An oral glutamine load enhances renal acid secretion and function

In a recent study, a small oral glutamine load acutely elevated plasma bicarbonate concentrations in healthy adults (Am J Nutr 1995;61:1058-61). The present study was designed to elucidate the renal mechanism underlying the base-generating response to L-glutamine. Accordingly, vehicle (489 mL diet soda) or vehicle plus 2 g L-glutamine (28 mg/kg body wt) was ingested and the gain in extracellular fluid volume bicarbonate was compared with renal acid elimination as either ammonium excretion or tubular acid secretion (titratable acid plus bicarbonate reabsorption). Vehicle alone, which contained 27 mmol acid, did not increase extracellular fluid volume bicarbonate over the 90-min period. In contrast, L-glutamine increased plasma bicarbonate concentration (from 25.4+/-2 to 27.9+/-1 mmol/L, P < 0.05) and extracellular fluid volume bicarbonate by an estimated 39+/-10 mmol. When added to that required to neutralize the ingested acid, the combined total for new bicarbonate generated gave an estimated 66+/-10 mmol. Surprisingly, ammonium excretion accounted for < 2% of this newly generated bicarbonate. However, acid secreted and excreted as net acid (5.2+/-4.0 mmol/90 min) as well as that coupled to enhanced bicarbonate reabsorption (76+/-20 mmol/90 min) readily accounted for the estimated base gain (81+/-24 compared with 66+/-10 mmol/90 min). Concomitant with enhanced renal acid secretion, the oral glutamine load elicited an increase in glomerular filtration rate. These results rule out a role for L-glutamine as a direct precursor of bicarbonate and instead point to an indirect role in accelerating acid secretion, apparently coupled to increased glomerular filtration rate.     

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lyme carditis: a clinical presentation and long time follow-up

1. We evaluated the effects of the dietary restriction of sodium chloride on blood pressure and systemic calcium metabolism in 19 in-patients with essential hypertension (11 men and 8 women, mean age 49.9 +/- 12.1 years). 2. All patients received a high-sodium diet (250 mmol/day) for 1 week, followed by a low-sodium diet (10 mmol/day) for another week. Intake of potassium (100 mmol/day) and of calcium (15 mmol/day) were kept constant throughout the study. 3. Sodium restriction significantly reduced the mean blood pressure (from 114.0 +/- 1.9 to 105.0 +/- 13.7 mmHg, P < 0.01). Urinary calcium excretion was significantly reduced (from 5.1 +/- 2.4 to 2.2 +/- 1.0 mmol/day, P < 0.01). 4. The change in mean blood pressure after sodium restriction was not correlated with a change in any parameter of calcium metabolism [whole blood ionized calcium, plasma intact parathyroid hormone, or 1,25-(OH)2 vitamin D3]. 5. Plasma renin activity during a regular sodium diet, an index of renin status, was significantly and inversely correlated with the change in blood pressure during sodium restriction, but not with any change in the parameters of calcium metabolism. 6. We conclude that sodium restriction reduces blood pressure and decreases urinary calcium excretion. However, we observed no significant role of extracellular calcium concentration or of calciotropic hormone concentration in the mechanism of sodium sensitivity.     

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.     

Effect of enalapril on proteinuria, phosphaturia, and calciuria in insulin-dependent diabetes

Elevated urinary calcium and phosphate excretion have been observed in children with insulin-dependent diabetes mellitus (IDDM). This may be related to a defect in tubular reabsorption. It is well known that converting enzyme inhibition decreases microalbuminuria and may prevent or retard diabetic nephropathy. We investigated whether enalapril also improves the defect in calcium and phosphate reabsorption. We studied 16 children and young adults (age 12-21 years) with IDDM and persistent microalbuminuria before and during 12 weeks of enalapril treatment. Before treatment microalbuminuria, urinary calcium excretion, and fractional tubular phosphorus reabsorption (TPR) were 153+/-53 microg/min, 5.5+/-0.9 mg/kg per day, and 71.4+/-3.6%, respectively. At the end of the 12th week, microalbuminuria had decreased to 20.3+/-7.9 microg/min and calcium excretion to 3.3+/-0.4 mg/kg per day (P<0.01), while the TPR increased to 80.1+/-3.8% (NS). The renal threshold phosphate concentration increased from 1.8+/-0.15 to 2.92+/-0.23 mg/dl (P<0.01). The fasting serum glucose and hemoglobin Alc levels did not change significantly during the study. Systolic and diastolic blood pressures were 120.4+/-2.2 / 79.3+/-1.4 mm Hg and 110.5+/-1.8 / 71.3+/-0.9 mm Hg before and after 12 weeks, respectively. We conclude that enalapril treatment improves not only microalbuminuria but also abnormal calcium and phosphate excretion in microalbuminuric children with IDDM.     

