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Biomedical subjects

J D Kopple

Publications and source records attributed to J D Kopple.

At least 91 records · Page 5Linked to original sources
PubMed1989

The delayed effect of growth hormone on renal function in humans.

Growth hormone is reported to increase renal plasma flow (RPF) and glomerular filtration rate (GFR) in some but not all studies. The discrepant results could be due to a delay in the effects of growth hormone on renal function. We therefore examined whether a growth hormone injection does increase RPF and GFR, whether this increase is delayed, and whether elevation in RPF and GFR is associated with increased plasma levels of insulin-like growth factor I (IGF-I). Seven normal adults received a single intramuscular injection of growth hormone, 0.15 mg/kg, and serial PAH and inulin clearances were then monitored for three consecutive days. Plasma growth hormone levels peaked an average of 2.25 hours after injection, at 128 +/- 12 SEM ng/ml, and then began to decrease; on the second day values were only slightly elevated and on the third day they were not different from baseline. Plasma IGF-I, analyzed by direct radioimmunoassay, did not change on the first day during 5.5 hours of measurements after injection. By the second day, plasma IGF-I was elevated to over twice baseline levels (P less than 0.05) and remained elevated on the third day (P less than 0.05). RPF and GFR did not change from baseline (546 +/- 19 and 100 +/- 3 ml/min/1.73 m2, respectively) during the 5.5 hours after injection on the first day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Clinical utility of kidney biopsies in the diagnosis and management of renal disease.

A prospective study was undertaken to assess the utility of the renal biopsy as a tool in the clinical practice of nephrology. Nephrologists performing this procedure were surveyed concerning prebiopsy diagnosis, plans for therapy and estimation of prognosis, before and after biopsy results were disclosed. On the basis of 108 specimens from both academic centers and community hospitals, clinical and pathological diagnoses differed in 63% and therapeutic approach was altered in 34% of the cases. These results were greatest for nephrotic syndrome and for renal failure of rapid onset. The change in treatment was frequently of major consequence: decisions for the use of corticosteroids, cytotoxic agents and/or plasma exchange were altered based upon biopsy diagnoses. There were no differences either in diagnostic acumen or therapeutic approach between academic and community nephrologists. We conclude that renal biopsies are an important and frequently used part of the nephrologists' approach to patient care.

Acute Kidney Injury↗
PubMed1989

Comparative acute effects of aspirin, diflunisal, ibuprofen and indomethacin on renal function in healthy man.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, suppress renal prostaglandins and markedly reduce renal perfusion and diuretic response in some renal disorders. Mild renal impairment may occur in healthy subjects. Pharmacodynamic characteristics of certain NSAIDs, such as the nonacetylated salicylates, suggest that they may have less deleterious renal effects. We compared the renal effects of standard therapeutic doses of indomethacin, ibuprofen, aspirin, and the nonacetylated salicylate, diflunisal, in 6 healthy supine volunteers. Only indomethacin significantly reduced creatinine clearance (by 13%) and renal plasma flow (by 23%; p less than 0.05). Indomethacin also tended to reduce furosemide-induced diuresis and natriuresis, and this effect was significantly greater than with diflunisal (p less than 0.05). Serum thromboxane, a reflection of platelet cyclo-oxygenase activity, was reduced by 99% with aspirin, ibuprofen and indomethacin, but by only 78% with diflunisal. Nonacetylated salicylates may be the preferred drugs, at least in short-term usage, when it is necessary to minimize the effects of NSAIDs on platelet or kidney function.

Adult↗
PubMed1989

Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats.

The mechanisms whereby growth hormone may increase renal plasma flow (RPF) and GFR are not known, but circumstantial evidence has implicated insulin-like growth factor I (IGF-I) as a mediator of this effect. This study examined whether an infusion of IGF-I will increase RPF and GFR, whether this effect occurs quickly, and if this effect is dependent on eicosanoids or peptide hormones known to affect renal function. Rats fasted for 3 d to reduce IGF-I and IGF-I plasma binding proteins were anesthetized; then the rats received an intravenous injection of 25 micrograms/kg IGF-I, and an infusion of 25 micrograms/kg IGF-I within 20 min. Controls received infusion of the vehicle. RPF (para-aminohippurate clearances), GFR (inulin clearances), renal vascular resistance (RVR), mean arterial blood pressure (MABP), plasma IGF-I, and glucose concentrations were measured repeatedly. At the end of the 20-min infusion, plasma IGF-I tended to be increased in the animals that received IGF-I (P = 0.069), but did not increase in the control rats. IGF-I induced a significant and sustained fall in RVR and rise in RPF and GFR without any change in MABP. A small, transient, but significant decrease in plasma glucose concentrations was observed during IGF-I but not during vehicle infusion. Indomethacin, but not somatostatin, blocked the renal response to IGF-I infusion. Thus, IGF-I infusion increases RPF and GFR and reduces RVR in fasted rats. This effect requires the presence of eicosanoids but does not seem to require other peptide hormones suppressed by somatostatin.

