NDT Advance Access published online on September 15, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn452
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Citrate supplementation of PD fluid: effects on net ultrafiltration and clearance of small solutes in single dwells
1 Institute of Biomedicine 2 Institute of Medicine, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
Correspondence and offprint requests to: Magnus Braide, Department of Biomedicine, University of Gothenburg, Box 420, SE-40530 Gothenburg, Sweden. Tel: +46-31-7863310; Fax: +46-31-416108; E-mail: magnus.braide{at}gu.se
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Abstract |
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Background. Inflammatory reactions affect the general performance as well as the technique survival of peritoneal dialysis (PD). Anti-inflammatory additives like heparin and sodium citrate have shown favourable results in these respects. The present study is the first to evaluate citrate-supplemented PD fluids (PDFs) in humans.
Methods. Crossover design was used to evaluate sodium citrate and heparin-supplemented Gambrosol Trio® (2.5% glucose) in 28 stable outpatients from the PD unit. Comparisons were made between single dwells of each fluid. Citrate supplementation at 5 mM/L was compared with standard PDF, and citrate supplementation at 10 mM/L was compared with low-molecular-weight heparin (4500 units of tinzaparin) supplementation and standard PDF. The initial osmolarity of the fluids was equalized by adding sodium chloride.
Results. Citrate supplementation at 5 mM/L significantly increased net ultrafiltration, measured as drained volume gain, by 126 mL. Creatinine and phosphate clearance, but not glucose clearance, was significantly improved by supplementation with citrate or heparin. Heparin supplementation created an insignificant trend towards an increased ultrafiltration (P = 0.08). No negative side effects were reported for any of the treatments; however, citrate supplementation led to a small calcium loss by the drained PD fluid (0.4 mmol) and a transient fall in the plasma concentration (0.04 mM/L) of free calcium ions at 5 mM/L citrate. Effects on plasma bicarbonate concentration were insignificant.
Conclusions. Citrate supplementation of PD fluid improved ultrafiltration and clearance of small solutes with only minor effects on calcium turnover. The mechanism is unknown and, according to the results, not related to complement inhibition.
Keywords: citrate; humans; lactate; peritoneal dialysis; ultrafiltration
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Introduction |
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An improvement in the technique survival and general efficiency of peritoneal dialysis (PD) would make this treatment more competitive in relation to haemodialysis, the alternative replacement therapy in end-stage renal failure.
Recent research on PD has focused on the negative long-term effects of PD on the peritoneal membrane. A number of mechanisms behind this interaction have been identified and some of them have been connected to various components of the PD fluids (PDFs) in clinical use. New PD fluids have been designed to improve biocompatibility; however, so far, the development of commercial PD fluids has not included pharmacologically active additives.
Obviously some manifestations of PD fluid exposure are possible to control pharmacologically [1,2], and a number of drugs have been evaluated experimentally [3]. Several strategies involve anti-inflammatory effects, and there is ample evidence that inflammation is involved in the reaction to PD fluid exposure. Inflammation has potential effects on the efficiency of each PD dwell as well as on the transformation of peritoneal tissue over time on PD.
For several reasons, separate administration of a drug may have an advantage over adding it to the PD fluid. There are already attempts to combine PD with pharmacological intervention in order to improve residual renal function [4]. Although some evaluations have been performed [5], no such complementary drug treatment has been introduced in combination with clinical PD. Regarding pharmacological PD fluid additives, manufacturing techniques introduce problems. Autoclaving is the only sterilization technique that is feasible for industrial scale manufacturing, and PD fluid additives thus have to survive this procedure. This problem rules out many macromolecules that otherwise show promising results including heparins and related glycosaminoglycans [5–7]. In clinical studies, low-molecular-weight (LMW) heparin has shown positive long-term effects on ultrafiltration and on markers of inflammation [6,7]. Data from animal models show that LMW heparin improves ultrafiltration in acute experiments [8], but it has not been evaluated clinically in acute single dwells.
In addition to heparin, we have studied a number of anti-inflammatory additives in animal models of PD and chosen sodium citrate as the most suitable candidate for a PD fluid additive [9]. Sodium citrate is a chelator of calcium ions that are blocked from interactions with several calcium-dependent reaction systems including coagulation and complement. In addition, citrate acts as a scavenger, reducing actions of reactive oxygen species in vitro [10]. Citrate is a naturally occurring metabolite and well established clinically as anticoagulant in blood transfusion and haemodialysis. An excess of citrate that appears in plasma is metabolized by the liver and is not dependent upon renal excretion [11].
