Metabolic abnormalities in patients with caliceal diverticular calculi

PURPOSE: We determined the incidence and spectrum of metabolic abnormalities in patients with caliceal diverticular calculi. MATERIALS AND METHODS: Five men and 9 women with caliceal diverticular calculi underwent metabolic evaluation, including determination of serum electrolytes, calcium, phosphate and uric acid, and 24-hour urinary volume, creatinine, calcium, oxalate, uric acid and citrate. RESULTS: Of the 14 patients 7 (50%) had urinary excretion abnormalities promoting stone formation, including hypercalciuria in 3, hyperoxaluria in 1, hypercalciuria combined with hyperuricosuria in 1 and hyperoxaluria combined with hyperuricosuria in 2. Two patients had a history of gout while another had radiographic evidence of medullary sponge kidney. Of the patients 9 (64.3%) had a history of synchronous or metachronous calculi distant from the involved caliceal diverticular stone and 5 (55.6%) of these 9 had definable metabolic disorders. However, there was no statistically significant difference in urinary excretion values between patients with or without a history of additional extra diverticular stones. CONCLUSIONS: Urinary stasis alone does not explain stone formation in a significant number of patients with caliceal diverticular calculi. Rather, the local physiological environment of the urine likely has a predisposing role and evaluation for metabolic abnormalities should be considered. In some patients cure may be effected by treating the stone and any associated metabolic disorders rather than the diverticulum.     

Nephrolithiasis--rational etiological assessment

Although underlying metabolic abnormalities do not differ fundamentally in patients with either first or recurrent nephrolithiasis and 35% of patients with a first event may have to face a recurrence 5 years later, extended metabolic investigations in patients with a first renal calculus should be restricted to particular, exceptional cases. However, in patients with a first calculus basic investigations with respect to specific causes for a concrement such as primary hyperparathyroidism, incomplete renal-tubular acidosis, recurrent urinary tract infection and cystinuria are mandatory. This includes, in addition to a laboratory investigation of blood and urine after a 2-hour-fasting period, analysis of the stone and a urography. The extended metabolic investigation in patients with recurrences or a first occurrence in a patients with a risk constellation includes evaluation of the most important lithogenic (calcium, oxalate, phosphate, uric acid) and inhibiting components (citrate) in the 24-hour urine, in patients with cystine calculi quantitation of cystine. A metabolic investigation should never be undertaken in the hospital or under standardized diet, but always under accustomed, unrestricted nutrition. At least 2 urine samples should be investigated from each patient, preferably not prior to 3-4 months after the event when homeostasis of the patient is restored analogously to the onset of concrement development.     

Oestrogen-progestogen oral contraceptives and urinary calcium excretion

To examine the effects of age and use of oestrogen-progestogen oral contraceptive agents (OCA) on urinary calcium excretion, 24 h urine collections were obtained from 525 women aged 16-69 years during a health survey, and measurements made of the amounts of calcium, creatinine, sodium, potassium and magnesium excreted. Younger women using OCA excreted more potassium and creatinine but less calcium, and less calcium and magnesium relative to creatinine, than corresponding controls using no OCA. Older women excreted less creatine, but significantly greater amounts of calcium, sodium, potassium and magnesium relative to creatinine than younger women. It is postulated that the diminished urinary calcium excretion observed in women using OCA resulted from suppression of bone resorption by oestrogens in OCA.     

Oxalate: its role in lithogenesis and composition of calcium oxalate lithiasis

A prospective study was conducted on 374 patients with urinary lithiasis, aiming to analyze the participation of oxalate in the lithogenesis and composition of the calcium oxalate calculi, alone or associated to other factors. METHODOLOGY: Metabolic urinary study of the patient and analysis of calculi with infrared spectrography and optical microscopy. RESULTS: 26.3% patients had hyperoxaluria and 77.5% of the calculi contain calcium oxalate; these are 167 cases of calcium oxalate, 110 of oxalate and calcium phosphate and 13 cases of mixed calcium oxalate and uric acid lithiasis. 43.4% patients with pure monohydrate calcium oxalate calculi have hypercalciuria, 22.6% hyperoxaluria and 19% hyperuricosuria. Dihydrated calcium oxalate calculi are related to high hypercalciuria in 65% cases and to significant hyperoxaluria in 35% cases. 45% patients present a single lithogenic factor, either hypercalciuria (49.6%), hyperoxaluria (20.6%), hyperuricosuria (13.74%), hypocitraturia (9%), urinary infection (1.5%), A.T.R. (2.25%) or acid oliguria (3%).     

