Calcium mass transfer with dialysate containing 1.25 and 1.75 mmol/L calcium in peritoneal dialysis patients.

Studies with 1.75 mmol/L calcium dialysate have shown that patients gain calcium from dialysate. Thus, hypercalcemia, especially when calcium compounds are used for phosphate control, is a commonly seen complication. Dialysate with 1.25 mmol/L calcium has been available since 1989. Little is known about calcium mass transfer (CMT) with dialysate of this calcium concentration. CMT was measured in 20 stable adult peritoneal dialysis patients. Each CMT study consisted of a 2-L continuous ambulatory peritoneal dialysis (CAPD) exchange with a dwell time of 4 hours. CMT studies were performed using 1.25 and 1.75 mmol/L calcium dialysate with 1.5, 2.5, and 4.25 g/dL dextrose concentrations. CMT with 1.25 mmol/L calcium dialysate was compared to that with 1.75 mmol/L for each dextrose concentration. With a dextrose concentration of 1.5 g/dL, the mean CMT for 1.25 mmol/L calcium dialysate was -0.1 +/- 0.3 mmol versus 0.6 +/- 0.3 mmol for 1.75 mmol/L calcium dialysate (P < 0.0001). A dextrose concentration of 2.5 g/dL resulted in a mean CMT of -0.4 +/- 0.2 mmol for 1.25 mmol/L calcium versus 0.45 +/- 0.25 mmol for 1.75 mmol/L calcium (P < 0.0001). Using a dextrose concentration of 4.25 g/dL, the mean CMT was -0.7 +/- 0.25 mmol for 1.25 mmol/L calcium versus -0.05 +/- 0.35 mmol for 1.75 mmol/L calcium (P < 0.0001). Mean serum ionized calcium (SiCa) was between 1.15 and 1.20 mmol/L for all study groups. CMT inversely correlated with SiCa for each type of dialysate used. CMT was dependent on the concentrations of calcium and dextrose in the dialysate and the SiCa level at the time of the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of intraperitoneal calcitriol on calcium and parathyroid hormone

Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D3 in patients undergoing continuous ambulatory peritoneal dialysis. Eleven patients were dialyzed for two months with standard Ca dialysate (3.5 mEq/liter) followed by two months with 4.0 mEq/liter Ca, then by three months of i.p. 1,25(OH)2D3. During the latter period, patients were randomized to groups whose dialysate contained either 3.5 mEq/liter or 4.0 mEq/liter Ca. We found that 4.0 mEq/liter Ca dialysate more than doubled Ca MT (37 +/- 17 mg/day to 84 +/- 6 mg/day) leading to a modest fall (P less than 0.05) in PTH levels (84 +/- 5.5% of controls). Ionized calcium levels did not change. With i.p. 1,25(OH)2D3, however, ionized calcium rose significantly (P less than 0.001) leading to a decline in PTH levels to 53.9 +/- 7.9% of control values. Serum 1,25(OH)2D3 levels rose from undetectable to 47.7 +/- 7.2 pg/dl (normal range 20 to 35). These studies indicate that increasing Ca MT using a 4.0 mEq/liter Ca dialysate leads to a small reduction in PTH concentrations. On the other hand, i.p. 1,25(OH)2D3 is well absorbed into the systemic circulation, raises ionized calcium levels, and leads to a marked suppression of PTH. Thus, i.p. 1,25(OH)2D3 may be a simple and effective means to suppress secondary hyperparathyroidism in patients undergoing CAPD.     

Hysteresis of the parathyroid hormone response to hypocalcemia in hemodialysis patients with low turnover aluminum bone disease.

