Fortification of Yogurts with Vitamin D and Calcium Enhances the Inhibition of Serum Parathyroid Hormone and Bone Resorption Markers: A Double Blind Randomized Controlled Trial in Women over 60 Living in a Community Dwelling Home.

OBJECTIVE: To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures. DESIGN: A randomized double-blind controlled trial. SETTING: A community dwelling home. PARTICIPANTS: Forty-eight women over 60 years (mean age 73.4). INTERVENTION: Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium. MEASUREMENTS: Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX). RESULTS: The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY. CONCLUSION: This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods.

Impact of phosphorus restriction and vitamin D-substitution on secondary hyperparathyroidism in a proteinuric mouse model.

BACKGROUND/AIMS: Since the discovery of FGF23, secondary hyperparathyroidism (SHPT) in renal disease has been considered to result primarily from phosphorus retention rather than vitamin D deficiency. However, the impact of phosphorus restriction and vitamin D supplementation on SHPT is still ill defined. METHODS: We investigated the development of SHPT in a doxorubicin-induced proteinuric mouse model and tested different treatment strategies including a low phosphorus diet and substitution with native or active vitamin D in 129 S1/SvImJ wild-type mice. RESULTS: Development of SHPT at day 30 was strongly related to the magnitude of induced proteinuria. In mice with a proteinuria <100 mg/mg creatinine, SHPT was mild (PTH increase 2.4-fold), and serum levels of FGF23, phosphate and urea remained almost stable, whereas mice with heavy proteinuria (>100 mg/mg creatinine) developed marked SHPT (PTH increase 10.1-fold) accompanied by massive increase in FGF23 (27.0-fold increase), hyperphosphatemia (1.8-fold increase), renal failure (7.3-fold urea increase) and depletion of both 25-OH vitamin D and 1,25-OH vitamin D. Substitution with native or active vitamin D was unable to suppress SHPT, whereas a low-phosphorus diet (Pi content 0.013%) completely suppressed SHPT in mice with both mild and heavy proteinuria. CONCLUSIONS: The development of SHPT resulted from phosphate retention in this proteinuric model and could completely be suppressed with a low-phosphorus diet.

Consumption of yogurts fortified in vitamin D and calcium reduces serum parathyroid hormone and markers of bone resorption: a double-blind randomized controlled trial in institutionalized elderly women.

CONTEXT: Nutritional prevention of bone deterioration with fortified foods seems particularly suitable in institutionalized elderly women at risk of vitamin D deficiency, secondary hyperparathyroidism, increased bone resorption, and osteoporotic fracture. OBJECTIVE: The objective was to evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum PTH and bone resorption markers as compared with isocaloric and isoprotein dairy products in elderly women. DESIGN: A randomized double-blind controlled-trial, 56-day intervention was conducted in institutionalized women (mean age 85.5 years) consuming 2 125-g servings of either vitamin D- and calcium-fortified yogurt (FY) at supplemental levels of 10 µg/d vitamin D3 and 800 mg/d calcium or nonfortified control yogurt (CY) providing 280 mg/d calcium. MAIN OUTCOMES: The endpoints were serum changes from baseline (day 0) to day 28 and day 56 in 25-hydroxyvitamin-D (25OHD), PTH, and bone resorption markers tartrate-resistant acid phosphatase isoform-5b (TRAP5b), the primary outcome, and carboxyl-terminal cross-linked telopeptide of type I collagen (CTX). RESULTS: At day 56, serum 25OHD increased (mean ± SEM) by 25.3 ± 1.8 vs 5.2 ± 2.5 nmol/L in FY (n = 29) and CY (n = 27), respectively (P < .0001). The corresponding changes in PTH were -28.6% ± 7.2% vs -8.0% ± 4.3% (P = .0003); in TRAP5b, -21.9% ± 4.3% vs 3.0% ± 3.2% (P < .0001); and in CTX, -11.0% ± 9.7% vs -3.0% ± 4.1% (P = .0146), in FY and CY, respectively. At day 28, these differences were less pronounced but already significant for 25OHD, PTH, and TRAP5b. CONCLUSIONS: This study in institutionalized elderly at high risk for osteoporotic fracture suggests that fortification of dairy products with vitamin D3 and calcium provides a greater prevention of accelerated bone resorption as compared with nonfortified equivalent foods.

