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Biomedical subjects

J D Kopple

Publications and source records attributed to J D Kopple.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cross-sectional comparison of malnutrition in continuous ambulatory peritoneal dialysis and hemodialysis patients.

Although malnutrition is not uncommon in continuous ambulatory peritoneal dialysis (CAPD) and maintenance hemodialysis (MHD) patients, there has never been a large-scale comparison study of nutritional status with these two dialysis modalities. We therefore assessed protein-calorie nutrition in 224 CAPD patients and 263 MHD patients who were treated in eight centers in Italy. The CAPD patients were slightly older than the MHD patients (60.2 +/- 14.2 years v 56.3 +/- 15.1 years; P < 0.01), had undergone dialysis for less time (2.32 +/- 2.10 years v 3.66 +/- 2.66 years; P < 0.0001), and had higher residual renal function (1.83 +/- 2.29 mL/min v 0.27 +/- 0.91 mL/min; P < 0.0001). Protein nitrogen appearance was 60.5 +/- 16.6 g/d and 61.9 +/- 16.5 g/d in the CAPD and MHD patients, respectively. In CAPD versus MHD patients, serum total protein and albumin tended to be lower; serum transferrin and midarm muscle circumference were similar; and relative body weight, skinfold thickness, and estimated percent body fat tended to be greater. These greater values in CAPD patients were particularly evident in those who were 65 years of age or older. Serum glucose, total cholesterol, and triglycerides also were greater in CAPD patients. The subjective global nutritional assessment indicated a significantly greater proportion of malnourished CAPD patients than MHD patients (42.3% v 30.8%). The greater prevalence of malnutrition in CAPD patients diminished with age. Maintenance hemodialysis patients older than 76 years were more likely to be malnourished than CAPD patients. In patients less than 65 years of age, protein-calorie malnutrition was more likely to be present in CAPD patients than in MHD patients.

Adult↗
PubMed1995

Pharmacokinetics of recombinant human insulin-like growth factor-1 in dialysis patients.

Six maintenance hemodialysis (MHD), six continuous ambulatory peritoneal dialysis (CAPD) and six normal adults underwent pharmacokinetic studies of insulin-like growth factor-1 (IGF-1). Each subject received two separate subcutaneous injections of recombinant human IGF-1 (rhIGF-1) (50 or 100 micrograms/kg) in random order separated by 7 to 21 days. Two different responses were observed. With the 50 micrograms/kg dose, serum IGF-1 levels and the pharmacokinetic parameters were not different between the three groups. With the 100 micrograms/kg dose, peak serum IGF-1 concentrations were significantly greater in the MHD and CAPD patients than in normals. However, by 12 to 14 hours after injection, serum IGF-1 was not different in the three groups. Although the Tmax, area under the curve and serum clearance of IGF-1 were similar in the three groups, the half-life and volume of distribution of rhIGF-1 was significantly decreased in both MHD and CAPD patients. These data indicate that IGF-1 pharmacokinetics are abnormal in maintenance dialysis patients.

Adult↗
PubMed1995

Impaired metabolic response to recombinant insulin-like growth factor-1 in dialysis patients.

The acute metabolic effects of recombinant human insulin-like growth factor-1 (rhIGF-1) were studied after an overnight fast in six maintenance hemodialysis (MHD) patients, six chronic peritoneal dialysis (PD) patients and six normal subjects. Each subject received a subcutaneous injection of rhIGF-1, 50 or 100 micrograms/kg body wt, given in random order on two occasions separated by 7 to 21 days. After the rhIGF-1 injection, plasma insulin, C-peptide, cortisol, amino acids and glucose decreased. The magnitude of the decrease was greater with the larger rhIGF-1 dose. The fall in plasma insulin, C-peptide and many amino acid concentrations was less and the decrease in glucose was similar in the MHD and CAPD patients as compared to normals. With 50 micrograms rhIGF-1/kg, plasma insulin and C-peptide decreased more quickly and often to a greater magnitude in normal individuals. With 100 micrograms rhIGF-1/kg, the decrease in plasma insulin, C-peptide and amino acids in the MHD and CAPD patients was almost as frequent as in the normal subjects, but the magnitude of the fall was often significantly less. This impaired response occurred in both MHD and CAPD patients even though, with the 100 micrograms rhIGF-1/kg dose, their plasma IGF-1 was significantly higher than in normals during most of the first four hours after injection. These results provide the first in vivo evidence for resistance to the metabolic effects of rhIGF-1 in patients with advanced renal failure.

