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Keywords:

  • 1α-hydroxycholecalciferol oral;
  • calcitriol;
  • calcium;
  • continuous ambulatory peritoneal dialysis;
  • parathyroid hormone;
  • secondary hyperparathyroidism

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Brandi L, Nielsen PK, Bro S, Daugaard H, Olgaard K (Rigshospitalet, University of Copenhagen, Denmark). Long-term effects of intermittent oral alphacalcidol, calcium carbonate and low-calcium dialysis (1.25 mmol L−1) on secondary hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis. J Intern Med 1998; 244: 121–31.

Objectives

(i) To examine the effect of alphacalcidol [1α(OH)D3] given as an oral dose twice weekly in combination with CaCO3 and low-calcium dialysis (1.25 mmol L−1) on the secondary hyperparathyroidism in continuous ambulatory peritoneal dialysis (CAPD). (ii) To examine the changes in peritoneal mass transfer for calcium, phosphorus, magnesium, lactate, creatinine, urea, glucose, pH and albumin after shift to low-calcium dialysis solution.

Design

An open study in patients on CAPD.

Setting

Renal division, Rigshospitalet, Copenhagen.

Subjects

Thirty-nine patients were included and completed 12 weeks of treatment. Thirty of the patients completed 52 weeks of treatment. A peritoneal equilibrium test (PET) was performed in seven patients.

Interventions

Following two sets of blood samples obtained as basal values the calcium concentration was reduced in the dialysis fluid from 1.75 mmol L−1 to 1.25 mmol L−1. Increasing doses of oral 1α(OH)D3 were then administered under careful control of p-ionized calcium (p-Ca2+) and p-inorganic phosphate (p-Pi). Blood samples were obtained every 2–4 weeks for 52 weeks. PET was performed using standard dialysis fluid and 1 week later using low-calcium dialysis fluid after a preceding overnight dwell. Two litres of glucose 22.7 mg mL−1 were used.

Main outcome measures

Intact parathyroid hormone (PTH), p-Ca2+, p-Pi, doses of CaCO3, doses of 1α(OH)D3, peritoneal mass transfer for calcium, inorganic phosphate, magnesium, lactate, creatinine, urea, glucose and albumin.

Results

Thirty nine patients with initial PTH values 144 ± 26 pg mL−1 were followed for 12 weeks and 30 patients for 52 weeks. A negative calcium balance was induced after shifting to low-calcium dialysis fluid. After 2 weeks of treatment a significant increase of PTH by approximately 60% and a small but significant decrease of p-Ca2+ was observed. After 12 weeks of treatment with increasing doses of 1α(OH)D3 and CaCO3, PTH was again reduced to levels not significantly different from the initial values. After 52 weeks of treatment no deterioration of the secondary hyperparathyroidism was seen.