Animals↗
PubMed1989

Nutritional status of patients with different levels of chronic renal insufficiency. Modification of Diet in Renal Disease (MDRD) Study Group.

This study evaluated the nutritional status of 95 patients with chronic renal insufficiency who participated in the feasibility phase of the NIH funded Modification of Diet in Renal Disease (MDRD) Study. All patients were seen monthly by a physician and dietitian. After a baseline period, the patients were randomly assigned either to a mildly protein-restricted control diet or to one of three low protein, low phosphorus diets. Patients with clear evidence for protein-calorie malnutrition were excluded from the study. Patients were followed for an average of 12.4 months (range, 0 to 22 months). The glomerular filtration rate (GFR) at the commencement of the experimental diets ranged from 8 to 56 ml/min/1.73 m2. Assessment of the nutritional parameters indicated that none of the four diet treatment groups developed protein-calorie malnutrition. At the end of treatment with the experimental diets, most nutritional parameters were normal and few had worsened. Nonetheless, the following observations indicated that some patients had developed subtle evidence for protein-calorie malnutrition. There were positive correlations between the GFR and the serum transferrin and creatinine:height ratio. In men, arm muscle area and, at the onset of the experimental diets, the % standard body weight also correlated with the GFR. In women, GFR correlated with dietary energy intake. When patients were grouped according to their GFR level, those with the lowest GFR also tended to have lower energy intakes, serum transferrin levels and creatinine:height ratios. Patients with a GFR of 24 ml/min/1.73 m2 or lower tended to lose body mass during the study. In all groups of patients, the estimated actual energy intake was significantly lower than the prescribed intake. On the other hand, in the patients assigned to one of the three low protein, low phosphorus diets, nitrogen intake was above the prescribed level. The low energy intake of those patients with the lower GFR levels may contribute to their propensity to become malnourished.

Body Weight↗
PubMed1989

Effects of growth hormone and IGF-I on renal function.

There have now been many studies on the effects of growth hormone (GH) on renal function. Chronically elevated GH levels, such as occur in acromegaly, are associated with an increase in renal plasma flow (RPF), glomerular filtration rate (GFR) and kidney size. When GH falls in these individuals (such as, after hypophysectomy in acromegalic patients), RPF, GFR and renal size decrease. A rapid increase in plasma GH in normal or growth hormone deficient adults, such as occurs after GH injection, causes an increase in RPF and GFR. However, these effects on renal function are delayed, occurring between 5.5 and 23 hours after the GH injection and in association with an elevation in the plasma concentrations of insulin-like growth factor I (IGF-I). These observations suggest that IGF-I may mediate the GH stimulated increase in RPF and GFR. We evaluated this question in rats starved for three days. A 20 minute infusion of IGF-I causes an increase in RPF and GFR in these animals. This effect could be blocked by indomethacin but not by somatostatin. These findings suggest that: 1) GH injection does increase RPF and GFR; 2) this effect on GH, which is delayed for several hours seems to be mediated by IGF-I; and 3) a 20-minute IGF-I infusion itself increases RPF and GFR in starved rats. The effect of IGF-I on renal function seems to require the presence of eicosanoids. Further studies will be necessary to examine whether IGF-I is a physiological regulator of renal function.

Adult↗
PubMed1988

Nutrition and protease activity.

