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J D Kopple

Publications and source records attributed to J D Kopple.

At least 37 records · Page 2Linked to original sources
PubMed1998

The hemodialysis pilot study: nutrition program and participant characteristics at baseline. The HEMO Study Group.

OBJECTIVE: Describe the nutrition program (assessments and interventions) and the participants' baseline nutritional characteristics in the Hemodialysis Pilot Study. DESIGN: Cross sectional survey in which hemodialysis patients were examined during 10 weeks of baseline (BL), before randomization study interventions (dose and flux). SETTING: Four hemodialysis centers (eight dialysis units in total). PATIENTS: Twenty-nine male (mean age, 63 years; range, 34 to 75) and 20 female (mean age, 61 years; range, 29 to 73) hemodialysis patients. INTERVENTIONS: None during BL. MAIN OUTCOME MEASURES: Feasibility of implementing the proposed nutrition program before conducting the full-scale trial, and description of baseline characteristics related to nutrition. RESULTS: A nutrition program was developed to assess nutritional status during BL and follow-up periods and to intervene in patients with weight loss or decreasing serum albumin. Methods for collecting biochemical, dietary and anthropometric data were implemented at four clinical centers. At baseline, mean protein intake estimated by single pool normalized protein catabolic rate was 0.95 +/- 0.21 gm/kg adjusted body weight (ABW) (n = 42) and by diet record assisted recalls (n = 47) 0.94 +/- 0.36 gm/kg ABW/d, respectively. Mean energy intake was 22.8 +/- 8 kcal/kg ABW/day (n = 39). Mean serum albumin concentration using the bromcresol green method was 3.8 +/- 0.4 gm/dL (n = 40). Mean body mass index was within the normal limits of 19-27 kg/m2. Mean skinfold thicknesses in females, but not males, were shifted toward the lower end of usual distributions for healthy individuals. CONCLUSIONS: The goal of designing, developing, and implementing the diet and nutrition component, and related data collection for the HEMO pilot study was accomplished at four separate clinical centers. Baseline mean protein and energy intake were low, suggesting that continuing dietary surveillance is needed. The ongoing full-scale HEMO study will provide the first prospective analysis of dietary intake, nutritional status, and outcome in maintenance hemodialysis patients as a function of dialysis dose and membrane flux.

Adult↗
PubMed1998

IGF-I binding proteins, IGF-I binding protein mRNA and IGF-I receptor mRNA in rats with acute renal failure given IGF-I.

BACKGROUND: Recombinant human insulin-like growth factor-I (rhIGF-I) accelerates recovery from acute renal failure (ARF) in rats. IGF-I acts through the IGF-I receptor (IGF-IR) and its actions may be modified by IGF-I binding proteins (IGFBPs). It therefore would be of value to determine the effects of both ARF and rhIGF-I treatment on serum IGFBPs and mRNA for IGFBPs and IGF-IR. METHODS: Rats with ARF and sham-operated control rats were randomized to receive rhIGF-I or vehicle injections thrice daily for 72 to 74 hours starting five hours after surgery. Serum IGFPBs 1 to 6 were measured serially, and mRNA for IGFBPs 1 to 6 and for IGF-IR were measured in several tissues obtained 72 to 74 hours after surgery. RESULTS: At 72 to 74 hours, serum IGFBP-1 and IGFBP-2 levels were higher in rhIGF-I treated rats. Serum IGFBP-3 was affected by both ARF and rhIGF-I. IGFBP-4 rose transiently only in ARF groups. At 72 to 74 hours, mRNA for several IGFBPs was reduced in renal cortex of ARF rats. Low mRNA for IGFBP-4 and -6 was observed in renal medulla of the ARF rats, particularly in comparison to the sham-operated rats receiving vehicle. Renal medullary IGFBP-2 mRNA was decreased in ARF and sham rats given rhIGF-I as compared to sham animals given vehicle. Hepatic IGFBP-2 mRNA was higher in both rhIGF-I treated groups versus those given vehicle. Otherwise, there were no differences in IGFBP mRNAs among the four groups in lung, heart, and skeletal muscle. IGF-IR mRNA was decreased in renal cortex and medulla of both ARF groups and was not detected in liver in any group. CONCLUSIONS: Thus, ARF and rhIGF-I treatment each affected certain serum IGFBPs and jointly affected some IGFBPs. ARF suppressed gene transcription for renal cortical and medullary IGF-IR and some IGFBPs. rhIGF-I independently affected some renal cortical or medullary IGFBP mRNAs. rhIGF-I increased hepatic IGFBP-2 mRNA and serum IGFBP-2. These effects of ARF or rhIGF-I may influence rhIGF-I actions in rats with ischemic ARF.