Randomized long-term evaluation of bicarbonate-buffered CAPD solution

BACKGROUND: Over the past 15 years, lactate has been used successfully as a buffer in peritoneal dialysis solutions, although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system, allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution were evaluated in this study. METHODS: This open, randomized, controlled, multicenter study comparing a 34 mmol/liter bicarbonate- with a 35 mmol/liter lactate-buffered peritoneal dialysis solution was performed in two consecutive 12-week-treatment phases. Fourteen Centers participated in this trial. RESULTS: A total of 69 out of initially 123 randomized patients completed the six-month study period (36 patients in the bicarbonate group and 33 in the lactate group). While the arterial acid base status of the total study population did not change during the study period and no significant difference was observed between the two treatment groups, the acid-base status of patients in the bicarbonate group entering the study with a metabolic acidosis significantly improved (mean +/- SD; blood pH: baseline = 7.361 +/- 0.05, week 12 = 7.380 +/- 0.04, P < 0.05; week 24 = 7.388 +/- 0.03 P < 0.05; plasma bicarbonate: baseline = 19.49 +/- 3.01 mmol/liter, week 12 = 21.16 +/- 2.63 mmol/liter, P < 0.01; week 24 = 21.51 +/- 2.42 mmol/liter, P < 0.01). No significant changes were recorded in acidotic patients treated with the conventional lactate-buffered solution. The changes in plasma bicarbonate from baseline during the study was significantly different between the groups (week 12: lactate = +0.11 +/- 2.21 mmol/liter, bicarbonate = +1.69 +/- 2.55 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.21 to 2.94 mmol/liter; week 24: lactate = +0.03 +/- 2.48 mmol/liter, bicarbonate = +1.82 +/- 2. 96 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.16 to 3.42 mmol/liter). The normalized protein catabolic rate (nPCR) slightly but significantly decreased in the lactate group (baseline -0.90 +/- 0.23 g/kg/day, week 24 -0.83 +/- 0.21 g/kg/day, P < 0.01) and increased in the bicarbonate group (baseline +0.89 +/- 0.28 g/kg/day, week 24 +0.92 +/- 0.26 g/kg/day, P < 0.05). Changes from baseline between groups were significant (week 24, lactate = -0. 099 +/- 0.15 g/kg/day, bicarbonate = 0.049 +/- 0.12 g/kg/day, P < 0. 01, 95% confidence interval for the difference 0.068 to 0.229 g/kg/day). Other evaluated parameters (biochemical profile, peritoneal function parameters, dialysate protein loss) did not differ significantly between the two groups. No adverse effects related to the study solution were recorded. CONCLUSIONS: These results support the efficacy and safety of bicarbonate-buffered peritoneal solutions in a controlled randomized comparison for up to six months. Peritoneal dialysis solutions containing the physiological buffer bicarbonate might effectively replace conventional lactate-buffered CAPD solutions.     

NCI? What is it? What do they do?

BACKGROUND: Omeprazole, a H+/K+ ATPase inhibitor, has been shown to reduce gastric bicarbonate secretion in cats. However, there has been no study on the effect of omeprazole on bicarbonate secretion in patients with duodenal ulcer (DU). METHODS: Fifteen men with duodenal ulcer (mean age 38 years, range 22-57) were included. Baseline gastric acid output, bicarbonate secretion, and parietal and nonparietal secretions were estimated before and after omeprazole therapy (20 mg/day) for four weeks. RESULTS: Omeprazole administration did not significantly alter bicarbonate secretion (3.3 [1.2] vs 2.4 [0.4] mmol/h), though there was significant reduction in gastric acidity (44.2 [6.6] vs 20.7 [4.6] mmol/L, p < 0.01). CONCLUSION: Omeprazole reduces acid secretion but does not affect gastric bicarbonate secretion in patients with DU.     