Clearly, both the metabolism of many proteins and the size of protein pools are affected or regulated by the nutrient intake. At least some of these effects are probably due to changes in the activities of proteolytic enzymes. Indeed, starvation, protein-calorie malnutrition and protein malnutrition probably increase activities of a number of proteases in plasma, liver, skeletal muscle and heart. Pancreatic secretion of proteases and other enzymes is impaired. However, the changes in proteolytic activities often follow rather than precede alterations in the net rate of protein degradation. Thus, the contribution of the proteolytic enzymes to changes in protein degradation in these conditions is not clear. The effects of nutrition on proteases also are difficult to evaluate because the protease activities have been measured in vitro. These activities may not necessarily reflect the protease activity in vivo, where lysosomes, membrane barriers and transport systems are intact, and inhibitors and facilitators of proteinases may act differently from the in vitro state. Also, proteinase activities often are expressed per weight of tissue or per mg of protein. Tissue weight and protein content often fall during protein and/or calorie malnutrition. Hence, the previous reports of increased protease activities in malnutrition may be incorrect. The observed increase is only relative to the fall in weight and protein content of the tissue. When expressed in terms of total tissue or organ mass, there was no rise in protease activities in many of these studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Hyperglobulinemia may spuriously elevate measured serum inorganic phosphate levels.

Pseudohyperphosphatemia was noted in four patients with hyperglobulinemia when inorganic phosphate levels were measured on the Vickers M-300 discrete automated analyzer (Vickers, Raritan, NJ) used by our clinical laboratory. When the same samples were reanalyzed after protein removal by sulfosalicylic acid precipitation, ultrafiltration, or more extensive dilution, the measured serum inorganic phosphate levels were invariably normal. The addition of human globulin (but not albumin), to pooled normal sera, caused an increase in serum inorganic phosphate levels as measured by the discrete analyzer. The increase correlated with the amount of globulin added (r = 0.72, P less than 0.05), but measured levels did not reach those observed in the hyperphosphatemic, hyperglobulinemic patients. Identification of 13 additional hyperglobulinemia patients revealed that hyperglobulinemia was not invariably associated with hyperphosphatemia. These data suggest that (1) with discrete automated analyzer use, hyperglobulinemia but not hyperalbuminemia may falsely elevate serum inorganic phosphate levels; (2) increased measured serum inorganic phosphate levels appear to be determined by both the concentration and the physicochemical characteristics of the globulin; (3) physicians should avoid prescribing phosphate binders to hyperglobulinemia patients with "hyperphosphatemia" unless they have ascertained that the serum inorganic phosphate level has been measured in a specimen that is free of protein; and (4) the occurrence of "pseudohyperphosphatemia" should suggest the need for an evaluation to rule out the presence of a monoclonal gammopathy.

Blood Chemical Analysis↗
PubMed1988

Glucagon and prostaglandins are mediators of amino acid-induced rise in renal hemodynamics.

An oral protein load or infusion of amino acids induces a rise in renal hemodynamics in normal subjects, but the mechanisms mediating this phenomenon are unknown. We investigated whether glucagon may mediate the increase in RPF and GFR induced by an arginine infusion and whether prostaglandins are required for this effect. In four different studies, normal subjects underwent 13 inulin and PAH clearances of 30 minutes each. During the fourth and tenth clearance periods arginine HCl, 250 mg/kg, was infused over 30 minutes. At the beginning of the fifth clearance period several subjects ingested indomethacin, 150 mg, (N = 8) or ibuprofen, 800 mg (N = 6). Control subjects (N = 4) did not receive cyclooxygenase inhibitors. Six subjects underwent a similar protocol except that they were infused with glucagon, 6 ng/kg/min, instead of arginine, for 30 minutes during the fourth and tenth periods. They also ingested indomethacin, 150 mg, in the fifth period. In all four studies, a transient and significant rise in RPF and GRF and fall in RVR occurred during the first arginine or glucagon infusion. These changes in renal hemodynamics were blocked when the arginine or glucagon infusion was repeated after administration of indomethacin or ibuprofen. Urinary excretion of 6-keto-PGF1 alpha did not rise with either arginine infusion in the control subjects or in the individuals who received indomethacin. As predicted, urinary 6-keto-PGF1 alpha fell significantly after ingestion of indomethacin before the second infusion of arginine. Plasma norepinephrine and epinephrine concentrations were unaffected by the arginine infusions or by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Plasma and urine taurine levels in vegans.

Plasma taurine levels and urinary taurine excretion were measured in 12 strict vegetarian (vegan) males who had maintained a vegan diet for 53 +/- 26 mo (SD) and in 14 male nonvegetarian control subjects. Plasma taurine levels differed (45 +/- 7 vs 58 +/- 16 mumol/L, respectively). Urinary taurine excretion was lower (266 +/- 279 vs 903 +/- 580 mumol/d), urinary N pi-methylhistidine was barely detectable, and urinary N tau-methylhistidine was significantly reduced (296 +/- 87 vs 427 +/- 19 mumol/d) in the vegans. Analysis of 3-d dietary diaries kept by the vegans indicated marginal to adequate intake of protein, carbohydrate, vitamin B-6, methionine, and cystine; inadequate intake of zinc; and negligible intake of taurine. Prolonged absence of dietary taurine intake causes decreased plasma taurine and severely restricted urinary taurine output.