Hypernatriuria and kaliuresis in enuretic children and the diurnal variation

PURPOSE: We investigate the underlying pathophysiological cause of primary nocturnal enuresis by comparing electrolyte alterations in urine samples of enuretics during the daytime and nighttime compared with those of nonenuretic subjects. MATERIALS AND METHODS: Urine output, urine specific gravity and urinary electrolytes in 15 enuretic and 12 nonenuretic children were measured. We collected daytime serum and urine samples of children fed a similar diet between 7 a.m. and 7 p.m., and nighttime between samples 7 p.m. and 7 a.m. Urinary calcium/creatinine ratio, tubular reabsorption of phosphorus and excretions of fractional sodium and potassium were calculated. RESULTS: There was no significant difference between the calcium/creatinine ratio ratios. There was a significant increase in fractional sodium and fractional potassium values in enuretics compared to nonenuretics during the day and at night. Daytime and nighttime fractional sodium and fractional potassium values in enuretics were similar. In contrast to nonenuretics, enuretic patients had no diurnal variation of fractional sodium. There was significant positive correlation between bedwetting status, and fractional sodium and fractional potassium. CONCLUSIONS: Since sodium and potassium excretions were higher in enuretic patients than nonenuretic children, and no significant diurnal variation in urinary excretion of these ions there might be a difference in the mechanism of reabsorption of sodium and potassium between enuretic and nonenuretic children.     

Calciotropic hormones and nephrolithiasis

In recurrent calcium stone formers interfering factors or changes in receptor sensitivity may alter the interrelationships among calcium-regulating hormones, and hormonal behavior often does not fit with the theoretical assumptions. The vitamin D system appears to have the most important metabolic and clinical effects. Abnormal up-regulation of the synthesis of calcitriol and the consequent parathyroid hormone (PTH) suppression can induce hypercalciuria. Consequently, the hypocalciuric effect of thiazide would be caused by an enhanced response to PTH and by a reduction in 1,25(OH)2-vit D. A negative role of vitamin D on the skeleton has been observed in the presence of a negative calcium balance. Moreover, vitamin D also plays a role in urine oxalate excretion. PTH seems not to be directly stimulated in hypercalciuria and recurrent calcium nephrolithiasis, and patients with hyperparathyroidism and recurrent calcium nephrolithiasis show a similar degree of bone demineralization, irrespective of the presence of absence of the so-called 'primary hyperparathyroidism.' Calcitonin plays a contributory role in the pathogenesis of recurrent calcium nephrolithiasis that seems to be strictly related to dietary calcium intake. A higher sensitivity of thyroid C cells, particularly in absorptive hypercalciuric patients, could be related to the pathogenesis of hypercalciuria and contribute to its persistence.     

Effect of hydrochlorothiazide in pseudohypoaldosteronism with hypercalciuria and severe hyperkalemia

Severe hyperkalemia resistant to treatment with sodium chloride (NaCl) supplements plus cation exchange resins can be found in pseudohypoaldosteronism type I. In a patient with the multiple target organ variant of this condition, hyperkalemia persisted at dangerous levels (8.5 mmol/l) despite large doses of NaCl (50 mmol/kg per day) and cation exchange resins (6 g/kg per day). Hypercalciuria was also present. The total volume of fluids and supplements required was not tolerated orally. Indomethacin (2 mg/kg per day) and later hydrochlorothiazide (2 mg/kg per day) were tried to further correct imbalance. Plasma potassium (K) and Na levels, the urinary Na/K ratio, transtubular potassium gradient (TTKG), and urinary calcium/creatinine (Ca/Cr) ratio were used to evaluate the effect of hydrochlorothiazide. Under treatment, plasma Na was stable (137-144 mmol/l), K levels decreased from 8.5 to 5 mmol/l, urinary Na/K from 90 to 24, and TTKG increased from 0.3 to 1.8. Ca/Cr decreased from 3.5 to 1.5 mmol/mmol. The dosage of cation exchange resins was decreased, oral fluids were tolerated, and the patient's general condition improved. Hence: hydroclorothiazide can be useful in the treatment of severe hyperkalemia and hypercalciuria of pseudohypoaldosteronism type I.     