During the study of parathyroid function in 19 hemodialysis patients with low turnover aluminum bone disease, it was observed that serum parathyroid hormone (PTH) levels were higher during the induction of hypocalcemia than during the recovery from hypocalcemia. This type of PTH response has been termed hysteresis. Hypocalcemia was induced during hemodialysis with a calcium-free dialysate. When the total serum calcium level decreased to 7 mg/dL, the dialysate calcium concentration was changed to 3.5 mEq/L and the dialysis session was completed. One week later, hypercalcemia was induced during hemodialysis with a high-calcium dialysate. The mean basal PTH level was 132 +/- 37 pg/mL (normal, 10 to 65 pg/mL; immunoradiometric (IRMA), Nichols Institute, San Juan Capistrano, CA) and increased to a maximal PTH level of 387 +/- 91 pg/mL during hypocalcemia. For the same ionized calcium concentration, the PTH level was higher during the induction of hypocalcemia than during the recovery from hypocalcemia. Conversely, for the same ionized calcium concentration, the PTH level was greater when hypercalcemia was induced from the nadir of hypocalcemia than when hypercalcemia was induced from basal serum calcium. The set point of calcium (defined as the serum calcium concentration required to reduce maximal PTH by 50%) was greater during the induction of hypocalcemia than during the recovery from hypocalcemia (4.44 +/- 0.10 versus 4.25 +/- 0.09 mg/dL; P = 0.03). The mean basal ionized calcium concentration and the mean ionized calcium concentration at the intersection of the two PTH-calcium curves were the same (4.61 +/- 0.13 versus 4.61 +/- 0.12 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium carbonate is an effective phosphate binder when dialysate calcium concentration is adjusted to control hypercalcemia

The efficacy of calcium carbonate (CaCO3) as a phosphate binder has been limited by its tendency to cause hypercalcemia. Since standard dialysate calcium concentrations (3.0-3.5 mEq/l) increase the risk of developing hypercalcemia with large doses of CaCO3 by inducing positive calcium balance during hemodialysis (HD), we compared control of hyperphosphatemia in 41 HD patients during 4 months each of aluminum hydroxide (Al(OH)3) and CaCO3 when the dialysate calcium concentration was lowered, as required, to maintain the predialysis serum calcium concentration within the normal range. Mean predialysis serum phosphorus and calcium concentrations were 5.0 +/- 0.2 mg/dl and 9.3 +/- 0.1 mg/dl, respectively, during 4 months CaCO3 (9.2 +/- 0.3 g/day) and 4.9 +/- 0.2 g/dl and 9.1 +/- 0.1 mg/dl during the previous 4 months Al(OH)3 therapy (2.9 +/- 0.2 g/day). Reducing the dialysate calcium concentration to below 3.0 mEq/l (mean 2.1 +/- 0.04) in the 11 patients who developed hypercalcemia on CaCO3 decreased serum calcium (-1.1 +/- 0.15 mg/dl) and ionized calcium (-0.3 +/- 0.04 mEq/l) during HD, enabled CaCO3 (8.8 +/- 0.4 g/day) to be continued, and maintained predialysis serum calcium and phosphorus at 10.4 +/- 0.1 mg/dl and 5.2 +/- 0.3 mg/dl, respectively. No improvement in acidosis or biochemical hyperparathyroidism was observed during CaCO3 therapy but serum aluminum was significantly decreased after CaCO3 (p less than 0.005). We conclude that CaCO3 prevents interdialytic hyperphosphatemia as effectively as Al(OH)3 without increasing the predialysis serum calcium x phosphorus product, provided serum calcium is maintained within the normal range by adjusting the dialysate calcium concentration.     

Reversal of adynamic bone disease by lowering of dialysate calcium

Adynamic bone disease (ABD) is increasingly recognized, especially in dialysis patients treated with oral calcium carbonate, vitamin D supplements, or supraphysiological dialysate calcium. We undertook this study to assess the effect of lowering dialysate calcium on episodes of hypercalcemia, serum parathyroid hormone (PTH) levels as well as bone turnover. Fifty-one patients treated with peritoneal dialysis and biopsy-proven ABD were randomized to treatment with control calcium, 1.62 mM, or low calcium, 1.0 mM, dialysate calcium over a 16-month period. In the low dialysate calcium group, 14 patients completed the study. This group experienced a decrease in serum total and ionized calcium levels, and an 89% reduction in episodes of hypercalcemia, resulting in a 300% increase in serum PTH values, from 6.0+/-1.6 to 24.9+/-3.6 pM (P<0.0001). Bone formation rates, all initially suppressed, at 18.1+/-5.6 microm2/mm2/day rose to 159+/-59.4 microm2/mm2/day (P<0.05), into the normal range (>108 microm2/mm2/day). In the control group, nine patients completed the study. Their PTH levels did not increase significantly, from 7.3+/-1.6 to 9.4+/-1.5 pM and bone formation rates did not change significantly either, from 13.3+/-7.1 to 40.9+/-11.9 microm2/mm2/day. Lowering of peritoneal dialysate calcium reduced serum calcium levels and hypercalcemic episodes, which resulted in increased PTH levels and normalization of bone turnover in patients with ABD.     