Dietary saturated fatty acids increase cholesterol synthesis and fecal steroid excretion in healthy men and women

In a strictly controlled 6-week trial with 47 healthy volunteers we have determined the effect of replacement of polyunsaturated by saturated fatty acids on the fecal steroid excretion and on the rate of whole body cholesterol synthesis, as measured both by the sterol balance method and by the concentration of the cholesterol precursor lathosterol in serum. Subjects were fed mixed natural diets, of which the total fat content was kept constant at 45% energy. Consumption of polyunsaturated fatty acids, mainly linoleic acid, was 21% energy for the first 3-week period (P:S ratio 1.9), and 5% of energy (P:S ratio 0.2) for the next 3-week period, or vice versa. Cholesterol intake as determined by analysis of duplicate diets was 41 mg MJ-1 (about 500 mg day-1) during both periods. Feces were collected for 5 days at the end of both periods. The steroid composition of the feces was not affected by the change of diets. The fecal excretion of neutral steroids was significantly higher on the low P:S high-saturated-fat (2.25 +/- 0.68 mmol day-1) than on the high P:S high-linoleic-acid diet (2.00 +/- 0.69 mmol day-1; P < 0.01). The excretion of bile acids was similar (0.77 +/- 0.40 and 0.79 +/- 0.41 mmol day-1, respectively). The cholesterol balance and the rate of cholesterol synthesis were higher during the low P:S (1.86 +/- 0.83 mmol day-1) than during the high P:S period (1.55 +/- 0.85 mmol day-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary creatinine excretion in the ICU: low excretion does not mean inadequate collection

BACKGROUND: It has been assumed that a urinary creatinine excretion rate of less than 10 mg/kg per day means an inadequately collected urine sample. OBJECTIVE: To determine the frequency of a urinary creatinine excretion rate of less than 10 mg/kg per day in intensive care unit patients with an adequately collected urine sample. METHOD: In a prospective study of creatinine excretion rates, 24-hour urine samples were evaluated for urinary creatinine in 209 critically ill patients with indwelling Foley catheters. Patients from three adult intensive care units in New York City were divided into two groups. Group 1 patients excreted less than 10 mg/kg per day of urinary creatinine, and group 2 patients excreted at least 10 mg/kg per day. Groups 1 and 2 were first evaluated by dividing the creatinine excretion data by actual body weight. Since actual body weight may overestimate body weight in the critically ill patient, data from groups 1 and 2 were also evaluated using lean body weight. RESULTS: Urinary creatinine excretion was less than 10 mg/kg per day in 36.8% of patients using actual body weight and 29.7% of patients adjusted for lean body weight. The average age of patients in group 1 was 74 +/- 17 years for both actual body weight and lean body weight. The average age of group 2 patients was 60 +/- 19 years for actual body weight and 62 +/- 19 years for lean body weight. There was a significant difference in age between group 1 and group 2 patients for both actual body weight and lean body weight. The proportion of female vs male patients with reduced creatinine excretion was significantly greater, whether the actual body weight or lean body weight adjustment was used. CONCLUSIONS: A urinary creatinine excretion rate of less than 10 mg/kg per day occurs in about one third of critically ill patients, who are more likely to be elderly and female.     

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.     

Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects

This study was designed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study. The two 6-day diet periods were separated by a 5-day washout period. On day 6, the subjects were water loaded, and blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced no significant changes in blood pressure, glomerular filtration rate, or renal blood flow in these water-loaded subjects, whatever the sodium diet. In subjects on a low-salt diet, losartan markedly increased urinary sodium excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The fractional excretion of endogenous lithium was unchanged, suggesting no effect of losartan on the early proximal tubule in our experimental conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to 13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/- 6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium, calcium, and phosphate. In subjects on a high-salt diet, similar effects of losartan were observed, but the changes induced by the angiotensin II antagonist did not reach statistical significance. In addition, losartan demonstrated significant uricosuric properties with both sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.     

