Low Phosphate Diet Research Articles

Dopamine enhances the phosphaturic response to parathyroid hormone in phosphate-deprived rats.

Phosphate deprivation results in a resistance to the phosphaturic effect of parathyroid hormone. Dopamine is phosphaturic and is synthesized by kidney proximal tubule, the nephron subsegment where parathyroid hormone inhibits phosphate transport. Thus, to test the hypothesis that phosphate deprivation is associated with low intrarenal dopamine synthesis and that dopamine infusion will overcome the resistance to the phosphaturic response to parathyroid hormone, the following study was performed. The effect of dietary phosphate intake on intrarenal dopamine synthesis, as reflected by urinary dopamine excretion, was determined. Rats were placed in metabolic cages (N = 5) and were fed a low-phosphate diet (0.07% Pi) for 4 days and then a high-phosphate diet (1.8% Pi) for 4 days. Twenty-four-hour urinary dopamine excretion was significantly lower in rats fed a low-phosphate diet (2.53 +/- 0.06 versus 4.10 +/- 0.30 micrograms/day). Further, the effect of dopamine infusion on the blunted phosphaturic response to parathyroid hormone was studied in rats fed a low-phosphate diet for 1, 2, and 3 days. Control clearances were taken 2 h after thyroparathyroidectomy; then, parathyroid hormone (33 U/kg plus 1 U/kg/min), dopamine (25 micrograms/kg/min), or parathyroid hormone plus dopamine were infused for 60 min. Changes in the fractional excretion of phosphate were significantly greater in rats fed a low-phosphate diet infused with parathyroid hormone plus dopamine than in rats fed a low-phosphate diet infused with parathyroid hormone alone (delta 27.9 +/- 5.8 versus 11.2 +/- 2.6% for day 1; 28.4 +/- 1.4 versus 7.1 +/- 3.6% for day 2; and 10.7 +/- 2.8 versus -0.2 +/- 0.2% for day 3; N = 5 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

Ninety-five patients (63 male, 32 female), age 45 +/- 2 years (mean +/- SEM) with chronic renal failure of varied aetiology were randomized to receive either a conventional low protein diet (0.6 g/kg/day protein, 800 mg phosphate; n = 33), a low phosphate diet (providing approximately 1000 mg phosphate plus an orally administered phosphate binder, minimum protein intake 0.8 g/kg/day; n = 30) or to control (minimum protein intake 0.8 g/kg/day, no phosphate restriction; n = 32). Patients were reviewed for a minimum of 6 months before randomization and were withdrawn from the study if plasma creatinine exceeded 900 mumol/l, plasma phosphate was greater than 2.0 mmol/l or at the onset of uraemic symptoms. Following randomization patients were studied for an average of 19 +/- 3 months. Mean plasma creatinine rose from 398 +/- 33 to 600 +/- 50 mumol/l. Dietary protein intake was estimated at 0.69 +/- 0.02 g/kg/day in the low protein group, 1.02 +/- 0.05 in the low phosphate and 1.14 +/- 0.05 in the controls, phosphate intake was 815 +/- 43, 1000 +/- 47, and 1315 +/- 57 mg/day, respectively. Urinary urea excretion and protein catabolic rates were significantly reduced (p less than 0.01) only in those on protein restriction, at 213 +/- 9 mmol/24 hours and 0.71 g/kg/day, respectively. Phosphate excretion was significantly lower (p less than 0.05) in both the low protein group (17.9 +/- 0.8 mmol/24 hours) and the low phosphate group (18.6 +/- 1.0 mmol/24 hours) compared to controls. Changes in body weight, muscle mass and serum transferrin, albumin and immunoglobulins were comparable between the groups. Mean blood pressure following randomization was 150/89 +/- 3/1 (low protein), 148/87 +/- 3/1 (low phosphate) and 146/87 +/- 3/1 (controls). Progression of renal failure was analysed by rate of all of creatinine clearance (ml/min/1.73 m2/month), by rate of deterioration derived from reciprocal plasma creatinine against time plots (1/mmol/year) and to assess individual patient's response to treatment by two phase linear regression ('breakpoint') analysis of reciprocal plasma creatinine/time plots. Progression was analysed only in patients seen for at least 3 months following randomization. The rate of fall of creatinine clearance was not significantly different between the groups (ANOVA): 0.56 +/- 0.08 ml/min/1.73 m2/month (low protein, n = 28), 0.44 +/- 0.07 (low phosphate, n = 23) and 0.69 +/- 0.11 (control, n = 27).(ABSTRACT TRUNCATED AT 400 WORDS)