Our recent study of citrate in a rat model of PD showed that citrate improves net ultrafiltration in a single dwell without noticeable side effects on the animals [9].
Potential risks associated with citrate-supplemented PD fluid include metabolic alkalosis and calcium loss. Lack of kidney function leads to metabolic acidosis due to insufficient renal acid secretion. In dialysis patients, acidosis is balanced by alkali from the dialysis fluids, either as bicarbonate or as metabolic precursors such as citrate or lactate [12]. Citrate generates three times more bicarbonate than equimolar amounts of lactate. The calcium-binding effect of citrate leads to a temporary accumulation of calcium intraperitoneally, and the fraction of the citrate-calcium complex that remains in the peritoneal cavity will be lost in the drainage of PD fluid after the dwell, leading to calcium loss.
The present study was performed in order to evaluate the safety of sodium citrate-supplemented PD fluid in a single dwell and to characterize any acute effects on the transperitoneal transport in comparison with standard PD fluid and PD fluid supplemented with low-molecular-weight heparin. Special attention was paid to bicarbonate production and calcium loss. Two different citrate concentrations were evaluated concerning the balance between negative and positive effects.
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Subjects and methods |
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Objective of the study
The present study was performed in order to make a first evaluation of the acute efficiency and safety of citrate as an additive to PD fluids. The effects of citrate supplementation were compared with those of low-molecular-weight heparin supplementation (4500 U tinzaparin per 2 L PDF), known from the literature to improve ultrafiltration in PD [7].
For citrate, only animal data were available [9] indicating a dose-dependent improvement of ultrafiltration in the concentration range 5–15 mM/L in rats. We performed a small number of pilot experiments in humans at citrate concentrations of 2.5, 5, 7.5 and 10 mM/L. Data suggested an improved ultrafiltration at citrate concentrations of 5 mM/L and higher but no further improvement at concentrations up to 10 mM/L. Therefore, the citrate concentrations of 5 and 10 mM/L were chosen for the present evaluation. For practical reasons, citrate was added to a standard PD fluid (Gambrosol Trio® at 2.5% glucose) instead of replacing a fraction of the lactate buffer as done in the earlier animal study [9]. Each citrate concentration (5 and 10 mM/L) was compared with unsupplemented PDF as a separate evaluation, and 10 mM/L citrate was also compared with heparin. The higher initial osmolarity of the citrate-supplemented fluids was compensated by adding NaCl to the citrate-free fluids. The analyses were focused on ultrafiltration, transport of small solutes and albumin, turnover of citrate and effects on calcium homeostasis and acid–base status.
Patients
In all, 28 adult outpatients of the PD unit at Sahlgrenska University Hospital in Göteborg were initially included in the study. All patients gave written informed consent, and the local ethical committee approved the study.
Inclusion criterion was PD treatment since at least 6 months. Exclusion criteria were ultrafiltration failure, treatment with anticoagulants or steroids, peritonitis during the last 2 months and pregnancy in progress. Personal dialysis capacity (PDC) measurements [13] performed during the clinical follow-up of the patients were used as baseline data in the study.
Three patients were excluded during the evaluations, one according to choice, one due to peritonitis and one due to an unpredicted opportunity for transplantation.
Exposure protocols and evaluations
All experiments were performed as single dwells according to two different experimental protocols, approved by the regional ethical committee. Informed consent was obtained from all patients.
In the first evaluation (study group 1), 13 patients were exposed to two different fluids: unsupplemented PDF and PDF supplemented with 5 mM/L citrate. In the second evaluation (study group 2), 17 patients were exposed to three different fluids: unsupplemented PDF, PDF supplemented with 10 mM/L citrate and 4500 U tinzaparin/2 L fluid.
Experimental procedures
Patients were exposed to 2 L dwells, one with each fluid according to the protocol, and the order of appearance of the fluids was randomized. The dwells were 4 h long and separated by at least 2 weeks. The study dwell was started after preparation of the PDF with supplements and volume tracer (125I-albumin). The type of supplement was blinded to the patient and to the nurse performing the dwell and the sampling. The PD bag set was weighed before filling. Samples of PDF were taken at times 0, 30, 60, 120, 180 and 240 min. Samples of venous blood were taken at 0, 60, 120 and 240 min. In study group 2, blood samples were also taken at 30 and 180 min. At the end of the dwell, the intraperitoneal fluid was drained, a new bag of fluid was infused and the drainage bag was weighed in order to determine the drained volume. A last sample of PDF was taken for determination of the intraperitoneal residual volume. The patient then answered an enquiry on symptoms and sensations felt during the dwell. Nausea and infusion pain were specifically addressed.
