Management of renal osteodystrophy.
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Chronic Kidney Disease-Mineral and Bone Disorder↗
Biomedical subjects
K Sakhaee
Publications and source records attributed to K Sakhaee.
Assessment by reflection ultrasound method of the effect of intermittent slow-release sodium fluoride-calcium citrate therapy on material strength of bone.
It has been suggested that fluoride therapy, while increasing bone mass, produces bone with inferior mechanical properties. In the present report this hypothesis was tested using a novel reflection ultrasound technique. Transiliac crest bone biopsies were obtained from 16 patients with osteoporosis and vertebral compression fractures (12 women and 4 men, mean age 56 years) before and after approximately 2 years of intermittent slow-release sodium fluoride therapy (25 mg twice a day) combined with continuous calcium citrate supplementation. Samples were analyzed by a reflection ultrasound method, which analyzes ultrasound velocity with a sample site resolution of 200 microns and thus provides a measure of the mechanical property of single trabeculae (material). For the group, mean fractional change in velocity increased 6.1 +/- 2.3% (SEM) from a mean value of 3303 +/- 80 to 3484 +/- 55 m/s (p = 0.028). A total of 13 patients (81%) demonstrated higher velocities after treatment. Thus reflection ultrasound analysis of bone appears to provide a sensitive means of assessing changes in the material property of bone. Furthermore, these results suggest that the treatment regimen utilized in these patients improves strength of bone at the material or trabecular level largely independently of change in bone mass. The combination therapy also increased spinal (L2-L4) bone density for the group as assessed by dual-photon absorptiometry (5.3 +/- 2.0%). There was no significant correlation between the change in ultrasound velocity and bone density (r = 0.0026, p = 0.996).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Fluoride bioavailability from immediate-release sodium fluoride with calcium carbonate compared with slow-release sodium fluoride with calcium citrate.
The circadian variation in serum fluoride was compared between treatment with immediate-release sodium fluoride (IR-NaF) (30 mg) and calcium carbonate (500 mg calcium) and slow-release sodium fluoride (SR-NaF) (25 mg) and calcium citrate (400 mg calcium) in seven patients with postmenopausal osteoporosis maintained on long-term fluoride treatment. During 12 h following a dose of SR-NaF, serum fluoride levels could be largely kept within the therapeutic window (believed to be 95-190 ng/ml or 5-10 mumol/l). In contrast, IR-NaF produced a wide circadian fluctuation with peak-to-trough change of about 200 ng/ml. Compared to SR-NaF, IR-NaF caused a significantly higher peak fluoride concentration in serum (322 vs. 158 ng/ml), and greater area under the curve (2269 vs. 1321 ng.h/ml) and urinary fluoride (6.72 vs. 3.80 mg/12 h). Thus, fluoride absorption from IR-NaF was twice as high as that from SR-NaF.
Aged↗
Contrasting effects of various potassium salts on renal citrate excretion.
Mechanisms for the citraturic response to potassium citrate treatment were sought by assessing renal citrate clearance and acid-base status after oral administration of potassium citrate, potassium bicarbonate, and potassium chloride. After 2 weeks of treatment of eight patients with stones at a dose of 80 meq/day, urinary citrate rose significantly from 2.5 +/- 1.6 mmol/day (no drug) to 5.1 +/- 1.7 mmol/day with potassium citrate and to 4.5 +/- 1.5 mmol/day with potassium bicarbonate (P less than 0.05), but did not change significantly with potassium chloride. Citrate clearance increased from 8.0 to 27.4 mL/min with potassium citrate and 25.8 mL/min with potassium bicarbonate (P less than 0.05), but did not increase with potassium chloride. Both potassium citrate and potassium bicarbonate significantly raised urinary bicarbonate and decreased urinary ammonium, titratable acid, and net acid excretion. Potassium chloride was without effect. Effects of potassium citrate on urinary citrate, citrate clearance, and acid-base status tended to be more prominent than those of potassium bicarbonate, but these changes were not significant. Thus, the citraturic action of potassium citrate is largely accountable for by provision of an alkali load. Potassium itself had no effect in the absence of potassium deficiency.