The effect of dialysate calcium levels on blood pressure during hemodialysis

A controlled double-blind prospective study was undertaken of the effect of dialysate calcium levels on BP during hemodialysis. Twenty patients and 240 dialyses were studied using a protocol in which patients underwent alternate hemodialyses with dialysate calcium of 2.5 and 3.5 mEq/L. Dialysate composition was otherwise the same. Mean BPs during dialysis were significantly lower at 1.5, 2.5, and 3.5 hours of dialysis when the lower dialysate calcium was used (P = .007 to .02). However, the difference in BP between the high and low dialysate calcium treatments was clinically minor, with a maximum mean difference (at 1.5 hours) of 4.6 mm Hg. Subgroups of patients with frequent hypotension and low or normal serum calcium did not appear more sensitive to the hypotensive effect of low calcium dialysate. Dialysate calcium levels of 2.5 and 3.5 mEq/L thus differ in their effect on intradialytic BP in a statistically significant, but clinically minor, way. Low calcium dialysate thus may prove useful in the management of patients in whom large amounts of enteric calcium absorption are indicated or unavoidable.     

Role of dialysis in the treatment of severe hypercalcemia: report of two cases successfully treated with hemodialysis and review of the literature.

The role of dialysis in the treatment of patients with severe hypercalcemia is uncertain. The fourteen previously reported cases of hypercalcemia treated with either peritoneal or hemodialysis have been reviewed. Two additional patients treated with hemodialysis are described in this report. Because the use of large volumes of intravenous fluids was contraindicated, each of the patients received a low calcium bath (0-1 mEq calcium per liter) hemodialysis for three and a half hours. After dialysis, the serum calcium fell to normal in both and remained normal thereafter with treatment of the underlying disease (multiple myeloma in one and vitamin D intoxication in the other). Hemodialysis can clear up to 682 mg of calcium per hour as compared to 124 mg per hour for peritoneal dialysis and 82 mg per hour with forced saline diuresis. Low calcium bath hemodialysis is indicated when the presence of renal and/or cardiac failure prevents the administration of large volumes of intravenous fluids to hypercalcemic patients.     

Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis

The effect of intravenous calcitriol on parathyroid function was evaluated in nine chronic hemodialysis patients with secondary hyperparathyroidism. Two micrograms of calcitriol were administered intravenously after dialysis thrice weekly for ten weeks. Parathyroid function was assessed by inducing hypo- and hypercalcemia with low calcium (1.0 mEq/liter) and high calcium (4.0 mEq/liter) dialyses before and after ten weeks of intravenous calcitriol therapy. To avoid hypercalcemia during calcitriol administration, the dialysate calcium was reduced to 2.5 mEq/liter. Parathyroid hormone (PTH) values (pg/ml) from dialysis-induced hypo- and hypercalcemia were plotted against serum ionized calcium, and the sigmoidal relationship between PTH and calcium was evaluated. Basal PTH levels fell from 902 +/- 126 pg/ml to 466 +/- 152 pg/ml (P less than 0.01) after therapy without a significant change in the serum total calcium concentration. The ionized calcium-PTH sigmoidal curve shifted to the left and downward after calcitriol therapy. The maximal PTH response during hypocalcemia decreased after calcitriol from 1661 +/- 485 pg/ml before calcitriol to 1031 +/- 280 pg/ml afterward (P less than 0.05). The PTH level at maximal inhibition due to hypercalcemia decreased from 281 +/- 76 pg/ml before calcitriol to 192 +/- 48 pg/ml afterward (P less than 0.05). The slope of the sigmoidal curve changed from -2125 +/- 487 to -1563 +/- 385 (P less than 0.05). The set point of ionized calcium (4.60 +/- .11 mg/dl before vs. 4.44 +/- .07 mg/dl after) did not change significantly with calcitriol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iatrogenic hypercalcemia in hemodialysis patients.

