Adaptive responses to very low protein diets: The first comparison of ketoacids to essential amino acids

Adaptive responses to very low protein diets: The first comparison of ketoacids to essential amino acids. Eight patients with chronic renal failure (GFR 18.8 ± 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28g protein and 35kcal per kg per day, plus an isomolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days before hospital admission and following a four-day equilibration, a five-day nitrogen balance (BN) was performed. Whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Even though the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Nitrogen conservation with KA was due to a reduction in urea nitrogen appearance. Rates of WBPT measured during fasting and feeding did not differ between the KA or EAA regimens. During both regimens, feeding decreased protein degradation, whereas protein synthesis was unchanged. Although feeding stimulated leucine oxidation, rates were 50 to 100% lower than reported in CRF patients consuming 0.6 or 1.0g protein/kg/day. Thus, neutral BN with the VLPD regimen is achieved by a marked reduction in amino acid oxidation and a postprandial inhibition of protein degradation

Pharmacokinetics of darbepoetin alfa in pediatric patients with chronic kidney disease

Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3–16 years of age with CKD were randomized and received a single 0.5 µg/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42306/1/s00467-002-0932-0.pd

Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study

Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study. The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/day). In Study B, 255 patients with a GFR of 13 to 24 ml/min/1.73m2 were randomly assigned to the low-protein diet or a very-low-protein diet (0.28 g/kg/day), supplemented with a ketoacid-amino acid mixture (0.28 g/kg/day). The low-protein and very-low-protein diets were also low in phosphorus. Mean duration of follow-up was 2.2 years in both studies. Protein and energy intakes were lower in the low-protein and very-low-protein diet groups than in the usual-protein group. Two patients in Study B reached a “stop point” for malnutrition. There was no difference between randomized groups in the rates of death, first hospitalizations, or other “stop points” in either study. Mean values for various indices of nutritional status remained within the normal range during follow-up in each diet group. However, there were small but significant changes from baseline in some nutritional indices, and differences between the randomized groups in some of these changes. In the low-protein and very-low-protein diet groups, serum albumin rose, while serum transferrin, body wt, percent body fat, arm muscle area and urine creatinine excretion declined. Combining patients in both diet groups in each study, a lower achieved protein intake (from food and supplement) was not correlated with a higher rate of death, hospitalization or stop points, or with a progressive decline in any of the indices of nutritional status after controlling for baseline nutritional status and follow-up energy intake. These analyses suggest that the low-protein and very-low-protein diets used in the MDRD Study are safe for periods of two to three years. Nonetheless, both protein and energy intake declined and there were small but significant declines in various indices of nutritional status. These declines are of concern because of the adverse effect of protein calorie malnutrition in patients with end-stage renal disease. Physicians who prescribe low-protein diets must carefully monitor patients' protein and energy intake and nutritional status

Na+, K+, and BP homeostasis in man during furosemide: Effects of prazosin and captopril

Na+, K+, and BP homeostasis in man during furosemide: Effects of prazosin and captopril. Furosemide increases sodium (Na+) and potassium (K+) excretion but if dietary salt is provided, a compensatory reduction in Na+ and K+ excretion follows which restores neutral balances within 18 to 24 hours. This compensation is not interrupted by blockade of the renin–angiotensin–aldosterone system (RAA) alone with captopril. Since plasma norepinephrine concentration increases after furosemide and alpha, adrenoreceptors can mediate enhanced Na+ reabsorption, we administered prazosin (2mg 6hr-1) to six normal volunteers consuming a daily intake of 270mmol of Na+ and 75mmol of K+, and added captopril (25mg 6hr-1) for an additional day to block the RAA system concurrently. Furosemide (40mg day-1) was given for the last four days. Prazosin given alone before the diuretic reduced (P < 0.05) BP and plasma angiotensin II (AII) concentration and increased body weight and heart rate. However, when given with furosemide, neither prazosin nor prazosin with captopril modified the short–term natriuretic or kaliuretic responses to furosemide, or the ensuing compensatory reductions in Na+ and K+ excretion. Accordingly, cumulative balances for Na+ and K+ remained neutral over four days of diuretic administration. Neither drug altered the renal responsiveness to the diuretic which was assessed from the relationship between renal Na+ and K+ excretion and diuretic elimination. Although the BP was maintained when furosemide was given alone, when given with prazosin and captopril, the mean BP fell by 13 ± 5mm Hg (P < 0.05). In conclusion, in normal human subjects consuming a liberal salt intake, neither the alpha1 adrenoreceptor nor the RAA systems are required for maintenance of Na+ and K+ balances during administration of furosemide