Supplemental vitamin D and calcium in the management of African Americans with heart failure having hypovitaminosis D.

INTRODUCTION: A dyshomeostasis of macro- and micronutrients, including vitamin D and oxidative stress, are common pathophysiologic features in patients with congestive heart failure (CHF). In African Americans (AA) with CHF, reductions in plasma 25(OH)D are of moderate-to-marked severity (<20 ng/mL) and may be accompanied by ionized hypocalcemia with compensatory increases in serum parathyroid hormone (PTH). The management of hypovitaminosis D in AA with CHF has not been established. METHODS: Herein, a 14-week regimen: an initial 8 weeks of oral ergocalciferol (50,000 IU once weekly); followed by a 6-week maintenance phase of cholecalciferol (1400 IU daily); and a CaCO3 (1000 mg daily) supplement given throughout was designed and tested. Fourteen AA patients having a dilated (idiopathic) cardiomyopathy with reduced ejection fraction (EF, <35%) were enrolled: all completed the initial 8-week course; and 12 complied with the full 14 weeks. At baseline, 8 and/or 14 weeks, serum 25(OH)D and PTH; serum 8-isoprostane, a biomarker of lipid peroxidation, and echocardiographic EF were monitored. RESULTS: Reduced 25(OH)D at entry (14.4 ± 1.3 ng/mL) was improved (P < 0.05) in all patients at 8 weeks (30.7 ± 3.2 ng/mL) and sustained (P < 0.05) at 14 weeks (30.9 ± 2.8 ng/mL). Serum PTH, abnormally increased in 5 patients at baseline (104.8 ± 8.2 pg/mL), was reduced at 8 and 14 weeks (74.4 ± 18.3 and 73.8 ± 13.0 pg/mL, respectively). Plasma 8-isoprostane at entry (136.1 ± 8.8 pg/mL) was reduced at 14 weeks (117.8 ± 7.8 pg/mL; P < 0.05), whereas baseline EF (24.3 ± 1.7%) was improved (31.3 ± 4.3%; P < 0.05). CONCLUSIONS: Thus, the 14-week course of supplemental vitamin D and CaCO3 led to healthy 25(OH)D levels in AA with heart failure having vitamin D deficiency of moderate-to-marked severity. Albeit a small patient population, the findings suggest that this regimen may attenuate the accompanying secondary hyperparathyroidism and oxidative stress and improve ventricular function.

The effect of combined calcium and vitamin D3 supplementation on serum intact parathyroid hormone in moderate CKD.

BACKGROUND: Studies addressing the effects of vitamin D(3) supplementation on secondary hyperparathyroidism in patients with moderate chronic kidney disease are scarce. STUDY DESIGN: Post hoc analysis of the randomized clinical trial Vitamin D, Calcium, Lyon Study II (DECALYOS II) to assess effects according to baseline estimated glomerular filtration rate (eGFR). SETTING & PARTICIPANTS: Multicenter, randomized, double-blinded, placebo-controlled study of 639 elderly women randomly assigned to calcium-vitamin D(3) fixed combination; calcium plus vitamin D(3) separate combination, or placebo. INTERVENTIONS: Placebo or calcium (1,200 mg) and vitamin D(3) (800 IU) in fixed or separate combination. OUTCOMES & MEASUREMENTS: Proportion of participants with a mean decrease in intact parathyroid hormone (iPTH) level of 30% or greater. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and categorized as 60 or greater, 45 to 59, and less than 45 mL/min/1.73 m(2). RESULTS: 610 participants had an eGFR at baseline: 288 (47.2%), 222 (36.4%), and 100 (16.4%) were in each decreasing eGFR category. Across decreasing eGFR groups, 88%, 86%, and 89% had 25-hydroxyvitamin D (25[OH]D) levels less than 15 ng/mL at baseline. On treatment, similar improvements in the proportion of participants achieving 25(OH)D levels greater than 30 ng/mL at 6 months were seen in all kidney function groups (43%, 49%, and 41%, respectively). Active regimens versus placebo increased mean 25(OH)D levels from baseline in all eGFR groups at all times (P < 0.001 for all). The proportion with a 30% or greater decrease in iPTH level at 6 months was 50% in all eGFR groups on treatment versus 6% to 9% for placebo (P < 0.001 for all). The effects of the intervention on iPTH levels did not differ according to baseline eGFR (interaction P > 0.1 for all times). LIMITATIONS: This study included only elderly white women. CONCLUSION: Vitamin D(3) was effective in increasing 25(OH)D and decreasing iPTH levels in patients with moderate chronic kidney disease.