Fluids
Gambrosol Trio® 10 at the M setting (2.5% glucose) was modified by addition of citrate (5 or 10 mM/L) or heparin and compared with osmotically compensated but otherwise unmodified PD fluid. The citrate-supplemented fluids received the appropriate doses of sodium citrate as a sterile 1 M sodium citrate solution (10 or 20 mL per bag). The heparin-supplemented fluids were injected with 4500 units of tinzaparin (0.45 mL Innohep® 10 000 U/mL) and 32 mmols of NaCl (8 mL Addex®-natriumklorid 4 mM/ mL). The standard PD fluids were supplemented with 16 or 32 mmols of NaCl (4 mL or 8 mL Addex®-natriumklorid 4 mM/mL). Addition of NaCl to heparin and standard PD fluids compensated for the osmolarity increase caused by citrate supplementation at 5 mM/L and 10 mM/L, respectively. 125I-labelled human serum albumin (50 kBq) diluted in NaCl (0.25–0.37 mL of 200 kBq/mL initial activity) was added to PDF bags as a volume marker.
Analyses of samples
Analyses of albumin, calcium ions, total calcium, sodium, phosphate, creatinine, urea, glucose and bicarbonate were performed by the clinical chemistry laboratory of the Sahlgrenska University Hospital.
Concentrations of C3a-desArg in plasma and dialysate were determined by EIA (complement C3a des Arg EIA kit # 900-058, Assay Designs, Inc.).
Radioactivity was determined by 5-min counting in a Beckman gamma counter at the standard setting for 125I. Values were compensated for the radioactivity decay over time.
Estimations of ultrafiltration and reabsorption
Drained volume gain (net ultrafiltration) was determined from the weight gain of the PD bags, supplemented by the dead-space volume of the sampling bag and the total volume of samples taken during the dwell.
Reabsorption of PDF was assumed to occur at a constant flow rate over the dwell time, leading to a loss of the volume marker dissolved in the reabsorbed fluid. Thus, the total loss of volume marker was determined from the difference between 125I activity added to the PDF initially and the sum of 125I activities detected in the drained volume and the intraperitoneal residual volume. The reabsorbed volume was calculated from the total loss of volume marker divided by the time average of the volume marker concentration of the PD fluid samples.
Statistics
Parametric statistics were used throughout the study. Comparisons between different treatments were performed as paired t-tests. Associations between variables were analysed by paired correlations. Multiple comparisons were compensated for by applying a sequentially rejective Bonferoni correction as indicated in the text.
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Results |
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All dwells were carried out without signs of discomfort, and no symptoms were reported. The two study groups were similar with respect to age and sex. Study group 1 (5 mM/L citrate) included five females and eight males, aged 68.6 ± 8.3 (mean ± SEM) years. Study group 2 (heparin and 10 mM/L citrate) included eight females and nine males, aged 68.8 ± 6.7 years. Average time on PD was longer in the 10 mM/L group (27.0 ± 26.8) compared with the 5 mM/L group (17.6 ± 10.2) mostly due to an outlayer value of 102 months in one patient. PDC measurements performed during normal clinical follow-up prior to the study dwells did not differ between the two study groups (Table 1).
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The experimentally measured drained volume gains obtained with standard PDF (Figure 1) were not significantly different between the study groups. Supplementation with 5 mM/L citrate in study group 1 but not supplementation with 10 mM/L citrate in study group 2 significantly increased the drained volume gain (Figure 1). In study group 1, standard PDF induced 0.31 ± 0.08 L and 5 mM/L citrate induced 0.44 ± 0.07 L of drained volume gain. The increment of ultrafiltration (drained volume gain) produced by 5 mM/L of citrate was 126 ± 54 mL. For heparin supplementation (study group 2) there was a trend towards an increase in drained volume gain (P = 0.08; heparin = 0.32 ± 0.04 L; standard PDF = 0.24 ± 0.05 L). The reabsorption of intraperitoneal fluid was not significantly affected by any of the additives; however, 10 mM/L citrate tended to reduce the reabsorption volume calculated at 4 h of dwell time (P = 0.09; Figure 1).
