Effects of short-term recombinant human growth hormone therapy on plasma leptin concentrations in dialysis patients.

BACKGROUND: Hyperleptinaemia is a well-known biochemical feature found in uraemic patients. However, little is known about the hormonal regulation of leptin in chronic renal disease. Recent studies have shown that circulating leptin levels are modified by treatment with recombinant human growth hormone (rhGH), by recombinant insulin-like growth factor I (rhIGF I), or by a combination of rhIGF I plus rhGH in patients with chronic renal failure. We performed a prospective study to assess plasma leptin concentrations in a group of dialysis patients both before and during short-term rhGH therapy. METHODS: We studied eight dialysis patients (four haemodialysis (HD) and four on continuous ambulatory peritoneal dialysis (CAPD); three female, five male; mean age 63.9 +/- 3.1 years). All patients were instructed to maintain a stable diet (35 kcal/kg/day and 1 g protein/kg/day ideal body weight) and were treated with rhGH (0.2 IU/kg/day s.c.) for 4 weeks. Blood samples were taken at 0, 2, 4, and 8 weeks for determination of leptin, GH, and IGF I. Serum insulin concentrations were assessed at 0 and 4 weeks. RESULTS: Mean plasma leptin concentrations were elevated (36.2 +/- 12.8 ng/ml) at study outset and increased progressively throughout the 4 weeks of rhGH therapy (43.7 +/- 13.5 ng/ml (2 weeks, NS) and 70.6 +/- 18.4 ng/ml (4 weeks, P<0.0001)). These values returned to baseline levels (38.0 +/- 12.0 ng/ml, NS) at 1 month after rhGH withdrawal. rhGH therapy was accompanied by the development of direct correlations between leptin and IGF I concentrations at 2 weeks (r=0.86, P<0.01), and with correlations between leptin and IGF I (r=0.84, P<0.01) and between leptin and insulin (r=0.88, P<0.01) after 4 weeks of rhGH administration. CONCLUSION: These results confirm the presence of high circulating plasma leptin in dialysis patients and show that these levels are further increased by exogenous rhGH administration. The increase in plasma leptin after rhGH therapy may be related to the rhGH-induced changes in insulin in these patients.     

Differential effects of growth hormone therapy in malnourished hemodialysis patients

BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is associated with increased morbidity and mortality. Several factors such as metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth hormone (rhGH) has been proposed as treatment of malnutrition because of its anabolic effects. METHODS: In the present placebo-controlled, double blind study, the effects of three months of rhGH therapy on nutritional and anthropometric parameters, on bone metabolism and bone mineral density (BMD), as well as on polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a week during the first four weeks and 0.25 IU/kg thereafter three times a week after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I) concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4 ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin, cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase, predialytic creatinine, and blood urea nitrogen showed no significant changes during the three months in both groups. Total body fat (%TBF) was slightly reduced after three months (P = NS) in the patients receiving GH, whereas lean body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal peptide (PICP), a marker of bone formation, increased significantly after three months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH-treated patients, whereas parameters of bone resorption like telopeptide ICTP showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS). BMD at the lumbar spine decreased significantly after three months in the treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at the femoral neck remained stable in both groups. Phagocytic activity of PMNLs increased significantly after three months of therapy with rhGH, whereas other parameters of PMNL function were not affected by GH. QoL was slightly improved in the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS: Three months of treatment with rhGH in malnourished patients on chronic hemodialysis causes a significant increase in IGF-I levels without significant changes in nutritional and anthropometric parameters. In contrast, bone turnover was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic activity of PMNLs was increased.     