Salt intake, urinary sodium, and hypercalciuria

Several studies have reported that high sodium (Na) intake increases not only urinary Na but also urinary calcium (Ca), suggesting that high Na intake could be involved in the pathogenesis of hypercalciuria. No research data are available on the relationship of Na intake to the prevalence of hypercalciuria within the general population. Moreover, it is not clear if Na intake relates only to urinary Ca or also to other indices of Ca homeostasis, including intestinal Ca absorption. In the present paper, two distinct studies addressed these points using 24-hour urinary Na as an index of salt intake in individuals on their habitual unrestricted free diet. Study 1 analyzed the relationship between 24-hour urinary Na and hypercalciuria (24-hour urinary Ca > or = 7.5 mmol in men, > or = 6.25 mmol in women) in a population sample of 203 men and women, aged 20-59 years. Study 2 analyzed the relationship between 24-hour urinary Na and intestinal strontium (Sr) absorption, used as an index of intestinal Ca absorption, urinary (24-hour and fasting) and plasma Ca, and plasma parathyroid hormone in 36 healthy men and women, aged 18-65 years. Within the population sample (study 1), 24-hour urinary Na was directly and significantly correlated with prevalence of hypercalciuria when controlling for gender, age, weight, and urinary creatinine: the relationship was continuous and linear for urinary Na ranging between 40 and 200 mmol/24 h. In the 36 volunteers (study 2), 24-hour urinary Na was related to 24-hour and fasting urinary Ca (p < 0.001) but not to intestinal Sr absorption: the relationship between 24-hour urinary Na and urinary Ca (both 24 h and fasting) was also significant, controlling for other variables. The results indicate that in adults on their habitual diet, urinary Na, which reflects dietary salt intake, correlates with the prevalence of hypercalciuria independently of intestinal Ca absorption and mainly via renal mechanisms.     

Effect of intravenous furosemide on the renal excretion of digoxin

The effect of an 80-mg intravenous dose of furosemide on the urinary excretion of digoxin was determined in three adult men with normal renal function, each of whom was taking 0.25 mg digoxin daily on a chronic basis. On two separate days, serum samples were taken and urine was collected every 2 hours over an 8-hour period for determination of digoxin, creatinine, calcium, and sodium concentrations. On the first day of study, a saline bolus was given intravenously, and on the second day, furosemide was given. In all subjects, urinary digoxin excretion increased after furosemide in direct proportion to the increase in urine volume. No consistent correlation was seen between digoxin excretion and creatinine, calcium, or sodium output. No significant changes in serum digoxin were found in this active study. These results are consistent with the hypothesis that increasing glomerular filtration rate or total urine volume increases the renal excretion of digoxin and may result in increased total urinary output of this glycoside.     

Sustained reduction in urinary calcium during long-term treatment with slow release neutral potassium phosphate in absorptive hypercalciuria

PURPOSE: We tested whether UroPhos-K, a new slow release neutral form of potassium phosphate (155 mg. phosphate, 8 mEq. potassium per tablet) in a dose of 4 tablets twice daily would produce a sustained hypocalciuric response and maintain bone mass in patients with absorptive hypercalciuria, a major cause of nephrolithiasis characterized by excessive intestinal calcium absorption accompanied in some patients by excessive bone loss. MATERIALS AND METHODS: A total of 25 patients with absorptive hypercalciuria were studied in a 4-year, prospective, open trial with UroPhos-K at yearly intervals during a 4-day inpatient physiological study with a constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate daily. RESULTS: Treatment with UroPhos-K caused a sustained, marked reduction in urinary calcium (264 to 181 mg. daily). Fractional 47calcium absorption decreased modestly (74.0 to 64.6%) commensurate with a reduction in serum 1,25-dihydroxyvitamin D (42 to 34 pg./ml.). Intact parathyroid hormone increased within the normal range (30 to 42 pg./ml.). Bone mineral density was stable at the lumbar spine, femoral neck and distal third of the radius. CONCLUSIONS: UroPhos-K may provide a long-term alternative for hypercalciuric patients in whom thiazide therapy fails.     