Adult↗
PubMed1995

Treatment of malnourished CAPD patients with an amino acid based dialysate.

Nineteen malnourished chronic peritoneal dialysis patients who were ingesting a low protein intake underwent metabolic balance studies to test whether a dialysate that contained amino acids would improve their protein nutrition. Patients lived in the hospital for 35 days while they ate a constant diet and underwent their usual regimen of continuous ambulatory peritoneal dialysis (CAPD). The first 15 days served as a Baseline Phase. For the last 20 days, the usual dialysate was substituted with a dialysate of essentially the same composition except that it contained 1.1% essential and nonessential amino acids and no glucose. Patients received one or two dialysate exchanges with amino acids each day depending on the amount necessary to bring the individual's dietary protein plus dialysate amino acid intake to 1.1 to 1.3 g/kg body weight/day. During Baseline, patients were in neutral nitrogen balance; net protein anabolism was positive, as determined from 15N-glycine studies. After commencing intraperitoneal amino acid therapy, nitrogen balance became significantly positive, there was a significant increase in net protein anabolism, the fasting morning plasma amino acid pattern became more normal, and serum total protein and transferrin concentrations rose. Patients generally tolerated the treatment well, although some patients developed mild metabolic acidemia. These findings indicate that a dialysate containing amino acids may improve protein malnutrition in CAPD patients ingesting low protein intakes.

Acidosis↗
PubMed1994

Patterns of fasting plasma amino acid levels in chronic renal insufficiency: results from the feasibility phase of the Modification of Diet in Renal Disease Study.

Fasting plasma amino acid levels were measured in 78 patients with chronic renal insufficiency (glomerular filtration rate [GFR], 8.0 to 56.0 mL/min), who had been enrolled in phase II of the Modification of Diet in Renal Disease study, prior to their beginning the experimental portion of the protocol. Alterations in many plasma amino acid levels were observed in the patients with the mildest degrees of renal insufficiency, and the number and severity of abnormalities tended to be greater in the patients with more severe renal failure. In patients with GFRs greater than 24.5 mL/min, 15 to 24.5 mL/min, and less than 15 mL/min, statistically significant abnormalities were observed in the concentrations or ratios of 9, 14, and 18 amino acids, respectively. The following correlations of amino acid levels or ratios with GFR were observed (all P < 0.001): citrulline, r = -0.41; citrulline to arginine ratio, r = -0.42; glycine to serine ratio, r = -0.37; N-tau methylhistidine, r = -0.65; and cystine, r = -0.37. Other weaker correlations observed were valine, r = 0.26 (P < 0.025); valine to glycine ratio, r = 0.32 (P = 0.004); and sum of isoleucine, leucine, and valine, r = 0.21 (P = 0.061). N-tau methylhistidine and the essential to nonessential amino acid ratio became altered with declining GFR in a nonlinear fashion. Thus, many of the characteristic alterations in the plasma amino acid profile that are observed in chronic end-stage renal disease are already present in mild renal insufficiency. Progressive loss of renal function generally results in increasing abnormalities; these changes in plasma amino acid concentrations with reduction in GFR were usually linear.

Adult↗
PubMed1994

Effect of nutrition on morbidity and mortality in maintenance dialysis patients.