Calcium carbonate is frequently used in large doses as a phosphorus binder in hemodialysis patients, which often results in hypercalcemia. In most studies in which calcium carbonate is prescribed to control serum phosphorus levels the patients are not given calcitriol. However, calcitriol may be necessary for suppression of parathyroid hormone. The risk of hypercalcemia when calcium supplements are used in conjunction with calcitriol has not previously been examined in detail. We reviewed the charts of 74 hemodialysis patients (119 patient dialysis years) to determine the relationship of serum calcium to calcitriol, calcium therapy, and PTH levels. Twenty-eight patients (38%) were hypercalcemic at some point. Calcitriol therapy significantly increased the risk of hypercalcemia, independently of calcium therapy (p = 0.032). However, patients on a low dose of calcitriol were more than twice as likely to be hypercalcemic than patients on higher doses. Mean PTH levels were lower in the patients on the lower doses of calcitriol, indicating less severe hyperparathyroid disease. We conclude that hypercalcemia is a common complication in hemodialysis patients on calcitriol and calcium carbonate. Whether lowering the dialysate calcium, as suggested by other investigators, will successfully decrease the risk of hypercalcemia without worsening hyperparathyroidism remains to be determined.     

Reversible peritoneal calcification in a patient treated by CAPD

The patient, a female, aged 65 years, developed diffuse peritoneal calcification nine years after commencing CAPD therapy. No abdominal symptoms or evidence of peritonitis were discovered during this period. Before peritoneal calcification was detected, a dialysate with a high glucose concentration (3.86%) had been used once daily for 16 months. In the case of this patient, it was not possible to discover any of the previous indicated etiologies of peritoneal calcification such as significantly elevated values for the product Ca x P, overt secondary hyperparathyroidism, or relapsing peritonitis. It was realized that the use of a high-glucose dialysate in a patient on long-term CAPD treatment had been one causative factor. After peritoneal calcification had been confirmed, the calcium concentration of the dialysate changed from 3.5 mEq/l to 2.5 mEq/l and the patient was put on a regime of 2.0 g alumigel (aluminum-containing phosphate binders) a day. Eight months later, a CT scan was taken. The peritoneal calcification has clearly been mitigated. At present, CAPD therapy is being continued in the absence of any abdominal symptoms.     

SEIZURES: I

A 25-year-old man with end-stage renal disease (ESRD) secondary to obstructive uropathy suffered a generalized tonic-clonic seizure 3 hr after a routine hemodialysis treatment. The associated conditions included well-controlled mild hypertension and typical anemia of renal disease. There was no prior history of seizures, loss of consciousness, headaches, tremor, symptomatic neuropathy, or notable head trauma. His medications included nifedipine, recombinant erythropoietin, ferrous sulfate, folate, calcitriol, aluminum hydroxide, and calcium carbonate. Physical examination was remarkable only for the presence of a grade I/VI systolic ejection murmur and a patent dialysis access in the left arm. Routine predialysis laboratory data obtained two weeks previously revealed the following: Na 141, K 4.9, Cl 112, CO₂ 13 (all electrolyte values are mmol/ l), blood urea nitrogen (BUN) 68 mg/dl, calcium 6.8 mg/dl, phosphorus 4.6 mg/dl, albumin 3.5 g/dl, hematocrit 29, aluminum <1 μg/l. The electrocardiogram was within normal limits. On the day of admission the patient underwent a routine dialysis treatment for 3 hr using a new cellulose acetate dialyzer, bicarbonate-based dialysate containing potassium 1 mmol/l and calcium 2.5 mmol/l. The patient was well and asymptomatic during dialysis, and his arterial blood pressure was stable at approximately 140/90 mm Hg. Three hours after leaving the dialysis center, he began to experience facial twitching and numbness in his fingers, followed by a single 30-sec generalized tonic-clonic seizure. Upon arrival at the emergency department, he was alert and oriented, and complained only of paresthesias in his hands. Review of his medications revealed that he had failed to take the prescribed calcitriol and calcium carbonate for several weeks. Physical examination was unchanged from the previous evaluation except for the presence of Chvostek and Trousseau signs. Laboratory studies revealed the following: Na 145, K 4.6, Cl 110, CO₂ 27 (all electrolyte values are mmol/l), BUN 43 mg/dl, glucose 100 mg/dl, albumin 4.9 g/dl, total Ca 7.5 mg/dl, ionized Ca 3.0 mg/dl, magnesium 3.0 mg/dl, and phosphorus 7.0 mg/dl. EKG was normal except for a prolonged QT interval. Upon admission to the hospital, the patient was treated with intravenous calcium gluconate, followed by oral calcium carbonate and calcitriol. Within 48 hr, the patient's serum total and ionized calcium concentrations increased to 8.5 and 4.0 mg/dl, respectively. A CT scan of the head showed no abnormalities. The seizure was felt to be due to hypocalcemia, exacerbated by rapid correction of acidosis with dialysis, leading to further reduction in the ionized calcium concentration. The observed hypocalcemia was attributable to the patient's discontinuation or oral calcium and calcitriol and the absence of a high calcium dialysate, which is appropriate when combined with calcitriol and calcium supplementation, but necessary in their absence. Since discharge, the patient has experienced no further seizure activity and with consistent use of the prescribed oral calcium and calcitriol, his serum calcium has remained above 8 mg/dl, with phosphorus levels ranging from 5–6 mg/dl.     