Adult↗
Fluoride bioavailability from slow-release sodium fluoride given with calcium citrate.
Clinical pharmacology of slow-release sodium fluoride given with calcium citrate was examined in acute and long-term studies. Following a single oral administration of 50 mg slow-release sodium fluoride, a peak serum fluoride concentration (Cmax) of 184 ng/ml was reached in 2 h; thereafter, serum fluoride concentration declined with a T1/2 of 5.9 h. The concurrent administration of calcium citrate (400 mg calcium) gave an equivalent Tmax (time required to attain Cmax) and T1/2, but a lower Cmax of 135 ng/ml. The coadministration of a meal with fluoride also reduced Cmax but increased Tmax. The area under the serum concentration curve of slow-release sodium fluoride was reduced 17-27% by a meal or calcium citrate. Thus, calcium citrate reduced fluoride absorption and peak fluoride concentration in serum of slow-release sodium fluoride but did not affect the time required to reach peak concentration or the rate of subsequent decline. The effect of a meal was similar, except for a longer period required to reach peak serum concentration. During long-term administration of 25 mg slow-release sodium fluoride coadministered with 400 mg calcium as calcium citrate on a twice daily schedule, the trough level of serum fluoride could be kept between 95 and 190 ng/ml, believed to be the therapeutic window.
Adult↗
Effect of intermittent therapy with a slow-release fluoride preparation.
Long-term clinical effects of intermittent sodium fluoride (slow-release) therapy were assessed in 71 patients with primary osteoporosis. In Group I (receiving 1,25-(OH)2D3 2 micrograms/day for 2 weeks before 3 months of sodium fluoride treatment 25 mg twice a day, in each 5-month cycle), vertebral (L2-L4) bone mineral content did not change significantly. However, the L2-L4 bone mineral content significantly increased by 3.1% in Group II (those who did not receive 1,25-(OH)2D3 during 5-month cycle), 3.5% per patient year in Group III (combined NaF 25 mg twice a day with 1,25-(OH)2D3 0.5 micrograms/day for 12 months in each 13-month cycle), and by 7.8% per patient year in Group IV (combined NaF with calcium citrate for 12 months in each 13-month cycle). The rise in vertebral bone mineral content was sustained, with an annual increment of 4.2% during the third year compared with 4.4% during the first year. The vertebral fracture rate declined significantly from the pretreatment value in all groups, but comparison with a placebo control group was not available. There was no significant change in the bone density of the radial shaft or of the proximal femur. The rate of hip fracture (nontraumatic) during treatment was 1.8% per patient year, the same as before treatment. The drug was well tolerated with only minor infrequent gastrointestinal and rheumatic side effects. Thus, intermittent slow-release sodium fluoride treatment with adequate calcium supplementation augments spinal bone mass and apparently inhibits vertebral fractures, with a satisfactory safety of usage; however, it has no effect on appendicular bone mass or on hip fracture rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Density↗
The spectrum of metabolic abnormalities in patients with cystine nephrolithiasis.
To elucidate the pathophysiology of mixed stone formation in cystinuria, 27 patients with documented cystine nephrolithiasis underwent an inpatient evaluation under a constant dietary regimen. All patients had homozygous cystinuria, since the daily urinary cystine excretion exceeded 250 mg. per gm. creatinine. Hypercalciuria was noted in 5 patients (18.5 per cent), 4 of whom had fasting hypercalciuria. Hyperuricosuria was found in 6 patients (22.2 per cent) and it was not caused by a consumption of a diet rich in animal proteins, since urinary pH was higher and urinary sulfate lower than in control subjects. Serum uric acid was slightly lower and uric acid clearance was higher in hyperuricosuric patients than in control subjects. Hypocitraturia was found in 12 patients (44.4 per cent) and it was associated with defective renal acidification in 4 of 5 patients in whom it was tested. Thus, hypercalciuria, hyperuricosuria and hypocitraturia frequently accompany cystinuria in patients with cystine nephrolithiasis. These conditions might be renal in origin, rather than a result of dietary or environmental aberrations. They may contribute to the formation of calcium and uric acid stones, which sometimes complicate cystine nephrolithiasis.