Conclusions

A calcium concentration of 1.25 mmol L−1 in the CAPD dialysate made it possible to reduce the amount of aluminium-containing phosphate binder, to increase the doses of CaCO3 and to use pulse oral 1α(OH)D3 without causing severe hypercalcaemia in the patients. After a short elevation of PTH, the PTH levels remained at normal or near normal levels and the long-term results clearly demonstrated that an aggravation of the secondary hyperparathyroidism could be inhibited.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Renal osteodystrophy is a common finding in patients undergoing chronic dialysis [ 1]. A change in the spectrum of bone disease from predominant osteitis fibrosa to adynamic bone disease, especially in patients on continuous ambulatory peritoneal dialysis (CAPD), has been found in the last decade, presumably due to continuously higher p-ionized (p-Ca2+) levels in patients on CAPD than in those on chronic haemodialysis [ 1]. The high calcium concentration of the dialysate (1.75 mmol L−1), the change of the oral phosphate binder therapy from aluminium hydroxide to CaCO3 and the more frequent use of active vitamin D metabolites during the recent years may all contribute to this development [ 2]. The reduced 1,25(OH)2D3 levels in uraemia result in a reduced suppression of parathyroid hormone (PTH) synthesis and are an important factor in the development of secondary hyperparathyroidism (HPT) [ 3]. Thus several human studies have shown a positive effect on suppression of PTH secretion from supplementation with active vitamin D metabolites in CAPD patients [ [4][5][6][7][8][9][10]4–11]. A common feature in most of the studies is a limitation in the use of high dosages of active vitamin D, when CaCO3 is used as oral phosphate binder. Therefore, a reduction of the calcium concentration of the dialysate was introduced in some clinical studies [ 5, 7, 8]. The route of administration and the frequency of dosing of the active vitamin D metabolites have been discussed carefully [ 12]. Intravenous treatment has been claimed to provide a more optimal control of the secondary HPT and to have a less calcaemic effect than daily oral administration in patients on chronic haemodialysis [ 13]. Recently, however, two studies in patients on chronic haemodialysis found an equal beneficial effect on the suppression of PTH by intermittent oral and intermittent intravenous 1,25(OH)2D3 [ 14, 15]. Thus, intermittent rather than intravenous treatment may be of importance. Intravenous administration of vitamin D is inconvenient and not practical for patients on CAPD, although it has been tried [ 8]. Intermittent (once a week) [ 11] and daily intraperitoneal administration [ 10] and intermittent (3 times a week) subcutaneous administration [ 9] has been attempted with positive results, but not with results superior to those of oral treatment. Therefore, intermittent oral administration has been the first choice in patients on CAPD and positive results have been reported with the use of both high (1.75 mmol L−1) [ 6] and low-calcium dialysis (1.25 mmol L−1) [ 7].

Frequent episodes of hypercalcaemia using high calcium dialysis and a suspicion of an increased representation of adynamic bone disease have lead to reluctance to use active vitamin D metabolites in patients on CAPD. In our experience the combination of low-calcium dialysis (1.25 mmol L−1), CaCO3 and pulse intravenous 1α(OH)D3 prevented the development of secondary HPT in patients on haemodialysis with normal PTH at the initiation of the study, and induced a long-term (88 weeks) suppression of PTH in patients with secondary HPT. By careful monitoring, severe hypercalcaemia and hyperphosphataemia were avoided, and there was no indication, either clinically or biochemically, of development of adynamic bone disease [ 16]. Therefore, our intention was to evaluate whether it was possible to use a similar regime, but with intermittent oral instead of intermittent intravenous 1α(OH)D3, in order to achieve the same positive long-term results in patients on CAPD. The present study presents in patients on CAPD the effects on the secondary HPT of 1 year of intermittent (twice weekly) oral use of 1α(OH)D3 in combination with CaCO3 and low-calcium dialysis (1.25 mmol L−1). In order to examine for changes in the peritoneal mass transfer after shifting to low-calcium dialysis solution, a peritoneal equilibrium test (PET) [ 17] was performed and analysed for calcium, inorganic phosphate, magnesium, lactate, creatinine, urea, glucose and albumin in seven patients.

Materials and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Patients

All eligible CAPD patients dialysed with a solution containing 1.75 mmol L−1 of calcium were invited to join the study and 41 patients at the Renal Division, Rigshospitalet, Copenhagen entered the study. The total observation period was 52 weeks. Thirty nine patients completed the first 12 weeks of treatment, whilst one patient had a renal transplantation after 2 weeks and one diabetic patient with severe vascular disease wanted to stop after 6 weeks of treatment in relation to an episode of peritonitis. A further nine patients were withdrawn after 12 weeks of treatment. One died from an acute myocardial infarction (AMI), three patients underwent a renal transplantation, one had a severe exacerbation in a chronic obstructive lung disease and was unable to carry out CAPD, one had a ventral hernia operation and stopped CAPD for several weeks, one patient was transferred to haemodialysis due to his own wish, whilst two patients were temporarily transferred to haemodialysis after recurrent peritonitis. Thus, 30 patients were followed for 52 weeks. The demographic data, primary diseases and clinical data for the 39 patients followed for at least 12 weeks are described in Table 1. Initially all patients used a standard peritoneal dialysis fluid (Dianeal®, Baxter Healthcare Corp., Deerfield, Chicago, USA). The electrolyte concentrations were the following: calcium 1.75 mmol L−1, lactate (D + L) 35 mmol L−1, potassium 0 mmol L−1, magnesium 0.75 mmol L−1, sodium 132 mmol L−1 and chloride 102 mmol L−1. Two weeks after initiation of the study the dialysis fluid was changed to a low calcium dialysis solution (PD4®; Baxter Healthcare Corp., ) with the following electrolyte concentrations: calcium 1.25 mmol L−1, lactate (D + L) 40 mmol L−1, potassium 0 mmol L−1, magnesium 0.25 mmol L−1, sodium 132 mmol L−1 and chloride 95 mmol L−1. At the start of the study seven patients were already treated daily by oral 1α(OH)D3. One patient was treated with an angiotensin-converting enzyme (ACE) inhibitor, eight with a calcium-antagonist, 12 with a beta blocker, seven with a loop diuretic, five with digoxin, three with omeprazol, 13 with H2-antagonist, whilst none received a potassium calcium-resin.