Effect of hypercalcemia on the anion gap

It has been assumed, but not documented, that hypercalcemia induces an appreciable reduction in the serum anion gap (AG) because it represents an increase in the level of unmeasured cations. To test this question, we retrospectively compared the data of 59 hypercalcemic patients with malignancy [group 1, serum Ca 13.3 +/- SE 0.3 mg/dl] with those of 108 patients whose hypercalcemia was of parathyroid origin (group 2, serum Ca 12.1 +/- 0.1 mg/dl), and those of 51 control subjects (group 3, serum Ca 9.5 +/- 0.1 mg/dl). The AG of group 2 subjects (8.7 +/- 0.3 mEq/l) was significantly lower than that of the other two groups (p less than 0.001 for both) despite their higher serum albumin and lower serum Ca in comparison to group 1. The AGs of group 1 (11.1 +/- 0.4 mEq/l) and group 3 (11.1 +/- 0.3 mEq/l) were identical. There was no statistically significant correlation between the AG and serum Ca in the hypercalcemic patients. The major finding that the association of hypercalcemia with reduced AG is seen in hyperparathyroidism, but not in malignancy-related hypercalcemia, is not explained by differences in serum albumin, renal function, or acid-base status. Overlap of values between groups limits the diagnostic usefulness of the AG in an individual patient. Nevertheless, in the absence of multiple myeloma, the finding of an AG of 5 mEq/l or less in a hypercalcemic patient may be a helpful clue suggesting that malignancy is not the etiology.     

The negative Ca(2+) balance is involved in the stimulation of PTH secretion

The low calcium (Ca(2+)) dialysate have been developed to diminish the risk of hypercalcemia with the administration of active vitamin D and Ca(2+) carbonate as phosphate binder. Today, increasing numbers of hemodialysis (HD) patients have been on the low Ca(2+) dialysate (Ca(2+) = 2.5 mEq/l). However, the clinical consequences of a negative calcium net-balance which may be induced by the use of low Ca dialysate are not well evaluated. In the present study, we explored the effects of low Ca(2+) dialysate on the calcium balance and the PTH secretion. Eighty one chronic HD patients (male/female: 47/34; mean age: 60.2 +/- 1.5 years; mean HD periods: 11.1 +/- 0.8 years) who had been dialyzed with 3.0 mEq/l Ca(2+) dialysate were studied. All patients were transferred to the low Ca dialysate, which actually brought about a negative net-balance in Ca (mean: -94.5 mg) and an increase in serum intact PTH levels (mean: +23.7%: p = 0.03) during a single HD session. However, no changes in serum ionized Ca(2+) were found in spite of negative Ca(2+) balance. One month after change to the low Ca(2+) dialysate (total 12 sessions in each case), serum intact PTH levels increased significantly (186.7 +/- 19.5 vs. 216.2 +/- 21.9 pg/ml: p = 0.01) in spite of the fact that no changes were found in serum ionized Ca(2+), Pi and Mg. This result indicates that the negative Ca(2+) balance during low-Ca(2+) hemodialysis-stimulated PTH secretion, which offset the decrease of serum Ca(2+); a trade-off phenomenon between negative Ca balance and PTH. This suggests that low Ca(2+) dialysate may exaggerate the progression of secondary hyperparathyroidism.     