Secondary hyperparathyroidism in primary osteoporosis and osteopenia: optimizing calcium and vitamin D intakes to levels recommended by expert panels may not be sufficient for correction.

OBJECTIVE: To compare biochemical variables, renal function and calcium and vitamin D intakes in euparathyroid and hyperparathyroid patients with primary osteoporosis and osteopenia and describe the measures necessary to normalize serum PTH in the patients with secondary hyperparathyroidism. DESIGN AND PATIENTS: We reviewed the charts of normocalcemic patients with primary osteoporosis and osteopenia first seen during the years 1991-2003 and identified 75 with elevated serum PTH levels at baseline. These patients were compared to all the 143 euparathyroid patients first seen in 1998 and 1999. Patients were restudied after 1 year and we attempted to follow patients with secondary hyperparathyroidism until PTH levels became normal. MEASUREMENTS: At baseline serum PTH, ionized calcium, inorganic phosphate, alkaline phosphatase, creatinine, a complete blood count and serum 25 hydroxy vitamin D were measured in the early morning fasting state. These tests were repeated at follow up. RESULTS: In one-third of the hyperparathyroid patients, the standard baseline treatment failed to correct the secondary hyperparathyroidism necessitating extraordinary measures including unusually large doses of vitamin D (i.e. 50 000 IU vitamin D(2) twice weekly) or the substitution of calcium citrate for calcium carbonate as a calcium supplement. CONCLUSION: Large doses of vitamin D are frequently necessary to suppress secondary hyperparathyroidism in patients with primary osteoporosis and osteopenia. This suggests that vitamin D metabolism may be altered in some of these patients.

Unusual case of osteopenia associated with nutritional calcium and vitamin D deficiency in an adult dog.

A 6-year-old, spayed female rottweiler was presented for facial enlargement from swelling of the maxilla and mandible. The dog was fed a homemade diet deficient in calcium and vitamin D, suggesting that rubber jaw syndrome was a secondary nutritional disorder. Radiographic and tomodensitometric examinations revealed diffuse bone resorption in the skull. The plasma parathormone concentration was high, and serum 25-hydroxycholecalciferol concentration was low. Based on these findings, nutritional calcium and vitamin D deficiency associated with secondary hyperparathyroidism was diagnosed. Dietary correction resulted in clinical and biological improvement, with an increase in skull mineralization.

Calcium deficiency-induced secondary hyperparathyroidism and osteopenia are rapidly reversible with calcium supplementation in growing rabbit pups.

The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a 'hypercalcaemic' animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0.026 % Ca) for 10 weeks. As compared with those fed with a normal chow diet (0.45 % Ca), CaDef pups developed significant hypocalcaemia (P < 0.05), hypocalciuria (urinary Ca 76 (SEM 12) v. 17 (SEM 1) mg/l; P < 0.005), hypophosphataemia (serum inorganic P 100 (SEM 6) v. 65 (SEM 4) mg/l; P < 0.005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18.2 (SEM 1.4) v. 125.0 (SEM 4.5) pg/ml; P < 0.001) and elevated serum calcitriol levels (34.0 (SEM 3.9) v. 91.0 (SEM 1.0) pg/ml; P < 0.005). Elevated urinary C-terminal telopeptide of class I collagen (P < 0.005) and total serum alkaline phosphatase (P < 0.005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro. Supplementation of adequate Ca (0.45 % Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.

Multidisciplinary approach for prescriptive management of mineral and bone metabolism in chronic kidney disease: development of a dietetic led protocol.