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The clearance of small solutes from plasma to PDF was affected consistently by citrate supplementation. Measured mean values for clearance of urea, phosphate and creatinine all seemed to increase; however, only phosphate, at 5 mM/L citrate, and creatinine, at 10 mM/L citrate, increased significantly (Table 2). Clearance of creatinine increased significantly also in response to heparin. Dialysate over plasma concentrations of creatinine and urea increased significantly at 10 mM/L citrate. The transport of glucose and albumin was not significantly affected by citrate (Table 2).
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There was an accumulation of calcium intraperitoneally during the dwell. After 30 min and onwards, the difference between standard PDF and citrate-supplemented PDF was significant (Figure 2). At the end of the dwell, the calcium concentration difference between standard PDF and 10 mM/L citrate was 0.32 ± 0.020 mM/L,
50% larger than the difference between standard PD and 5 mM/L citrate (0.21 ± 0.027 mM/L). There were no significant differences in the intraperitoneal calcium concentration between heparin-supplemented PDF and standard PDF at any time.
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Citrate elimination from the peritoneal cavity occurred linearly over time at < 5 mM/L (Figure 3). At concentrations of >5 mM/L, elimination seemed to occur more rapidly (Figure 3). For standard PDF, citrate levels were zero at all time points.
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In plasma, the concentration of free calcium ions (Ca2+) fell initially under the influence of citrate-supplemented PDF and then recovered. For 5 mM/L citrate supplementation, there was a significant reduction of plasma calcium at 60 min. With 10 mM/L citrate, plasma calcium was significantly lowered at 30, 60, 120 and 180 min (Figure 4).
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The bicarbonate concentrations in plasma did not increase significantly over dwell time, and there were no significant differences between the two fluids at any time. There was, however, a significant correlation between dwell time and bicarbonate concentration of 10 mM/L citrate. Linear regression analysis yielded a relationship corresponding to a 2.05 mM/L increase in plasma bicarbonate concentration over the 4-h dwell time. Citrate levels in plasma were not detectable.
Initial dialysate concentrations of complement factor C3a-desArg were significantly lower at 10 mM/L citrate supplementation than in standard PD (19.3 ± 6.25 and 32.6 ± 6.64 ng/mL, respectively). Differences at 60 and 240 min were insignificant. At 5 mM/L citrate, the C3a-desArg concentrations were not significantly affected. For all fluids, C3a-desArg concentrations increased to 150 ng/ mL during the dwell.
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Discussion |
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This is the first clinical study of citrate in peritoneal fluids, and the effects are promising. The supplementation of standard PDF with 5 mM/L of sodium citrate significantly increased the net ultrafiltration measured as drained volume gain after a single dwell (Figure 1). No signs of distress were noted from the patients, and unwanted effects as seen in laboratory data were mild and dependent on the dose of citrate given. The measurements indicate an average ultrafiltration increase of 126 mL, which is substantial in dwells where the average ultrafiltration using standard PDF was 310 mL. Since this was the first study of citrate-supplemented PDF in humans, only single dwells were performed. Future studies will establish whether the citrate effect remains stable over repeated dwells.
An important hypothesis behind the introduction of citrate was that complement inhibition improves ultrafiltration [8]. Therefore, two known complement inhibitors, heparin [14] and citrate, were compared in one of the evaluations. Data show evidence for complement inhibition at 10 mM/L citrate in the present study, since the concentrations of C3a-desArg in the samples taken at time zero (actually representing a few minutes of PDF exposure) were significantly lowered. At 5 mM/L citrate supplementation, there were no signs of complement inhibition although ultrafiltration increased significantly. Consequently, the present results do not support a causal connection between complement inhibition and the ultrafiltration increase induced by citrate.
Unexpectedly, 5 mM/L citrate created a significant ultrafiltration increase in contrast to 10 mM/L citrate that did not. The citrate effect in terms of mean ultrafiltration increment in relation to standard PDF was 0.089 ± 0.061 L at 10 mM/L citrate and 0.126 ± 0.054 L at 5 mM/L citrate and did not differ significantly between the two citrate concentrations. Thus, there was no statistical support for a difference between the two concentrations of citrate. Moreover, the positive increment of ultrafiltration at 10 mM/L may indicate that this citrate concentration improves ultrafiltration, but, due to lack of statistical power (P = 0.16), this could not be demonstrated.