Growth hormone treatment in hemodialysis patients--a randomized, double-blind, placebo-controlled study

OBJECTIVE: Renal failure and hemodialysis (HD) affect the anabolic growth hormone (GH)-insulin-like growth factor (IGF) axis. A positive correlation between serum IGF-I and normalized protein catabolic rate (PCRn) in HD patients has been reported, and the aim of this study was to assess the metabolic impact of recombinant human (rh)GH in these patients. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled study, rhGH was given to 35 HD patients for 8 weeks: 0.025 IU/kg/day for 1 week, increasing to 0.05 IU/kg/day. Patients with diabetes, malignancy or clinical signs of infection and those receiving steroid treatment were excluded. RESULTS: All patients completed the study. Side-effects were rare and equally distributed between the two groups. Post-treatment, serum IGF-I and IGF-I standard deviation score (IGF-I SD) increased in the rhGH group compared to the placebo group: 283+/-33 vs 151+/-16 mg/l (p = 0.001) and 1.8+/-0.6 vs -0.2+/-0.6 (p = 0.002), respectively. IGF binding protein-3 was higher in the rhGH group compared to the placebo group: 5859+/-285 vs 4369+/-321 mg/l (p = 0.002). PCRn was significantly higher in the rhGH group compared to the placebo group: 1.09+/-0.06 vs 0.90+/-0.06 g/kg/day (p = 0.029). No differences were found in body weight, serum albumin or leptin between the two groups. There was no change in C-reactive protein (CRP) in the rhGH group compared to the placebo group: 17.4+/-9.0 vs 12.3+/-4.6 mg/l (p = NS). When the patients were subgrouped according to the CRP level (< or > 10 mg/1), the effect on PCRn persisted only in rhGH-treated subjects with a normal CRP level: 1.10+/-0.08 vs 0.81+/-0.09 g/kg/day (p = 0.025). CONCLUSION: Treatment of HD patients with rhGH at a moderate dose causes augmentation of PCRn which is considered to indicate a higher dietary protein intake. The anabolic effect of rhGH seems to be abolished by subclinical inflammation.     

Serum erythropoietin levels and hematocrit in end-stage renal disease: influence of the mode of dialysis

Serum erythropoietin (Ep) levels were measured by radioimmunoassay in 70 patients with end-stage renal disease (ESRD) to evaluate the influence of the mode of dialysis on the relationship between serum Ep levels and the severity of anemia. Thirty-five patients were on hemodialysis (HD), seven were on intermittent peritoneal dialysis (IPD), and 28 were on continuous ambulatory peritoneal dialysis (CAPD). Compared to HD, CAPD patients had higher serum Ep (CAPD), 46.1 +/- 13.4 v HD, 16.9 +/- 2.2 mU/mL) and hematocrit (CAPD, 33.9 +/- 2.5 v HD, 24.8 +/- 1.4%; P less than 0.05). The Ep and Hct values for IPD patients were intermediate between the other two groups. Serum Ep levels were higher in CAPD patients in the first 4 weeks of initiation of CAPD (144 +/- 35 mU/mL, n = 6) than later (39 +/- 6.4 mU/mL, n = 24). A significant fluctuation in serum Ep and Hct values was noted in patients on all three modes of dialysis, when multiple samples were obtained at different time intervals. There was a weak correlation between serum Ep and Hct in the three groups of dialysis patients; r = 0.36, P less than 0.005. The data suggest that CAPD provides a better biochemical milieu for Ep production and responsiveness than HD treatment of ESRD.     

Recombinant human insulin-like growth factor-1 induces an anabolic response in malnourished CAPD patients