Renal Adaptation to Dietary Phosphate Restriction in Rats: Interactions With Insulin and Calcitriol

Insulin may contribute to the increase in tubular reabsorption of phosphate during dietary phosphate restriction. Moreover, insulin is required for the stimulation of calcitriol under this experimental condition. To evaluate whether calcitriol plays a role in the antiphosphaturic effect of insulin during phosphate restriction, phosphate uptake was measured in brush border membrane vesicles (BBMVs) obtained from the following six experimental groups of rats: normal (0.8%)-phosphate diet for 1 wk, low (0.03%)-phosphate diet for 1 wk, normal-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low-phosphate diet and streptozocin and exogenous insulin, and low-phosphate diet and streptozocin and exogenous calcitriol. BBMV phosphate uptake was higher in the nondiabetic rats on a low-phosphate diet than in the controls on a normal-phosphate diet. BBMV phosphate uptake was not different between diabetic rats on a normal-phosphate diet than in nondiabetic controls on the same diet. In contrast, BBMV was significantly lower in diabetic rats on a low-phosphate diet than in nondiabetic controls on the same diet. Exogenous insulin but not calcitriol restored the increase in BBMV phosphate uptake in diabetic rats on a low-phosphate diet. Plasma calcitriol levels were increased threefold in nondiabetic rats fed a low-phosphate diet. Streptozocin-induced diabetes abolished the adaptive increase in plasma calcitriol. Exogenous insulin and calcitriol administration to diabetic rats on a low-phosphate diet resulted in similar increases in plasma calcitriol levels. These results suggest that, during dietary phosphate restriction, insulin stimulates renal phosphate retention independently of its effect on calcitriol.

Effects of maleic acid on renal phosphorus transport: role of dietary phosphorus

The effects of maleic acid on renal phosphate (Pi) transport were examined by clearance and brush-border membrane vesicle (BBMV) transport studies. In normal rats, maleic acid 50 mg.kg body wt-1.h-1 increased the phosphaturia (P less than 0.001). Intraperitoneal administration of a similar dose of maleic acid decreased the BBMV uptake of Pi but not glucose. In rats fed a low-phosphate diet (0.03%), the maleic acid-induced phosphaturia was blunted, but the inhibitory effect on the BBMV transport of Pi persisted. In chronic parathyroidectomized rats fed a low-phosphate diet, where the filtered load of Pi was higher than in the previous groups, the phosphaturia was abolished, but the inhibition of the BBMV transport of Pi was sustained. Both the in vitro incubation of BBMVV and in vivo administration of maleic acid were associated with a competitive inhibition of Pi transport. These studies indicate that the maleic acid-induced phosphaturia is expressed at the apical membrane entry step of Pi, and the enhanced distal tubular reabsorption accounts for the lack of phosphaturia in dietary Pi deprivation.

Mechanisms of phosphate transport in sheep intestine and parotid gland: response to variation in dietary phosphate supply

The transport of phosphate in intestinal brush-border membrane and parotid basolateral membrane vesicles isolated from sheep maintained on high and low phosphate diets have been studied. The mechanism of the transport of phosphate in the intestine is via a proton symporter whilst in the parotid gland it is effected by a Na+ coupled transporter. In sheep fed a low-P diet there is no change in the capacity of the parotid basolateral membrane to transport phosphate into the parotid end piece cells. This is in marked contrast to the response of the enterocyte brush-border membrane, where there is a significant enhancement of the capacity of the membrane to transport phosphate. We conclude that in sheep the gut appears to play a major role in response to phosphate deprivation, by increasing the capacity to transport phosphate. This enhancement is not achieved by increases in the levels of circulating 1,25-dihydroxycholecalciferol.