BACKGROUND: A number of mineral metabolism abnormalities occur as kidney function declines, these include hyperphosphatemia, hyperparathyroidism and altered vitamin D metabolism. These derangements are associated with increased morbidity and mortality amongst the chronic kidney disease patient group. Treatment requires a multidisciplinary team approach in which the dietitian plays a pivotal role. OBJECTIVES: The development of protocols to aid implementation of various international, national and local treatment strategies is described. Audit the protocol to evaluate their clinical effectiveness. RESULTS: A prescriptive Protocol for the management of mineral and bone metabolism abnormalities in chronic kidney disease was developed and implemented. Initial audit findings suggest the protocol has had a positive effect on the control of phosphate, corrected calcium and parathyroid (PTH) levels. CONCLUSION: The development and implementation of a dietetic-led prescriptive therapy protocol allows dietitians and clinicians to adopt an integrated approach for the diagnosis and timely management of these complicated conditions.

Calcium and vitamin D supplementation failed to improve bone mineral density in Indo-Asians suffering from hypovitaminosis D and secondary hyperparathyroidism.

BACKGROUND: The association of low bone mineral density (BMD) in Asians with hypovitaminosis D (HD) and when complicated with secondary hyperparathyroidism (HD-SHPT) has been shown previously. OBJECTIVE: Our aim was to study the effectiveness of calcium and vitamin D therapy in Indo-Asians with HD and HD-SHPT. METHODS: One hundred forty-three patients attending our rheumatology clinic, including 97 (68%) with HD aged 48.9+/-11.6 years (86% female) and 46 (32%) with HD-SHPT aged 55.9+/-12.6 years (85% female), were recruited. Baseline investigations included routine biochemistry and 25-hydroxy vitamin D [25(OH)D], and parathyroid hormone (PTH) assays. Bone mineral densities (BMDs) of femoral neck, lumbar spine (LS), and distal radius (DR) were measured by dual energy X-ray absorptiometry. Patients were commenced on 1.0-1.25 g of calcium plus 400 IU of vitamin D. Blood tests were repeated at 6 and 12 months. Thirty-six patients with t scores of <-1 had their BMDs remeasured at 2 years. Unpaired t- and Mann-Whitney U tests were used in statistics. Results were considered significant at P< or =0.05. RESULTS: Femur t and z scores failed to improve in either group. The reduction in LS t scores but not z scores was significant in both groups. Significant reductions in DR t and z scores occurred in the HD group only. Calcium and 25(OH)D increased significantly in both groups. Alkaline phosphatase and PTH were suppressed significantly only in HD-SHPT. CONCLUSION: The failure of BMD to improve could be due to lack of compliance with medication between years 1 and 2, when most patients were under the supervision of primary care. To overcome this, we recommend continuance of blood monitoring at least once a year.

Nutritional secondary hyperparathyroidism in a white lion cub (Panthera leo), with concomitant radiographic double cortical line.

A captive-bred white lion cub was presented with hindquarter pain, lameness and reluctance to move. Radiographs revealed generalised osteoapenia, multiple fractures, a severely collapsed pelvic girdle, bilateral lateral bowing of the scapulae and mild kyphosis of the caudal vertebrae. A double cortical line, a distinct sign of osteopaenia, was repeatedly seen on the pelvic limbs, most strikingly along both femurs. Based on radiographic findings and a history of an exclusive meat diet since weaning, a diagnosis of nutritional secondary hyperparathyroidism was made. The diet was changed to a commercial kitten food and the cub was given cage rest for 6 weeks. Signs of pain abated and the cub became more active. A guarded prognosis was given for full recovery, as changes to the pelvis were considered potentially irreversible.

[Early treatment of secondary hyperparathyroidism in moderate renal insufficiency: low-phosphorus diet versus calcium carbonate]. / Tratamiento precoz del hiperparatiroidismo secundario en insuficiencia renal moderada: dieta baja en fósforo frente a carbonato cálcico.

