Vasilios I. Giapros

Renal function and effect of aminoglycoside therapy during the first ten days of life

Abstract. The effect of aminoglycoside administration on kidney functional maturation was evaluated in groups of 30 preterm and 30 fullterm infants who were treated for 7 days because of suspected infection. One of three different aminoglycosides was administered to each subgroup of ten preterm and ten fullterm infants. Changes in tubular function in groups of ten preterm and ten fullterm infants who were not given antibiotics were also compared. The mean gestational age for preterm infants from 32.5 to 33.6 weeks and for fullterm infants between 39.2 and 39.5 weeks. The renal tubular function was assessed by examining the fractional excretion of sodium (FENa), potassium (FEK), phosphorus (FEP), magnesium (FEMg) and uric acid (FEUA) as well as by the urinary excretion of calcium as the calcium/creatinine (UCa/UCr) ratio. Gentamicin affected the normal plasma creatinine (PCr) decline in both treated groups (fullterm and preterm). Disturbances in FENa and UCa/UCr were more pronounced in treated preterm than in fullterm infants especially after netilmicin and gentamicin administration. FEMg was significantly affected in preterm infants treated with gentamicin. The findings of this study indicate that the effect of aminoglycosides on tubular function is dependent upon kidney maturity and the type of the aminoglycoside used for therapy.

Renal function in premature infants during aminoglycoside therapy.

The effect of three different aminoglycosides on renal function was evaluated in 30 premature infants of similar gestational age who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (10 infants, group B) or netilmicin (10 infants, group C), for a period of 7 days. Ten infection-free premature infants of similar post-conceptional age were used as controls. Serial determinations of plasma creatinine concentration (PCr), as well as the fractional excretion of sodium (FENa), potassium, magnesium (FEMg), phosphate (FEP) and uric acid (FEUA), and the urinary excretion of calcium (UCa/UCr ratio) were assessed before, during and after treatment. During the treatment period a significant increase in FENa, FEMg and UCa/UCr was observed in group B (P<0.05 andP<0.01, respectively) and an increase in FENa and UCa/UCr in group C (P<0.01) compared with controls. These disturbances were observed with trough concentrations of aminoglycosides but were accentuated at peak serum concentrations and were restored to normal 2 days after stopping therapy. In addition, a significant correlation was demonstrated between FENa, FEMg and UCa/UCr ratio in treated patients. PCr levels decreased similarly in all patient groups, but in 8 of 30 infants (27%) they remained elevated and returned to control values only 10 days after stopping therapy. Such renal functional disturbances, although transient, may result in significant electrolyte and mineral imbalance in the sick premature infant.

Acute effects of gentamicin on urinary electrolyte excretion in neonates

It has recently been shown that a single dose of gentamicin causes immediate and transient calcium and magnesium renal wasting in adults. The aim of this study was to determine the acute effect of gentamicin administration on renal electrolyte handling in preterm and full-term neonates. Twenty-three neonates treated with gentamicin for suspected infection were enrolled in the study. Serum and 3-h urine electrolytes were measured before and immediately after gentamicin infusion on the 1st, 3rd, 4th, and 7th day of treatment. Serum gentamicin levels were monitored. Gentamicin caused a statistically significant post-infusion increase in fractional excretion of sodium and magnesium and in the urine calcium to urine creatinine ratio. Potassium and phosphate fractional excretion remained unchanged. The disturbances in electrolyte excretion were observed in full-term as well as in preterm neonates. Serum electrolyte levels remained unchanged. In conclusion, therapeutic doses of gentamicin result in urinary loss of sodium, calcium, and magnesium in neonates immediately after the infusion of the drug. These electrolyte changes may be of clinical importance, especially for sick preterm neonates.

Effect of aminoglycoside therapy on renal function in fullterm infants

Abstract. The effect of aminoglycosides on renal function was evaluated in 30 fullterm infants who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (9 infants, group B), or netilmicin (10 infants, group C). Renal function was assessed before, during, and 48 h after discontinuation of therapy by measuring the plasma creatinine concentration (PCr), the fractional excretion of sodium (FENa), potassium, magnesium, phosphate (FEP), uric acid, and the urinary excretion of calcium (UCA/UCr ratio) immediately before (trough) and after (peak) the infusion of the aminoglycosides. The results were compared with 10 control newborns who did not receive antibiotics. Significant alterations in renal function were observed only during therapy with gentamicin (group B). These consisted of a sustained elevation of FENa and UCa/UCr ratio throughout therapy, a latent increase in FEP on the 7th day (P <0.05), and lack of the normal postnatal decline of PCr in 3 of 9 infants (P <0.01). These abnormalities persisted up to 2 days after discontinuation of therapy. Therapeutic doses of gentamicin may result in significant electrolyte disturbances in sick fullterm infants.

