Thiazide treatment for calcium urolithiasis in patients with idiopathic hypercalciuria. [The role of thiazides in the prophylaxis of recurrent calcium lithiasis]. Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences. Unprocessed bran and intermittent thiazide therapy in prevention of recurrent urinary calcium stones. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. Physiological effects of slow release potassium phosphate for absorptive hypercalciuria: a randomized double-blind trial. A randomized trial of intermittent versus continuous oral alfacalcidol treatment of hyperparathyroidism in end-stage renal disease. Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients.
In a randomised trial based on a parallel design to determine the prophylactic effect of thiazide on stone formation, 210 calcium urolithiasis patients with idiopathic hypercalciuria were allocated either to treatment with trichlormethiazide (4 mg/day) or no treatment with only close follow-up; 35 patients were excluded for various reasons, including voluntary withdrawal. The background of the remaining 175 patients (82 in the thiazide group and 93 in the control group), including age and sex, was similar for both groups. In patients treated with thiazide there was a statistically significant fall in urinary calcium output. Statistical analyses also demonstrated that the stone formation rate in the thiazide group was significantly less than that in the control group. Adverse clinical reactions probably due to the drug were observed in 9 patients. These findings indicate that trichlormethiazide has a prophylactic effect on calcium urolithiasis in patients with idiopathic hypercalciuria. To show the prolonged efficacy of thiazides in the prophylaxis and treatment of recurrences in patients with calcium oxalate and phosphate lithiasis.
                A randomised prospective study is conducted, with a three-year follow-up, in 150 patients diagnosed with recurrent calcium lithiasis. The patients are divided into three groups: A) 50 cases subject to observation with no treatment, B) 50 cases treated with 50 mg/day of hydrochlorothiazide, and C) 50 cases treated with 50 mg of hydrochlorothiazide and 20 mlEq of potassium citrate/day. Each group is subject to a renal study with imaging techniques and a urinary metabolic study at baseline, 12, 24 and 36 months.
                The patients treated with thiazides (Groups B and C) obtain a significant reduction in lithiasis recurrence compared with the control group (Group A). The most common abnormality found in the metabolic study was hypercalciuria, 52% of cases; 16% present a mixed lithogenic pattern. The number of recurrences and need for new sessions of extracorporeal lithotripsy in patients with hypercalciuria treated with thiazides is significantly smaller than in Group A (p=0.003).
                We observe a significant relation between lithogenic pattern and lithiasis recurrence. Thiazides help us to control lithogenic factors and recurrences in patients with calcium lithiasis. This effect is prolonged and significant in patients with hypercalciuria. We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients. Both urinary calcium excretion and renal stone episodes are increased during the summer in Finland. Since thiazide and unprocessed bran are known to decrease urinary calcium excretion, we treated 73 patients with recurrent urinary stone formation by giving them unprocessed bran and intermittent thiazide. Of the patients, 32 had absorptive hypercalciuria and 41 had normal urinary calcium values. All patients were on a low-calcium and low-oxalate diet and took 40 g bran daily. Fourteen of the hypercalciuric and 14 of the normocalciuric patients were randomly allocated to use hydrochlorothiazide 50 mg b.i.d. from May to September. Reduction of stone formation was seen in all groups. The combination of thiazide + bran was superior to the bran on its own in inhibition of stone formation. Only 3/11 (27%) stones passed through during the summer in the thiazide + bran group as compared with the 11/17 (65%) in the bran group. We define the role of urine volume as a stone risk factor in idiopathic calcium stone disease and test the actual preventive effectiveness of a high water intake.
                We studied 101 controls and 199 patients from the first idiopathic calcium stone episode. After a baseline study period the stone formers were divided by randomization into 2 groups (1 and 2) and they were followed prospectively for 5 years. Followup in group 1 only involved a high intake of water without any dietetic change, while followup in group 2 did not involve any treatment. Each year clinical, laboratory and radiological evaluation was obtained to determine urinary stone risk profile (including relative supersaturations of calcium oxalate, brushite and uric acid by Equil 2), recurrence rate and mean time to relapse.
                The original urine volume was lower in male and female stone formers compared to controls (men with calcium oxalate stones 1,057 +/- 238 ml./24 hours versus normal men 1,401 +/- 562 ml./24 hours, p < 0.0001 and women calcium oxalate stones 990 +/- 230 ml./24 hours versus normal women 1,239 +/- 440 ml./24 hours, p < 0.001). During followup recurrences were noted within 5 years in 12 of 99 group 1 patients and in 27 of 100 group 2 patients (p = 0.008). The average interval for recurrences was 38.7 +/- 13.2 months in group 1 and 25.1 +/- 16.4 months in group 2 (p = 0.016). The relative supersaturations for calcium oxalate, brushite and uric acid were much greater in baseline urine of the stone patients in both groups compared to controls. During followup, baseline values decreased sharply only in group 1. Finally the baseline urine in patients with recurrences was characterized by a higher calcium excretion compared to urine of the patients without recurrences in both groups.
                We conclude that urine volume is a real stone risk factor in nephrolithiasis and that a large intake of water is the initial therapy for prevention of stone recurrences. In cases of hypercalciuria it is suitable to prescribe adjuvant specific diets or drug therapy. We examined the physiological effects and tolerance of UroPhos-K, a slow release neutral form of potassium phosphate (155 mg. phosphate and 8 mEq. potassium per tablet) in patients with absorptive hypercalciuria.