Abnormal renal glucose handling in X-linked hypophosphataemic mice

1. The renal handling of glucose was determined in male X-linked hypophosphataemic (Hyp/Y) mice and in control littermates (+/Y) aged 4 months. Plasma glucose concentration and urinary glucose excretion were measured before and during stepwise increase in glycaemia induced by an acute infusion of glucose. The relationship between plasma glucose concentration and urinary glucose excretion was monitored per ml of glomerular filtrate in mice fed high and low phosphate diets. 2. Hyp/Y mice fed the high phosphate diet showed a significantly higher glucosuria compared with +/Y littermates. When glycaemia was increased, Hyp/Y mice developed frank glucosuria earlier than +/Y animals. In Hyp/Y mice we could not find a threshold below which virtually no glucose was excreted in the urine, whereas this was clearly visible in +/Y mice. These differences persisted in animals fed the low phosphate diet. 3. Using the acute response to the glucoregulatory hormones, glucagon and insulin, administered exogenously, we found that the regulation of plasma glucose concentration did not differ between Hyp/Y and +/Y mice. 4. The significantly lower plasma glucose concentration observed in Hyp/Y as compared with +/Y mice decreased further during fasting. 5. We conclude that the renal reabsorptive capacity for glucose is defective in Hyp/Y mice and their low plasma glucose concentration may be explained by the renal leak. Therefore the X-linked phosphataemic mouse appears not only to be characterized by a defect in renal phosphate and calcium reabsorption but also by an altered glucose reabsorption.

Bioactivity of Amino Terminal Fragments of Parathyroid Hormone and Parathyroid Hormone Related Peptide in Rat Kidney Slices: No Effect of Dietary Phosphate Deprivation

Humoral hypercalcemia of malignancy has been associated with the production of a recently cloned peptide human parathyroid hormone related protein (hPTHRP). One of the markers of this disease is an increased urinary excretion of cyclic AMP. The postreceptor mechanism of action and physiological role of hPTHRP remain obscure. To study the activity of hPTHRP 1-34 compared to rat and human parathyroid hormone (PTH) 1-34 we incubated these peptides with rat kidney slices and measured the cyclic AMP generated in the supernatant. hPTHRP 1-34 was equipotent with human PTH 1-34 but both were 5 times less active than rat PTH 1-34. Previous studies have suggested that a low dietary phosphate intake results in renal resistance to the phosphaturic action of PTH perhaps mediated by reduced adenylate cyclase activation by PTH. To determine whether, during dietary phosphate restriction, hPTHRP 1-34 has actions different from hPTH 1-34 we studied their effects following dietary phosphate deprivation. Dietary phosphate restriction had no significant effect on the cyclic AMP generating activity of any of the peptides. We conclude that hPTHRP 1-34 may be operating through similar mechanisms as human PTH 1-34 and that the previously observed effects of dietary phosphate deprivation on PTH mediated cyclic AMP generation in a broken cell preparation do not occur in intact cell preparations.

Rapid nongenomic inhibition of renal 25-hydroxyvitamin D3 1-hydroxylase by 1,25-dihydroxyvitamin D3