Table 1.  Demographic data, primary diseases and clinical data of the 39 patients on continuous ambulatory peritoneal dialysis (CAPD) treated with low-calcium dialysis (1.25 mmol L−1)', 1α(OH)D3 orally twice weekly and CaCO3 as principal oral phosphate binder Thumbnail image of

Treatment schedule

Two sets of blood samples were obtained as basal values. The calcium concentration in the dialysis fluid was then reduced from 1.75 mmol L−1 to 1.25 mmol L−1 in order to avoid hypercalcaemia when 1α(OH)D3 and CaCO3 were administered together. 1α(OH)D3 (Leo Pharmaceutical, Copenhagen, Denmark) was given orally twice weekly beginning at day 0. The doses of 1α(OH)D3 were adjusted with reference to levels of p-Ca2+ and p-inorganic phosphate (p-Pi). If p-Ca2+ >1.35 mmol L−1 or p-Pi >2.5 mmol L−1 the 1α(OH)D3 treatment were temporarily stopped or a lower dose was given. A smaller increase in p-Pi resulted in an increase in the dose of CaCO3. Treatment with aluminium-containing phosphate binder (Almin® [aluminiumaminoacetate]; ) was changed to CaCO3.

P-Ca2+ was measured every week for the first 4 weeks, then every 2nd week for the following 2 months and then every month. PTH 1–84 and p-Pi were measured every 2nd week for the first 3 months and then every month. P-total calcium and p-1,25(OH)2D3 were measured after 0, 2, 4, 8, 12, 16, 24, 36 and 52 weeks of treatment. P-magnesium, s-albumin and p-alkaline phosphatase were measured after 0, 4, 8, 12, 24, 36 and 52 weeks. Doses of 1α(OH)D3, CaCO3 and aluminium-containing phosphate binder were currently registered.

PET was performed in seven patients using standard dialysis fluid and 1 week later using low-calcium dialysis fluid, after a preceding overnight dwell according to the recommendation of Twardowski [ 16].

All patients gave their informed consent to participate in the study, which was approved by the Danish Ethical Committee for Medical Research.

Methods

PTH 1–84 was measured by an immunoradiometric assay (IRMA) (Allegro; Nichols Institute, San Juan, CA, USA). Sensitivity was 1 pg mL−1. Intra-assay variation was 3%, interassay variation was 6%. The normal range was 10–55 pg mL−1, determined in 255 normal subjects [ 18].

Plasma-1,25(OH)2D3 was extracted from plasma with diethylether, and extracts were chromatographed, as described by Reinhardt et al. [ 19]. Levels of 1,25(OH)2D3 were measured by a competitive protein binding assay using calf thymus cytosol as the source of binding protein. Sensitivity was 3 pg mL−1. Intra-assay variation was 3.8% and interassay variation was 14.7%. In our laboratory normal values were 37.7 ± 11.2 pg mL−1.