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is an anabolic hormone that mediates most of the growth effects of growth hormone. This study tested the hypothesis that recombinant human IGF-1 (rhIGF-1) will induce an anabolic response in malnourished patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Six CAPD patients with protein-energy malnutrition underwent nitrogen balance studies in a clinical research center for 35 days each. Throughout the study, patients were maintained on their same CAPD regimen prior to hospitalization, and were fed a constant protein and energy intake that was similar to their diet prior to hospitalization. The first 15 hospital days were a baseline period; during the subsequent 20-day period, patients were given subcutaneous injections of rhIGF-1 (100 microg/kg/12 h), except for one patient who received 50 microg/kg/12 h for the first five days, followed by 100 microg/kg/12 h for the following 15 days. RESULTS: During the treatment with rhIGF-1, serum IGF-1 increased by about 100% (P = 0.03), and nitrogen balance became strongly positive (+2.0 g/day, P = 0.015 vs. baseline). This anabolic effect was observed within hours after commencing the rhIGF-1 treatment and was largely caused by a 20% decrease in peritoneal dialysate effluent nitrogen. There was a proportionate reduction in urine nitrogen and serum urea nitrogen. This decrease in nitrogen output was sustained during the entire 20 day of treatment with rhIGF-1. Serum phosphorus decreased significantly during the first several days of rhIGF-1 treatment, whereas serum calcium increased significantly during the rhIGF-1 treatment. Serum potassium and albumin did not change during the rhIGF-1 injections. There was no change in body weight and body composition, as assessed by anthropometry during the baseline or treatment phases of the study. Some patients exhibited minor possible adverse events that included a reduction in blood pressure and transient tachycardia. CONCLUSION: Injections of rhIGF-1 induce a strong and sustained anabolic effect, as indicated by a positive nitrogen balance in CAPD patients with protein-energy malnutrition. rhIGF-1 administration may be an effective method for treating malnutrition in maintenance dialysis patients.     

联合应用重组人生长激素和胰岛素样生长因子-1对烫伤大鼠创面愈合及蛋白质代谢影响的实验研究

目的　了解联合应用重组人生长激素(rhGH)和胰岛素样生长因子-1(IGF-1)对烫伤大鼠创面愈合及蛋白质代谢的影响。方法　Wistar大鼠40只,深Ⅱ度烫伤,随机分成四组,分别接受rhGH(每天0.1 U/kg 称A组)、rhGH加IGF-1(每天rhGH 0.1U/kg 加IGF-1 2.0 m g/kg称C组)、IGF-1(每天2.0 m g/kg 称B组)和林格氏液(每天2 m l/kg 称D组)治疗2 周后,分析比较各组大鼠一般状况、创面愈合时间和蛋白质代谢情况。结果　治疗2 周后C、A 组体重开始增加,4 周后C组体重是A组的1.65 倍,而D组在4～5 周后才开始增加;C组创面愈合天数为(17.1±4.4)天,A组为(20.5±4.8)天,D组为(29.7±6.3)天,C组创面愈合时间明显短于D组,而B组则差异不明显;C组蛋白质升高比A 组和B组明显,有统计学意义(P< 0.01)。结论　联合应用rhGH和IGF-1 比单纯应用rhGH 或IGF-1 对缩短创面愈合时间、促进蛋白质合成均有明显的效果     

Lower erythropoietin and iron supplementation are required in hemodialysis patients with hepatitis C virus infection

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common infectious agent in chronic hemodialysis (HD) patients. In this prospective case-control study, we aimed to investigate the influence of chronic HCV infection on erythropoietin (EPO) and iron requirement in HD patients. PATIENTS AND METHODS: 49 HD patients (24 male, 25 female, mean age 47 +/- 15 years) were included. The mean time spent on dialysis was 39 +/- 38 months, and follow-up time was 1 year for this study. Biochemical analyses and complete blood counts together with iron status of the patients (transferrin saturation and serum ferritin levels) were measured monthly. Highly sensitive C-reactive protein (hs-CRP) levels were measured within 3-month intervals. Endogenous EPO levels were measured by enzyme-linked immunoassay 2 weeks after cessation of EPO treatment. RESULTS: Eleven of the HD patients (22%) were anti-HCV(+). There was no difference in age, sex, time on dialysis, distribution of primary renal diseases, predialytic BUN, Kt/V, albumin and i-PTH levels between HCV(+) and (-) patients. Anti-HCV-positive patients required significantly lower weekly doses of EPO (87 +/- 25 IU/kg vs 129 +/- 11 IU/kg, p = 0.042) and iron (16.8 +/- 12.2 mg vs 32.6 +/- 16.1 mg, p = 0.02) replacement than anti-HCV(-) group; hs-CRP levels were similar between study groups. Serum endogenous EPO levels were significantly higher in HCV(+) patients than HCV(-) HD patients (9.43 +/- 6.47 mU/ml vs 3.59 +/- 2.08 mU/ml, p = 0.008). CONCLUSION: Anti-HCV(+) HD patients had higher serum EPO levels and required less EPO and iron replacement as compared to anti-HCV(-) patients. Because of the changes in iron metabolism, iron treatment should be carefully administered in HD patients with HCV.     

