but also from free ionic calcium. At the end of the dialyser, the total blood-diffusible calcium has increased. This is not the case with the DF with acetate, which has a much lower affinity for calcium than citrate.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The concentration of calcium in the DF is different from the theoretical concentration. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the actual measurements of calcium in the DF with both citrate and acetate; the total calcium concentration is 0.16<span class="elsevierStyleHsp" style=""></span>mg/dL (0.04<span class="elsevierStyleHsp" style=""></span>mmol/L) less than the theoretical concentration. This is explained by the fact that, in the hydraulic circuit of haemodialysis machines, there is always a certain degree of microprecipitation, which is more pronounced if both bicarbonate and calcium levels are increased. The DF with citrate has a significantly lower ionic calcium concentration, due to the calcium-citrate complexes; therefore, the greater concentration of diffusible calcium in the blood and the lower concentration in the DF explain a lower Calcium balance with citrate than with acetate, as demonstrated by those who have measured it.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">It is difficult to know the “gradients” of calcium during haemodialysis. Changes in iPTH variations during the dialysis session is an indirect manner to assess changes in calcaemia. In publications on DF with citrate,<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3–5</span></a> even with calcium concentrations of 1.65<span class="elsevierStyleHsp" style=""></span>mmol/L, the iPTH increases or remains unchanged, but such changes in concentration may not be identical to the balance.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Thus, we believe calcium balances should be calculated using the entire DF, including the ultrafiltration. Baxter™ recommends increasing the calcium concentration in the DF with citrate by 0.15<span class="elsevierStyleHsp" style=""></span>mmol/L compared to the DF with acetate in order to maintain the same balance.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> It could be that the DF with citrate with 1.5<span class="elsevierStyleHsp" style=""></span>mmol/L is an intermediate solution between the 1.25 and 1.5<span class="elsevierStyleHsp" style=""></span>mmol/L with acetate.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-05-31" "fechaAceptado" => "2016-09-27" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Pérez-García R, Albalate M, Sequera P, Ortega M. El balance de calcio es menor con un líquido de diálisis con citrato que con acetato. Nefrologia. 2017;37:109–110.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1240 "Ancho" => 1448 "Tamanyo" => 77229 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Concentrations of calcium in the blood (mmol/L) entering and leaving the dialyser, with the different components. Ionized calcium plus that bound to citrate and bicarbonate form the diffusible calcium in blood; all DF calcium is diffusible. Note that the concentration of blood-diffusible calcium is greater than that of the DF leaving the dialyser.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">On 7 occasions, the DF contained 1<span class="elsevierStyleHsp" style=""></span>mmol/L of citrate and 3.25<span class="elsevierStyleHsp" style=""></span>mEq/L of calcium, and on 13, 3<span class="elsevierStyleHsp" style=""></span>mmol/L of acetate and 3<span class="elsevierStyleHsp" style=""></span>mEq/L of calcium. The same dialysis monitors (AK200 Us (Baxter<span class="elsevierStyleSup">®</span>)) were used.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No.° \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Average Ca++ (mmol/L) (DE) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Average total Ca (mg/dL) (DE) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Theoretical Ca in concentrate (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total Ca – theoretical Ca (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Citrate DF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.05 (0.156) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.34 (0.097) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Acetate DF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.22 (0.102) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.84 (0.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">p \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1375933.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Total calcium and ionic calcium concentrations measured in the dialysis fluid at the dialyser entry point.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Individualization of dialysate calcium concentration according to baseline pre-dialysis serum calcium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. 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