Adolescent↗
Safe and effective treatment of osteoporosis with intermittent slow release sodium fluoride: augmentation of vertebral bone mass and inhibition of fractures.
The value of intermittent slow release sodium fluoride treatment in the management of osteoporosis was studied by a comprehensive metabolic and clinical assessment during a long term trial. Its effect was compared with that of a large dose of 1,25-dihydroxyvitamin D [1,25-(OH)2D] given for a short period preceding each fluoride treatment period in another group of randomly selected patients. The 24 patients in group I (3 idiopathic and 21 postmenopausal) received cyclic treatment in repeated 5-month cycles; each cycle was initiated by 1,25-(OH)2D (2 micrograms/day) for 2 weeks, followed for 3 months by sodium fluoride (slow release, 25 mg twice daily) with 25-hydroxyvitamin D (50 micrograms twice weekly) and calcium supplements (to bring total calcium intake to 1500 mg/day), and was concluded by 6 weeks of 25-hydroxyvitamin D and calcium supplementation without sodium fluoride. The 21 patients in group II (3 idiopathic and 18 postmenopausal) received the same treatment, except for the omission of 1,25-(OH)2D. In both groups, the serum fluoride level was maintained within 5-10 mumol/L (95-190 ng/mL) during fluoride treatment, and serum osteocalcin concentrations correlated positively with the duration of treatment. However, vertebral bone mineral content (L2-L4) did not increase significantly in group I, whereas it rose significantly in group II (fractional change, +0.031/2.4 yr in group I vs. + 0.118/2.9 yr in group II; P less than 0.005). Although bone histomorphometric analyses disclosed overall improvement in both groups, only group II had significant increases in the mineral apposition rate [0.5 +/- 0.2 (+/- SE) to 1.4 +/- 0.2 micron/day; P less than 0.05] and the adjusted apposition rate (0.2 +/- 0.1 to 0.7 +/- 0.1 micron/day; P = 0.04). The vertebral fracture rate significantly declined in both groups, but more so in group II. Excluding the first year of treatment, the fracture rate during treatment in group II of 0.03/patient yr was significantly lower than that of 0.28/patient yr in group I (P less than 0.05). The treatment was well tolerated in both groups; only 16% of patients had either gastrointestinal or rheumatic complications. We conclude that intermittent sodium fluoride treatment without 1,25-(OH)2D provides safe and effective treatment of osteoporosis, marked by formation of new adequately mineralized bone, a rise in vertebral bone mass, and reduced frequency of vertebral fractures. The addition of 1,25-(OH)2D treatment before initiation of each fluoride phase yielded a less favorable response.
Adult↗
Lack of effect of 24,25-dihydroxyvitamin D3 administration on parameters of calcium metabolism.
Seven patients with disordered calcium metabolism and high normal or elevated serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] were studied before and after the administration of 24,25-(OH)2D3 to determine its effects on calcium metabolism. Despite a significant increase in the mean serum 24,25-(OH)2D level [2.1 +/- 0.6 (+/- SE) to 16.7 +/- 6.2 nmol/L; P less than 0.05] after a daily dose of 20 micrograms for 1 month, there were no consistent changes in serum calcium, immunoreactive PTH, or 1,25-(OH)2D concentrations. Intestinal calcium absorption and urinary calcium excretion rose slightly during 24,25-(OH)2D administration in the majority of the patients. In the three patients in whom it was measured, serum 1,24,25-trihydroxyvitamin D levels did not change (19 +/- 5 vs. 20 +/- 5 pmol/L). We conclude that exogenous 24,25-(OH)2D3 at this dose has no significant antagonistic action on 1,25-(OH)2D and may have weak agonistic action.
24,25-Dihydroxyvitamin D 3↗
Alkali action on the urinary crystallization of calcium salts: contrasting responses to sodium citrate and potassium citrate.