Plasma-Ca2+, pH and p-Ca2+ adjusted to 7.4 was measured by a calcium ion electrode analyser (ICA 2; Radiometer, Copenhagen, Denmark). Unless otherwise stated, the p-Ca2+ adjusted to pH 7.4 was used. Total plasma-calcium was measured by flame absorption, plasma-phosphate by photometry. Serum-aluminium was measured by electrothermical atomic absorption photometry.

Blood samples for determination of plasma-Ca2+ and pH were measured immediately. Blood samples for determination of PTH and 1,25(OH)2D3 were immediately placed on ice until separated. The remaining plasma was stored at −20°C until analysis.

P-magnesium, p-lactate (L + D), p-creatinine, p-urea, p-glucose, and s-albumin were measured by standard laboratory test.

For the PET, 2 L of glucose 22.7 mg mL−1 were used. Samples of blood and dialysate were taken after 0, 1, 2, 3 and 4 h and analysed for calcium, phosphorous, magnesium, lactate, creatinine, urea, glucose, pH and albumin. Mass transfer (MT) was calculated from the formula:

inline image

where A is the instilled dialysate concentrations of the solute, B the instilled dialysate volume, C the dialysate concentration of solute drained and D its volume (D).

Statistical analysis

For comparison of mean values during the treatment periods two-way analysis of variance was used [ 20]. For comparison of mean values between specific days, the paired Student's t-test was used. For comparison between groups the unpaired Student's t-test was used. Correlation coefficients were calculated as Pearson's r (r2). All significance limits are two-sided and expressed as mean ± SE.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The relationships between changes in p-PTH 1–84, p-Ca2+, p-Pi, p-1,25(OH)2D3 and doses of 1α(OH)D3 are presented in Fig. 1 for the 39 patients who completed the first 12 weeks of treatment and for the 30 patients who completed 52 weeks of treatment. 13 out of 39 patients had PTH of <55 pg mL−1, 19 had PTH in the range 55–300 pg mL−1, whilst seven had PTH of >300 pg mL−1. Initial mean p-PTH levels were moderately elevated, about 3 times the upper normal limit ( Fig. 1, Table 2).

image

Figure 1. Mean values (± SE) of p-intact parathyroid hormone (PTH), p-ionized calcium, p-inorganic phosphate (p-Pi) and p-1,25(OH)2D3 in relation to oral weekly doses of 1α(OH)D3 and time of treatment in 39 patients on continuous ambulatory peritoneal dialysis (CAPD) treated for 12 weeks (–á–á–) and 30 patients for 52 weeks (———). Doses of 1α(OH)D3 were administered orally at home twice a week. For statistical analysis see text and Table 2. For the sake of clarity the error-bars are only shown for the long-term treatment period.

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Table 2.  Response to low-calcium dialysis (1.25 mmol L−1), 1α(OH)D3 orally twice a week and CaCO3 as principal oral phosphate binder for 2, 12, 36 and 52 weeks in patients on continuous ambulatory peritoneal dialysis (CAPD) (mean ± SE) Thumbnail image of

After 2 weeks of treatment a significant increase of PTH by approximately 60% (P < 0.005 compared to initial levels, Fig. 1, Table 2) was observed together with a small, but significant decrease in p-Ca2+ (P < 0.006).

After 12 weeks of treatment with increasing doses of 1α(OH)D3 and CaCO3, PTH was again reduced to levels not significantly different from initial values ( Fig. 1; Table 2). PTH remained stable and was still not significantly different from initial levels after 52 weeks of treatment ( Fig. 1; Table 2). Exactly the same course was observed in all patients, independent of initial PTH levels.

P-Ca2+ was initially 1.27 ± 0.01 mmol L−1. After 2 weeks of treatment with low-calcium dialysis fluid p-Ca2+ decreased significantly to 1.23 ± 0.01 mmol L−1 (P < 0.0001, compared to initial level). P-Ca2+ increased again due to treatment with 1α(OH)D3 and CaCO3 and was after 12 weeks of treatment not significantly different from initial levels, but after 52 weeks of treatment significantly higher than initial levels (1.33 ± 0.02 mmol L−1, P < 0.0001). During the treatment period only a few episodes of clinically relevant hypercalcaemia were observed ( Table 3). In one case treatment with calcitonin was necessary, otherwise a reduction or temporary discontinuation of 1α(OH)D3 and CaCO3 were sufficient to reduce p-Ca2+.