Acute Kidney Injury↗
PubMed1998

Leucine turnover in patients with nephrotic syndrome: evidence suggesting body protein conservation.

Whole-body leucine flux was measured in eight patients with nephrotic syndrome and in five healthy subjects by primed-constant infusion of L-[1-13C leucine]. Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured by isotope ration mass spectrometry. Leucine kinetics, calculated from the primary pool enrichment [13C leucine], showed no difference between the nephrotic patients and the control subjects. Kinetics derived from the reciprocal pool [1-13C KIC] enrichment, however, showed that leucine turnover rates were reduced in the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the patients and the control subjects are as follows: rate of leucine release from protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate, 15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and 4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18 g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5 and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine turnover rates and protein intake were highly significant. This study found that nephrotic patients given a modestly protein-restricted diet were able to maintain positive nitrogen balance. Moreover, leucine flux measurements showed downregulation of protein degradation and amino acid oxidation, reflecting appropriate adaptation to a lower protein intake.

Adult↗
PubMed1997

Dietary protein, urea nitrogen appearance and total nitrogen appearance in chronic renal failure and CAPD patients.

This study was carried out to examine the mathematical relationships between the urea nitrogen appearance (UNA), total nitrogen appearance (TNA) and dietary nitrogen intake (DNI) in patients with chronic renal failure. Studies were conducted in 20 nondialyzed patients with advanced chronic renal failure (CRF) who were fed 27 constant protein diets for 24.8 +/- 9.5 days (SD) and eight patients undergoing continuous ambulatory peritoneal dialysis (CAPD), who ingested 13 constant protein diets for 20.3 +/- 4.9 days. All patients lived in a hospital research ward throughout the study and underwent full nitrogen balance measurements. Data were analyzed after patients attained equilibrium or near equilibrium with each dietary protein intake. In the CRF patients, using the mean values obtained during the equilibrium phase, there was a direct and precise correlation between the TNA and UNA, where TNA g/day = 1.19 UNA g/day + 1.27 g/day, r = 0.948. The correlation between DNI and UNA was also highly significant, but less precise, with somewhat greater 95% confidence intervals: DNI g/day = 1.20 UNA g/day + 1.74 g/day, r = 0.865. The relationship between DNI and TNA was not much more precise: DNI g/day = 0.97 TNA g/day + 0.65 g/day, r = 0.880. With the CAPD patients, the relationships were as follows: TNA g/day = 0.94 UNA g/day + 5.54 g/day, r = 0.956; DNI g/day = 0.97 UNA g/day + 6.80 g/day, r = 0.705; DNI g/day = 1.07 TNA g/day + 0.63 g/day, r = 0.760. For the CAPD patients, the lowest 95% confidence intervals were also found for the correlation between TNA and UNA. Thus, in both CRF and CAPD patients, the TNA is highly and precisely correlated with the UNA. The DNI is also significantly correlated with UNA and TNA, but the relationship is less precise. In both of these two groups of patients, the difference between the regression equations for TNA versus UNA and DNI versus UNA was, to a substantial degree, accounted for by the intercept.

Adult↗
PubMed1997

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/1.73 m2 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/1.73 m2 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.

Adolescent↗
PubMed1997

Dialytic nutrition: provision of amino acids in dialysate during hemodialysis.

