Is spironolactone safe for dialysis patients?

BACKGROUND: Spironolactone is useful in heart failure, but is not given to dialysis patients for fear of hyperkalaemia. This study evaluated the safety of spironolactone administration in haemodialysis patients. METHODS: Fifteen haemodialysis outpatients with mean serum potassium <5.6 mEq/l over the preceding 4 months were treated with spironolactone 25 mg daily for 28 days. Serum potassium was measured before every haemodialysis during the study. Aldosterone and renin were measured at the beginning and end of the study. Patients were monitored for side effects. Data were examined with a paired t-test, with patients serving as their own controls and P < 0.05 considered significant. A sample size of 14 was required to achieve a power of 0.8 and a P = 0.05 to detect a potassium difference of 0.5 +/- 0.6 mEq/l. All patients were analysed as intention-to-treat. RESULTS: The mean potassium level was 4.6 +/- 0.6 mEq/l at baseline and 4.9 +/- 0.9 mEq/l at study completion (P = 0.14). Thirteen patients completed the trial with no potassium levels >6.0 mEq/l. Four patients had potassium levels between 5.5 and 6.0 mEq/l. One patient was withdrawn at day 20 after developing hyperkalaemia (7.6 mEq/l). Another patient was withdrawn at day 25 after missing a dialysis treatment. There were no differences in either baseline or 28 day aldosterone or renin levels (16.8 +/- 28.8 vs 11.7 +/- 6.1 ng/dl and 3.5 +/- 3.9 vs 3.5 +/- 3.5 ng/ml/h, respectively). Infrequent side effects included dry mouth, nosebleed, pruritis, gynecomastia and diarrhoea. No significant leukopenia or anaemia was noted. CONCLUSIONS: Spironolactone may be considered as a treatment option for selected chronic haemodialysis patients with heart disease.     

Dietary potassium and laxatives as regulators of colonic potassium secretion in end-stage renal disease.

BACKGROUND: In end-stage renal disease (ESRD), colonic potassium (K+) secretion increases as renal K+ excretion declines. The nature of this adaptive process is poorly understood, but post-prandial increases in plasma K+ concentration may be a determining factor. In addition, even though colonic K+ secretion increases in ESRD, interdialytic hyperkalaemia is a serious problem in haemodialysis patients, which might be reduced by stimulating colonic K+ secretion still further using laxatives. METHODS: Plasma K+ concentrations were measured in the fasting state, and for 180 min after the oral administration of 30 mmol of K+ to nine control subjects and 16 normokalaemic patients with ESRD (eight "predialysis" patients and eight patients undergoing continuous ambulatory peritoneal dialysis (CAPD)). Plasma K+ concentrations were also monitored for 180 min in fasting controls and ESRD patients who were not given the oral K+ load. To study the effect of laxatives on interdialytic hyperkalaemia, plasma K+ concentrations were measured in eight control subjects and 13 haemodialysis patients before and during 2 weeks treatment with bisacodyl (a cAMP-mediated laxative) and in five haemodialysis patients before and during 2 weeks treatment with lactulose (an osmotic laxative). RESULTS: Oral K+ loading caused plasma K+ concentration to rise within the normal range (3.5-5.1 mmol/l) in control subjects, while significantly higher concentrations were achieved in the "predialysis" patients and sustained hyperkalaemia developed in the CAPD patients. Bisacodyl treatment had no effect on plasma K+ concentrations in control subjects, but significantly decreased the mean interdialytic plasma K+ concentration (from 5.9+/-0.2 to 5.5+/-0.2 mmol/l, P<0.0005) in haemodialysis patients, whereas plasma K+ concentration did not change during lactulose treatment. CONCLUSIONS: Higher plasma K+ concentrations after food may help to maintain K+ homeostasis in ESRD by enhancing colonic K+ secretion. Bisacodyl may be useful for reducing interdialytic hyperkalaemia in patients undergoing haemodialysis.     

Effect of fludrocortisone acetate on reducing serum potassium levels in patients with end-stage renal disease undergoing haemodialysis.