Adult↗
PubMed1988

Captopril augments the renal response to an amino acid infusion in diabetic adults.

This study examined whether patients with insulin-dependent diabetes mellitus and normal renal function have an altered response to an amino acid infusion when they are pretreated with a converting-enzyme inhibitor. Three groups of adults received amino acid infusions for 20 min on two occasions separated by a 240-min interval. Groups 1 (6 normals) and 2 (6 diabetics) ingested captopril (12.5 mg) 120 min before starting the second infusion. Group 3 (4 diabetics) did not receive captopril. Diabetics had normal base-line renal plasma flow, as indicated by para-aminohippuric acid clearance (CPAH), and glomerular filtration rate (GFR). In group 1, the maximum increase in CPAH was significant and similar with both infusions, 23 +/- 5 vs. 15 +/- 3% (SE); maximal changes in GFR were also significant and similar, 20 +/- 5 vs. 20 +/- 6%. In Group 2, the maximal increase in CPAH and GFR with the first infusion was 28 +/- 7 and 23 +/- 6%, respectively. After captopril, the increases in CPAH and GFR were significantly greater than with the first infusion (64 +/- 8%, P less than 0.002, and 67 +/- 9%, P less than 0.002, respectively). In Group 3 diabetics, there was no difference in either CPAH or GFR with the first vs. the second infusion. Thus captopril enhances the renal hemodynamic response to an amino acid load in diabetic patients but not in normal adults.

Adult↗
PubMed1988

Effects of keto acid supplements on renal function and histology in azotemic rats fed high-protein diets.

The mechanism by which keto-acid-supplemented diets may retard the progression of renal failure is not known. We examined whether the protective effect of keto acids may be independent of a low nitrogen intake. Azotemic subtotally nephrectomized Sprague-Dawley rats were pair-fed a 30% casein diet supplemented with a 10% keto acid mixture (n = 10) or 10% cornstarch (n = 10) for 18 weeks. No differences were observed between the two groups of rats with regard to survival, weight gain, plasma urea, blood pressure, albuminuria, or, at the termination of the study, PAH and inulin clearances. Creatinine clearances, measured weekly during the study, were transiently higher in the keto acid group. There was no difference in the incidence or severity of segmental glomerulosclerosis or tubular atrophy in the two groups. These results indicate that the keto acid mixture used did not exert a protective effect against glomerular sclerosis and progressive albuminuria in azotemic rats fed high-protein diets.

Albuminuria↗
PubMed1988

Increase in renal plasma flow and glomerular filtration rate during growth hormone treatment may be mediated by insulin-like growth factor I.

The temporal relationships between the changes in inulin and p-aminohippurate clearances and plasma growth hormone (GH) and insulin-like growth factor I (IGF I levels were examined in a man with hypothalamic GH deficiency before and during the first 6 days of treatment with daily GH injections. The patient ate a diet with a constant protein and salt content from 1 week before the study until it was completed. During the 4-hour period immediately after the first GH injection, plasma GH rose markedly, but plasma IGF I was not detectable, and effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) did not change from baseline. On the next day, before the second GH injection was given, plasma GH was only slightly elevated, plasma IGF I had increased, and ERPF and GFR had risen by +35.5 +/- 2.1% (SEM) and +22.7 +/- 2.8%, respectively. On the 4th and 7th days, immediately before the GH injections, there was no further rise in ERPF and GFR, both of which remained well above baseline values. At these times, plasma GH levels were at baseline, but plasma IGF I continued to rise progressively. These data are consistent with the thesis that the low ERPF and GFR in GH deficiency is due to the lack of synthesis of IGF I rather than the deficiency in GH per se. The data are also consistent with a stimulatory effect of IGF I on ERPF and GFR.

Adult↗
PubMed1987

Role of growth hormone in the amino acid-induced acute rise in renal function in man.