Protein-calorie malnutrition is common in maintenance dialysis patients. Malnutrition is mild to moderate in approximately 33% of maintenance dialysis patients and severe in approximately 6% to 8%. There are many causes of protein-calorie malnutrition in maintenance dialysis patients; the three major causes are probably low nutrient intakes, intercurrent or underlying illnesses, and the dialysis procedure itself. Malnutrition is a major risk factor for mortality in maintenance dialysis patients. This has been shown most clearly for serum albumin, which is the nutritional parameter that has been most heavily studied. Low dietary of protein or other nutrients and protein-calorie malnutrition revealed by the results of different chemistry analyses are also directly correlated with mortality rates. These data do not prove that poor nutritional intake or malnutrition is a cause of the high morbidity and mortality in maintenance dialysis patients, and randomized, prospective controlled clinical trials are necessary to answer this question. However, the data are consistent with the thesis that malnutrition or inadequate nutrient intake do contribute to high morbidity and mortality in these patients. Although it is possible that increasing the dose of dialysis (eg, Kt/V) will lead to increased appetite and nutrient intake, experience suggests that raising the dose of dialysis, by itself, will not optimize nutritional intake in these individuals. To achieve satisfactory nutritional intake and healthy nutritional status, other interventions will need to be developed.

Blood Urea Nitrogen↗
PubMed1994

The biblical view of the kidney.

The biblical view of the kidney differs radically from the modern perception. For example, there is no reference in the Bible to the fact that the kidneys make urine. The kidneys were viewed as the seat of conscience and of ethical feelings and yearnings, and the source of mortality and ethical activity. The kidneys were believed to be associated with the innermost parts of the personality. There are references to God examining the ethical nature of man through the kidneys or punishing man by injuring the kidneys. The fat around the kidneys was considered to be of special value for sacrifice and may have symbolized luxury or opulence. Much of the biblical understanding of the anatomy of the kidneys and the anatomic relationships between the kidneys, perirenal fat and the liver appears to be derived from observations made in domestic animals.

Bible↗
PubMed1993

Fingernail creatinine as a predictor of prior renal function.

When a patient presents with renal failure, it is often difficult to ascertain whether the individual is suffering from acute or chronic renal failure. Fingernail creatinine might help to differentiate between the two. To test this possibility, the relationship between the fingernail creatinine and the serum creatinine obtained concurrently or 1 or more months previously was examined in 22 normal adults, nine patients with acute renal failure, seven patients with chronic renal failure not undergoing dialysis, 16 maintenance hemodialysis patients, and 33 patients with a functioning renal transplant who had been transplanted 0.2 to 3.9 months (n = 21) or 4.3 to 33 months previously (n = 12). Fingernail creatinine was significantly greater than normal in the patients with chronic renal failure, patients undergoing maintenance hemodialysis, and patients who had a functioning renal transplant implanted 0.2 to 3.9 months previously. In contrast, fingernail creatinine was not different from normal in the patients with acute renal failure and in patients who had a functioning renal transplant placed 4.3 to 33 months previously. In the maintenance hemodialysis patients, fingernail creatinine showed the strongest correlation with the serum creatinine obtained between 5 and 10 months previously, with the highest correlation at 9 months. In the renal transplant recipients, the fingernail creatinine decreased to normal or near normal values within approximately 90 to 120 days after transplantation. These findings indicate that fingernail creatinine may reflect the serum creatinine values several months previously. The fingernail creatinine may help to identify whether patients have recent onset as compared with longstanding renal failure.

Acute Kidney Injury↗
PubMed1993

Effects of insulin-like growth factor I on renal function in normal men.