BACKGROUND: Hyperkalaemia is a commonly encountered problem in dialysis patients with end-stage renal disease (ESRD). The aim of the present study was to assess the effect of fludrocortisone acetate (FCA) on reducing serum potassium levels in haemodialysis (HD) patients with hyperkalaemia. METHODS: Prospectively, 21 HD patients with hyperkalaemia were enrolled in this study. Patients were divided into two groups, including FCA (0.1 mg/d, n = 13) administration or no treatment (control, n = 8) for 10 months. No changes in dialysis or drug regimens were made during this period. Result. There were no significant differences in the baseline characteristics and biochemical parameters between the two groups (FCA therapy and control). At 10-months after FCA therapy, serum potassium levels were not significantly different between the treatment and control groups [median value (range): 5.2 (4.4-6.0) vs 5.8 (4.8-6.3) mEq/l, P = 0.121]. However, using the Wilcoxon signed ranks test, serum potassium levels were significantly lower at the end of the 10 month time period after FCA therapy compared with serum potassium levels of the pre-treatment period [5.2 (4.4-6.0) vs 6.1 (5.3-6.8), P = 0.01]. The biochemical values, including sodium, chloride, protein, albumin, blood nitrogen, creatinine, interdialytic weight change and blood pressure, did not show significant difference in comparisons between the two groups and pre-and post-FCA therapy period. CONCLUSIONS: FCA therapy appears to slightly decrease serum potassium value in hyperkalaemic HD patients. However, these results are insufficient to explain the effectiveness of FCA. Therefore, potentially large-scale studies with increased dose concentrations are needed to minimize the positive potassium balance in hyperkalaemic HD patients.     

Treatment of hyperkalaemia in renal failure: salbutamol v. insulin

Three groups of patients with acute or chronic renal failure (GFR less than 5 ml/min) and hyperkalaemia (K+ greater than or equal to 6 mEq/l), similar in age, serum creatinine and pretreatment K+. Group A (n = 24) received salbutamol 0.5 mg i.v. in 15 min, group B (n = 10) received glucose 40 g i.v. plus 10 units insulin i.v. in 15 min, and group C (n = 10) received salbutamol 0.5 mg i.v., glucose 40 g i.v. and insulin 10 units i.v. over a 15-min period. Serum potassium was measured at 30, 60, 180 and 360 min after administration of treatment. All treatments reduced serum potassium, maximal at 30 or 60 min, and ranging from -0.5 +/- 0.1 to -1.5 +/- 0.2 mEq/l; patients in group C exhibited a significantly greater decrement in serum potassium, when compared to group B at 60 (-1.5 +/- 0.2 vs -1 +/- 0.1 mEq/l, respectively; P less than 0.01) and 180 min (-1.2 +/- 0.2 vs -0.7 +/- 0.1 mEq/l, respectively; P less than 0.05). There were no significant differences between groups A and C. Patients from group C had moderate tachycardia and more prolonged hyperglycaemia than those from group B, but all treatments were well tolerated.     

No impact of hyperkalaemia with renin-angiotensin system blockades in maintenance haemodialysis patients.

BACKGROUND: Renin-angiotensin system (RAS) blockades, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well accepted for the cardiorenal-protective benefits added to antihypertensive effects in chronic kidney diseases (CKD), but associated with an increased risk of hyperkalaemia. However, few studies have investigated the effect of RAS blockades on serum potassium in dialysis patients. METHODS: Hyperkalaemia associated with RAS blockades by ACEI and/or ARB was evaluated in 69 patients on maintenance haemodialysis, who underwent a three-period crossover study in four groups (no exposure to RAS blockades, ACEI or ARB alone and ACEI plus ARB treatments), lasting one month in each period. RESULTS: Sixty-two patients completed this prospective 3-month study, and no one stopped the study because of the development of hyperkalaemia and/or complications. Mean serum K was similar among the four periods (no exposure, 5.54+/-0.67 mmol/l; ACEI alone, 5.54+/-0.75 mmol/l; ARB alone, 5.50+/-0.66 mmol/l; ACEI+ARB combination, 5.42+/-0.66 mmol/l) and was also equal when compared between the two groups with and without exposure to RAS blockades (5.48+/-0.68 vs 5.54+/-0.67 mmol/l, P=NS). The incidence of severe hyperkalaemic episodes (>6.0 mmol/l) upon monthly predialysis serum K determination was 25.8% with no exposure to RAS blockades, 29.8% for ACEI alone, 19.6% for ARB alone and 17.7% for ACEI+ARB combination without statistically significant differences among the four periods (P=NS). Among covariables, the degree of Kt/V, intakes of other medications interfering with potassium homeostasis and diabetes mellitus did not result in any significant hyperkalaemic changes during the 3-month study period except anuric patients compared with non-anuric patients (5.58+/-0.69 vs 5.19+/-0.65 mmol/l, P<0.001). CONCLUSION: Neither monotherapy (ACEI or ARB) nor combination therapy (ACEI plus ARB) is associated with the additional risk of hyperkalaemia in patients on maintenance haemodialysis. However, those patients with anuria on RAS blockades warrant the cautious monitoring of serum K to prevent hyperkalaemia.     