                A total of 31 patients with absorptive hypercalciuria were studied at baseline and after 3 months of treatment with 4 tablets twice daily of UroPhos-K or placebo (identical in appearance) in a prospective randomized, placebo controlled, double-blind trial during a 4-day inpatient study with a daily constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate.
                Treatment with UroPhos-K did not cause significant gastrointestinal side effects, increase fasting serum potassium or phosphorus, or reduce hemoglobin or creatinine clearance. It reduced urinary calcium excretion from 277 +/- 72 to 166 +/- 43 mg. per day (p < 0.001), associated with a reduction in serum 1,25-dihydroxyvitamin D concentration from 50 +/- 11 to 42 +/- 9 pg./ml. (p < 0.001). Indexes of intestinal calcium absorption and markers of bone turnover also decreased modestly. None of these changes was seen in the placebo group.
                In patients with absorptive hypercalciuria UroPhos-K seems to correct hypercalciuria by a combination of reduced intestinal absorption, bone resorption and improved renal calcium reabsorption. The drug is well tolerated compared to placebo. Secondary hyperparathyroidism, a major clinical problem in patients with chronic renal failure, develops in response to phosphate retention and impaired calcitriol [1,25-dihydroxyvitamin D3] synthesis. Vitamin D therapy, particularly alfacalcidol [1 alpha-hydroxyvitamin D3], has been shown to be effective in the treatment of secondary hyperparathyroidism. The aim of this study was to compare the effect of a 12-week course of continuous versus intermittent oral alfacalcidol therapy on parathyroid hormone suppression.
                34 patients were selected and randomly divided into 2 groups to receive either intermittent or continuous oral alfacalcidol. Baseline data were obtained on serum calcium, phosphorus, alkaline phosphatase and PTH. All but the PTH were monitored monthly. PTH levels were measured again until the end of the protocol. The intervention was 2 microg of alfacalcidol given after each dialysis session (intermittent group) or 1 microg given 6 days/week (continuous group).
                Serum calcium and phosphorus showed a tendency to increase from baseline levels in both groups. Mean PTH levels for both groups showed a progressive reduction over time during the study period. This decrement showed no significant difference with regard to the schedule of alfacalcidol administration when comparing the 2 groups. There also was no difference in the incidence of side effects--hypercalcemia and hyperphosphatemia--between the intermittent and continuous intervention.
                Feedback regulation of PTH with oral alfacalcidol therapy is efficient in the treatment of hyperparathyroidism. However, intermittent and continuous oral administration are equally effective in suppressing an elevated PTH level in hemodialysis patients, with similar safety margins. Calcitriol lowers parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4, but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease. We evaluated doxercalciferol (1alpha-hydroxyvitamin D2) as an alternative therapy in a randomized, double-blinded, placebo-controlled, multicenter trial.
                Fifty-five adults with stage 3 or 4 CKD and an intact PTH (iPTH) level greater than 85 pg/mL (ng/L) completed 8 baseline weeks, followed by 24 weeks of oral therapy with doxercalciferol or placebo. Pretreatment demographics and biochemical features did not differ between groups. Dosages were increased gradually if iPTH level was not decreased by 30% or greater and serum calcium and phosphorus levels were stable. Regular monitoring included plasma iPTH, serum calcium and phosphorus, urinary calcium, bone-specific serum markers, and serum lalpha,25-dihydroxyvitamin D levels. Glomerular filtration rate (GFR) was measured before and after treatment.
                Mean plasma iPTH level decreased by 46% from baseline after 24 weeks of doxercalciferol treatment (P <0.001), but was unchanged with placebo. After 6 weeks, iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals (P <0.001). No clinically significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia, hyperphosphatemia, or hypercalciuria were noted between groups. Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo (P <0.01). Adverse-event rates and changes in GFR did not differ between groups.
                Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4. Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients. Its efficacy in patients with severe hyperparathyroidism is diminished, in part, due to glandular hyperplasia associated with decreased calcitriol and calcium receptors.
                We, therefore, developed a prospective, randomized trial comparing i.v. calcitriol plus calcium carbonate (CaCO3) compared to CaCO3 alone (control) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis. Patients underwent calcium (Ca) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gland hyperplasia.
                In the calcitriol group, the amino-terminal parathyroid hormone (N-PTH) decreased significantly from a baseline value of 70 +/- 12 pg/ml at month zero to 22 +/- 7 and 19 +/- 6 pg/ml at months 6 and 12, respectively (the conversion factor of amino-terminal PTH to intact PTH is 6, i.e., 10 pg/ml N-PTH equals 60 pg/ml intact PTH). In contrast, the N-PTH levels in the CaCO3 alone group did not change. The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 +/- 7% in the calcitriol group but increased by 96 +/- 59% in the control group (p < 0.05). In addition, the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 +/- 6% at month 12 compared to month zero but increased by 61 +/- 42% in the control group. Although total calcium and phosphorus levels were not different between the two groups, ionized calcium values were higher in the calcitriol group. The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic.
                Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease. Based on Ca suppression/stimulation tests, calcitriol was more successful in preventing gland growth than CaCO3 alone. Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in patients.
There is some evidence that in patients with idiopathic hypercalciuria and recurrent stones, the addition of thiazides to a normal or modified diet for short to long periods (five months to three years) reduced the number of stone recurrences and decreased the stone formation rate. Thiazides and neutral potassium phosphate decreased calciuria in symptomatic patients with idiopathic hypercalciuria. There were no studies investigating the effect of pharmacological treatment on other clinical complications or asymptomatic idiopathic hypercalciuria.