Reversible changes of the muscle cell in experimental phosphorus deficiency

Both animal and human studies suggest that either phosphorus depletion or hypophosphatemia might have an adverse effect on muscle function and composition. Recently a possible deleterious effect was noted in patients with chronic alcoholism. In this unexplained disease, a variety of toxic and nutritional disturbances could affect the muscle cell, thus obscuring the precise role of phosphorus. Accordingly, we examined eight conditioned dogs for the possibility that phosphorus deficiency per se might induce an abnormally low resting transmembrane electrical potential difference (Em) and alter the composition of the muscle cell. Eight conditioned dogs were fed a synthetic phosphorus-deficient but otherwise nutritionally adequate diet plus aluminum carbonate gel for a 28-day period followed by the same diet with phosphorus supplementation for an additional 28 days. Sequential measurements of Em and muscle composition were made at 0 and 28 days during depletion and again after phosphorus repletion. Serum inorganic phosphorus concentration (mg/100 ml) fell from 4.2 +/- 0.6 on day 0 t0 1.7 +/- 0.1 on day 28. Total muscle phosphorus content (mmol/100 g fat-free dry wt [FFDW]) fell from 28.5 +/- 1.8 on day 0 to 22.4 +/- 2.1 on day 28. During phosphorus depletion, average Em (-mV) fell from 92.6 +/- 4.2 to 77.9 +/- 4.1 mV (P less than 0.001). Muscle Na+ and Cl- content (meq/100 g FFDW) rose respectively from 11.8 +/- 3.2 to 17.2 +/- 2.8 (P less than 0.01) and from 8.4 +/- 1.4 to 12.7 +/- 2.0 (P less than 0.001). Total muscle water content rose from 331 +/- 12 to 353 +/- 20 g/100 FFDW (P less than 0.05). A slight, but nevertheless, significant drop in muscle potassium content, 43.7 +/- 2.0-39.7 +/- 2.2 meq/100 g FFDW (P less than 0.05) was also noted. After 4 wk of phosphorus repletion, all of these measurements returned toward control values. We conclude that moderate phosphorus depletion can induce reversible changes in skeletal muscle composition and transmembrane potential in the dog, and it apparently occurs independently of profound hypophosphatemia.     

The interaction of dietary fibers and cholesterol upon the plasma lipids and lipoproteins, sterol balance, and bowel function in human subjects

To identify any metabolic effects of dietary fiber upon cholesterol metabolism in man, six adult volunteer subjects were fed eucaloric cholesterol-free formula diets, with and without added dietary fiber for two 4-wk periods. A large quantity of dietary fiber was fed, some 60 g of plant cell wall material (or 16 g of crude fiber) derived from corn, beans, bran, pectin, and purified cellulose. This provided about five times the fiber intake of the typical American diet. The addition of fiber to the cholesterol-free diet did not change either the plasma cholesterol level (171+/-21 mg/dl, SEM, to 167+/-18) or the triglyceride (103+/-39 to 93+/-27 mg/dl). The excretion of both endogenous neutral steroids and bile acids were unchanged with fiber (505+/-41 to 636+/-75 mg/day and 194+/-23 to 266+/-47 mg/day, respectively.) However, total fecal steroid excretion was increased 699+/-29 to 902+/-64 mg/day, P < 0.025). With fiber, intestinal transit time was decreased (59+/-9 to 35+/-8 h, P < 0.005), and both the wet and dry stool weights were greatly increased.A second group of six subjects was fed similar diets containing 1,000 mg cholesterol derived from egg yolk. The addition of fiber to the 1,000-mg cholesterol diet did not alter either plasma cholesterol level (233+/-26 to 223+/-36 mg/dl) or triglyceride (102+/-19 to 83+/-11 mg/dl). The excretion of endogenous neutral steroids (618+/-84 to 571+/-59 mg/day), of bile acids (423+/-122 to 401+/-89 mg/day), and of total fecal steroids (1,041+/-175 to 972+/-111 mg/day) were unchanged by fiber. The absorption of dietary cholesterol was not altered when fiber was added to the 1,000-mg cholesterol diet (44.0+/-3.3 to 42.9+/-2.5%). A two-way analysis of variance utilizing both groups of subjects indicated a significant (P < 0.001) effect of dietary cholesterol upon the plasma cholesterol concentration. We concluded that a large quantity of dietary fiber from diverse sources had little or no effect upon the plasma lipids and sterol balance in man in spite of the fact that intestinal transit time and stool bulk changed greatly.     

Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause--a clinical research center study

To assess the mechanism by which estrogen replacement therapy (ERT) enhances renal calcium conservation in perimenopausal women, we studied 18 normal women in early postmenopause before and after 6 months of ERT (cyclic treatment with transdermal estradiol at 100 micrograms/day and medroxyprogesterone acetate at 10 mg/day for the first 12 days of each cycle). The changes after ERT were: serum ionized calcium and ultrafiltrable calcium, no change; serum intact PTH, 38.2% increase (P < 0.0001); serum 1,25-dihydroxyvitamin D, 23.8% increase (P < 0.0001); urinary calcium excretion, 33.3% decrease (P < 0.001); and deoxypyridinoline (a marker for bone resorption), 19.5% decrease (P < 0.0001). Also, ERT increased tubular reabsorption of calcium (TRCa; 97.6% +/- 0.2% to 98.7% +/- 0.1%; P < 0.0001), and this increase correlated with that in serum PTH (r = 0.49; P < 0.05). After the infusion of human PTH-(1-34), the TRCa maximum was greater after ERT than at baseline (99.4% +/- 0.1% vs. 99.0% +/- 0.1%; P < 0.0001), resulting in decreased calcium excretion (0.9 +/- 0.20 vs. 1.43 +/- 0.20 mumol/dL glomerular filtrate; P < 0.001). Thus, in early postmenopause, the major mechanism of increased renal calcium conservation after ERT is an increase in TRCa due to an increase in serum PTH because of estrogen-induced inhibition of bone resorption. However, ERT also may directly increase the TRCa maximum in response to PTH.     

Health care coverage and access for children in an urban state: the New York perspective

To clarify the role of the intestine, kidney, and bone in maintaining calcium homeostasis during pregnancy and lactation and after the resumption of menses, a longitudinal comparison was undertaken of 14 well-nourished women consuming approximately 1200 mg Ca/d. Measurements were made before conception (prepregnancy), once during each trimester of pregnancy (T1, T2, and T3), early in lactation at 2 mo postpartum (EL), and 5 mo after resumption of menses. Intestinal calcium absorption was determined from the enrichment of the first 24-h urine sample collected after administration of stable calcium isotopes. Bone mineral of the total body and lumbar spine was measured by dual-energy X-ray absorptiometry and quantitative computerized tomography, respectively. Twenty-four-hour urine and fasting serum samples were analyzed for calcium, calcitropic hormones, and biochemical markers of bone turnover. Despite an increase in calcium intake during pregnancy, true percentage absorption of calcium increased from 32.9+/-9.1% at prepregnancy to 49.9+/-10.2% at T2 and 53.8+/-11.3% at T3 (P < 0.001). Urinary calcium increased from 4.32+/-2.20 mmol/d at prepregnancy to 6.21+/-3.72 mmol/d at T3 (P < 0.001), but only minor changes in maternal bone mineral were detected. At EL, dietary calcium and calcium absorption were not significantly different from that at prepregnancy, but urinary calcium decreased to 1.87+/-1.22 mmol/d (P < 0.001) and trabecular bone mineral density of the spine decreased to 147.7+/-21.2 mg/cm3 from 162.9+/-25.0 mg/cm3 at prepregnancy (P < 0.001). Calcium absorption postmenses increased nonsignificantly to 36.0+/-8.1% whereas urinary calcium decreased to 2.72+/-1.52 mmol/d (P < 0.001). We concluded that fetal calcium demand was met by increased maternal intestinal absorption; early breast-milk calcium was provided by maternal renal calcium conservation and loss of spinal trabecular bone, a loss that was recovered postmenses.     

Nitrogen homeostasis in man: influence of protein intake on the amplitude of diurnal cycling of body nitrogen

1. The diurnal nature of nitrogen (N) homoeostasis was investigated in adults fed increasing protein intakes. N balance was estimated during a 48 h period of consecutive 12 h periods of feeding hourly meals and fasting, after 12 days of adaptation to diets containing 0.36 +/- 0.01, 0.77 +/- 0.03, 1.59 +/- 0.08 and 2.31 +/- 0.65 g of protein day-1 kg-1. N losses were determined from measured urinary N excretion corrected for changes in the body urea pool, and estimated faecal and miscellaneous losses. [13C]Leucine and [2H5]phenylalanine balances were measured during a primed, continuous infusion of the two amino acids during the fasting and feeding phase on the second day. 2. Increasing fasting N losses were observed (47 +/- 7, 60 +/- 6, 95 +/- 15 and 140 +/- 36 mg day-1 kg-1) on the four intakes, with corresponding increasing fed gains of 8.2 +/- 3.9, 40.2 +/- 7.1, 112 +/- 24 and 180 +/- 56 mg day-1 kg-1. 3. Increasing fed-state amino acid gains with increasing protein intake were observed with both [13C]leucine and [2H5]phenylalanine, whereas increasing fasting amino acid losses were confirmed with [13C]leucine. 4. The N equivalent of the leucine oxidation rate was mostly in the range of 10-50% lower than expected from the N excretion rates. This may reflect the timing of the amino acid balance measurements and non-uniform rates of gain and loss throughout the diurnal cycle. 5. We conclude on the basis of both N and amino acid balances that the amplitude of the diurnal cycling of body protein N in human adults increases with increasing dietary protein intake. Thus one component of the protein requirement for N balance reflects a demand for repletion of fasting losses which increases with increasing habitual protein intake.     