Electrographic alterations induced by hyperkalaemia simulating acute myocardial infarction

In general, severe hyperkalaemia produces classic electrocardiographic manifestations including tenting of T waves, widening of the QRS complex, loss of P waves, and eventually, sine waves and asystole. This report concerns a patient with chronic renal failure on maintenance haemodialysis who developed a severe hyperkalaemia associated with chest pain, manifested electrocardiographically by elevation of the S-T segment resembling acute myocardial infarction. After haemodialysis, serum potassium decreased and the electrocardiogram returned to normal. We review the literature and discuss the possible physiology of this electrocardiographic alteration.     

Control of serum potassium during fasting in patients with end-stage renal disease

In order to evaluate internal potassium balance in patients with end-stage renal disease (ESRD), epinephrine (0.015 micrograms/kg/min) was infused intravenously into normal control (N = 9) and ESRD subjects (N = 7) after a 26 hour fast. Hyperkalemia developed in ESRD patients after 16 hours of fasting, as compared with control subjects (P = 0.02). The hemodynamic response to epinephrine was similar in the two groups. During epinephrine infusion for one hour, the serum potassium decreased in normal subjects, from 4.3 +/- 0.2 mEq/liter to 3.9 +/- 0.1 mEq/liter, but did not change in ESRD patients (P = 0.005). Serum CO2 declined in ESRD, but not in control subjects, while glucose levels were not different in the two groups. Plasma aldosterone was significantly higher in fasting ESRD patients and failed to decrease during epinephrine infusion as compared to controls. Plasma insulin levels remained low in both groups even though serum glucose levels increased. These results demonstrate that hyperkalemia occurs during fasting in ESRD probably as the result of insulinopenia, and suggest that a diminished response to epinephrine may contribute to hyperkalemia.     

Hypokalaemia and subsequent hyperkalaemia in hospitalized patients.

BACKGROUND: The objective was to study the epidemiology of hypokalaemia [serum potassium concentration (S(K)) <3.5 mmol/l] in a general hospital population, specifically focusing on how often and why patients develop subsequent hyperkalaemia (S(K) > or =5.0 mmol/l). METHODS: In a 3-month hospital-wide study we analysed factors contributing to hypokalaemia and subsequent hyperkalaemia. RESULTS: From 1178 patients in whom S(K) was measured, 140 patients (12%) with hypokalaemia were identified (S(K) 3.0 +/- 0.3 mmol/l). One hundred patients (71%) had hospital-acquired hypokalaemia. Common causes of hypokalaemia included gastrointestinal losses (67%), diuretics (36%) and haematological malignancies (9%). In 104 patients (74%), hypokalaemia was multifactorial. Hypokalaemia frequently coexisted with hyponatraemia (24%) and, when measured, hypomagnesaemia (61%). Twenty-three patients (16%) developed hyperkalaemia (highest S(K) 5.7 +/- 0.7 mmol/l) following hypokalaemia. In these patients, potassium suppletion was not more common (70 vs 59%, P = 0.5), but when potassium was given, the total amount administered was significantly higher (median 350 mmol vs 180 mmol, P = 0.02). Furthermore, these patients more often received total parenteral nutrition (17 vs 4%, P = 0.02) and magnesium suppletion (30 vs 9%, P = 0.009), and more often had haematological malignancies (22 vs 6%, P = 0.03). CONCLUSIONS: Hypokalaemia is a multifactorial and usually hospital-acquired condition associated with hyponatraemia and hypomagnesaemia. One out of every six patients with hypokalaemia developed subsequent hyperkalaemia. Besides potassium suppletion, total parenteral nutrition (source of potassium), magnesium suppletion (may reduce kaliuresis) and haematological malignancy (may cause cell lysis) contribute to hyperkalaemia following hypokalaemia. Caution with potassium suppletion and frequent monitoring of S(K) may prevent iatrogenic hyperkalaemia.     