The significance of urinary N-acetyl-beta-D-glucosaminidase for predicting early stage diabetic nephropathy

We studied urinary N-acetyl-beta-D-glucosaminidase (NAG) in the early stage of diabetic nephropathy in 27 non-insulin-dependent diabetes mellitus (NIDDM) patients with a microalbumin level below 20 mg on 24-hour urine sample. Microalbumin and NAG excretion were measured in 24-hour urine samples collected on three separate occasions within seven days of admission. Creatinine clearance was determined simultaneously. There was a significant negative correlation between the creatinine clearance and 24-hour urinary NAG (r = -0.38, p < 0.05). Elevation of urinary NAG may indicate decreased renal function during early stage NIDDM nephropathy.     

Effect of furosemide oral solution versus furosemide tablets on diuresis and electrolytes in patients with moderate congestive heart failure

Oral furosemide solution was claimed to produce a greater diuretic response than furosemide tablets in patients with congestive heart failure. The aim of this study was to assess this observation and to further investigate the effects on the electrolyte balance. We compared the effects of oral furosemide in tablets versus oral furosemide solution on serum levels as well as on 4- and cumulative 24-hour urinary volume and sodium, potassium, calcium, magnesium and zinc excretions in 10 patients with moderate congestive heart failure due to ischemic heart disease. Oral furosemide (40-80 mg) was given at the usual once-daily dosage. No change in serum electrolyte levels has been found. All urinary parameters, except zinc, were significantly greater during the first 4 h following oral solution as compared with tablets (volume p < 0.001, sodium p < 0.001, potassium p < 0.05, calcium p < 0.003, magnesium p < 0.05). However, after 24 h, significant differences were found in urinary volume (p < 0.03) and sodium excretion (p < 0.004) only. We conclude that: (1) oral furosemide solution provides a more potent 24-hour diuretic and natriuretic effect than an identical dosage in tablet form, without entailing greater cumulative urinary losses of potassium, calcium, magnesium, and zinc; (2) following the first 4 h of furosemide solution, brisk diuresis, kaliuresis, and magnesiuria are produced, and (3) despite the urinary losses, serum electrolytes remained within normal limits at 4 and 24 h.     

Idiopathic hypercalciuria in childhood

This review describes the supposed mechanisms leading to idiopathic hypercalciuria (IHU) in childhood, further the diagnostic criteria and the proposed treatment modalities are discussed. IHU is not only one of the main causes of renal stone disease in children but it's also at the origin of the postglomerular haematuria and the frequency-dysuria syndrome. Its role in the development of osteoporosis in adults is also documented. The diagnosis of raised calcium excretion is based on age specific values during early infancy. In older children and adults a urinary calcium/creatinine ratio exceeding 0.6 mmol/mmol is regarded as elevated. Dietary calcium restriction can no longer be recommended for the treatment of IHU because it results in secondary hyperoxaluria and on the long-term causes decreased bone mineral density. Patients should be kept on dietary sodium restriction and high fluid intake. In cases IHU associated with recurrent episodes of macroscopic haematuria or recurrent stone disease a therapeutic trial with hydrochlorothiazide in the dose of 0.5-1 mg/kg/day with potassium-citrate supplementation and possibly magnesium citrate should be started. In some special forms of hypercalciuria such as the X-linked recessive nephrolithiasis syndrome or Bartter syndrome the localization and in some cases even the molecular mechanism of the events leading to increased calcium excretion are elucidated. In IHU enhanced Ca(++)-ATPase, and Na-Li countertransport activity and decreased Na+/K+ ATPase activity were described in the erythrocyte membrane model. It is expected that with the molecular genetic development the clinical classification of the hypercalciuric syndromes will become a rational genome-based one.     