Maintenance hemodialysis (MHD) patients are frequently malnourished, a condition associated with high morbidity and mortality. Amino acid (AA) losses in dialysate may enhance protein malnutrition in patients with low food intake. We studied the possibility of providing AA in dialysate during MHD to either prevent AA losses or as a nutritional supplement. Six clinically stable men were studied during three hemodialysis treatments. The first treatment was performed using the usual dialysate (0XAA). The two other treatments were performed using a dialysate containing an amount of AA equal to normal plasma AA concentrations (1XAA) or to three times the normal plasma AA concentrations (3XAA). During the OXAA treatment, the total AA losses were 10.0 +/- 0.9 (SEM) grams (g) and the total AA concentrations in plasma decreased by 49 +/- 4%. During the 1XAA treatment, the total AA balance was +0.8 +/- 1.8 g and there was no significant change in the postdialysis plasma total AA. With the 3XAA treatment, the patients gained 36.9 +/- 4.1 g of AA during the hemodialysis treatment and the plasma total AA levels increased by 45 +/- 9%. No side effects were observed. These findings indicate that it may be feasible to provide AA supplements to MHD patients by adding AA to hemodialysate.

Adult↗
PubMed1997

McCollum Award Lecture, 1996: protein-energy malnutrition in maintenance dialysis patients.

There is a high prevalence of protein-energy malnutrition in patients with chronic renal failure who are undergoing maintenance dialysis therapy. The high prevalence of malnutrition is a potentially serious problem because indexes of protein-energy malnutrition are powerful predictors of mortality in maintenance dialysis patients. Although the data do not prove that improving nutritional intake will reduce mortality, nonrandomized studies suggest that provision of addition amino acids and energy to such patients is associated with reduced mortality. There are many causes for protein-energy malnutrition in maintenance dialysis patients. Among the three most important factors are the nutritional status of the patient before commencing dialysis therapy, inadequate protein and energy intakes after they become dialysis patients, and acute and chronic illnesses. Improving the nutrient intake of maintenance dialysis patients is a challenging task because most chronic renal failure patients with malnutrition are anorectic, and dietary counseling has had limited success at increasing their nutrient intake. Other methods for improving nutritional status in adults, infants, and children with chronic renal failure that have been tried with varying degrees of success include increasing the dose of dialysis and the use of food supplements and tube feeding. Less well-proven techniques for the treatment of protein-energy malnutrition include intradialytic parenteral nutrition. The use of appetite stimulants and such growth factors as rhGH and rhIGF-I are still in the experimental stage.

Adult↗
PubMed1996

Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect.

The actions of insulin-like growth factor 1 (IGF-1) on protein turnover and of the IGF-1 receptor (IGF-1R) were examined in skeletal muscle of rats with chronic renal failure (CRF) and sham operated (SO), pair-fed controls. Acidemia was prevented in CRF rats with NaHCO3. Serum IGF-1 and skeletal muscle IGF-1 and IGF-1 mRNA were reduced in CRF rats. Dose-response studies revealed impaired stimulation of protein synthesis and suppressed inhibition of protein degradation by IGF-1 in epitrochlearis muscle of CRF rats. Neither IGF-1 analogues with low affinity to IGF binding proteins nor proteinase inhibitors obliterated the IGF-1 resistance. In CRF rats, skeletal muscle IGF-1R mRNA was increased; displacement ligand binding studies and affinity labeling of the IGF-1R alpha subunit indicated increased total skeletal muscle IGF-1R number with normal affinity. However, both autophosphorylation of the IGF-1R beta subunit (i.e., IGF-1R tyrosine kinase) and the IGF-1R tyrosine kinase activity towards exogenous insulin receptor substrate-1, a natural substrate for IGF-1R tyrosine kinase, were reduced in CRF fats. These data indicate that in skeletal muscle of CRF rats there is resistance to the IGF-1 effects on protein synthesis and degradation and decreased IGF-1 and IGF-1 mRNA levels; IGF-1R mRNA and number are increased; but activity of IGF-1R tyrosine kinase is impaired. This postreceptor defect may be a cause of the skeletal muscle resistance to IGF-1 in CRF.

