Role of diet in the progression of chronic renal failure: experience with human studies and proposed mechanisms by which nutrients may retard progression.
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Dietary Fats↗
Biomedical subjects
J D Kopple
Publications and source records attributed to J D Kopple.
Effects of recombinant human insulin-like growth factor I on glomerular dynamics in the rat.
This study was undertaken to investigate the mechanisms by which an infusion of recombinant human insulin-like growth factor I (rhIGF-I) increases GFR and renal plasma flow (RPF) in rats. Glomerular micropuncture studies were carried out in 14 nonstarved Munich Wistar rats and in 12 rats deprived of food for 60-72 h. Animals were given an intravenous injection and infusion of either rhIGF-I or vehicle. In both nonstarved and starved animals, the IGF-I injection and infusion increased the serum IGF-I levels, left kidney GFR, single nephron glomerular filtration rate (SNGFR), single nephron blood flow rate (SNBF), and single nephron plasma flow rate (SNPF). The increase in SNPF and SNGFR was in part due to a fall in efferent arteriolar resistance (RE); there was a tendency, not significant, for afferent arteriolar resistance (RA) to fall in comparison to controls. The increase in SNGFR was partly caused by a rise in SNPF but was primarily due to an increase in glomerular ultrafiltration coefficient (LpA) to twice the control values. The increase in LpA resulted in an increase in SNGFR because the rats operated at ultrafiltration pressure disequilibrium. Control starved as compared with nonstarved rats had lower SNGFR, SNBF, and SNPF. This reduction was due to a tendency, not significant, for both RA and RE to be higher. Decreased SNGFR in food-deprived rats resulted from a reduced SNPF, a lower glomerular transcapillary hydrostatic pressure difference (delta P), and possibly a somewhat reduced LpA. These data indicate that IGF-I increases SNGFR, SNPF, and SNBF primarily by increasing LpA and also by decreasing RE without affecting delta P. Short-term starvation lowers SNGFR, SNPF, and SNBF primarily by decreasing delta P and possibly by lowering LpA and increasing RA and RE. IGF-I reverses some of the glomerular hemodynamic effects of short-term food deprivation.
Animals↗
Response of insulin-like growth factor I and renal hemodynamics to a high- and low-protein diet in the rat.
An increase in plasma insulin-like growth factor I (IGF-I) levels by growth hormone injection or IGF-I infusion can raise renal plasma flow and glomerular filtration rate. However, it is not known whether a more physiological stimulus for IGF-I will also increase IGF-I in the kidney and whether the increase in renal or serum IGF-I is correlated with the increase in renal plasma flow and glomerular filtration rate. Male rats were pair fed either a high-protein (36% protein, N = 9) or a low-protein but isocaloric diet (9% protein, N = 9) for 10 to 14 days. Renal plasma flow and glomerular filtration rate were then estimated by clearance measurements, and IGF-I was measured in extracted serum, liver, renal cortical tissue, and glomeruli. Body weight gain and combined kidney weight were higher in high-protein rats as compared with low-protein animals (0.86 +/- 0.02 SEM versus 0.77 +/- 0.02 g/100 g body wt; P less than 0.05), but liver weights were not different. Serum, liver, and glomerular IGF-I levels were also higher in the high-protein rats as compared with the low-protein animals (serum, 1.12 +/- 0.03 versus 0.80 +/- 0.06 U/mL, P less than 0.05; liver, 183 +/- 17 versus 117 +/- 16 mU/g wet wt, P less than 0.05; glomeruli, 7.43 +/- 0.73 versus 4.81 +/- 0.59 mU/mg of protein, P less than 0.05). In contrast, the renal cortical IGF-I levels were not different in high-protein versus low-protein rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Growth hormone treatment for patients with renal failure.
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Blood Urea Nitrogen↗
Growth Failure in Children with Renal Diseases Study: an overview from the National Institutes of Health and the Advisory Committee.
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Calcitriol↗
Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects.
Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.