Table 3.  Number (n) of intercurrent hypercalcaemic episodes in 39 patients on continuous ambulatory peritoneal dialysis (CAPD) treated with low-calcium dialysis (1.25 mmol L−1), 1α(OH)D3 orally twice a week and CaCO3 as principal oral phosphate binder for 12 weeks and 30 patients for 52 weeks Thumbnail image of

After changing to CaCO3 as the principal oral phosphate binder some insignificant fluctuations of p-Pi were observed ( Fig. 1; Table 2). Initially 31 of the 39 patients (80%) were treated with CaCO3 as oral phosphate binder. At the end of the study the doses of CaCO3 were significantly increased (from 2.6 ± 0.4 to 4.1 ± 0.5 g per day, P < 0.006, Table 2). 12 of 39 patients (31%) had initially to be treated with Almin®. At the end of the study, the number of patients on Almin® was reduced to seven out of 30 (23%, but the dose was the same, Table 2). P-Al3+ was significantly higher in those patients who were treated with Almin® than in those who were not (with Almin®: 50.4 ± 8.7, without Almin®: 15.2 ± 2.3 mg L−1), and no significant changes in p-Al3+ were observed during the study period ( Table 2).

Levels of p-1,25(OH)2D3 were initially very low ( Table 2). During the treatment period ( Fig. 1), p-1,25(OH)2D3 increased to 25.6 ± 3.5 pg mL−1 after 8 weeks of treatment ( Fig. 1, P < 0.0001) followed by a gradual decrease, when doses of 1α(OH)D3 were reduced. After 52 weeks of treatment p-1,25(OH)2D3 was still significantly higher than initial level (P < 0.0001, Fig. 1; Table 2). Samples for measurement of p-1,25(OH)2D3 were drawn together with the other blood samples at the visit at the out-patient clinic. Thus the values measured did not reflect the possible transient high levels of p-1,25(OH)2D3 during the first hours after administration of 1α(OH)D3.

The doses of 1α(OH)D3 were gradually increased to a maximum of 3.1 ± 0.4 mg per week after 10 weeks of treatment. To keep p-Ca2+ and p-Pi at acceptable levels, doses of 1α(OH)D3 were decreased gradually to 1.4 ± 0.3 mg per week after 52 weeks of treatment, still significantly higher than initial levels (P < 0.004).

Total p-Mg was initially 1.19 ± 0.03 mmol L−1 and decreased during the treatment period to 0.86 ± 0.04 mmol L−1 (P < 0.0001, Table 2).

P-alkaline phosphatase levels were initially normal and no significant changes were observed during the treatment period ( Table 2).

Initial p-lactate (D + L) was higher than normal ( Fig. 3, 1.74 ± 0.23 mmol L−1; normal range 0.55–1.38 mmol L−1) and no significant changes were observed during the treatment period ( Fig. 3).

image

Figure 3. P-lactate (mean ± SE) during a 4 hour peritoneal equilibrium test (PET) (2 L glucose 22.7 mg mL−1) and peritoneal mass transfer (mmol per exchange) of lactate in seven patients on continuous ambulatory peritoneal dialysis (CAPD) when using two different dialysis solutions – Dianeal® (d-calcium 1.75 mmol L−1, d-lactate 35 mmol L−1) and PD4® (d-calcium 1.25 mmol L−1, d-lactate 40 mmol L−1).