Oral 1,25(OH)2D3 pulse therapy

Conclusion In our experience, after a few months of therapy, every patient showed a marked improvement in both X-ray abnormalities derived from osteitis fibrosa and symptoms of renal osteodystrophy, especially bone pain, unless the serum phosphorus level was very high. The effectiveness of this therapy on the suppression of PTH secretion apparently depends on the initial PTH level, and also on the size of the gland itself. One of the major current difficulties in this therapy is the prevention of hypercalcemia when calcium carbonate is used. The calcium concentration of the dialysate must be reduced to 2.5 mEq/l not only for pulse therapy, but also for conventional therapy by vitamin D with calcium carbonate. Parathyroidectomy should be indicated only for the patient who does not respond to pulse therapy.     

Improving the delivery of continuous renal replacement therapy using regional citrate anticoagulation

AIMS: Regional citrate anticoagulation during acute renal replacement therapy (RRT) effectively prevents extracorporeal thrombosis and avoids bleeding risk. There have been a number of citrate anticoagulation protocols published; but a simple and predictable scheme with standardized components and procedures, as well as clearly defined citrate pharmacokinetics, is needed for continuous RRT (CRRT) that is now used frequently in the critical care setting. The present study sets forth methodology with standardized blood flow and dialysate composition, and with citrate and calcium infusions that are quantitatively linked to extracorporeal blood flow rate--a predictable and easily replicated CRRT paradigm. MATERIALS AND METHODS: CRRT using continuous venovenous hemofiltration with dialysis (CVVHD) was standardized using 150-200 ml/min blood flow, calcium-free dialysate with only moderate sodium (135 mEq/l) and bicarbonate (28 mEq/l) concentrations, and ultrafiltration limited to that needed for overall fluid balance in the intensive care unit. Citrate infusion (ACD-A solution) into the extracorporeal blood and calcium repletion in blood returned to the patient were proportional to blood flow. Anticoagulation was accomplished by keeping extracorporeal ionized calcium below 0.4 mM/l. Filter performance, citrate removal and changes in calcium, sodium and alkali were evaluated longitudinally. RESULTS: CVVHD using this protocol delivered urea clearance exceeding 2 l/h (48 l/d) when filter function was sustained. Filter longevity was markedly improved using citrate when compared with standard heparin anticoagulation, and nursing time spent on initiating and troubleshooting CRRT was approximately halved using this protocol. Sieving coefficients for urea, creatinine and citrate were approximately 0.9 and were sustained through nearly 3 days of filter use. Citrate clearance and removal were quantitatively linked to dialysate and ultrafiltration flow, resulting in 35-50% direct removal of the citrate-calcium chelate and reduced systemic citrate load. Serum tonicity and acid-base status were not problematic. The only notable side effect was modest calcium accumulation that necessitated reduction in calcium repletion rate. CONCLUSIONS: CVVHD is well suited to regional citrate anticoagulation. The present protocol is straightforward and predictable, with minor metabolic consequences that can be anticipated and adjusted. These results commend regional citrate anticoagulation to wider application.     

Mass transfer of calcium across the peritoneum at three different peritoneal dialysis fluid Ca2+ and glucose concentrations