Rare causes of acute hyperkalemia in the 1st week of life

We describe three neonates with hyperkalemia and renal salt wasting during the 1st week of life. Endocrinological evaluation led to the diagnosis of selective hypoaldosteronism (HA) in two neonates and secondary pseudohypoaldosteronism (PHA) in one. The infant with PHA developed a urinary tract infection, and radiological investigation demonstrated a small dysplastic left kidney with vesicoureteral reflux. The electrolyte and hormonal disturbances in this infant persisted throughout the first months of life. The two infants with selective HA improved rapidly after administration of fludrocortisone orally and the electrolytes and renin values returned to normal. Secondary PHA and selective HA should be considered in the differential diagnosis in salt-losing neonates during the first days of life. Renal ultrasonography, urine culture, and assays of aldosterone and plasma renin activity should be performed in any infant presenting with hyperkalemia and salt wasting after the exclusion of congenital adrenal hyperplasia.

Visfatin Levels in Prepubertal Children Born Small or Large for Gestational Age

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3 ng/ml vs. 12.5±6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.

Vitamin D Levels and Insulin Resistance in Children Born with Severe Growth Restriction

This study was designed to examine differences in serum 25(OH)D levels between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) prepubertal children in correlation with birth weight and indices of insulin resistance and β-cell function. Sixty-five nonobese children were examined at age 5-7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and waist circumference were recorded and fasting serum levels of glucose, insulin, 25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) and the β-cell function index (HOMA-β%) were estimated. The mean level of 25(OH)D was higher in the SGA group (26.2±10 vs. 17.2±7 ng/ml, p<0.01) but that of PTH was no different. The insulin resistance and β-cell function indices were higher in the SGA group: HOMA-IR 1.34±0.67 vs. 0.99±0.53, and HOMA-β% 135±56 vs. 97±60 in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated with HOMA-β% but not with HOMA-IR or insulin. In multiple regression, in the total cohort 25(OH)D and HOMA-IR were independently negatively correlated with birth weight (β= - 0.31, β= - 0.36, p<0.05) respectively. In conclusion, at prepuberty severely in utero growth restricted children have increased birth weight dependent levels of 25(OH)D, which might exert a regulatory role on β-cell function.

Effect of intravenous phosphate on the red cell phosphate metabolites of the preterm infant

Abstract The effect of two different amounts of intravenous phosphorus (Pi) supplementation on intracellular phosphorus (RBCPi) and 2,3 diphosphoglycerate (2,3 DPG) was studied in two groups of preterm newborn infants on total parenteral nutrition (TPN) during the first 7–10 days of life. Group A ( n = 10) neonates received 30 mg/kg/day and group B ( n = 15) 60 mg/kg/day inorganic Pi intravenously. Sixteen preterm neonates who were fed with milk formula from day 2 (group C) were used as controls. Blood and spot urine specimens were collected on days 1, 4, 7, 15 and 30 after birth. By the end of the first month of life, group B neonates had levels of plasma Pi (PlPi) higher than group A (5.69 ± 0.8 mg/dl vs 4.71 ± 0.3 mg/dl, p p p p p p

Growth factors of premature infants in relation to parenteral nutrition during the first month of life

Abstract The changes in the circulating levels of growth factors were followed during the first month of life in order to determine any effects of parenteral nutrition on insulin-like growth factors in preterm infants. Thirty-five preterm infants were assigned into two groups. Group one (n = 21, gestational age (GA) 32.1 ± 1.8 wks, birth weight (BW) 1676 ± 112 g) was receiving total parenteral nutrition (TPN) for the first 2–11 days and the other group (n = 14, GA 31.7 ± 1.9 wks, BW 1700 ± 96 g) was milk fed from the 2nd day of life. Serum total and free IGF-I and IGFBP-3 concentrations were determined and auxologic measurements were carried out. One month after birth total and free IGF-I and IGFBP-3 circulating levels had increased similarly in both study groups. However on day 15 the TPN group neonates while they were on lower calorie and protein intakes demonstrated smaller changes in the total IGF-I and IGFBP-3 peptides (IGF-I: 36.3 ± 3.9 vs 58.6 ± 10.6 ng/mL in the milk fed group, p