Acute and chronic studies in rats have shown that administration of human recombinant insulin-like growth factor I (rhIGF-I) lowers renal vascular resistance and increases RPF, GFR and proximal tubular phosphate absorption. In the present study we examined the effects of subcutaneous injections of rhIGF-I on glomerular and tubular function in eight normal men. Individuals were studied for 5.5 consecutive days in a clinical research center while they ate a constant diet. Four subjects were studied in a non-volume expanded state (Group 1) and four individuals were evaluated during a saline load. From the second to the fourth day, subjects received subcutaneous injections of rhIGF-I, 60 micrograms/kg, at 0800, 1400 and 2000 hours. After commencing the rhIGF-I injections, serum IGF-I levels rose quickly and remained at about three to four times that of baseline throughout the period of rhIGF-I injections. In both the normal and the saline loaded subjects, renal vascular resistance decreased and RPF and GFR (PAH and inulin clearances) rose quickly and were clearly altered within six hours after starting the rhIGF-I injections. RPF had increased by 32 +/- 3% and 33 +/- 2% (grand mean +/- SEM) in the normal and the saline loaded subjects, and GFR rose by 22 +/- 3% and 36 +/- 4% in the two groups. In both groups the absolute and the fractional excretion of phosphate decreased markedly during rhIGF-I treatment, but the absolute and fractional excretion of calcium did not change. The urinary fractional and absolute excretion of albumin and IgG also increased, although slightly, with rhIGF-I injections. There was no consistent effect of IGF-I on tubular sodium handling. These findings demonstrate that in normal men subcutaneous injections of rhIGF-I greatly increase RPF, GFR, and tubular phosphorus reabsorption and enhances microproteinuria.

Albumins↗
PubMed1993

Recombinant human insulin-like growth factor-I accelerates recovery and reduces catabolism in rats with ischemic acute renal failure.

This study evaluated whether recombinant human insulin-like growth factor-I (rhIGF-I) enhances recovery of renal function and reduces catabolism in rats with ischemic acute renal failure (ARF). ARF and sham rats received subcutaneous injections of either rhIGF-I or vehicle three times daily starting 5 h after surgery. Serum creatinine and urea, which initially rose similarly in the ARF+vehicle and ARF+rhIGF-I rats, increased more slowly after commencing the rhIGF-I injections. 72 h after surgery, the ARF+rhIGF-I rats, in comparison with ARF+vehicle animals, showed significantly greater renal plasma flow and filtration fraction, a fivefold higher glomerular filtration rate, greater renal cortical IGF-I levels, increased proliferating cell nuclear antigen expression in proximal tubule nuclei and enhanced DNA synthesis in the renal cortex, corticomedullary junction, glomeruli, and tubules as demonstrated by [3H]thymidine incorporation and in corticomedullary junction tubules as determined by autoradiography. Estimated total nitrogen output (ETNO) was greater in ARF+vehicle than in ARF+rhIGF-I or sham rats throughout the study. ETNO in ARF+rhIGF-I rats returned to sham values by the second day after surgery. 72 h after surgery, protein degradation was increased and protein synthesis reduced in the epitrochlearis muscle of ARF+vehicle as compared with ARF+rhIGF-I or sham+vehicle rats. Thus, treatment with rhIGF-I starting 5 h after inducing ischemic ARF in rats increases recovery of renal function, enhances formation of new renal tubular cells, lowers protein degradation, and increases protein synthesis in skeletal muscle and reduces net catabolism.

Acute Kidney Injury↗
PubMed1992

The growth hormone-insulin-like growth factor I axis and renal glomerular function.

This study examined whether maneuvers that chronically raise or lower serum insulin-like growth factor I (IGF-I), within physiological and pathophysiological ranges, will affect glomerular hemodynamics. Pair-fed Munich Wistar rats received, for 6 to 7 days, continuous s.c. infusions of human recombinant IGF-I (rhIGF-I; 125 micrograms/day), vehicle, or s.c. injection of a synthetic growth hormone-releasing hormone antagonist (GHRH-ANT) (N = 7 in each group). Infusion of rhIGF-I raised serum IGF-I to about 180% of control values, and GHRH-ANT injections lowered serum IGF-I to about 33% of control. The IGF-I infusion induced an increase in left kidney weight when expressed in absolute units but not when expressed as a percentage of body weight; there was also an increase in glomerular volume in the IGF-I treated rats. GFR, single nephron GFR, and single nephron plasma flow also rose with IGF-I infusion, and these changes were associated with decreased afferent and efferent arteriolar resistance and increased glomerular ultrafiltration coefficient. GHRH-ANT injection did not affect kidney weight or glomerular volume; however, GFR, single nephron GFR, and single nephron plasma flow were reduced in association with an increase in efferent arteriolar resistance. There also was a tendency, not significant, for the glomerular ultrafiltration coefficient to decrease. The findings that a low dose of rhIGF-I, which raised the serum IGF-I only modestly, increased glomerular ultrafiltration and that reducing serum IGF-I below control values decreased glomerular dynamics suggest that physiological or pathophysiological changes in IGF-I may affect and possible help to regulate glomerular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The rationale for the use of growth hormone or insulin-like growth factor I in adult patients with renal failure.

