Eva Horak

Hypophosphatemia and hypercalciuria in small premature infants fed human milk: evidence for inadequate dietary phosphorus.

Phosphorus and calcium balance was measured prospectively in stable premature infants (less than or equal to 1600 gm) fed human milk or a standard commercial formula. Throughout the study, the P and Ca intakes of the infants fed human milk were two to three times less than those of infants fed formula. Infants fed human milk showed low serum P and normal serum Ca concentrations, complete renal reabsorption of P, and elevated renal Ca excretion. The net effect in infants fed human milk was a 50% reduction in the P and Ca retention, compared with the formula-fed group. Despite the unfavorable P and Ca balance in the group fed human milk, the only evidence of rickets was elevated alkaline phosphatase activity. Nevertheless, based on the biochemical changes in these infants, low serum P values, and excess urinary calcium losses, we conclude that the stable small premature infant fed human milk exclusively is deficient in phosphorus and only slightly more sufficient in calcium.

EFFECT OF CALCIUM/PHOSPHORUS RATIO ON MINERAL RETENTION IN PARENTERALLY FED PREMATURE INFANTS

We hypothesized that retention of parenterally delivered calcium (Ca) and phosphorus (P) is affected by the ratio of the delivered minerals and that a 1.7:1 ratio would be optimal since this is the ratio of retention of these minerals by the fetus. Forty-one very low birth weight (VLBW) infants were randomly assigned to one of three total parenteral nutrition (TPN) solutions that were different only in their Ca:P ratios: 2:1 (76 mg/kg/day Ca and 38 mg/kg/day of P), and 1.3:1 (58 mg/kg/day Ca and 45 mg/kg/day P), and 1.3:1 (58 mg/kg/day of Ca and 45 mg/kg/day of P). Serum levels of calcium, phosphorus, and alkaline phosphatase, retentions of calcium and phosphorus and urinary cyclic AMP levels were measured after 48 h on the assigned Ca to P ratio. Calcium retentions were higher with the 2:1 and 1.7:1 ratios and phosphorus retentions were higher with the 1.3:1 and 1.7:1 ratios. The 1.7:1 ratio allowed for the highest absolute retention of both minerals and was the closest to published in utero accretion of calcium and phosphorus. The serum and urine studies demonstrated no abnormalities on any of the three ratios. Cyclic AMPs were not different among groups and were not elevated compared to previous reports suggesting that none resulted in parathyroid hormone (PTH) stimulation. We conclude that the 1.7:1 ratio is better than higher or lower ratios for delivery of calcium and phosphorus in TPN solutions at the quantities studied.

Achievement of in utero retention of calcium and phosphorus accompanied by high calcium excretion in very low birth weight infants fed a fortified formula

Calcium and phosphorus retention was evaluated in 13 very low birth weight infants who were fed an experimental formula designed to deliver quantities of calcium and phosphorus sufficient to meet the intrauterine accretion rates for these minerals. Retention of calcium and phosphorus in slight excess of these rates was achieved without any apparent difficulties for the infants. Biochemical measurements demonstrated normal serum calcium (9.8 +/- 8 mg/dL) and alkaline phosphatase (242 +/- 51.6 IU) values. However, there was evidence of high tubular reabsorption of phosphate (98.1% +/- 3.3%), hypercalciuria (7.2 +/- 3.8 mg/kg/d), and a relatively low serum phosphorus concentration (5.7 +/- 0.6 mg/dL). This biochemical picture is similar to that seen in phosphorus deficiency except for the low alkaline phosphatase activity. The latter finding, in concert with the high retention of calcium and phosphorus in these balance studies, makes such a diagnosis unlikely. We speculate that this biochemical picture is the result of an inappropriately high calcium/phosphorus ratio.

Effects of triethylenetetramine upon the metabolism and toxicity of 63NiCl2 in rats

Abstract Triethylenetetramine (TETA, 0.75 mmol/kg, im) was administered to Fischer rats immediately prior to 63NiCl2 (0.068 or 0.10 mmol/kg, ip or im) to determine (a) effects of TETA upon 63Ni-kinetics, and (b) antidotal effects of TETA upon Ni-induced nephrotoxicity and hyperglycemia. TETA markedly reduced plasma 63Ni concentrations and greatly increased urine 63Ni excretion during 6 hr after injection of 63NiCl2, compared to values in control rats that received only 63NiCl2. In rats killed 6 hr after injections of TETA and 63NiCl2, 63Ni concentrations in liver, kidney, spleen, lung, and heart averaged 3.4, 0.72, 0.27, 0.22, and 0.12 times corresponding 63Ni concentrations in organs from control rats that received only 63NiCl2. The results supported the hypothesis that combined administration of TETA and 63NiCl2 resulted in partition of the body pool of 63Ni between two major 63Ni-components: (a) 63Ni-TETA complex, and (b) nonchelated-63Ni, and that each 63Ni-component was eliminated from plasma according to its respective clearance. The renal clearance of 63Ni-TETA complex was estimated to be >20 times that of nonchelated-63Ni. Administration of TETA substantially reduced Ni-induced proteinuria and aminoaciduria. TETA did not prevent Ni-induced hyperglycemia and hyperglucagonemia, but TETA did partially inhibit Ni-induced hyperinsulinemia.