The physiological role of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in inhibition of its own formation remains obscure. This study utilizes a kidney slice system to study the effect of physiological concentrations of 1,25(OH)2D3 on 25-hydroxyvitamin D3 1-hydroxylase (1-hydroxylase) formation in vitamin D-replete rats fed a normal-phosphate (NP) or low-phosphate (LP) diet. In vitro, 1-hydroxylase activity was assessed by measuring 1,25(OH)2D3 accumulation at 30 or 60 min after addition of 25-hydroxyvitamin D3 substrate. Degradation of 1,25(OH)2D3 was also assessed over 60 min. Rats fed the LP diet had a threefold increase in 1-hydroxylase activity but the same rate of degradation of 1,25(OH)2D3 as those fed the NP diet. The addition of 50 pM 1,25(OH)2D3 caused a proportional inhibition of 1-hydroxylase in NP and LP rats when added before or 10 min after addition of substrate but not at later time points; 150 pM 1,25(OH)2D3 completely inhibited 1-hydroxylase in the NP but not the LP rats. This inhibitory effect was not reversed by actinomycin D or cycloheximide. These results indicate that physiological concentrations of 1,25(OH)2D3 directly and rapidly modulate 1-hydroxylase activity via a nongenomic mechanism in both LP and NP diet rats.

Effect of propranolol on phosphate reabsorption by superficial nephron segments in response to parathyroid hormone in phosphate-deprived rats.

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone. The decreased phosphaturic response to parathyroid hormone in rats fed a low phosphate diet for 1 day can be restored by propranolol infusion. Free-flow micropuncture studies were performed to localize the nephron site of restoration of the phosphaturic effect of parathyroid hormone by propranolol in rats deprived of phosphate for one day. In animals fed low phosphate diet and in the presence of parathyroid hormone, propranolol infusion did not change phosphate delivery to the late proximal tubule; however, fractional delivery of phosphate to the early distal tubule was significantly increased from 18.3 +/- 2.9 to 32.2 +/- 4.1%. In rats fed a normal phosphate diet, propranolol infusion did not change phosphate delivery along the nephron. We conclude that the restoration of the phosphaturic effect of parathyroid hormone by propranolol infusion in rats deprived of phosphate for 1 day is primarily due to decreased reabsorption of phosphate by superficial loop segments, most likely the pars recta segment of the proximal tubule.

Effect of parathyroid hormone and dietary phosphate on phosphate transport in renal outer cortical and outer medullary brush-border membrane vesicles

Two distinctive sodium-dependent phosphate transport systems have been identified in early and late proximal tubules; a high-capacity process located only in outer cortical tissue, and a high affinity present in both outer cortical and outer medullary brush-border membranes ( K m 0.1-0.25 mM). A third, sodium-independent, pH gradient-stimulated system ( V max 4.7 ± 0.3 nmol · mg −1 · min −1, K m 0.15 ± 0.002 mM) is present in the outer medulla, but absent in outer cortex. Brush-border vesicles were prepared from outer cortical and outer medullary tissue of pigs maintained on low (< 0.05%), normal (0.4%), or high (4%) phosphate diets. Sodium-dependent phosphate uptake of the high-capacity system decreased ( V max, 9.4 to 2.2 nmol · mg −1 · min −1) from low to high phosphate diet, whereas uptake rates decreased about 50% in the high-affinity system. There were no changes in the respective K m values. The pH gradient-stimulated uptake also decreased ( V max, 6.9 to 3.0 nmol · mg −1 · min −1) with no change in mean K m value (0.15 ± 0.001 mM) with dietary manipulation. Administration of 1 U parathyroid hormone prior to study resulted in a decrease in sodium-dependent uptake by 40–50% and in pH-dependent uptake (36%) with no change in the respective K m values. In conclusion, the antecedent dietary phosphate intake and parathyroid hormone administration appropriately alters phosphate uptake across the brush-border membrane of all three systems, sodium-dependent and pH gradient-stimulated phosphate transport.