Safety of low-dose spironolactone administration in chronic haemodialysis patients.

BACKGROUND: Prevention of cardiovascular diseases is essential in chronic haemodialysis patients. Recently, low-dose spironolactone has been shown to decrease cardiovascular mortality in patients with severe heart failure. However, since haemodialysis patients are prone to hyperkalaemia, a known side effect of spironolactone, this treatment is not used in this population. We performed a study to assess whether low-dose spironolactone (3 x 25 mg/week) could be administered without inducing hyperkalaemia in haemodialysis patients. METHODS: The study design included a 2-week baseline period, followed by a 4-week treatment period in which doses of spironolactone were started at 12.5 mg three times/week for 2 weeks, then increased to 25 mg three times/week, and followed by a 2-week wash-out period. Fourteen patients receiving low-dose spironolactone after each dialysis were compared with 21 haemodialysis patients (control group). RESULTS: Low-dose spironolactone did not change mean serum potassium (4.9 +/- 0.7 vs 4.9 +/- 0.3 mmol/l: control). The mean plasma canrenone level induced by administration of spironolactone 25 mg three times/week in the 14 treated patients was 13 +/- 5.3 ng/ml. Serum aldosterone was not significantly modified by the administration of spironolactone in these patients [before, median 0.35; interquartile range (IQR) 0.11-2.83 nmol/l vs after, median 0.22; IQR 0.12-0.60 nmol/l, NS]. Dietary potassium intake and the use of ion-exchange resin, angiotensin-converting enzyme inhibitors and beta-blockers were similar for the two groups throughout the study. CONCLUSION: This non-randomized and non-blinded study shows that administration of 25 mg spironolactone thrice weekly is not associated with an increased frequency of hyperkalaemia in haemodialysis patients when they are carefully monitored. More studies are required, however, before concluding that spironolactone administration is safe in the chronic haemodialysis population.     

Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline.

BACKGROUND: Gender differences in the chronotropic effects of infused isoprenaline have previously been described. The aim of the present study was to investigate possible gender differences in hypokalaemic, chronotropic, and electrocardiographic effects of inhaled terbutaline. METHODS: Twenty healthy volunteers (10 female) were recruited (mean age 24 years for women (F) and 22 years for men (M). Subjects were given either inhaled terbutaline 5 mg or placebo in single blind, randomised crossover fashion and the following measurements were made for four hours after inhalation: (a) serum potassium concentration; (b) heart rate; (c) electrocardiographic sequelae (T wave amplitude, Q-Tc interval). The effects of terbutaline on serum potassium was chosen as the primary end point for detecting a 0.3 mmol/l difference between sexes, with a beta error of 0.2 and alpha set at 0.05. RESULTS: The hypokalaemic effects of terbutaline were significantly greater in women, the potassium results (means and 95% CI) being as follows: lowest potassium concentration--F 3.12 (2.96-3.28) mmol/l v M 3.65 (3.49-3.81) mmol/l; percentage change from baseline at one hour--F 15.4% (11.5-19.3%) v M 8.5% (4.6-12.3%); average potassium concentration during the four hours--F 3.39 (3.33-3.46) mmol/l v M 3.78 (3.72-3.85) mmol/l. There was no significant regression between body weight and the potassium response to terbutaline. There were also significant sex differences for T wave, Q-Tc, and heart rate response. The percentage fall in T wave amplitude 30 minutes after terbutaline was: F 44.6% (32.1-57.0%) v M 22.4% (9.9-34.8%). CONCLUSIONS: Women are more sensitive to the hypokalaemic, chronotropic, and electrocardiographic sequelae of inhaled terbutaline.     

Length of interdialytic interval influences serum calcium and phosphorus concentrations.