Since the development of recombinant DNA technology, there has been a rapid expansion of research concerning the use of recombinant DNA synthesized human growth hormone (rhGH) for the treatment of clinical disorders. rhGH has been used to treat patients with acute catabolic stress caused by surgery, trauma and sepsis, children with chronic renal insufficiency and impaired growth, patients undergoing maintenance hemodialysis who are malnourished, and individuals on weight reduction diets. These studies indicate that rhGH enhances protein balance in acutely stressed patients and in malnourished maintenance hemodialysis patients, promotes catch-up growth in children with chronic renal failure, and may reduce protein wasting and enhance lipolysis in obese individuals on weight reduction diets. Experimental studies suggest that in addition to enhancing anabolism, rhGH may increase both immune function and the rate of wound healing. Many, but not all, of the effects of rhGH are mediated through insulin-like growth factor I (IGF-I). For example, the hyperglycemic and lipolytic effects of rhGH do not seem to be caused by IGF-I. Animal or human studies suggest that with severe malnutrition or severe sepsis, rhGH treatment may neither increase serum IGF-I levels nor promote anabolism. These observations provide a rationale for administering IGF-I as an anabolic hormone for severely malnourished or septic patients with renal failure. Further studies will be necessary to examine both the short-term and long-term potential benefits and adverse effects of rhGH or rhIGF-I treatment in these conditions.

Adult↗
PubMed1991

Characteristics of taurine transport in rat liver lysosomes.

Taurine (2-aminoethanesulfonic acid) is a unique sulfur amino acid derivative that has putative nutritional, osmoregulatory, and neuroregulatory roles and is highly concentrated within a variety of cells. The permeability of Percoll density gradient purified rat liver lysosomes to taurine was examined. Intralysosomal amino acid analysis showed trace levels of taurine compared to most other amino acids. Taurine uptake was Na(+)-independent, with an overshoot between 5-10 minutes. Trichloroacetic acid extraction studies and detergent lysis confirmed that free taurine accumulated in the lysosomal space. Kinetic studies revealed heterogeneous uptake with values for Km1 = 31 +/- 1.82 and Km2 greater than 198 +/- 10.2 mM. The uptake had a pH optimal of 6.5 and was stimulated by the potassium specific ionophore valinomycin. The exodus rate was fairly rapid, with a t1/2 of 5 minutes at 37 degrees C. Analog inhibition studies indicated substrate specificity similar to the plasma membrane beta-alanine carrier system, with inhibition by beta-alanine, hypotaurine, and taurine. alpha-Alanine, 2-methylaminoisobutyric acid (MeAIB), and threonine were poor inhibitors. No effects were observed with sucrose and the photoaffinity derivative of taurine NAP-taurine [N-(4-azido-2-nitrophenyl)-2-aminoethanesulfonate]. In summary, rat liver lysosomes possess a high Km system for taurine transport that is sensitive to changes in K+ gradient and perhaps valinomycin induced diffusional membrane potential. These features may enable lysosomes to adapt to changing intracellular concentrations of this osmotic regulatory substance.

Adenosine Triphosphate↗
PubMed1991

Hepatic uptake and release of glucose, lactate, and amino acids in acutely uremic dogs.