Propranolol restores phosphaturic effect of PTH in short-term phosphate deprivation

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone (PTH). The present study evaluated the role of the beta-adrenergic system in this resistance phenomenon. In clearance experiments performed on acutely thyroparathyroidectomized male Sprague-Dawley rats, the phosphaturic response to PTH was determined in the presence and absence of propranolol in rats fed a low-phosphate diet (LPD) for 0.5, 1, 2, 3, or 4 days. Fractional excretion of phosphate (FEPi) in control rats fed a normal-phosphate diet (NPD) increased from 4.37 +/- 1.6 to 38.5 +/- 3.4% in response to PTH infusion. Propranolol did not change FEPi in NPD animals in the absence or in the presence of PTH (2.0 +/- 1.1 vs. 36.7 +/- 1.6%). LPD resulted in a gradual decrease in the phosphaturic response to PTH infusion as compared with NPD animals. PTH increased FEPi to 24.2 +/- 6.0% after one-half day of LPD, but when the infusion was supplemented with propranolol, PTH increased FEPi to 38.0 +/- 4.7%, similar to that in NPD animals. In the group fed LPD for one day, PTH increased FEPi to 16.9 +/- 4.3%, whereas in the presence of propranolol FEPi was restored to a similar level as in the NPD group (36.0 +/- 5.9%). Two days of LPD markedly decreased FEPi in response to PTH to 7.9 +/- 3.8% as compared with NPD rats, and propranolol infusion did not change this value significantly. Three and 4 days of LPD induced complete resistance to the phosphaturic effect of PTH in the presence as well as in the absence of propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Phosphate Deprivation on Enzymes of the Cyclic Adenosine Monophosphate Metabolism in Rat Proximal Convoluted and Proximal Straight Tubules

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone (PTH). The present study determined whether acute phosphate deprivation alters basal or stimulated activities of key enzymes of the cyclic adenosine monophosphate (cAMP) metabolism in microdissected proximal convoluted and proximal straight tubules, since blunted cAMP levels in these proximal subsegments might account for refractoriness to the effect of PTH on phosphate reabsorption in the proximal convoluted and proximal straight tubule segments. In the proximal convoluted tubules of rats fed a normal-phosphate diet (NPD), PTH increased the adenylate cyclase activity by tenfold. In the proximal convoluted tubule of rats fed a low-phosphate diet (LPD), PTH also increased the adenylate cyclase activity by tenfold. In addition, forskolin increased the adenylate cyclase activity to levels similar to PTH in the proximal convoluted tubule of rats fed NPD or LPD. In the proximal straight tubule of rats fed NPD, PTH resulted in an approximately fivefold increase in adenylate cyclase activity. In the proximal straight tubule of rats fed LPD, PTH resulted in a fourfold increase in adenylate cyclase activity. The forskolin-stimulated adenylate cyclase activity was markedly decreased (46%) in the proximal straight tubule of phosphate-deprived rats. The cAMP-phosphodiesterase activity in the proximal convoluted tubule was significantly increased by 26% in phosphate-deprived rats. The cAMP-phosphodiesterase activities in the proximal straight tubules from rats fed NPD or LPD were similar. We conclude that distinct differences in key enzymes of cAMP metabolism exist in the proximal convoluted and proximal straight tubule subsegments. Further, phosphate deprivation affects the cAMP-phosphodiesterase and adenylate cyclase activities differently in these nephron subsegments.(ABSTRACT TRUNCATED AT 250 WORDS)

Different mechanisms of adaptive increase in Na+-Pi cotransport across renal brush-border membrane

We explored the biochemical mechanism by which thyroid hormone (T3) and low-phosphate diet (LPD) cause an adaptive increase in Na+-Pi cotransport across renal brush-border membrane (BBM). The rate of Na+-Pi cotransport was determined by 32Pi uptake by BBM vesicles (BBMV), and the number of Na+-Pi symporters was assessed by binding of [14C]phosphonoformic acid (PFA) on BBMV. In BBMV of both T3-treated rats and LPD-fed rats, the Na+ gradient-dependent 32Pi uptake increased (Vmax increased; Km Pi was not changed). The Na+-dependent [14C]PFA binding on BBMV increased (higher Vmax, no change in Km PFA) in response to T3, but it remained unchanged in rats fed LPD. Both the increase of Na+-Pi cotransport and of Na+-dependent [14C]PFA binding in response to T3 were blocked by actinomycin D or cycloheximide. Addition of benzyl alcohol to BBMV in vitro increased Na+-Pi cotransport, but [14C]PFA binding did not change; the [3H]phlorizin binding and cotransports of other solutes decreased or did not change. The exposure of BBMV to cholesterol decreased Na+-Pi cotransport without changing [14C]PFA binding. We suggest that the adaptive increase of Na+-Pi cotransport elicited by T3 is due to an increase in number of Na+-Pi cotransporters in BBM. In contrast, in response to LPD the number of Na+-Pi cotransporters is unchanged, and the increased Na+-Pi cotransport is due to faster translocation of Na+ with Pi due to enhanced fluidity of BBM.