Effects of ambient temperature on broiler mineral balance partitioned into urinary and faecal loss

1. Two experiments were conducted on control (intact) and colostomised 4 to 7 week old broilers to evaluate the influence of 24 degrees C, diurnally cycling 24 to 35 degrees C and chronic 35 degrees C ambient temperatures on broiler mineral balance, urinary and faecal mineral excretion and urinary osmolar characteristics. 2. In the first experiment, colostomy had no significant effect on mineral balance. However, broilers exposed to high cycling ambient temperature reduced their retention of phosphorus, potassium, sodium, magnesium, sulphur, manganese, copper and zinc compared with birds housed at 24 degrees C. 3. Despite the minimal effect of high ambient temperature on urine production, minerals excreted disproportionately excreted in urine included potassium, magnesium, phosphorus and sulphur while copper and magnesium were lost primarily via the faeces. 4. In the second experiment, exposure to 35 degrees C increased urine output from 50.7 ml/12 h per kg of body weight at 24 degrees C to 101.3 ml/12 h per kg of body weight and was associated with an increased urine:water ratio and reduced urine osmolality. 5. Reduced urinary chloride and higher potassium, phosphorus, sulphur, sodium, magnesium, calcium and manganese excretion was observed for broilers housed in under high ambient temperatures compared to 24 degrees C. 6. These studies suggest that high ambient temperatures adversely influence mineral metabolism and, furthermore, that the route of excretion varies with the specific mineral and the environmental temperature exposure.     

Seasonal variations in the composition of urine from normal subjects: a longitudinal study

The volume, pH and composition of 24-h urine samples, collected by 13 healthy male adults, were followed over a period of one year. Significant and systematic variations in urine pH, calcium, phosphate, oxalate, uric acid, potassium and magnesium were observed. A significant but non-sinusoidal variation in sodium excretion was found but there were no significant changes in urinary volume, creatinine or hydroxyproline. Many of the observed changes could be attributed to variations in the pattern of food consumption throughout the year but calcium, phosphate and oxalate were exceptions in that seasonal variations in these parameters appeared to be due to the effects of sunlight (or vitamin D) rather than to the diet.     

Human leucocyte antigen-DQA1, -DQB1 polymorphism distribution in Shanghai Chinese women with pregnancy induced hypertension]

Our objective was to determine if maternal urinary calcium excretion is altered during treatment of mild preeclampsia remote from term with the calcium channel blocker nifedipine. One hundred forty-eight women with mild preeclampsia were randomly allocated to treatment with either bed rest alone (n=64) or in combination with nifedipine (n=84) at 26-36 weeks' gestation. All women had 24 hr urine samples collected for creatinine clearance and calcium excretion determination prior to therapy and during treatment. There was no difference in gestational age at the time of urine collection between the two groups. There were no differences in 24-hr creatinine clearance and calcium excretion between the groups prior to therapy. When followed longitudinally, there was a significant reduction in calcium excretion within each group (p=0.0005 control group, p <0.0001 nifedipine group). Further, a significant reduction in calcium excretion was noted following nifedipine therapy (62+/-94 mg Ca/24 hr) compared to the control group (143+/-153 mg Ca/24 hr), p <0.001. Consistent with previous studies, we have shown that progressive hypocalciuria is a feature of preeclampsia. Further, urinary calcium excretion decreased despite nifedipine therapy. Altered urinary calcium excretion may be less reflective of the progression in severity of preeclampsia in patients treated with nifedipine.     

Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred

Urine activity product ratios of uric acid (APRua), sodium urate (APRna), and ammonium urate (APRau), and urinary excretion of 10 metabolites were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of 4 diets containing approximately 11% protein (dry weight) and various protein sources: a 72% moisture, casein-based diet; a 10% moisture, egg-based diet; a 72% moisture, chicken-based diet; and a 71% moisture, chicken-based, liver-flavored diet. Significantly (P < 0.05) higher APRua, APRna, and APRau were observed when dogs consumed the egg-based diet, compared with the other 3 diets; there were no differences in these ratios among the other 3 diets. Twenty-four-hour urinary excretions of chloride, potassium, phosphorus, and oxalic acid were significantly (P < 0.05) higher when dogs consumed the egg-based diet. Twenty-four-hour urinary excretions of sodium were significantly (P < 0.05) higher when dogs consumed the egg-based diet, compared with the casein-based diet and the chicken-based, liver-flavored diet, but were not significantly different between the egg-based diet and chicken-based diet. Twenty-four-hour urine volume was similar when dogs consumed the 4 diets. Twenty-four-hour endogenous creatinine clearance was significantly (P < 0.05) lower when dogs consumed the casein-based diet; there were no differences among the other 3 diets. Although consumption of all diets was associated with production of alkaline urine, the 24-hour urine pH was significantly (P < 0.05) higher when dogs consumed the egg-based diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of growth hormone on urine calcium and serum vitamin D metabolites in renal failure

Growth hormone (GH) causes a modest increase in urine calcium excretion in normal adults, but uremic rats given both GH and calcitriol developed hypercalciuria. Ten short prepubertal children with renal insufficiency treated with recombinant human GH (rhGH) had urine calcium to creatinine (Ca/Cr) ratios and serum vitamin D metabolite concentrations monitored prospectively for up to 24 months. Six were also treated with calcitriol and two with other vitamin D preparations. Mean urine Ca/Cr ratios or mean serum concentrations of 1,25-dihydroxy vitamin D, 24,25-dihydroxy vitamin D, and 25-hydroxy vitamin D did not change significantly during treatment with rhGH. The risk for rhGH-induced hypercalciuria is small in children with renal insufficiency, even when treated concomitantly with a vitamin D preparation.     

Effect of acute water loading on urinary excretion of prostaglandin E in hypertensive patients

To assess the relationship or urine flow to the urinary excretion of prostaglandin E (PGE), urinary excretion of PGE was measured before and after acute water loading (20 ml/kg orally) in patients with hypertension. Water loading promptly increased urinary excretion of PGE as well as urine flow rate and decreased urine osmolality (all p less than 0.001), but did not affect urinary excretions of sodium, potassium and creatinine, plasma renin activity and plasma aldosterone concentration. There was a significant positive correlation between urine flow rate and urinary PGE excretion rate (p less than 0.01). Urinary PGE concentration correlated negatively with urine flow rate when the flow was lower than 5 ml/min (p less than 0.01). Urinary PGE concentration correlated negatively with urine flow rate when the flow was lower than 5 ml/min (p less than 0.01), whereas it did not change when the urine flow rate was larger than 5 ml/min. These results may support the hypothesis that urinary excretion of PGE is determined mainly by urine flow rate in the situation of water diuresis.     

Evidence of absorptive hypercalciuria in tuberculosis patients

In patients with granulomatous diseases, disturbances in calcium metabolism have been described. The aim of the study was to evaluate alterations in calcium metabolism in patients with tuberculosis. Forty patients with tuberculosis (TB) were studied in a baseline state (calcium intake 1000 mg/day). Fourteen of these patients were also studied after restrictive calcium diet (400 mg/calcium/day) and after a load of oral calcium of 1000 mg. In all the studies, calcium and phosphorus were measured in serum and urine, and parathyroid hormone (PTH) in plasma. In addition, serum 25OHD and 1,25(OH)2D (calcitriol) levels were measured in the baseline state and after the restrictive diet. In the baseline state, 25OHD levels were lower and urinary calcium higher in TB patients than in the control group. No patients had hypercalcemia, but hypercalciuria was present in 10 patients (25%). The patients with tuberculosis were divided according to the presence or absence of hypercalciuria. In both groups, the 25OHD levels were lower than in controls. Hypercalciuric patients had lower plasma parathyroid hormone levels and higher serum calcitriol levels than the control group and the TB patients without hypercalciuria. Urinary calcium excretion after a calcium load was higher in TB patients with hypercalciuria than in controls. A positive correlation was found between the calcitriol levels and postcalcium load urinary calcium excretion in patients with calcium hyperabsorption. These data indicate that absorptive hypercalciuria is frequently observed in patients with TB and is possible due to inappropriately high serum calcitriol levels.