Carnitine↗
Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects.
Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Carnitine↗
Fecapentaene excretion: aspects of excretion in newborn infants, children, and adult normal subjects and in adults maintained on total parenteral nutrition.
People in developed nations such as the United States and Canada have an increased risk of colon cancer. Fecal mutagens have been detected in the feces of individuals at high risk for colon cancer. We describe a rapid, sensitive, reliable, reproducible high-pressure liquid chromatography (HPLC) method for detecting fecapentaenes, the most active and chief mutagen found in human stool. We found fecapentaene in all the stool samples of adults on typical high-fat, low-fiber Western diets. These fecapentaene concentrations remained largely constant when subjects consumed constant diets. Fecapentaene concentrations were reduced for total-parenteral-nutrition (TPN) patients with severe intestinal malabsorption. This finding with TPN patients may reflect changes in important variables of gut microflora in fecapentaene production. Studies with newborns and children showed that fecapentaenes appeared very early in life but are not present in stool at birth.
Adult↗
Effect of intravenous taurine supplementation on plasma, blood cell, and urine taurine concentrations in adults undergoing long-term parenteral nutrition.
Thirty-four adults undergoing long-term parenteral nutrition (TPN) were treated either with or without intravenous taurine for less than or equal to 24 mo. Statistical comparisons were carried out in eight patients randomly assigned to receive intravenous taurine, usually 10 mg.kg-1.d-1, and 10 patients not receiving taurine. Compared with normal adults, baseline plasma taurine and urine taurine-creatinine ratios were decreased in both groups and platelet taurine was reduced in the taurine-treated group. During taurine treatment the mean of the mean values for taurine became normal in plasma and platelets and remained normal in erythrocytes, granulocytes, and lymphocytes; urine taurine-creatinine ratios rose to approximately five times normal. During follow-up, patients not given taurine had plasma, erythrocyte, and granulocyte taurine and urine taurine-creatinine ratios below normal values and the concentrations of taurine-treated patients. Their platelet taurine was also subnormal. Thus, 10 mg taurine.kg-1.d-1 intravenously normalizes plasma and blood cell taurine concentrations in long-term TPN patients.
Adult↗
Visual function in patients undergoing long-term total parenteral nutrition.
To evaluate the effects of long-term total parenteral nutrition (TPN) on eye function, 27 adults and 12 children in the UCLA Home TPN Clinic underwent ophthalmoscopic examination and visual-function testing. Direct inspection of the fundus showed a marked granularity of the retinal pigmented epithelium in some patients. About one-half of the children and one-third of the adults tested had at least one and usually two abnormalities in their electroretinogram. Determination of blood nutrients thought to affect vision revealed that zinc and vitamin E were within normal range. Vitamin A concentrations were above normal in 10 of 19 adults and selenium concentrations were below normal in 10 of 10 children and 17 of 21 adults tested. Linoleic and linolenic acid concentrations were low; plasma, platelet, and urine taurine concentrations were significantly lower than normal. Despite these diffuse nutrient abnormalities, only zinc and vitamin E concentrations correlated significantly with any index of visual function.
Adolescent↗
Plasma and dialysate immunoglobulin G in continuous ambulatory peritoneal dialysis patients: a multicenter study.
Peritoneal dialysate immunoglobulin (Ig)G concentrations were measured in 120 continuous ambulatory peritoneal dialysis (CAPD) patients evaluated at four dialysis centers in different countries to assess the normal range for dialysate IgG and to investigate the relationships of this protein levels with peritoneal episodes, For 65 of these patients, plasma IgG levels were determined, and IgG clearances were calculated. The mean dialysate concentration of IgG was 6.9 +/- 4.2 mg/dl, and there was no difference between men and women or between patients who had or had not previously undergone hemodialysis. Dialysate IgG concentrations were significantly related to residual renal creatinine clearance and negatively correlated with dialysate volume, plasma albumin and total protein. There were no significant correlations between IgG levels in the dialysate and age, protein losses in the dialysate, time on CAPD or time from the last peritonitis episode. Plasma and dialysate IgG were unrelated to the incidence of peritonitis, statistical analysis being performed with different methods. These results suggest that IgG levels in the dialysate or plasma are not a major factor in the prevention of CAPD peritonitis.