Fibronectin in patients with chronic renal failure undergoing dialysis

Fibronectin (FN) levels were determined in 64 cases with chronic renal failure (CRF), some of whom were undergoing dialysis. FN levels were 14.9 +/- 7.6 mg/dl in CRF (n = 20), 13.4 +/- 4.3 mg/dl in patients on continuous ambulatory peritoneal dialysis (CAPD) (n = 20) and 16.7 +/- 7.2 mg/dl in patients on hemodialysis (HD) (n = 24). All the levels were significantly lower than in normal subjects (23.1 +/- 4.6 mg/dl). Serum FN was compared with some nutritional indices. Positive correlations were found between serum FN and nitrogen balance (BN), serum prealbumin (PreA) and transferrin (Tf) in all the patients. With serum albumin (Alb), however, this correlation was only found in patients undergoing dialysis. Negative correlations were found between serum FN and the ratio of serum urea to serum creatinine (Surea/Scr) in CAPD and HD patients. In 10 CAPD patients, the low serum FN levels went up after increased protein intake. This indicates that it was the result of malnutrition due to decreased protein intake. Serum FN level reflects a negative BN earlier and better than serum PreA, Tf and Alb. It is a sensitive, reliable and simple index for judging the nutritional protein status and the effect of nutritional treatment in patients with CRF undergoing dialysis.     

Ultrasonic gallbladder function in chronic kidney disease: does predialysis, hemodialysis, or CAPD affect it?

BACKGROUND: There are contradictory reports about the prevalence of cholelithiasis in chronic kidney disease (CKD). The pathogenesis of gallstones is associated with the lithogenic changes of bile composition, increased tendency to nucleation, and decreased gallbladder motility. The studies related to these factors can predict the development of cholelithiasis. The aim of this study was to evaluate the ultrasonic gallbladder function in CKD and to compare it in predialysis (PreD), hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Age, gender, and body mass index matched 49 CKD patients (14 PreD, 19 HD, 16 CAPD), and 17 control individuals were included in the study. Diabetic and cirrhotic patients were not included. Ultrasonic gallbladder volume was evaluated in pre- and postprandial period, and ejection fraction was calculated. We also measured several biochemical parameters (cholesterol, triglyceride, blood urea nitrogen (BUN), creatinine, calcium, Phosphorus, parathormone, albumin, total protein) in blood. RESULTS: Preprandial gallbladder volume in PreD, HD, CAPD, and control groups were 26.7 +/-13.6, 20.8+/-10.4, 23.2+/-14.7, and 26.4+/-14.8 mL, respectively (p > 0.05). Ejection fractions were 54.1 +/- 22.9%, 54.9 +/- 23.9%, 48.6 +/- 15.9%, and 51.8 +/- 19.2% in PreD, HD, CAPD, and control groups, respectively (p > 0.05). Serum triglyceride was higher in PreD patients than control group (207 +/- 144 vs. 110 +/-48 mg/dL) (p<0.05). Serum BUN, Cre, P, and PTH levels were higher in CKD groups than the control group, whereas serum total protein and albumin levels were higher in the control group (p<0.05). Serum Ca was lower in PreD and HD patients than in the controls (p<0.05). CONCLUSIONS: In conclusion, CKD and renal replacement therapy (HD and CAPD) do not affect gallbladder functions, but more studies are needed to evaluate prevalence of gallstones, gallbladder motility, and the composition of bile in CKD.     