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.     

Consequences of selective blockade of septal noradrenergic afferents on anxiety and spatial working memory performance in mice

We have previously reported a high prevalence of endemic renal tubular acidosis (EnRTA) in the northeast of Thailand, and our subsequent studies provided evidence that K deficiency exists in the same region. Since tubulointerstitial damage is associated with K deficiency, we postulate that this might be implicated in the pathogenesis of EnRTA and, if so, that a spectrum of tubulointerstitial abnormalities can be anticipated. In this study we evaluated renal acidification ability in 4 patients and in 11 of their relatives. We used a 3-day acid load (NH4Cl 0.1 g/kg/day) followed by 20 mg oral furosemide and monitored the maximal renal concentrating ability using water deprivation and intranasal 1-deamino-D-arginine vasopressin. The results showed that the subjects could be divided into three groups; normal relatives of the patients, those with suspected renal tubular acidosis, and patients with overt EnRTA who had chronic metabolic acidosis and a low rate of excretion of NH4+. The rate of excretion of K was very low (20 +/- 4 mmol/day) in patients with EnRTA and in their relatives with suspected EnRTA. The transtubular K concentration gradient was also very low in their relatives, especially in patients with suspected EnRTA (2.8 +/- 0.2). With a 3-day NH4Cl load, the rate of excretion of NH4+ was very low in patients with EnRTA (32 +/- 9 mmol/day), and the relatives with suspected EnRTA also had a decreased capacity to excrete NH+4 (50 +/- 14 mmol/day). In contrast, the normal relatives excreted 92 +/- 12 mmol of NH+4/day. The patients with EnRTA could lower their urine pH to less than 5.5 after the acid loading (6.2 +/- 0.3). After furosemide (20 mg), the NH4+ excretion in the patients with EnRTA was lower than in the normal relatives. Moreover, the minimum urine pH in patients with EnRTA did not fall (6.1 +/- 0.2), but there was a fall to 4.8 +/- 0.1 in the patients with suspected EnRTA after furosemide treatment. In conclusion, there was a spectrum of tubulointerstitial abnormalities ranging from suspected to overt distal RTA in a geographic area known to have a high prevalence of K deficiency. K deficiency might be the important pathogenetic factor of EnRTA in the northeast of Thailand.     

Decreased fecal bile acid output in patients with coronary atherosclerosis

In most patients with atherosclerosis, the underlying metabolic derangement remains undefined. Animal experiments have suggested that the ability to produce and excrete large amounts of bile acids may be an adaptation mechanism to cholesterol overload protecting against the atherogenic effects of cholesterol. However, there are very few data on bile acid excretion in human atherosclerosis. In the present study, we have investigated fecal bile acid secretion in subjects with and without coronary artery disease. The target group consisted of 30 patients with proven coronary artery disease and the control group consisted of 27 matched subjects without clinical or laboratory evidence of coronary atherosclerosis. Fecal bile acids were measured by gas-liquid chromatography from 24-hr stool collections under a controlled diet. The patients excreted significantly less bile acids than the controls (325+/-135 vs. 592+/-223 mg/day, respectively, p < 0.0001). The difference was primarily due to a reduced excretion of secondary bile acids. Less than 50% of deoxycholate was excreted by patients (180+/-81 mg/day) as compared to controls (367+/-168 mg/day, p < 0.0002), while lithocholic acid excretion was 111+/-62 mg/day in patients vs. 190 +/-70 mg/day in controls (p < 0.005). The fecal output of the two primary bile acids, cholic and chenodeoxycholic acid, did not differ significantly between patients and controls. The fecal output of total bile acids correlated with that of both secondary bile acids in patients as well as in controls. These findings suggest that patients with coronary heart disease are unable to excrete adequate amounts of bile acids to rid themselves of excess cholesterol, even if they are able to maintain a plasma cholesterol level comparable to that of healthy controls.