Ascitic Fluid↗
Enalapril reduces albumin excretion in diabetic patients with low levels of microalbuminuria.
Although angiotensin-converting enzyme (ACE) inhibitors may lower urinary protein excretion, it is not known whether these agents can completely eliminate microalbuminuria. This study examined whether the ACE inhibitor, enalapril, can abolish low levels of microalbuminuria in diabetic patients. Six men with adult-onset, insulin-dependent diabetes mellitus, most of whom had low levels of microalbuminuria, were studied in a clinical research center, where they ate a controlled diet and performed regulated exercises daily. After 2 weeks of baseline measurements, the patients received 5-15 mg/day of enalapril for 4 weeks. They were then monitored for 2 more weeks without enalapril. Urinary albumin excretion (UAE) fell in each patient with enalapril treatment and was within the normal range at some time during enalapril treatment in 5 of 6 patients. After stopping enalapril, UAE rose. UAE was 53.6 +/- 20.7 (SEM), 31.5 +/- 8.9 and 39.4 +/- 8.0 mg/24 h during the baseline, enalapril and postenalapril periods, respectively (baseline vs. enalapril, p less than 0.02; postenalapril vs. enalapril, p less than 0.01). The magnitude of fall in UAE correlated with the baseline UAE (r = 0.90). During enalapril treatment, renal plasma flow and GFR did not change, although blood pressure fell slightly. These data suggest that enalapril can reduce or abolish UAE in diabetic patients with microalbuminuria. Whether long-term treatment with enalapril will continue to suppress microalbuminuria and prevent progressive diabetic nephropathy remains to be determined.
Albuminuria↗
Energy requirements in patients with renal failure.
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Energy Intake↗
Role of the splanchnic tissues in the pathogenesis of altered carbohydrate metabolism in patients with chronic renal failure.
To evaluate the contribution of the splanchnic area to the carbohydrate abnormalities associated with chronic uremia, the splanchnic exchange of glucose and gluconeogenic substrates was quantitated basally and after an iv glucose load in nine uremic patients with impaired glucose tolerance and seven control subjects. In the basal state, blood glucose and splanchnic glucose production were similar in the two groups. During glucose infusion (33 mumol/kg.min for 90 min), blood glucose reached significantly higher levels in the uremic patients than in controls (P less than 0.02). Plasma insulin increased slightly more in uremic patients than in controls (P less than 0.05 at 15 min). Both basal and postglucose glucagon levels were 2- to 3-fold higher in uremic patients than in normal subjects (P less than 0.05-0.02). In both groups, splanchnic glucose balance switched from net output in the basal state (-9.4 +/- 0.5 and -8.0 +/- 1.1 mumol/kg.min in normals and uremics, respectively) to net uptake with glucose infusion. However, this response was less marked in the uremic patients than in normal subjects (P less than 0.05-0.02 at 30 and 90 min). The cumulative net splanchnic glucose balance over the 90-min study period was 538 +/- 55 mumol/kg in normal subjects and 279 +/- 89 in uremic subjects (P less than 0.05). A net splanchnic lactate uptake was present in the basal state in normal (4.2 +/- 0.5 mumol/kg.min) and uremic subjects (3.4 +/- 0.5). During glucose infusion, in normal subjects splanchnic lactate exchange switched to a net output (-4.0 +/- 1.6 mumol/kg.min), whereas in the uremic group it remained as a net uptake (1.1 +/- 0.7) throughout the study period. Splanchnic gluconeogenic amino acid uptake was similar in the two groups in the basal state (1.8 +/- 0.1 mumol/kg.min and 2.2 +/- 0.2 in normal and uremic subjects, respectively). Glucose infusion caused a marked fall in amino acid uptake by liver in normal subjects, whereas no change was observed in the uremic group (0.9 +/- 0.3 and 1.9 +/- 0.2 mumol/kg.min, respectively). Splanchnic glycerol uptake was not different in the two groups in the basal state (0.75 +/- 0.2 and 1.1 +/- 0.2 mumol/kg.min) and decreased to a similar extent during glucose infusion. We conclude the following. 1) In uremic patients with glucose intolerance but normal fasting glycemia, the splanchnic metabolism of glucose and gluconeogenic substrates is normal in the postabsorptive state.(ABSTRACT TRUNCATED AT 400 WORDS)
Blood Glucose↗
Physiological effects of growth hormone and insulin-like growth factor I on the kidney.