Animals↗
PubMed1996

Effect of blood pressure control and antihypertensive drug regimen on quality of life: the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of carrying out a randomized, multicenter, 7-year clinical trial to determine the effects of two goal levels of blood pressure control and three antihypertensive drug regimens on decline in glomerular filtration rate in African Americans with clinically diagnosed hypertensive nephrosclerosis. Participants were randomized to either a usual mean arterial blood pressure (MAP) goal group (102-107 mm Hg) or a low-MAP goal group (< or = 92 mm Hg) and to a drug regimen (initial therapy with either atenolol, amlodipine, or enalapril). Quality of life was assessed by the Medical Outcomes Short-Form 36 (MOS SF-36) at baseline and the last follow-up visit for 84 of the 94 participants of the AASK Pilot Study. Symptoms were assessed at baseline and throughout the course of therapy by participant self-report. Mean SF-36 scores increased significantly on physical functioning (9.2), role limitations (physical) (19.0), social functioning (9.0), and vitality dimensions (5.6) from baseline to the last follow-up visit in the usual MAP goal group. Scores for the eight health dimensions assessed by the MOS SF-36 did not change significantly during the same time period either in the low-MAP goal group or in any of the drug regimens. The mean score for general health perception was significantly lower at the last follow-up visit in the enalapril drug regimen (49.9) compared to drug regimens with atenolol (65.4) or amlodipine (63.9). Physical functioning, role limitations (emotional), social functioning, mental health, vitality, and general health perception scores were negatively correlated with self-reported symptoms during treatment. We conclude that selected dimensions of quality of life improved during the AASK Pilot Study only in participants randomized to the usual MAP goal group. Significant differences between MAP goal groups and drug regimens at the end of follow-up were observed for only a few health dimensions.

Adult↗
PubMed1996

Enalapril attenuates the renal hemodynamic effect of acetazolamide in patients with diabetes mellitus: possible implications for tubuloglomerular feedback.

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, causes a fall in renal plasma flow and glomerular filtration (GFR). It is generally believed that the tubuloglomerular feedback (TGF) mechanism is responsible. This study examined whether, in patients with diabetes mellitus, the renal hemodynamic response to ACTZ is intact and whether the angiotensin-converting enzyme inhibitor, enalapril, which would be expected to block TGF, attenuates this response to ACTZ. Six men with insulin-dependent diabetes mellitus lived in a clinical research center for 8 weeks and received enalapril 5-15 mg/day from the third through sixth week. At 2, 6 and 8 weeks p-aminohippurate (PAH) and inulin clearances were performed over eleven 30-min periods. ACTZ (150 mg) was given intravenously after 180 min. In both the pre- and postenalapril studies, PAH clearance fell after ACTZ administration (-60 +/- 15 and -66 +/- 20 ml/min/l1.73 m2, respectively, p < 0.05 for each study). In contrast, with enalapril treatment PAH clearance after ACTZ tended to rise (29 +/- 12 ml/ min/1.73 m2, p = 0.07). GFR after ACTZ fell during the pre- and postenalapril studies (-19 +/- 3 and -13 +/- 1 ml/min/1.73 m2, respectively, p < 0.05 for each study) but not with enalapril treatment (-6 +/- 3 ml/min/1.73 m2). After ACTZ was administered, estimated renal vascular resistance rose during both the pre- and postenalapril studies (p < 0.05 and p < 0.01, respectively) and fell with enalapril treatment (p < 0.05). These data indicate that enalapril alters the renal hemodynamic effects of ACTZ in patients with diabetes mellitus, possibly by inhibiting tubuloglomerular feedback.

Acetazolamide↗
PubMed1995

A proposed glossary for dialysis kinetics.