Alkali therapy is used commonly to prevent recurrent stone formation in patients with distal renal tubular acidosis. We compared the effects of potassium citrate to those of sodium citrate in 6 well defined cases of incomplete distal renal tubular acidosis. The patients were studied during a control phase, during potassium citrate treatment (80 mEq. per day) and during sodium citrate treatment (80 mEq. per day) chosen in random order. Potassium citrate caused a decrease in urinary calcium and a significant increase in urinary citrate that resulted in a significant decrease in the urinary saturation of calcium oxalate. It did not alter the saturation of brushite and sodium urate. However, while sodium citrate also was able to increase the urinary citrate level, there was no decrease in the urinary calcium (owing to the increased sodium load). Thus, the urinary saturation of calcium oxalate did not decrease as much as with potassium citrate and the saturation of brushite increased significantly. Moreover, the urinary saturation of sodium urate increased significantly owing to the enhanced sodium excretion. The results suggest that potassium citrate therapy may retard the crystallization of calcium oxalate and may not cause calcium phosphate crystallization. In contrast, sodium citrate may have no effect or it sometimes may accentuate the crystallization of calcium salts. Thus, our study supports the potential clinical advantage of potassium citrate therapy over sodium alkali treatment in patients with incomplete distal renal tubular acidosis and recurrent calcium nephrolithiasis.
Acidosis, Renal Tubular↗
Hypercalciuria and altered intestinal calcium absorption occurring independently of vitamin D in incomplete distal renal tubular acidosis.
Negative calcium balance and calcium nephrolithiasis are two sequelae of chronic metabolic acidosis. To establish the effects of acidosis on calcium and vitamin D metabolism, we have examined a group of nine patients with incomplete distal renal tubular acidosis. Patients were studied during a control phase and after eight months of potassium citrate treatment, 60 to 80 meq daily. Potassium citrate caused a significant decrease in urinary calcium. The fractional intestinal calcium absorption increased significantly, yet no change was observed in serum vitamin D levels. The estimated calcium balance increased significantly from -70.2 +/- 63.8 to +66.7 +/- 48.7 mg/d (P less than 0.01). Thus, potassium citrate treatment improved the estimated calcium balance by lowering urinary calcium while increasing the fractional intestinal calcium absorption. The original hypercalciuric state, its correction to normocalciuria, and the augmentation of intestinal calcium absorption seen in these patients are probably independent of vitamin D control since there was no change noted in serum 1,25-dihydroxyvitamin D levels.
Acidosis, Renal Tubular↗
Nephrolithiasis from calcium supplementation.
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Calcium↗
Assessment of the pathogenetic role of physical exercise in renal stone formation.
The effects of moderate physical exercise (performed on a bicycle ergometer to 70-75% of maximum oxygen consumption) without fluid replenishment on urinary chemistries and crystallization of kidney stone-forming substances were compared to those of rest in six normal subjects. Moderate physical exercise significantly decreased urinary pH [from 6.35 +/- 0.32 (+/-SD) to 5.79 +/- 0.33; P less than 0.05] and citrate [from 121.1 +/- 63.5 to 88.2 +/- 44.4 mg/6-h period from initiation of physical exercise; P less than 0.05 (630 +/- 331 to 459 +/- 231 mumol/6 h)], owing to induced metabolic acidosis. The total renal excretion of stone-forming constituents decreased [for example, calcium from 31.2 +/- 15.8 to 21.4 +/- 6.5 mg/6 h (0.8 +/- 0.4 to 0.5 +/- 0.2 mmol/6 h), phosphorus from 155 +/- 42 to 127 +/- 27 mg/6 h (5.01 +/- 1.4 to 4.1 +/- 0.9 mmol/6 h), and uric acid from 172 +/- 60 to 117 +/- 13 mg/6 h (1.0 +/- 0.4 to 0.7 +/- 0.1 mmol/6 h), each P less than 0.05], probably due to extracellular volume contraction (from sweating) and enhanced renal tubular reabsorption. However, the urinary concentration of stone-forming constituents significantly increased during and after moderate exercise because of the fall in urinary volume from 847 +/- 312 to 290 +/- 36 ml/6 h (P less than 0.01). Thus, urinary calcium oxalate saturation increased significantly from 2.62- to 6.68-fold saturation (P less than 0.01). The urinary undissociated uric acid concentration significantly rose [from 31.6 +/- 24.8 to 125.7 +/- 60.3 mg/L (0.19 +/- 0.15 to 0.76 +/- 0.36 mmol/L; P less than 0.01)], due to higher total uric acid concentration and reduced urinary pH. The saturation of calcium phosphate (brushite) did not change significantly, because the rise in urinary calcium concentration was compensated for by reduced phosphate dissociation (from lower urinary pH). The propensity for spontaneous precipitation of calcium oxalate was greater after exercise, as less soluble oxalate was required to elicit nucleation of calcium oxalate [58.0 +/- 21.2 to 49.0 +/- 16.4 mg/L (644 +/- 236 to 544 +/- 182 mumol/L); P less than 0.05]. The results suggest that moderate physical exercise, without increased fluid intake to compensate for excessive sweating, may cause the crystallization of uric acid and calcium oxalate in urine and may enhance the risk of the formation of renal stones composed of these salts.