Calcitriol deficiency and phosphorus retention are mechanisms involved in the pathogenesis of renal hyperparathyroidism. The aim of this study was to evaluate the effect of dietary phosphorus restriction versus calcium carbonate treatment for one month on PTH and calcitriol levels in patients with mild renal failure. We studied two groups of patients: Group I: 21 patients (14M/7F); mean age 61 years old; mean glomerular filtration rate 51 ml/min. Their diet contained phosphorus 700 mg/day. Group II: 30 patients (21M/9F); mean age 58; mean glomerular rate 56 ml/min. They were divided in two subgroups: 18 patients treated with calcium carbonate 2.5 g/day and 12 patients with 5 g/day. Serum PTH, calcitriol, 25(OH)D3, calcium, phosphorus and urinary excretion of calcium and phosphorus were measured before and after a 30 day period. The low phosphorus diet (Group I) resulted in a significant decrease in PTH levels (81.3 +/- 35 vs 71 +/- 39 pg/ml, p < 0.05) and significant increase in calcitriol levels (22.4 +/- 4.4 vs 33.4 +/- 7.5 pg/ml, p < 0.05). In our study calcium carbonate treatment (Group II) had no effect on PTH and calcitriol levels.

Role of parathyroid intervention in the management of secondary hyperparathyroidism.

Measurement of the size of the parathyroid glands is mandatory for the selection of the optimal therapy for secondary hyperparathyroidism. Surgical parathyroidectomy or parathyroid intervention is indicated for patients with nodular hyperplasia as this form is seldom responsive to medical therapy. Selection of the intervention should be determined by the number, size and location of the parathyroid glands with nodular hyperplasia, including ectopic glands.

Tratamiento precoz del hiperparatiroidismo secundario en insuficiencia renal moderada: dieta baja en fósforo frente a carbonato cálcico / Early treatment of secondary hyperparathyroidism in moderate renal failure: a low phosphorus diet versus calcium carbonate

El déficit de calcitriol y la retención de fósforo son mecanismos implicados en la etiología del hiperparatiroidismo secundario. El objetivo de este trabajo fue comparar el efecto sobre los niveles de calcitriol y PTH de una dieta baja en fósforo frente al tratamiento con carbonato cálcico en pacientes con insuficiencia renal moderada durante un mes. Se estudiaron dos grupos de pacientes. Grupo I: 21 pacientes (14H/7M) con una edad media de 61 años y un filtrado glomerular medio de 51 ml/min a los que se sometió a una dieta con 700 mg/día de fósforo. Grupo II: 30 pacientes (21H/9M) con una edad media de 58 años y un filtrado glomerular de 56 ml/min, a los que se trató con 2,5 g/día de carbonato cálcico (18 pacientes) y 5 g/día (12 pacientes). Se midieron niveles de PTH, calcitriol, 25(OH)D3, calcio y fósforo séricos e índices urinarios fósforo/creatinina, calcio/creatinina y reabsorción tubular de fosfato de forma basal y al mes. En el grupo tratado con dieta baja en fósforo hubo disminución de las cifras de PTH (81,3 ± 35 vs 71 ± 39 pg/ml, p < 0,05) y aumento de las cifras de calcitriol (22,4 ± 4,4 vs 33,4 ± 7,5 pg/ml, p < 0,05). En los grupos tratados con carbonato cálcico no hubo cambios en las cifras de PTH ni calcitriol. En ningún grupo se modificaron las cifras de calcio, fósforo sérico ni 25(OH)D3. Nuestros pacientes con insuficiencia renal moderada muestran cifras elevadas de PTH y valores de calcitriol en los límites inferiores de la normalidad. La dieta baja en fósforo se muestra efectiva el elevar los niveles de calcitriol y disminuir la PTH. El tratamiento con carbonato cálcico no modifica los valores de calcitriol y PTH en nuestros pacientes (AU)