Concentrations of thyroxine-binding globulin in sera and peritoneal dialysates in patients on chronic peritoneal ambulatory dialysis

Losses in thyroxine-binding globulin (TBG) in peritoneal dialysate and thyroid function were evaluated in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), in comparison to patients on hemodialysis (HD) without TBG loss in the dialysate. The TBG concentration in the peritoneal dialysate was 0.26 +/- 0.09 microgram/ml (mean +/- SD, n = 24), with a daily loss of 2.47 +/- 0.94 mg. The serum TBG level in CAPD patients was 21.0 +/- 4.71 micrograms/ml (n = 24), which was not significantly different from that in HD patients (20.0 +/- 5.72 micrograms/ml, n = 24) or in healthy Japanese subjects. The serum TBG level correlated positively with the TBG loss and TBG level in the peritoneal dialysate (p less than 0.001). The serum T4 level in CAPD patients (4.93 +/- 1.38 microgram/dl, n = 24) was significantly greater than in HD patients (4.08 +/- 1.30 microgram/dl, n = 24, p less than 0.05).     

Impact of dialysis therapy on insulin resistance in end-stage renal disease: comparison of haemodialysis and continuous ambulatory peritoneal dialysis.

BACKGROUND: Insulin resistance contributes to the pathogenesis of atherosclerotic cardiovascular disease and, thus, has an important impact on the mortality of uraemic patients. Haemodialysis (HD) is known to improve insulin resistance observed in uraemia. However, it is not known whether continuous ambulatory peritoneal dialysis (CAPD) alleviates insulin resistance in adult uraemic patients. The objective of this study was to compare the effect of two different dialysis modalities, HD and CAPD, on insulin resistance in adult uraemic patients and to identify the possible predictive factors for changes in insulin resistance. METHODS: Insulin resistance was examined in 19 non-diabetic patients with end-stage renal disease (ESRD) before and after dialysis therapy (HD, n=10; CAPD, n=9), as well as in 10 healthy controls using the hyperinsulinaemic euglycaemic glucose clamp technique. The glucose disposal rate (GDR mg/kg/min) was used as an index of insulin sensitivity during the clamp technique. We also determined which of various biochemical parameters might be associated with change in insulin resistance by carrying out multiple logistic regression analysis. RESULTS: GDR was significantly lower (6.44+/-1.76) in ESRD subjects than in normal subjects (9.90+/-2.01). HD and CAPD therapies significantly normalized GDR from 6.53+/-1.84 to 9.74+/-2.88 and from 6.35+/-1.65 to 8.18+/-1.76 respectively. Multiple logistic regression analysis showed that changes in BUN, haematocrit and plasma bicarbonate were significant predictive factors for the change in insulin resistance. CONCLUSION: CAPD therapy, in spite of its possible adverse effects in patients with atherosclerotic disease, has been shown to improve insulin resistance in adult uraemic patients, similarly to HD therapy.     

The red blood cell deformability in patients suffering from end stage renal failure on hemodialysis or continuous ambulatory peritoneal dialysis

Anemia is the main problem for patients suffering from end stage renal disease (ESRD). This study aimed to determine whether the index of rigidity (IR), that shows red blood cells (RBCs) deformability and the possible IR disturbances can provide an explanation about the cause of anemia, in patients undergoing maintenance hemodialysis (HD) or on peritoneal dialysis. The IR was determined in 39 hemodialyzed patients, who were already in dialysis for a period of time ranging from 16 to 120 months (mean+/-SD=41.8 +/-24.1) (Group A). Furthermore, the IR was measured in 32 patients on continuous ambulatory peritoneal dialysis (CAPD), who were in CAPD for a period of time ranging from 6 to 60 months (mean+/-SD = 10.7+/-9.9) (Group B). Finally, the IR was determined in 17 normal individuals (group C). The RBCs IR was measured twice in group A (before and after the end of a hemodialysis session) and once in groups B and C. The IR was determined by hemorrheometry (method of filtration), using special equipment. In group A the IR was increased in comparison to the control group (C) (17.9+/-6.2 vs. 10.2+/-1.8, p<0.0001). This increase was even higher in the measurement at the end of the hemodialysis session (paired t-test, p < 0.0001). The RBCs IR in CAPD patients was significantly lower than that of HD patients (12+/-3.8 vs. 17.9+/-6.2, p<0.0001) and was not statistically different from the control group (12+/-3.8 vs. 10.2+/-1.8, p=0.068). It is concluded from the study that: 1) in HD patients occur disturbances in the deformability of the RBCs, that are worsened by the hemodialysis session; 2) the index of rigidity of RBCs is significantly higher in the HD patients than in CAPD patients; 3) in patients on CAPD, the disturbance of deformability of the RBCs was less in comparison to the control group, which however does not reach the statistically significant levels.     