To examine whether plasma growth hormone is necessary for the amino acid-induced rise in effective renal plasma flow (ERPF, PAH clearance) and GFR (inulin clearance), arginine HCl, 500 mg/kg, was infused for 30 minutes into eight normal and six growth hormone-deficient individuals. During infusion, ERPF increased in the normal and growth hormone-deficient subjects by 28.9 +/- 11.4 SD-% (P less than 0.01) and 46.5 +/- 14.4% (P less than 0.001). GFR rose by 23.7 +/- 5.9% (P less than 0.05) and 42.7 +/- 29.1% (P less than 0.001) in the two groups. Plasma growth hormone rose only in the normal subjects, while glucagon increased in both groups. Infusion of arginine HCl, 200 mg/kg, into normals increased ERPF and GFR without increasing plasma osmolality. Lower arginine doses essentially did not affect ERPF, GFR, growth hormone, or glucagon. Infusion of D-glucose into normals raised plasma osmolality as high as with arginine HCl, 500 mg/kg, but increased ERPF only slightly and not GFR; D-glucose infusion caused a delayed rise in growth hormone that was unassociated with an increase in ERPF or GFR. An infusion of ammonium chloride with sodium chloride, which provided an amount of chloride similar to the 500 mg/kg arginine HCl dose, did not change ERPF and GFR; this suggests that the chloride load did not cause the altered renal hemodynamics stimulated by arginine HCl. These findings indicate that neither normal plasma growth hormone levels nor a rise in growth hormone mediates the arginine-induced acute increase in ERPF or GFR. This effect is also not due to the osmolar load but could be caused by the rise in plasma glucagon.

Adult↗
PubMed1987

Altered plasma free and protein-bound sulfur amino acid levels in patients undergoing maintenance hemodialysis.

The plasma sulfur amino acid status of maintenance hemodialysis (MHD) patients has not previously been comprehensively investigated. We measured plasma sulfur amino acid levels in 24 MHD patients (12 fasted, 12 nonfasted) both before and after a routine 4-h hemodialysis and in 13 normal individuals (seven fasted, six nonfasted). Plasma free cystine, homocystine, cysteine-homocysteine-mixed disulfide (MDS), methionine, and taurine and protein-bound cysteine and homocysteine were measured. In nonfasted patients, plasma homocystine and MDS were not measured. Fasted patients predialysis had elevated plasma free cystine, homocystine, MDS, methionine, and taurine; all of these, except taurine, fell during dialysis. In nonfasted patients, plasma free cystine was elevated. Protein-bound cysteine and homocysteine were elevated predialysis and postdialysis in all patients; protein-bound cysteine fell during dialysis but remained above normal. In MHD patients predialysis, plasma free cystine levels correlated with plasma MDS, protein-bound cysteine, and age. These findings indicate pervasive alterations in plasma sulfur amino acid levels in MHD patients.

Adult↗
PubMed1987

Newer concepts of the indispensable amino acids.

In healthy adult humans, eight amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) were shown classically by nitrogen balance studies to be indispensable. Subsequent studies classifying histidine as indispensable are reviewed in this article. We also review the evidence that in certain nutritional or disease states or in certain stages of development otherwise dispensable amino acids may become indispensable. Arginine, citrulline, ornithine, cysteine, and tyrosine thus may be considered as acquired indispensable amino acids. Evidence for the indispensability of taurine is also considered. We propose a classification of the indispensability of amino acids based on clinical and therapeutic considerations.

Amino Acids, Essential↗
PubMed1987

Effect of dietary taurine on plasma and blood cell taurine concentrations in cats.

Taurine levels were measured in adult cats consuming casein-based diets supplemented with 0.2, 0.05, 0.02, 0.01 or 0% (wt/wt) taurine or with 0% taurine plus 5.0% L-cystine. Taurine concentrations in plasma, platelets, granulocytes and erythrocytes declined significantly with decreased dietary taurine. In the cats that did not receive the 5.0% cystine supplement, the relationship between dietary taurine intake and plasma and blood cell taurine level was nonlinear. The greatest increment in taurine concentrations occurred between the 0.02 and 0.05% taurine intakes. These findings suggest that the dietary taurine requirement for adult cats may be between 0.02 and 0.05%. Supplementation of the 0% taurine diet with 5.0% L-cystine raised taurine levels above those of the taurine-deficient diets in plasma and all blood cell types. The result of this study therefore suggest a close relationship between dietary taurine intake and blood cell taurine levels in cats. Five percent L-cystine stimulates taurine synthesis in these animals.

Animals↗