Quantification of the dialysis dose and assessment of nutritional status and response to nutritional therapy have become standard parts of the management of the chronic dialysis patient. Although advances in these areas have led to a more rational basis for therapy, certain misconceptions and points of confusion appear to have occurred. Recognizing the importance of a standard nomenclature to the development of concepts and the communication of research findings, we have attempted to compile a list of terms that are commonly used in the field of dialysis. New terms have been proposed for current ones that do not seem adequate. In addition, we have discussed potential methodologies for obtaining more accurate data for dialysis kinetics and for precise monitoring of nutritional intake and status. It is hoped that this glossary will stimulate discussion that will lead to refinements in terminology and concepts that will, in turn, improve research and practice in nephrology. It is anticipated that many of these definitions and recommendations will be modified or superseded as the management of patients with renal failure continues to advance.

Adolescent↗
PubMed1995

Altered physiology and action of insulin-like growth factor 1 in skeletal muscle in chronic renal failure.

Chronic renal failure is associated with abnormalities of skeletal muscle that include reduction in size, fibrosis, protein depletion, and functional disorders. These disorders may be caused by several factors, including protein-calorie malnutrition, acidemia, and superimposed illnesses. However, animal research suggests that these abnormalities may occur with chronic renal failure per se in the absence of the above complications. Insulin-like growth factor 1 (IGF-1) is an anabolic hormone that, in skeletal muscle, stimulates intracellular amino acid and glucose transport and protein synthesis, suppresses protein degradation, and causes hypertrophy. In chronic renal failure, there is evidence for inhibition of the actions of IGF-1. Studies in humans with chronic renal failure given a subcutaneous injection of recombinant human IGF-1 (rhIGF-1) indicate that the rhIGF-1 induced acute suppression of plasma amino acids, insulin, and C peptide is impaired. In skeletal muscle of rats with chronic renal failure, we observed reduced IGF-1 and IGF-1 mRNA levels, resistance to the rhIGF-1-induced suppression of protein degradation, and stimulation of protein synthesis, increased IGF-1 receptor mRNA and IGF-1 receptor number and impaired receptor tyrosine kinase activity. These findings suggest that in skeletal muscle in chronic renal failure there are several abnormalities in the physiology of IGF-1 and the sensitivity to IGF-1. It is possible that these alterations contribute to the disorders of skeletal muscle structure and function in chronic renal failure. Notwithstanding these abnormalities, repeated subcutaneous injections of rhIGF-1 in malnourished patients undergoing continuous ambulatory peritoneal dialysis led to strongly positive nitrogen balance that was sustained for the 20 days of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of recombinant human insulin-like growth factor 1 on renal handling of phosphorus, calcium, and sodium in normal humans.

The effects of insulin-like growth factor 1 (IGF-1) on renal handling of phosphorus, calcium, and sodium were evaluated in eight healthy men while they lived in a clinical research center for slightly more than 5 days. Subjects received a continuous intravenous infusion throughout the study of 0.45% saline and 2.5% d-glucose at 50 mL/hr (group 1, four subjects) or 150 mL/hr (group 2, four subjects). Recombinant human IGF-1 (rhIGF-1), 60 micrograms/kg body weight, was injected subcutaneously three times daily for 10 doses from day 2 until the beginning of day 5. After commencing the rhIGF-1 injections, there was a marked decrease in the fractional excretion of phosphorus in both groups that was sustained throughout the study. Urine phosphorus excretion also decreased significantly on days 2 to 5 in group 1 and on day 2 in group 2. In group 1, the fractional excretion of calcium decreased on day 2; urine calcium did not change. The fractional excretion of sodium decreased on days 2 and 4; urine sodium decreased significantly only on day 2. In group 2, the fractional and absolute urine excretion of calcium did not change. Fractional sodium excretion was not altered, and urine sodium increased only on day 5. The average serum phosphorus, calcium, and sodium did not change from baseline in groups 1 or 2. The pattern of the circadian rhythms for serum concentrations, urine excretion, and fractional excretion of phosphorus and calcium did not appear to be affected by the rhIGF-1 injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