Growth hormone increases renal plasma flow and glomerular filtration rate and reduces total renal vascular resistance. Evidence presented in this paper indicates that these effects of growth hormone are mediated by insulin-like growth factor I (IGF-I). Published literature indicates that growth hormone and IGF-I have a number of other physiological and morphological effects on the kidney. Further studies are indicated to evaluate under which conditions growth hormone and IGF-I are regulators of kidney function, and to identify the mechanisms of action. In addition, the role of both hormones, if any, in the development of progressive glomerular sclerosis and renal failure needs to be explored.
Gonadotropins↗
Amino acid metabolism in the kidney.
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Acidosis↗
Antimutagenic effects of taurine in a bacterial assay system.
Taurine (2-aminoethanesulfonic acid) was evaluated as an antimutagen in the Ames Salmonella tester strain assay. Taurine inhibited mutagenesis by doxorubicin (-74%), bleomycin (-55%), mitomycin C (-56%), and 2-aminofluorene (-52%), but not danthrone or benzo(a)pyrene, in strain TA102. In strain TA98, doxorubicin mutagenicity, but not that of 2-aminofluorene or benzo(a)pyrene, was inhibited by taurine. N-Methyl-N'-nitro-N-nitrosoguanidine (-73%), but not dexon, mutagenicity was inhibited by taurine in strain TA100. Taurine inhibited those mutagens against which it was effective in a dose-related fashion. Taurine was more effective in inhibiting doxorubicin mutagenicity in strain TA102 than its analogues hypotaurine, beta-alanine, and guanidinoethanesulfonic acid or alanine or glycine. The observed inhibition may indicate a role for taurine in modulating the activity of oxidant species.
Amino Acids↗
Effect of energy intake on nutritional status in maintenance hemodialysis patients.
Although maintenance hemodialysis (MHD) patients are often wasted, little is known about their dietary energy needs. We studied four men and two women in a clinical research center while they received diets providing 45, 35 and 25 kcal/kg desirable body weight/day; diets were fed, in random order, for 21 to 23 days each. Protein intake, 1.13 +/- 0.02 (SEM) g protein/kg/day, was similar with all three diets. Body weight rose with 45 and 35 kcal/kg/day (P less than 0.05) and fell with 25 kcal/kg/day (P less than 0.05). Nitrogen balance, adjusted for estimated unmeasured losses, was neutral with 45 and 35 kcal/kg/day and negative with 25 kcal/kg/day. Balance was neutral or positive in 6 of 6, 4 of 6, and 0 of 6 patients fed 45, 35, 25 kcal/kg/day, respectively. Nitrogen balance, many plasma amino acids and changes in body weight, mid-arm circumference, mid-arm muscle area and body fat each correlated with energy intake. Resting energy expenditure was normal. The energy intake estimated from regression equations to maintain neutral nitrogen balance was 38.5 kcal/kg desirable weight/day; for body fat and weight, it was 32 kcal/kg/day. These data suggest that MHD patients have normal energy expenditure and approximately normal requirements for maintenance of protein balance, body weight and body fat. An average energy intake of about 38 kcal/kg desirable weight/day may be necessary to maintain nitrogen balance in these patients.
Adult↗