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Peritoneal equilibrium test and mass transfer

After changing to low-calcium dialysis solution no significant differences were observed in the peritoneal transport rates (dialysate/plasma [D/P]-ratio) of urea, glucose corrected creatinine, glucose or albumin ( Fig. 2). Although the lactate concentration in the low calcium dialysis solution was higher than in the standard solution, no significant differences were observed in total p-lactate or lactate mass transfer (MT, Fig. 3). D/P-ratios concerning lactate and pH were also the same for the two different dialysis solutions ( Fig. 2). No significant changes concerning inorganic phosphate were found in D/P-ratio ( Fig. 2) or MT ( Fig. 4). On the other hand significant differences were observed concerning magnesium and calcium D/P-ratio (magnesium at 0, 1, 2, 3 h: P < 0.05; at 4 h: P= 0.07; calcium at 0, 1, 2, 3, 4 h, P < 0.05) and MT (magnesium P < 0.0001, calcium P < 0.0003) ( Figs 2 and 4). There was a clear correlation between initial p-Mg and magnesium MT ( Fig. 5, r2= 86.5%; P= 0.002) when low calcium/magnesium solution was used, whilst no correlation was observed when standard solution was used ( Fig. 5, r2= 7.8%; P= 0.531). The same was observed for calcium MT and initial p-Ca2+ ( Fig. 5, r2= 52.0%; P= 0.067) when the low calcium solution was used, whilst no correlation was observed when standard solution was used ( Fig. 5, r2= 18.9%; P= 0.508). Although only examined in a small number of patients, the loss of calcium tended to be highest in the patients with the highest initial p-Ca2+, when shifting to low calcium dialysis solution ( Fig. 5).

image

Figure 2. Mean ± SE of dialysate-to-plasma (D/P) ratios for calcium, inorganic phosphate (Pi), magnesium, lactate, pH, glucose, albumin, urea and creatinine in seven patients on continuous ambulatory peritoneal dialysis (CAPD) when using two different dialysis solutions: Dianeal® (d-calcium 1.75 mmol L−1, d-magnesium 0.75 mmol L−1, lactate 35 mmol L−1) and PD4® (d-calcium 1.25 mmol L−1, d-magnesium 0.25 mmol L−1, lactate 40 mmol L−1).

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image

Figure 4. Peritoneal mass transfer (mmol per exchange) of calcium, magnesium and inorganic phosphate (Pi) during a 4 h peritoneal equilibrium test (PET) (2 L glucose 22.7 mg mL−1) in seven patients on continuous ambulatory peritoneal dialysis (CAPD) when using two different dialysis solutions – Dianeal® (d-calcium 1.75 mmol L−1, magnesium 0.75 mmol L−1) and PD4® (d-calcium 1.25 mmol L−1, magnesium 0.25 mmol L−1). *P &lt; 0.0003.

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image

Figure 5. Actual p-Ca2+ plotted against calcium mass transfer (mmol per exchange) and p-total magnesium plotted against magnesium mass transfer (mmol per exchange) for a 22.7 mg mL−1 glucose solution in seven patients on CAPD when using two different dialysis solutions. Concerning calcium: Dianeal® (d-calcium 1.75 mmol L−1) r2= 18.9%, P= 0.508 and PD4® (d-calcium 1.25 mmol L−1) r2= 52.0%, P= 0.067. Concerning magnesium: Dianeal® (d-calcium 1.75 mmol L−1, magnesium 0.75 mmol L−1) r2= 7.8%, P= 0.531 and PD4® (d-calcium 1.25 mmol L−1, magnesium 0.25 mmol L−1) r2= 86.5%, P= 0.002.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The present study evaluated the effect of low-calcium dialysis, CaCO3 and intermittent oral 1α(OH)D3 on the secondary hyperparathyroidism in patients on CAPD. Except for a transient increase of p-levels of PTH, the transfer to low-calcium dialysis resulted in no further aggravation of the secondary hyperparathyroidism. The 1α(OH)D3 treatment was administered orally by the patients and the increase in p-1,25(OH)2D3 indicates compliance. Comparing the results obtained in the present CAPD study and the results obtained in our previous study on haemodialysis patients, who had intravenous administration of 1α(OH)D3 [ 16], it is notable that the prescribed weekly doses of 1α(OH)D3 in the present CAPD study were lower after 52 weeks of attempted optimal treatment (1.4 ± 0.31 mg per week), than in the haemodialysis study (2.88 ± 0.52 mg per week) for patients with exactly the same degree of secondary hyperparathyroidism (PTH in CAPD patients 151 ± 41, and PTH in haemodialysis patients 151 ± 44). The CaCO3 doses were higher and p-Ca2+ and p-Pi were lower in the haemodialysis study, than in the present CAPD study. The doses of 1α(OH)D3 were lower in the present CAPD study, than in other CAPD studies which have observed an improvement of the secondary hyperparathyroidism by using low-Ca dialysis and oral intermittent 1,25(OH)2D3 [ 6, 7].