Regarding the small-solute transport, the results suggest that 10 mM/L citrate had a stronger effect than 5 mM/L citrate on creatinine diffusion. This impression was supported by a significant difference in D/P creatinine increment between the two citrate concentrations (0.011 ± 0.017 at 5 mM/L and 0.073 ± 0.017 at 10 mM/L). For other variables expressing clearance or diffusion (D/P), the statistical evaluation could not detect differences in increments between the two citrate concentrations.
An alternative interpretation is that the dose dependence of D/P creatinine and the trend towards a difference in ultrafiltration increment between citrate concentrations could reflect differences between the patients in the two study groups. The clinical data, including the PDC measurements (Table 1), did not differ significantly between the study groups, but there were some trends that could have influenced the results. There were tendencies towards higher diffusion capacity (PDC area, creatinine clearance and D/P creatinine), lower reabsorption (PDC absorption and measured reabsorption) and higher ultrafiltration (drained volume gain) on standard PDF in study group 1. Analyses of correlations between those variables and the citrate effects on ultrafiltration and clearance provided one possible connection. Thus, D/P creatinine increment was negatively correlated to PDC area, and study group 1 had a trend towards a larger PDC area and showed a significantly smaller D/P creatinine increment. In contrast, ultrafiltration increment was positively correlated to reabsorption, but study group 1 had a trend towards a lower reabsorption and showed a higher ultrafiltration increment in response to citrate. To summarize, the significant difference in D/P creatinine increment between 5 and 10 mM/L citrate could partly be accounted for by the smaller PDC area in study group 2. The apparent difference in ultrafiltration increment between 5 and 10 mM/L citrate could neither be statistically supported nor be explained by differences between the patients in the two study groups.
Consequently we can neither confirm, nor refute ultrafiltration and diffusion dose responses to citrate, and the citrate effects on transperitoneal transport are likely to have complex mechanisms of action. A large number of calcium-dependent biological processes including coagulation, mast cell activation, integrin binding and smooth muscle contraction have a potential to interact with transperitoneal transport. Moreover, calcium-independent effects of citrate cannot be ruled out without specific investigations of this possibility. In our recent study in rats [9], net ultrafiltration was related to the citrate concentration through a positive, almost linear, relationship with a tendency for a plateau at the highest concentration that was 15 mM/L. In rats, the elimination of citrate was approximately three times faster than in humans. Therefore, the intraperitoneal concentrations in humans remained high much longer than in rats preventing a direct comparison of dose response data between species. In the rats, citrate reduced the glucose transport rate, indicating that the ultrafiltration increase was related to an improved retention of the osmotic gradient during the dwell. This effect would directly counteract the commonly described mechanism of ultrafiltration failure in ‘high transporters’. In the present study in humans, there was no evidence for changes in glucose transport despite that the clearance of creatinine and phosphate increased at both citrate concentrations. The improved clearances of those solutes (Table 2) were caused by equal contributions from increased intraperitoneal fluid volumes and elevated intraperitoneal concentrations (D/P) at the end of the dwell. Thus, diffusion of small solutes and ultrafiltration of water into the peritoneal cavity increased in parallel and out-transport of glucose remained unchanged. Possible explanations include changes in available vascular surface area and active glucose transport rates. The measurements of volume marker concentrations indicate that a major part of the improved ultrafiltration caused by citrate was due to a reduced reabsorption of fluid into the peritoneal tissue. There was a trend towards a reduced calculated reabsorption volume at 10 mM/L citrate (P = 0.09) and the measured changes in reabsorption at 5 mM/L point in the same direction (Figure 1). This type of effect has not been described earlier in humans; however, there are similarities with the actions of hyaluronan added to PD fluid in rats [15], attributed to the ‘filter cake’ phenomenon.
It has to be considered, though, that the calculation of reabsorption volumes presumed a constant reabsorption flow rate over time during the dwell. This type of presumption is common for all estimations of reabsorption based on volume marker dilution and a single determination of true intraperitoneal volume at the end of the dwell. At least part of the apparent reduction of reabsorption by citrate could therefore be due to a shift of reabsorption flow from an earlier to a later part of the dwell. Reabsorption of PD fluid is a complex issue. In the present study, reabsorption was calculated from the clearance of volume marker from the intraperitoneal cavity. As shown by other investigators, only a minor fraction of the cleared volume marker reaches the circulation during the dwell (in the present study 5%), presumably via the lymphatics. The fate of the remainder of the tracer is not known. It either distributes freely in the peritoneal extravascular fluid space (including the lymphatic system) or binds/adsorbs to cells or extracellular macromolecules. In the former case, the calculated reabsorption volumes are reasonably accurate, but in the latter case, they are overestimated and may obscure other effects of citrate. Nevertheless, the citrate effect on ultrafiltration, exerted through a reduced reabsorption, is a new phenomenon in peritoneal physiology and the underlying mechanisms can only be hypothesized. Calcium chelation has potentials to interact directly or indirectly with the functional status of the microvascular bed and with the properties of the extracellular matrix of the peritoneal connective tissue, both being barriers to transperitoneal transport.