Hyperphosphatemia from Hyperparathyroidism

A 50‐year‐old, generally compliant, male chronic hemodialysis patient has persistent severe r&gt; 8 mg/dr) hyperphosphatemia despite therapy with substantial doses of aluminum phosphate binders and compliance with a low phosphate diet. Since he has X‐ray evidence of hyperparathyroidism and marked elevations in serum parathyroid hormone, I wondered whether and to what extent bone sources of phosphate might contribute to the hyperphosphatemia. Are there any data available on this question?

P-31 nuclear magnetic resonance spectral changes in obstructed or dehydrated kidney

Rat kidneys subjected to urinary obstruction or dehydration in vivo both develop marked increases in the area under a peak resonating in the phosphodiester region on their P-31 nuclear magnetic resonance spectra. The chemical species responsible for these changes were assessed using physiologic manipulations which altered the concentration of phosphate in the urine or increased the urine pH. Obstructed kidneys of rats fed a normal diet had a 140 +/- 50% increase in a peak resonating at 3.31 +/- 0.05 ppm after three hours of obstruction (P less than 0.01). Low phosphate diet which decreased urine phosphate concentration by 98% virtually eliminated this increase in peak area, where saline diuresis which decreased urine phosphate concentration by 50% markedly attenuated it. Acute phosphate loading which doubled urine phosphate concentration markedly accentuated the increase in peak area. Alkalinizing the urine with acetazolamide (changing urine pH from 6.2 +/- 0.2 to 8.0 +/- 0.1) shifted the resonance frequency of this increasing peak from 3.31 +/- 0.06 to 5.45 +/- 0.11 ppm (P less than 0.01). Rats fed a normal diet developed increases (57 +/- 15%, P less than 0.05) in a peak resonating at 2.84 +/- 0.03 ppm following 48 hours of dehydration. Rats fed a low phosphate diet had a comparable increase in the relative area of this peak (46 +/- 16%, P less than 0.05). Alkalinization of the urine did not affect the position or intensity of this peak under conditions of dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Rat Atrial Natriuretic Factor (ANP-III) Inhibits Phosphate Transport in Brush Border Membrane from Superficial and Juxtamedullary Cortex

Previous studies have shown that administration of synthetic atrial natriuretic factor (ANF, 101-126) decreases sodium-dependent phosphate transport across renal brush border membrane vesicles (BBMV) in rats fed a normal or low phosphate diet. In the present study, infusion of rat ANF (atriopeptin III (ANP-III), 103-126 rat ANF) to rats fed a normal phosphate diet caused natriuretic and phosphaturic effects similar to those of ANF (101-126), but unlike ANF (101-126) did not increase the glomerular filtration rate. The effect of ANP-III infusion on sodium-dependent transport of phosphate was also determined in BBM vesicles isolated from the superficial cortex (BBMV-SC) and juxtamedullary cortex (BBMV-JM). The results indicate that ANP-III decreases phosphate transport across BBMV-SC and BBMV-JM similarly (20-24%). However, it had no effect on sodium-dependent transport of proline in these vesicles. The infusion of ANP-III to rats fed a normal phosphate diet inhibits phosphate uptake both in BBMV-SC and BBMV-JM and causes phosphaturia without increments in glomerular filtration rate.

Effect of cAMP analogue infusion on phosphate reabsorption in phosphate-deprived rats.