BACKGROUND: Higher levels of serum phosphorus and calcium are associated with increased haemodialysis (HD) patient mortality. Both of these factors act synergistically to promote vascular smooth muscle differentiation to an osteoblast-like phenotype and subsequent vascular calcification. The aim of this study was to investigate the influence of interdialytic interval on serum levels, as well as the influence of oral calcium-based phosphate binder load on the magnitude of the observed differences. METHODS: We studied 100 patients undergoing HD three times per week, over a 2 week period. Haemoglobin, albumin, calcium and phosphate were measured pre-dialysis before each HD session. Oral phosphate binder usage was recorded. All patients were treated with dialysate containing 1.25 mEq/l calcium. RESULTS: Both mean serum phosphate and calcium were higher after the long interdialytic interval (1.59+/-0.05 vs 1.45+/-0.04 mmol/l, P = 0.0005, and 2.46+/-0.03 vs 2.4+/-0.02 mmol/l, P = 0.001, for serum phosphate and uncorrected calcium, respectively). There were no significant differences in haemoglobin or serum albumin, indicating that variable dilution from an increased hydration status in the long interdialytic interval was unlikely to contribute to these observed differences. A total of 74 patients were treated with calcium-containing binders and 26 patients with sevelamer. Patients on sevelamer did not exhibit the observed cyclical increase in serum calcium seen in patients on calcium-containing binders (mean difference in serum calcium 0.09+/-0.01 mmol/l in the calcium-treated group vs 0.01+/-0.01 mmol/l in the sevelamer-treated patients, P = 0.0004). The increase in serum calcium after the long interval as compared with the short interval was proportional to the daily amount of the oral calcium-containing binder load ingested (r = 0.63, P<0.0001). CONCLUSION: Cyclical differences in interdialytic interval and overall exposure to both dietary phosphate and oral calcium load influence serum levels. This may have consequences for registry reporting, therapy modulation and potentially the pathogenesis of accelerated vascular calcification seen in HD patients.     

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes.The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.     

Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients

High serum fluoride (F-) in patients with chronic renal failure (CRF) and end-stage renal disease (ESRD) is associated with risk of renal osteodystrophy and other bone changes. This study was done to determine F- in normal healthy controls and patients with ESRD on haemodialysis (HD) or peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females) and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l) of F- content in drinking water. Control subjects showed a mean serum F- concentration of 1.08 +/- 0.350 microM/l. Males in control group showed slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F- concentration did not correlate significantly with age and sex among control subjects, whereas such correlation was observed in patients with ESRD on dialysis. Mean serum F- concentration was significantly higher in patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal controls. When grouped according to sex, the mean serum F- concentration in males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped according to age, it was observed that F- concentration was significantly higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated with age and sex, being higher in males and above 20 years. Despite appreciable clearance of F- (39-90%) across the peritoneum, patients on CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs 2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their serum F- concentration above 3.0 microM/l, posing the risk of renal osteodystrophy.      

An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.

BACKGROUND: Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats. METHODS: To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks. RESULTS: From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms. CONCLUSION: Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.     

Calcium mass transfer in peritoneal dialysis patients using 2.5 mEq/l calcium dialysate.

Standard peritoneal dialysate has a relatively high calcium concentration of 3.5 mEq/l. Peritoneal dialysis patients thus gain calcium from the dialysate which contributes to the risk of hypercalcemia. Dialysate with 2.5 mEq/l calcium is now available. Theoretically, using dialysate with this calcium content, calcium transfer should be negative (from the patient into the dialysate) when the patient is hypercalcemic, and positive when the patient is normocalcemic or hypercalcemic. Thus, 2.5 mEq/l calcium dialysate may allow larger doses of calcium carbonate to be prescribed. We compared calcium mass transfer (CMT) in 17 stable peritoneal dialysis patients using 3.5 and 2.5 mEq/l calcium dialysate. A solution of 2.05 l, 1.5 g/dl dextrose was dwelled for 4 hours. Calcium was measured in the drained dialysate and serum (total and ionized). Mean CMT was 0.7 +/- 0.5 mEq/exchange using 3.5 mEq/l calcium dialysate and -0.9 +/- 0.9 mEq/exchange using 2.5 mEq/l calcium dialysate (p less than 0.0001). At the time of the CMT studies, the mean serum ionized calcium levels were identical for the two groups (2.6 mEq/l). CMT correlated inversely with serum total calcium, serum ionized calcium, and drained dialysate volume. During hypercalcemia calcium transfer was from the dialysate to the patient when 3.5 mEq/l calcium dialysate was used, but from the patient to the dialysate when 2.5 mEq/l calcium dialysate was used. We conclude that 2.5 mEq/l calcium dialysate is effective in removing calcium and will be helpful in preventing hypercalcemia when large doses of oral calcium compounds are prescribed as a phosphate binder.     

Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders.

BACKGROUND: Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. METHODS: We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. RESULTS: During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). CONCLUSIONS: The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.     

A randomized trial comparing losartan with amlodipine as initial therapy for hypertension in the early post-transplant period.

BACKGROUND: Blockade of the renin-angiotensin-aldosterone system in the early post-transplant period remains controversial. Angiotensin II-receptor blockers (ARB) have many benefits to the patient with chronic kidney disease and these benefits may also apply to the renal transplant recipient (RTR). Additionally, there are theoretical benefits of ARB use in RTR. This study was designed to investigate the safety of early ARB use after renal transplantation. METHODS: RTR with serum creatinine levels <3.0 mg/dl were randomized to receive either ARB (n = 29) or calcium-channel blocker (CCB; n = 27) as initial therapy for post-transplant hypertension. Differences in potassium, creatinine and haemoglobin concentrations were compared at baseline, 3, 6 and 12 months after transplantation. RESULTS: Withdrawal from the assigned treatment was high: 12 in the ARB group (due to hyperkalaemia in six) and 17 in the CCB group (due to intractable oedema in seven and post-transplant erythrocytosis requiring an angiotensin-converting enzyme inhibitor in seven). There were no differences in blood pressure, haemoglobin or creatinine concentration at any time-points. Mean potassium concentrations were only slightly higher in the ARB vs CCB group (range: 4.2-4.3 vs 3.7-3.8 mEq/l, respectively, but clinically significant) and the number of patients with potassium values >6.0 mEq/l was higher in ARB (n = 7) vs CCB (n = 1). CONCLUSIONS: These data suggest that hyperkalaemia is the major complication that occurs with the use of ARB in the immediate post-transplant period. ARB use does not affect renal function or complicate the post-transplant management of RTR. Other than reducing the incidence of post-transplant erythrocytosis, ARB use does not cause an excess incidence of anaemia. Strategies to reduce the risk of hyperkalaemia may allow increased use of ARB immediately after kidney transplantation.     

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.     

Intravenous 1,25(OH)2 vitamin D3 therapy in haemodialysis patients: evaluation of direct and calcium-mediated short-term effects on serum parathyroid hormone concentration

Eleven patients on chronic haemodialysis treatment thrice weekly received 1 microgram 1,25(OH)2D3 i.v. after each dialysis for 3 weeks. Phosphate binders were mainly CaCO3, supplemented in a few patients by moderate amounts of Al(OH)3. Ionised calcium was measured by ion-selective electrode, normal values being 1.28-1.42 mmol/l. PTH was estimated by an N-terminal-sensitive assay; normal values are less than 0.25 ng/ml. Results before and after 1,25(OH)2D3 were: ionised calcium before haemodialysis, 1.19 +/- 0.12 and 1.17 +/- 0.14; ionised calcium after haemodialysis, 1.33 +/- 0.07 and 1.30 +/- 0.09; PTH before haemodialysis, 1.39 +/- 0.71 and 1.38 +/- 0.69; PTH after haemodialysis, 0.64 +/- 0.22 and 0.60 +/- 0.17; Phosphate before haemodialysis, 1.85 +/- 0.48 and 2.18 +/- 0.43 (P less than 0.05). No change of PTH concentration and ionised calcium before and after haemodialysis treatment could be documented after i.v. 1,25(OH)2D3 treatment. Mild and severe hyperparathyroidism were indistinguishable. Increased serum calcium concentrations therefore appear to be required for the suppression of PTH secretion by i.v. 1,25(OH)2D3 therapy.