Growth hormone induces anabolism in malnourished maintenance haemodialysis patients.

BACKGROUND: Growth hormone (GH) promotes anabolism in patients undergoing maintenance haemodialysis (MHD). However, no studies have examined the effects of GH on protein anabolism in MHD patients using full nitrogen-balance techniques. This study tested the hypothesis that recombinant human GH (rhGH) will induce an anabolic response, as assessed by long-term classic nitrogen-balance techniques, in malnourished MHD patients. METHODS: Six adult MHD patients with protein-energy malnutrition underwent nitrogen-balance studies in a general clinical research centre for 28-35 days each. Patients were maintained on a constant dialysis regimen and protein and energy intakes that were similar to their dialysis regimen and diet prior to hospitalization. The first 14-21 hospital days constituted a baseline phase; during the subsequent 8-21 days, patients were given daily subcutaneous injections of rhGH (0.05 mg/kg body weight/day). RESULTS: During treatment with rhGH, serum insulin-like growth factor-I (IGF-I) increased by approximately 225% (P = 0.002), nitrogen balance became strongly positive (+2.35 g/day; P = 0.034 vs baseline) and there was a reduction in serum urea nitrogen (-32%; P = 0.001). Two patients who became acutely ill and had the lowest dietary protein intakes developed a much smaller rise in serum IGF-I levels and increase in nitrogen balance when they received the rhGH treatment. In the remaining four responders, the decrease in nitrogen output was sustained throughout the entire period of treatment with rhGH. There was no change in body weight during the baseline or treatment phases of the study. CONCLUSIONS: Injections of rhGH induce a strong and sustained anabolic effect, as indicated by positive nitrogen balance, in MHD patients with protein-energy malnutrition. This response was attenuated in two patients who were acutely ill with low protein intakes, suggesting that they may have developed partial resistance to GH.     

Effects of insulin and amino acids on glucose and leucine metabolism in CAPD patients