Calcitriol deficiency and phosphorus retention are mechanisms involved in the pathogenesis of renal hyperparathyroidism. The aim of this study was to evaluate the effect of dietary phosphorus restriction versus calcium carbonate treatment for one month on PTH and calcitriol levels in patients with mild renal failure. We studied two groups of patients: Group I: 21 patients (14M/7F); mean age 61 years old; mean glomerular filtration rate 51 ml/min. Their diet contained phosphorus 700 mg/day. Group II: 30 patients (21M/9F); mean age 58; mean glomerular rate 56 ml/min. They were divided in two subgroups: 18 patients treated with calcium carbonate 2.5 g/day and 12 patients with 5 g/day. Serum PTH, calcitriol, 25(OH)D3, calcium, phosphorus and urinary excretion of calcium and phosphorus were measured before and after a 30 day period. The low phosphorus diet (Group I) resulted in a significant decrease in PTH levels (81.3 ± 35 vs 71 ± 39 pg/ml, p < 0.05) and significant increase in calcitriol levels (22.4 ± 4.4 vs 33.4 ± 7.5 pg/ml, p < 0.05). In our study calcium carbonate treatment (Group II) had no effect on PTH and calcitriol levels (AU)

Hiperparatiroidismo secundario. Una puesta al día / Secondary hyperparatiroidism, an update

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Vitamin D therapy in patients with chronic renal disease: the role of the renal dietitian.

Chronic renal failure causes decreased vitamin D production, which profoundly alters parathyroid hormone (PTH) metabolism, and calcium and phosphorus balance. Correcting this deficiency is an important strategy in managing secondary hyperparathyroidism (SHPT) and helping to restore mineral balance. However, hypercalcemia and hyperphosphatemia are common side effects that hamper vitamin D hormone therapy by increasing dietary calcium and phosphorus absorption. This limitation has led to the development of D-hormone analogs that retain the ability to suppress PTH levels without causing drastic changes in calcium and phosphorus metabolism. These analogs have the potential to advance the management of SHPT. Renal dietitians can play a leading role in ensuring successful management of SHPT by participating in early patient intervention for abnormal mineral and vitamin D metabolism, by encouraging long-term phosphorus control, and by updating and implementing clinical protocols that promote optimal hormone levels (D and PTH), mineral levels (phosphorus and calcium), and nutritional factors.

Chronic metabolic acidosis in azotemic rats on a high-phosphate diet halts the progression of renal disease.

BACKGROUND: Hyperphosphatemia and metabolic acidosis are general features of advanced chronic renal failure (RF), and each may affect mineral metabolism. The goal of the present study was to evaluate the effect of chronic metabolic acidosis on the development of hyperparathyroidism and bone disease in normal and azotemic rats on a high-phosphate diet. Our assumption that the two groups of azotemic rats (acid-loaded vs. non-acid-loaded) would have the same degree of renal failure at the end of the study proved to be incorrect. METHODS: Four groups of rats receiving a high-phosphate (1.2%), normal-calcium (0.6%) diet for 30 days were studied: (1) normal (N); (2) normal + acid (N + Ac) in which 1.5% ammonium chloride (NH4Cl) was added to the drinking water to induce acidosis; (3) RF, 5/6 nephrectomized rats; and (4) RF + acid (RF + Ac) in which 0.75% NH4Cl was added to the drinking water of 5/6 nephrectomized rats to induce acidosis. RESULTS: At sacrifice, the arterial pH and serum bicarbonate were lowest in the RF + Ac group and were intermediate in the N + Ac group. Serum creatinine (0.76 +/- 0.08 vs. 1.15 +/- 0.08 mg/dL), blood urea nitrogen (52 +/- 8 vs. 86 +/- 13 mg/dL), parathyroid hormone (PTH; 180 +/- 50 vs. 484 +/- 51 pg/mL), and serum phosphate (7.46 +/- 0.60 vs. 12.87 +/- 1.4 mg/dL) values were less (P < 0.05), and serum calcium (9.00 +/- 0.28 vs. 7.75 +/- 0.28 mg/dL) values were greater (P < 0.05) in the RF + Ac group than in the RF group. The fractional excretion of phosphate (FEP) was greater (P < 0.05) in the two azotemic groups than in the two nonazotemic groups. In the azotemic groups, the FEP was similar even though PTH and serum phosphate values were less in the RF + Ac than in the RF group. NH4Cl-induced acidosis produced hypercalciuria in the N + Ac and RF + Ac groups. When acid-loaded (N + Ac and RF + Ac) and non-acid-loaded (N and RF) rats were combined as separate groups, serum phosphate and PTH values were less for a similarly elevated serum creatinine value in acid-loaded than in non-acid-loaded rats. Finally, the osteoblast surface was less in the N + Ac group than in the other groups. However, in the acid-loaded azotemic group (RF + Ac), the osteoblast surface was not reduced. CONCLUSIONS: The presence of chronic metabolic acidosis in 5/6 nephrectomized rats on a high-phosphate diet (1) protected against the progression of RF, (2) enhanced the renal clearance of phosphate, (3) resulted in a lesser degree of hyperparathyroidism, and (4) did not reduce the osteoblast surface. The combination of metabolic acidosis and phosphate loading may protect against the progression of RF and possibly bone disease because the harmful effects of acidosis and phosphate loading may be counterbalanced.