Adult↗
Attainment of therapeutic fluoride levels in serum without major side effects using a slow-release preparation of sodium fluoride in postmenopausal osteoporosis.
The bioavailability, biochemical effects, and safety of a slow-release preparation of sodium fluoride were examined. In 8 normal volunteers, a single administration of slow-release sodium fluoride (25 mg) caused a slow rise and gradual decline in serum fluoride concentration, thus avoiding sharp peaks produced by a rapid-release preparation. In 37 patients with postmenopausal osteoporosis, serum fluoride concentration was kept within the "therapeutic window" (95-100 ng/ml) during long-term intermittent sodium fluoride (slow-release) therapy (25 mg twice/day, given for 3 months in each 5-month cycle over five cycles). Serum fluoride was also kept within the therapeutic window in 64 patients who took sodium fluoride (slow release) continuously over 12 months. Serum osteocalcin concentration increased progressively during fluoride treatment (correlation coefficient of 0.88, p less than .001 for the relationship between serum osteocalcin and duration of therapy). Side effects to slow-release sodium fluoride therapy, assessed in 101 patients at two study sites, were minor and included diarrhea in 2 patients, nausea in 2 patients, abdominal pain and cramping in 2 patients, foot pain in 2 patients, and joint pain in 6 patients. Thus, slow-release sodium fluoride confers desired level of fluoride in serum, while providing safety of usage.
Aged↗
Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine.
The effect of long-term treatment with alpha-mercaptopropionylglycine was examined in 66 patients with cystinuria. Of the patients 49 took D-penicillamine before therapy, whereas 17 did not. Over-all side effects to alpha-mercaptopropionylglycine were common, and occurred in 75.5 per cent of the patients with and 64.7 per cent without a history of D-penicillamine treatment, compared to 83.7 per cent who suffered toxicity to D-penicillamine. Serious adverse reactions requiring cessation of therapy were less common with alpha-mercaptopropionylglycine. Among the patients who took both drugs 30.6 per cent had to stop taking alpha-mercaptopropionylglycine, whereas 69.4 per cent could not tolerate D-penicillamine. Of the latter group with toxicity to D-penicillamine before therapy, whereas 17 did therapy only 5.9 per cent had side effects to alpha-mercaptopropionylglycine of sufficient severity to require withdrawal. Alpha-mercaptopropionylglycine was equally as effective as D-penicillamine in reducing cystine excretion. During long-term treatment with alpha-mercaptopropionylglycine (average dose 1,193 mg. per day) urinary cystine levels were maintained at 350 to 560 mg. per day and urinary cystine was kept at undersaturated levels. Commensurate with these changes, alpha-mercaptopropionylglycine produced remission of stone formation in 63 to 71 per cent of the patients and reduced individual stone formation rate in 81 to 94 per cent. Thus, alpha-mercaptopropionylglycine has a definite therapeutic role in cystinuric patients with toxicity to D-penicillamine.
Adolescent↗
Successful management of uric acid nephrolithiasis with potassium citrate.