Thus, further studies are required in order to characterize the mechanisms of action behind the citrate effects on different transperitoneal transport processes.
The effects of citrate on calcium turnover were directly related to the degree of citrate supplementation. The transient drop in plasma calcium during the dwell (Figure 4) as well as the calcium loss by the end of the dwell was directly related to the initial citrate concentration of the PDF. Taken together, the data strongly suggest that an optimum concentration for citrate supplementation should be close to 5 mM/L, where a positive effect on ultrafiltration was demonstrated and the negative effects on calcium homeostasis were relatively small. We detected an increase in plasma bicarbonate concentration during the dwell due to metabolism of the administered citrate [12] at 10 mM/L, but the analyses failed to confirm this for the lower concentration. Assuming that bicarbonate formation is proportional to the amount of citrate administered, 5 mM/L citrate would increase the plasma bicarbonate concentration by 1.0 mM/L during a 4-h dwell.
The data on supplementation with low-molecular-weight heparin showed a trend towards an improved net ultrafiltration (P = 0.08), although the effect did not reach statistical significance. Since the study included a relatively small number of patients, there may still be an effect of heparin that was overlooked due to insufficient statistical power. In this case, the acute heparin effect in humans is consistent with that seen in rats [8]. Moreover, this acute effect of heparin could be related to the heparin effect on ultrafiltration reported after 3 months of treatment in a clinical study by Sjöland et al. [7].
Considering the methodology of the present study, a truly explorative approach was used due to the novelty of the treatment. Two different concentrations of citrate were studied separately and in detail. The present results support further studies of a new fluid based on 5 mM/L citrate and a lactate concentration of <40 mM/L. Such a fluid could, hypothetically, improve ultrafiltration and clearance of small solutes substantially at a cost of a calcium loss limited to 0.5 mmol (20 mg) per dwell and negligible effects on the acid–base status. A gradually increasing number of repeated dwells will have to be evaluated in order to characterize the cumulative effects on peritoneal transport, on calcium homeostasis and on the acid–base balance and also to discover any unexpected effects of the treatment. Another concern is the low calcium levels created in the peritoneal tissue by citrate. Especially the mesothelial cell layer and the cells suspended in the intraperitoneal fluid perceive low calcium concentrations. Other cells are better supplied with calcium by diffusion from the blood. Citrate is, however, compared with e.g. EDTA, a weak calcium chelator, and the intraperitoneal concentrations of free calcium ions at 10 mM/L citrate did not fall below 100 µm in the recent animal study [9]. Reported damage to cells occurs at calcium concentrations of <10 µm and typically involves intracellular junctions and cytoskeletal structures [16]. The risk of cell damage by citrate has to be specifically evaluated by studying markers of cell death and cell integrity in humans.
In conclusion, supplementation of a standard lactate and glucose-based PD fluid with citrate at 5 mM/L significantly improved net ultrafiltration and small solute clearance in single dwells in PD patients. The ultrafiltration improvement was probably due to a reduced reabsorption of fluid into the peritoneal tissue. Apart from the evidence that complement inhibition was not involved, the mechanisms of action behind the observed effects remain unclear. Expected side effects on calcium homeostasis and acid–base balance were small, and no signs of distress were noted among the patients. The present results motivate further evaluation of PD fluids based on citrate.
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Acknowledgments |
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This study was supported by grant no. ALFGBG-3239 from the LUA-ALF agreement at the Sahlgrenska University Hospital, Gothenburg, Sweden and by grants from the Swedish Kidney Foundation, from the Göteborg Medical Society and from Gambro AB.
Conflict of interest statement. Magnus Braide participates in an application for patent involving citrate-based PD fluids and has received research grants from Gambro AB.
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[Abstract/Free Full Text]
Accepted in revised form: 15. 7.08
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