Simultaneous infusion of calcium and phosphorus in parenteral nutrition for premature infants: Use of physiologic calcium/phosphorus ratio

We hypothesized that parenteral delivery of calcium and phosphorus in a ratio of 1.7:1 would promote retention of these minerals and decrease urinary phosphorus excretion, and that delivery of increased amounts of this ratio would result in higher retentions. Serum levels and retention of calcium and phosphorus were measured as calcium intake was increased from 36 to 76 mg/kg/day in 10 mg increments and as phosphorus intake was adjusted to maintain the 1.7:1 ratio. Five different infants were studied at each of the five levels. The amounts of calcium and phosphorus retained increased steadily and at level 5 were 71.8 +/- 1.2 mg/kg/day and 40.9 +/- 1.7 mg/kg/day, respectively. Over the five levels the average percent calcium retention was 91.4 +/- 4.2 and the average percent phosphorus retention was 89.1 +/- 7.7. The provision of parenteral calcium and phosphorus in a 1.7:1 ratio resulted in a balanced retention of both minerals over the range studied. The use of this calcium/phosphorus ratio appears to be appropriate for the preterm infant receiving total parenteral nutrition.

Prediction of Glomerular Filtration Rate by Serum Creatinine and β2-Microglobulin

The reciprocal of serum creatinine concentration (1/Cr) is often used to predict glomerular filtration rate (GFR). Serum creatinine also varies with age, size, and muscle mass, and so it may inaccurately estimate GFR. The reciprocal of serum beta 2-microglobulin (1/beta 2mu) has been proposed as an alternative estimator of GFR. This study compares 1/Cr and 1/beta 2mu as predictors of GFR as measured by 125I-iothalamate clearance (CIOT) and creatinine clearance (CCr) in 29 subjects with a wide range of age, size and kidney function, and including 12 chronic hemodialysis patients. 1/beta 2mu was a better predictor of CIOT (r=0.90) and CCr (r=0.87) than 1/Cr (r=0.50 and 0.78) was. In fact, in the nondialysis population, 1/beta 2mu predicted CIOT (r=0.86) about as well as CCr predicted CIOT (r=0.87). Beta 2mu was less dependent on body size than Cr and unlike Cr, was not influenced by dialysis and did increase as GFR decreased with age. Beta 2mu can be useful as an alternative clinical estimate of GFR, particularly when Cr is considerably influenced by factors other than renal function.

Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide.

The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 + 37 mg/kg/day and retained 80 + 34 mg/kg/day of calcium, and 87 + 19 mg/kg/day and retained 52 + 14 mg/kg/day of phosphorus. The amounts retained were ~65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.

Alternate day infusion of calcium and phosphate in very low birth weight infants: wasting of the infused mineral.

Very low birth weight infants require greater intakes of calcium and phosphate than can be supplied simultaneously in parenteral nutrition. We investigated the biochemical effects and retention of calcium and phosphate when each was administered for 24 h on an alternate day schedule as part of total parenteral nutrition. Serum and urine were collected during a 24 h basal period and during randomly ordered 24 h infusions of either calcium or phosphate in 14 infants during the first week of life. In general, the urinary excretion of the infused mineral (calcium or phosphorus) increased during the 24 h period of its infusion. The serum phosphorus level fluctuated widely from day to day while the serum calcium level did not change. During the 24 h infusion of phosphate, phosphate retention was 67.9 +/- 7.4% and, during the 24 h infusion of calcium, calcium retention was 72.5 +/- 4.3%. However, ongoing excretion of each mineral on the day it was not infused meant that 48.3% of the 48 h phosphate intake and 42.2% of the 48 h calcium intake were lost in the urine. We conclude that excessive amounts of the administered mineral were excreted and that alternate day infusion of calcium and phosphate is an unsatisfactory method for providing these minerals. Attainment of sufficient retentions of calcium and phosphate will require development of novel methods of simultaneous administration which provide calcium and phosphate in high concentrations.

Urinary zinc and metallothionein in children with spina bifida

Defective embryonic cellular zinc utilization may contribute to abnormal neural tube formation and such a defect may be detectable in children with spina bifida (SB). To investigate this possibility, we examined urinary excretion of zinc and metallothionein (Mt), a cytoplasmic metal-binding protein, in 10 girls and 6 boys (ages 6 months to 19 years) with SB and 16 age-matched control subjects. Mean urinary zinc and Mt concentrations in the SB group were 65% and 72% greater than controls, respectively (p less than 0.05). There was was no evidence of renal dysfunction as judged by urinary creatinine and total protein excretion in the SB children. Increased excretion of zinc and Mt in some children with SB may reflect one or more underlying defects of zinc utilization.

Premature Infants Treated with Furosemide have Increased Urinary Calcium and Unchanged Urinary Citrate Excretion Compared to Controls

Nephrocalcinosis (NC) is a frequent complication in very low birth weight (VLBW, <1500 g) infants who are treated with furosemide (F) for bronchopulmonary dysplasia (BPD). Since most infants treated with F become hypercalciuric, yet only half develop NC, factors other than calcium excretion must contribute to the development of this disorder. We postulate that citrate excretion which appears to be under developmental control, may be one of these factors.