Eighteen patients with uric acid nephrolithiasis (six with uric acid stones alone and 12 with both uric acid and calcium stones) underwent long-term treatment (1 to 5.33 years, mean of 2.78 years) with potassium citrate (30 to 80 mEq/day, usually 60 mEq/day). Urinary pH increased from low (5.30 +/- 0.31 SD) to normal (6.19 to 6.46) during treatment. Urinary content of undissociated uric acid, which was high to begin with at 204 +/- 82 mg/day, decreased to the normal range (64 to 108 mg/day) following treatment. Urinary citrate rose from 503 +/- 225 mg/day to 852 to 998 mg/day. Urinary saturation of calcium oxalate significantly declined with potassium citrate treatment. New stone formation rate declined from 1.20 +/- 1.68 stones/year to 0.01 +/- 0.04 stones/year (P less than 0.001 by chi square). Remission was experienced in 94.4% of patients, and the group stone formation rate declined by 99.2%. Detailed case reports were obtained in five patients showing different responses between sodium alkali and potassium alkali treatment. All five patients had persistently low urinary pH (typically less than 5.5) and normouricosuria, and four had hyperuricemia. Before treatment, they had stones surgically removed or spontaneously passed, which were pure uric acid in composition. When sodium alkali was give (as bicarbonate or citrate, 60 to 118 mEq/day), new stone formation continued in four patients, and a radiolucent (uric acid) calculus become "calcified" in the remaining patient. The stone analysis disclosed calcium oxalate in five patients and calcium phosphate in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis.
Thirteen patients with hypercalciuric calcium nephrolithiasis continued to form calcium stones when treated with thiazide (4.69 +/- 6.62 [mean +/- SD] stones per patient-year to 5.12 +/- 10.87 stones per patient-year), despite adequate hypocalciuric response (a reduction in urinary calcium levels from 303 +/- 119 mg per day to 193 +/- 88 mg per day, p less than 0.01). Because they had hypocitraturia (250 +/- 86 mg per day versus 643 +/- 236 mg per day in normal subjects, p less than 0.001), potassium citrate (10 to 20 meq three times per day) was added to the ongoing treatment program. During combined treatment with thiazide and potassium citrate, urinary pH significantly rose, and normal levels of urinary citrate were restored. Ten patients stopped forming new stones and all 13 had reduced stone formation rate. Thus, potassium citrate supplementation should be considered in patients requiring thiazide therapy for the control of hypercalciuric nephrolithiasis, especially if they have concurrent hypocitraturia or if it develops during thiazide therapy.
Adult↗
Long-term treatment of calcium nephrolithiasis with potassium citrate.
The long-term effects of potassium citrate therapy (usually 20 mEq. 3 times daily during 1 to 4.33 years) were examined in 89 patients with hypocitraturic calcium nephrolithiasis or uric acid lithiasis, with or without calcium nephrolithiasis. Hypocitraturia caused by renal tubular acidosis or chronic diarrheal syndrome was associated with other metabolic abnormalities, such as hypercalciuria or hyperuricosuria, or occurred alone. Potassium citrate therapy caused a sustained increase in urinary pH and potassium, and restored urinary citrate to normal levels. No substantial or significant changes occurred in urinary uric acid, oxalate, sodium or phosphorus levels, or total volume. Owing to these physiological changes, uric acid solubility increased, urinary saturation of calcium oxalate decreased and the propensity for spontaneous nucleation of calcium oxalate was reduced to normal. Therefore, the physicochemical environment of urine following treatment became less conducive to the crystallization of calcium oxalate or uric acid, since it stimulated that of normal subjects without stones. Commensurate with the aforementioned physiological and physicochemical changes the treatment produced clinical improvement, since individual stone formation decreased in 97.8 per cent of the patients, remission was obtained in 79.8 per cent and the need for surgical treatment of newly formed stones was eliminated. In patients with relapse after other treatment, such as thiazide, the addition of potassium citrate induced clinical improvement. Thus, our study provides physiological, physicochemical and clinical validation for the use of potassium citrate in the treatment of hypocitraturic calcium nephrolithiasis and uric acid lithiasis with or without calcium nephrolithiasis.
Adult↗