Effect of protein and phosphate restricted and calcium and alphacalcidol supplemented diet on renal and parathyroid functions and protein status in chronic renal failure patients.

OBJECTIVE: To assess the effect of low protein (0.6 g/kg/day), low phosphate (5-10 mg/kg/day) diet with calcium (600 mg/day) and alpha-D3 (0.5 microgram/day) supplementation on renal and parathyroid functions in patients with chronic renal failure (CRF). METHODS: The study included 20 adult patients of CRF, maintained on diet therapy alone. The patients were followed up for renal and parathyroid functions and protein status for 6 months at monthly interval. RESULTS: There was symptomatic improvement in 88% patients. Blood urea and serum creatinine decreased significantly (p < 0.001 and < 0.01, respectively) and the slope of inverse serum creatinine against time changed to static or an upslope. Glomerular filtration rate (GFR) improved from a basal value of 29.35 +/- 18.2 ml/min to 39.25 +/- 27 ml/min after 6 months. Serum parathyroid hormone (PTH) level of 197.65 +/- 133.7 pg/ml and post treatment level of 254.55 +/- 217.19 after 6 months were not different (p > 0.05). Serum calcium remained stationary with a slight increase in serum phosphorus. Phosphorus had a negative correlation with calcium and GFR, whereas calcium had a negative correlation with PTH and phosphorus. PTH had a positive correlation with phosphorus and negative with GFR and calcium. CONCLUSION: There was an improvement in renal functions without any deleterious effect on the protein status of the patients of CRF. Also, there was halting of parathyroid dysfunction especially in those patients where there was no evidence of pre-existing hyperparathyroidism. Hence, dietry management should be strictly enforced in CRF patients early in the course of disease.

Secondary hyperparathyroidism in severe chronic renal failure is corrected by very-low dietary phosphate intake and calcium carbonate supplementation.

The main purpose of our study was to verify the effect of a very-low-protein, low-phosphorus diet, supplemented with essential amino acids and keto analogues and with calcium carbonate, on circulating levels of intact parathyroid hormone (i-PTH) in severe chronic renal failure patients with secondary hyperparathyroidism, not treated with any vitamin D preparation. To this aim, we shifted 21 chronic uremics (12 males, 9 females; age 56 +/- 13 years) with serum creatinine >6.5 mg/dl and i-PTH >150 pg/ml, from a standard low-protein diet (0.6 g/kg/day approximately) to a very-low-protein (0.3 g/kg/day), very-low-phosphorus (5 mg/kg/day) diet supplemented with a mixture of essential amino acids and calcium keto analogues (Ketodiet), calcium carbonate (2-4 g/day), iron, and vitamin B12 preparations. The energy supply of both diets was 30-35 kcal/kg/day. Exclusion criteria were a poor compliance with dietary or supplement prescriptions or signs of autonomic hyperparathyroidism. After 4 +/- 2 months of Ketodiet, the i-PTH serum levels decreased by 49% as a mean (from 441 +/- 233 to 225 +/- 161 pg/ml, p < 0.001); serum phosphorus and alkaline phosphatase decreased, whereas serum calcium increased. The great reduction of serum and urinary urea demonstrated a good compliance with Ketodiet, and no sign of protein malnutrition was observed. These findings confirm that even in severe chronic uremic patients dietary phosphorus restriction and calcium carbonate supplementation lower i-PTH serum levels. This is one of the goals of the dietary treatment that can be safely achieved, provided good compliance both with the dietary prescriptions and with adequate energy and supplement intakes.