BACKGROUND: In peritoneal dialysis, the rate of ultrafiltration has been predicted to be a major determinant of peritoneal calcium (Ca2+) removal. Hence, dialysis fluid glucose concentration should be an important factor governing the transperitoneal Ca2+ balance. The aim of this study was to test the effect of various dialysate glucose levels and selected dialysate Ca2+ levels on Ca2+ removal in peritoneal dialysis patients. METHODS: Patients (N = 8) received, during a 7-week period, 2 L of lactate (30 mmol/L)/bicarbonate (10 mmol/L)-buffered peritoneal dialysis solutions containing either 1.5% glucose and 1.0 mmol/L Ca2+ or 2.5% glucose and 1.6 mmol/L Ca2+, or 4% glucose and 2.5 mmol/L Ca2+, respectively, provided in a three-compartment bag (trio system). Patients underwent standardized (4-hour) dwells, one for each of the three dialysates to assess permeability-surface area product (PS) or mass transfer area coefficients (MTAC) for ionized and "freely diffusible" Ca2+, lactate, glucose, bicarbonate, phosphate, creatinine, and urea. RESULTS: There was a clear-cut dependence of peritoneal Ca2+ removal on the rate of ultrafiltration. For large peritoneal to dialysate Ca2+ gradients (2.5 mmol/L Ca2+ in 4% glucose) a close fit of measured to simulated data was predicted by the three-pore model using nonelectrolyte equations. For low transperitoneal Ca2+ concentration gradients, however, directly measured Ca2+ data agreed with the simulated ones only when the peritoneal Ca2+ PS was set lower than predicted from pore theory (6 mL/min). CONCLUSION: There was a marked ultrafiltration dependence of transperitoneal Ca2+ transport. Nonelectrolyte equations could be used to simulate peritoneal ion (Ca2+) transport provided that the transperitoneal ion concentration gradients were large. Based on our data 1.38 mmol/L Ca2+ in the dialysis fluid would have created zero net Ca2+ gain during a 4-hour dwell for 1.5% glucose, whereas 1.7 and 2.2 mmol/L Ca2+ would have been needed to produce zero Ca2+ gain for 2.5% glucose and 3.9% glucose, respectively.     

A double-blind evaluation of sodium gradient hemodialysis

In a double-blind, crossover trial, 7 chronic hemodialysis patients underwent three 4-week treatment periods. During one period, dialysate contained 135 mEq/l sodium. During another period, dialysate contained 143 mEq/l sodium. During the remaining period, we used "sodium gradient' dialysate, the sodium concentration of which was decreased from 160 to 133 mEq/l during each 4-hour dialysis session. Ultrafiltration was performed at a constant rate to achieve a predetermined post-dialysis weight. Interdialytic weight gain, thirst, blood pressure control, and incidence of side effects were monitored. There was a significant difference in interdialytic weight gain for the 3 treatments (p = 0.005). Interdialytic weight gain using 135 mEq/l sodium dialysate (2.2 +/- 0.9 kg, mean +/- SD) was significantly less than that using either 143 mEq/l sodium dialysate (2.6 +/- 0.8 kg) or sodium gradient dialysate (2.8 +/- 0.7 kg). Self-reported thirst tended to be less severe with 135 mEq/l sodium dialysate than with 143 mEq/l sodium dialysate or with sodium gradient dialysate, but changes in thirst were not statistically significant (p = 0.13). The incidence of intradialytic hypotensive episodes was comparable with the 3 levels of dialysate sodium. The results suggest that the described sodium gradient method does not prevent the increased interdialytic weight gain and thirst seen with other forms of high-sodium dialysis, and probably does not reduce the incidence of side effects.     

High‐calcium dialysate: A factor associated with inflammation,malnutrition and mortality in non‐diabetic maintenance haemodialysis patients

Aim: Chronic inflammation, which is common in dialysis patients, often causes malnutrition and even protein‐energy wasting. However, the association of high‐calcium dialysate with malnutrition and/or inflammation in non‐diabetic maintenance haemodialysis patients remains unclear. This study investigated the possible adverse effects of high‐calcium dialysate and mortality in this population. Methods: A total of 717 non‐diabetic haemodialysis patients participated in this 2 year prospective study. The subjects were categorized into three subgroups based on whether dialysate calcium concentrations were high (3.5 mEq/L), standard (3.0 mEq/L) or low (2.5 mEq/L). Demographic, haematological, nutritional and inflammatory markers, biochemical and dialysis‐related data were obtained for cross‐sectional analysis. Causes of death and mortality rates were also analyzed for each subgroup. Results: Patients with high‐calcium dialysate (n = 82) had a higher incidence of malnutrition and inflammation (61.0% vs 44.1% and 43.9%, respectively) than those with standard‐ and low‐calcium dialysate (n = 528 and 107). Backward stepwise multiple regression analysis revealed that high‐calcium dialysate was negatively correlated with nutritional index, serum albumin levels, but positively associated with the inflammatory marker of serum ferritin levels. At the end of the 2 year follow up, 45 patients had died. Cox multivariate analysis demonstrated that high‐calcium dialysate was a significant associated factor (relative risk 2.765; 95% confidence interval 1.429–5.352) for 2 year all‐cause mortality in these patients. Conclusion: The analytical results indicate that high‐calcium dialysate is associated with malnutrition and inflammation as well as 2 year mortality in non‐diabetic maintenance haemodialysis patients and the findings suggest that this population, even those with optimal mineral balance, should avoid high‐calcium dialysate.     