A change in dialysis solutions from Dianeal® to PD4® resulted in changes in dialysis concentrations of both calcium, magnesium and lactate. This shift was however without influence on the D/P ratio for urea, creatinine, glucose and albumin ( Fig. 2). Lactate in the peritoneal dialysis fluid is used as an alkalizing agent and an accumulation of D-lactate is known to cause D-lactate acidosis. The metabolism of lactate (D + L) in CAPD patients using dialysis solutions containing lactate 15 mmol L−1 (Baxter PD-1®) and lactate 20 mmol L−1 (Baxter PD-2®) has previously been carefully investigated [ 21]. It was found that the D-lactate load from the dialysate was metabolized without problems by the patients. Although we did not measure specific D- and L-lactate concentrations no increase was observed in the total p-lactate after changing the dialysis solutions. This would have been expected if an important accumulation of D-lactate had occurred. Furthermore, no differences were observed in lactate MT ( Fig. 3) or D/P pH ratio ( Fig. 2) between the two dialysis solutions, indicating that the increase in the concentration of lactate in the dialysate was of no significant importance.

P-Pi was continuously well-regulated. In this study, as in the study by Hutchison et al. [ 22], it was possible to reduce, but not to exclude Almin®. Inadequate removal of phosphorus by CAPD is well known and a positive phosphorus balance might be the result in the well-nourished CAPD patient, unless diet prescription and oral phosphate binders are used [ 23]. This study demonstrated a negative MT for phosphorus (–1.9 mmol per exchange) and changes in D/P ratios, as observed by other [ 23, 24]. The changes in dialysis solutions did not affect the results significantly.

As seen in earlier studies [ [24][25][26][27]24–28], the present study demonstrated a change from a positive to a negative calcium MT, when the calcium concentration in the dialysate was reduced from 1.75 to 1.25 mmol L−1 ( Fig. 4). It was not possible to demonstrate any relationship between initial p-Ca2+ and calcium MT, when standard solution was used presumably due to the very high d-calcium.

Slight hypermagnesaemia, as in the present study (1.19 ± 0.03 mmol L−1, normal range 0.7–1.1 mmol L−1), is very common in dialysis populations. The long-term consequences are not known. In CAPD patients hypermagnesaemia has been suggested to retard development of arterial calcifications [ 29] and in haemodialysis patients normalization of p-magnesium has been associated with an improvement of bone histology [ 30]. In this study magnesium MT, increased negatively when d-magnesium was reduced from 0.75 to 0.25 mmol L−1, as shown by other studies [ 27]. As with calcium a relationship between initial p-magnesium and magnesium MT was observed when d-magnesium 0.25 mmol L−1 was used ( Fig. 5). The negative MT was large enough to reduce p-magnesium to normal after 12 weeks of treatment (p-magnesium 0.95 ± 0.03 mmol L−1). No signs of hypomagnesaemia were observed, and after 1 year of treatment p-magnesium was still within the normal range (0.86 ± 0.04 mmol L−1).

In conclusion, a calcium concentration of 1.25 mmol L−1 in the CAPD dialysate made it possible to reduce the use of aluminium-containing phosphate binder, to increase the doses of CaCO3 and to use pulse oral 1α(OH)D3 without causing severe hypercalcaemia. A transient increase of PTH was, however, observed after the shift to low-calcium dialysate. Higher doses of 1α(OH)D3 were necessary to reduce PTH to normal or near normal levels. Due to the induced negative calcium balance, however, a reduction of the calcium concentration in the dialysate should only be used in strictly compliant patients.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

We thank Ms Betty Fischer for invaluable laboratory assistance.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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