The present study was performed to compare the effects of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (cAMP analogue) and parathyroid hormone (PTH) infusion on segmental phosphate reabsorption in phosphate-deprived rats. Micropunctures of the late proximal and the early distal tubules were performed in acutely thyroparathyroidectomized (TPTX) rats fed either a normal (NPD) or low phosphate diet (LPD), and the phosphaturic response to infusion of PTH and cAMP analogue was evaluated. In NPD rats, PTH (n = 10) and the cAMP analogues (n = 11) markedly increased urinary phosphate excretion, due to inhibition of phosphate reabsorption along the proximal convoluted tubule and pars recta. In phosphate-deprived rats, PTH (n = 10) or the cAMP analogue (n = 11) did not increase urinary phosphate excretion. However, PTH and the cAMP analogue inhibited phosphate reabsorption along the proximal convoluted tubule but not in the pars recta in phosphate-deprived rats. We conclude that cAMP analogue infusion mimics the effect of PTH infusion on phosphate reabsorption along the proximal convoluted and proximal straight tubule in normal and phosphate-deprived rats. The resistance to the phosphaturic effect of PTH and cAMP infusions is a result of a blunted inhibition of phosphate reabsorption by the proximal convoluted tubule and also an increased phosphate reabsorption by the proximal straight tubule.

Renal Adaptation to a Low Phosphate Diet in Spontaneously Hypertensive Rats

Renal Adaptation to a Low Phosphate Diet in Spontaneously Hypertensive Rats

Adaptation of phosphate transport to low phosphate diet in renal and intestinal brush border membrane vesicles: influence of sodium and pH.

The possible role of changes in the sodium (Na) affinity of the carrier for inorganic phosphate (Pi) in the adaptation of Pi transport to low Pi diet was examined in both renal and intestinal brush border membranes vesicles (BBMV) obtained from the same animal. This role was assessed by measuring the Na concentration resulting in half maximal activation of Pi transport (K0.5 Na) in renal and intestinal BBMV prepared from animals adapted to either low (LPD) or high (HPD) phosphorus diet for 7 days. The K0.5 Na was not modified by dietary Pi, in both renal and intestinal BBMV. LPD increased maximal Pi transport from 1794.8 +/- 198.0 to 2964.0 +/- 362.0 in renal and from 28.2 +/- 3.4 to 80.5 +/- 7.2 pmol/mg 10 s in intestinal BBMV. For both LPD and HPD lowering pH from 7.4 to 6 dramatically increased K0.5 Na in renal and intestinal BBMV. As compared to pH 7.4, it was enhanced by approximately 200% in both renal and intestinal membranes. This change of Na affinity with acidic pH prevented the expression of Pi transport adaptation at 100 mM Na concentration. However, at saturating Na concentrations (500 mM for renal, 300 mM for intestinal membranes), Pi transport adaptation was equally expressed at pH 6 and 7.4 in both types of membranes. Hill coefficient analysis indicates a 2:1 stoichiometry of Na to Pi in renal and intestinal membranes isolated from high or low Pi diet animals. This ratio was not modified by changes of the medium pH.

Pseudohipoparatiroidismo y cardiomiopatía hipocalcémica

A case of pseudohypoparathyroidism complicated with an hypocalcemic myocardiopathy and a convulsive syndrome is presented. At the time of diagnosis, the most outstanding characteristics of this patient were: distinct phenotypic features; radiologic cardiomegaly; electrocardiographic alterations that suggested hypocalcemia; generalized osteoporosis and soft tissue calcification on skeletal X-ray films; low plasma calcium (4.53 mg%) and high plasma phosphorus (7.7 mg%) concentrations. Following treatment with vitamin D3, calcium gluconate, aluminium hydroxide, acetildigitoxin, hydrochlorothiazide, and low phosphate diet, progressive improvement of plasma calcium and phosphate concentration and also normalization of the cardiac silohuette and of the electro car diographic tracing were observed. (