Calcium exposure and removal in chronic hemodialysis patients.

The risks associated with calcium exposure in chronic hemodialysis (HD) patients are becoming increasingly apparent. Current K/DOQI guidelines recommend an absolute maximum elemental calcium load of 2,000 mg/d, including calcium-containing medication and a maximum dialysate calcium concentration of 1.25 mmol/L (to avoid intradialytic calcium loading). The goal of this study was to characterize the total exposure to calcium from all sources that chronic HD patients are exposed to. We studied 52 patients. Each was requested to complete a 3-day food diary for analysis of daily calcium intake; 24-hour urine collections were taken and analyzed for calcium content. All patients underwent HD using Hospal Integra (Lyon, France) dialysis monitors, bicarbonate buffering, and dialysate sodium and calcium concentrations of 134 mmol/L and 1.25 mmol/L, respectively. Blood was sampled before and after HD for total serum calcium, albumin, bicarbonate, and phosphate, in addition to ionized calcium level measured at the bedside using a portable electrolyte analyzer. Calcium flux was determined from measurements of ionized calcium levels in dialyzer inlet samples and those in continuous partial waste dialysis collection (with reference to total waste dialysate and ultrafiltration volumes). There was marked interpatient variability of total calcium exposure; the mean was 2,346 +/- 293 mg (range, 230 to 7,309 mg) per day. The majority of enteral calcium exposure was from calcium-containing phosphate binders, with diet providing only a mean load of 581 +/- 34 mg (range, 230 to 1,309 mg). Calcium removal was evident in 83% of patients. Mean calcium flux was -187 +/- 232 mg (range, -486 to 784 mg). There was a linear correlation observed between the amount of calcium removed during dialysis and the predialysis ionized plasma calcium concentration, r2 = 0.42, P < .001 (calculated from actual measured dialysate ionized calcium concentration). This shows that calcium flux across the dialysis membrane is determined by the diffusion gradient. The amount of calcium removed during dialysis was found to be independent of exogenous calcium load. These results support previous reported data showing that the majority of HD patients are continually experiencing calcium overload. This may have a contributory role in the development of vascular calcification. In contrast to recent K/DOQI recommendations, an upper dialysate concentration of 1.25 mmol/L may not be ideal for every patient. To minimize the effects of exogenous calcium overload, dialysate concentrations should be prescribed with reference to plasma calcium levels.     

Effects of a magnesium-free dialysate on magnesium metabolism during continuous ambulatory peritoneal dialysis

While the use of magnesium-containing compounds is usually contraindicated in dialysis patients, the risk of toxicity from hypermagnesemia can be reduced by lowering the magnesium concentration in dialysate. We examined the effects of a magnesium-free dialysate on both serum magnesium level and the peritoneal removal rate of magnesium over 12 weeks in 25 stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). After 2 weeks, the serum magnesium level decreased from 2.2 to 1.9 mg/dL (0.9 to 0.8 mmol/L) (P less than .02) and the peritoneal removal rate increased from 66 to 83 mg/d (2.8 to 3.5 mmol/d) (P less than .05), with both values remaining stable thereafter. There was a strong association between these parameters (r = -0.62, P less than .05), suggesting that the serum magnesium level decreased as a result of the initial increased peritoneal removal rate. For an additional 4-week period, a subgroup of nine patients received magnesium-containing, phosphate binding agents instead of those containing only aluminum. During this phase, serum inorganic phosphorus was well controlled. The serum magnesium level increased only from 1.8 to 2.5 mg/dL (0.7 to 1.0 mmol/L) (P less than .05), due in great part to the concomitant 41% rise in peritoneal magnesium removal from 91 to 128 mg/d (3.8 to 5.3 mmol/d) (P less than .05). No toxicity was noted during the entire 16-week study period, nor did serum calcium change. Thus, serum magnesium levels remained within an acceptable range as magnesium-containing phosphate binders were given through the use of magnesium-free peritoneal dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)