This study evaluated the potential contribution of the liver to glucose intolerance and insulin resistance in acute uremia. Eight bilaterally nephrectomized dogs and eight sham-operated dogs were studied, while awake, 24 to 30 hours after surgery. Blood levels and hepatic balance of glucose, lactate, and amino acids were measured during a baseline period and during a 90-minute infusion of glucose and insulin that maintained plasma glucose at 9 to 10 mmol/L. During the basal state, the acutely uremic dogs, in comparison to control dogs, displayed decreased femoral artery plasma glucose, whole blood total amino acids, and elevated blood lactate. In the liver of the uremic dogs, there was lower glucose output, less uptake of alanine, greater uptake of glutamine, and similar uptake of lactate, as compared with controls during the basal state. In the control dogs during the hyperglycemic clamp, the liver took up glucose and released lactate; the hepatic uptake of alanine diminished, and the hepatic output of glutamine persisted. In contrast, during the hyperglycemic clamp in the uremic dogs, there was no hepatic uptake of glucose; the hepatic uptake of alanine, glutamine, and lactate persisted, and the hepatic uptake of total amino acids was greater than in controls. Peripheral glucose uptake was also impaired in the acutely uremic dogs. Moreover, the uremic dogs had insulin resistance, as indicated by a low ratio of the glucose infusion rate to the plasma insulin levels, and a higher urea nitrogen appearance. Thus, acutely uremic dogs have altered hepatic handling of glucose and its precursors, which only becomes evident during a glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Taurine levels in plasma and blood cells in patients undergoing routine maintenance hemodialysis.

We compared taurine levels in plasma, erythrocytes, platelets, lymphocytes, and granulocytes from 11 normal adults and 11 maintenance hemodialysis (MHD) patients immediately before and following a routine hemodialysis treatment. Taurine concentrations were elevated in plasma predialysis, as compared with normal subjects (90 +/- 16 [SEM] v 54 +/- 2 mumol/L [1.1 +/- 0.2 v 0.7 +/- 0.03, mg/dL]), but decreased with a dialysis treatment (to 34 +/- 3 mumol/L [0.4 +/- 0.04 mg/dL]). Erythrocyte taurine levels tended to be higher in MHD patients predialysis (1.2 +/- 0.2 v 0.7 +/- 0.1 nmol/10(9) cells, P less than 0.05 where P less than 0.025 is significant) as compared with controls; erythrocyte taurine was increased after dialysis (to 1.8 +/- 0.3 nmol/10(9) cells, P less than 0.006). In contrast, platelet taurine concentrations in MHD patients were lower than normal predialysis (18 +/- 2 v 27 +/- 2 nmol/10(9) cells) and declined further during the dialysis procedure (to 14 +/- 1). Granulocyte and lymphocyte taurine levels were not different in MHD patients, as compared with normal adults, either before or after dialysis. The observed differences in blood cell taurine content (expressed per 10(9) cells) could not be explained by variation in cell volumes among the groups examined. Thus, both chronic renal failure and a routine hemodialysis treatment produce changes in cell and plasma taurine levels that tend to be specific for the individual cell type.

Adult↗
PubMed1991

Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study.

We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition.

Adolescent↗
PubMed1991

Vitamin B-6 deficiency and renal function and structure in chronically uremic rats.

In preliminary studies, rats with chronic renal failure (CRF) demonstrated worsening renal function, as measured by urea clearance, when fed vitamin B-6-deficient diets. However, urea clearance is not a precise measure of glomerular filtration rate (GFR) and these studies did not indicate the mechanism for the reduced GFR. To measure renal function more precisely and to assess whether B-6 deficiency augments renal injury, we examined [14C]inulin clearance, urine oxalate excretion, and renal histopathology in rats with CRF pair fed to receive a pyridoxine-replete or -deficient diet for 3 or 6 wk. After 3 or 6 wk, pyridoxine-deficient rats had significantly lower [14C]inulin clearances and increased urine oxalate excretion. Histological evaluation indicated increased renal damage in kidneys from pyridoxine-deficient rats as compared with tissue from pyridoxine-replete rats. These findings suggest that in rats with CRF, vitamin B-6 deficiency reduces the GFR and increases renal scarring.

Animals↗