This study investigates the basal and insulin-stimulated glucose metabolism, substrate utilization, and protein turnover in eight patients maintained on continuous ambulatory peritoneal dialysis (CAPD) (mean age 39+/-5 yr, body mass index [BMI] 108+/-6) and 14 control subjects (mean age 33+/-4 yr, BMI 103+/-3). Euglycemic insulin clamp studies (180 min) were performed in combination with continuous indirect calorimetry and 1-14C leucine infusion (study I). Postabsorptive glucose oxidation was higher (1.75+/-0.18 versus 1.42+/-0.14 mg/kg per min) and lipid oxidation was lower (0.43+/-0.09 versus 0.61+/-0.12 mg/kg per min) in CAPD patients than in control subjects (P<0.05 versus control subjects). During the last 60 min of euglycemic hyperinsulinemia, the total rate of glucose metabolism was similar in CAPD and control subjects (6.33+/-0.51 versus 6.54+/-0.62 mg/kg per min). Both insulin-stimulated glucose oxidation (2.53+/-0.27 versus 2.64+/-0.37 mg/kg per min) and glucose storage (3.70+/-0.48 versus 3.90+/-0.58 mg/kg per min) were similar in CAPD and control subjects. Basal leucine flux (an index of endogenous proteolysis) was significantly lower in CAPD patients than in control subjects (1.21+/-0.15 versus 1.65+/-0.07 micromol/kg per min). Leucine oxidation (0.13+/-0.02 versus 0.26+/-0.02 micromol/kg per min) and nonoxidative leucine disposal (an index of protein synthesis) (1.09+/-0.16 versus 1.35+/-0.05 micromol/kg per min) were also reduced in CAPD compared with control subjects (P<0.01 versus control subjects). In response to insulin (study I), endogenous leucine flux decreased to 0.83+/-0.08 and 1.05+/-0.05 micromol/kg per min in CAPD and control subjects, respectively (all P<0.01 versus basal). Leucine oxidation declined to 0.06+/-0.01 and to 0.19+/-0.02 micromol/kg per min in CAPD and control subjects, respectively (P<0.01 versus basal). A second insulin clamp was performed in combination with an intravenous amino acid infusion (study II). During insulin plus amino acid administration, nonoxidative leucine disposal rose to 1.23+/-0.17 and 1.42+/-0.09 micromol/kg per min in CAPD and control subjects, respectively (both P<0.05 versus basal, P = NS versus control subjects), and leucine balance, an index of the net amino acid flux into protein, become positive in both groups (0.30+/-0.05 versus 0.40+/-0.07 micromol/kg per min in CAPD and control subjects, respectively) (both P<0.01 versus basal, P = NS versus control subjects). In summary, in CAPD patients: (1) basal glucose oxidation is increased; (2) basal lipid oxidation is decreased; (3) insulin-mediated glucose oxidation and storage are normal; (4) basal leucine flux is reduced; (5) the antiproteolitic action of insulin is normal; and (6) the anabolic response to insulin plus amino acid administration is normal. Uremic patients maintained on CAPD treatment show a preferential utilization of glucose as postabsorptive energy substrate; however, their anabolic response to substrate administration and the sensitivity to insulin are normal.     

Randomized prospective comparison between erythropoietin and androgens in CAPD patients

BACKGROUND: Anemia and malnutrition are significant complications in peritoneal dialysis (PD) patients. Previous studies in hemodialysis have shown that androgens are effective as therapy for anemia; however, this has not been tested in a randomized prospective trial in PD patients. Furthermore, the anabolic properties of androgens may exert additional benefits on the nutritional status in this population. METHODS: Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis (CAPD) therapy were randomized to receive recombinant human erythropoietin (rHuEPO; N = 14) or nandrolone decanoate (ND; 200 mg/week IM; N = 13) as therapy for anemia. The evolution of hematologic parameters and the impact on both nutritional anthorpometric and biochemical variables were evaluated after six months of treatment. RESULTS: Hemoglobin and hematocrit experienced similar increases in both groups: from 8.5 +/- 0.9 g/dL and 25.8 +/- 2.7% to 11.7 +/- 0.6 g/dL and 34.7 +/- 1.6% (P < 0.001) in patients receiving rHuEPO, and from 8.9 +/- 0.8 and 27 +/- 2.2% to 11.8 +/- 0.4 g/dL and 35.1 +/- 1.5% (P < 0.001) in subjects treated with ND. At the end of the study, out of the diverse nutritional variables included in this investigation, only weight and body mass index significantly increased in the rHuEPO group. Conversely, both anthropometric [weight, body mass index, triceps skinfold, mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum total proteins, albumin, prealbumin and transferrin) were significantly increased in patients treated with ND. In this group, serum urea nitrogen, urea net excretion and protein equivalent of nitrogen appearance significantly decreased. These facts, together with an increase in serum creatinine and no changes in dietary intake during the study, suggest a rise in muscle mass related to an anabolic effect of nandrolone decanoate. Interestingly, serum levels of insulin-like growth factor type 1 (IGF-1) increased in patients on the androgen group compared to subjects treated with rHuEPO. Moreover, there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin, hematocrit, MAC and MAMC. CONCLUSIONS: Androgens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO. Furthermore, compared with rHuEPO, androgen administration was associated with beneficial effects on nutritional status. The mechanism of action of androgens on hematologic and nutritional parameters might be mediated, at least in part, by IGF-1.     

Serum free carnitine, carnitine esters and lipids in patients on peritoneal dialysis and hemodialysis

Serum free and esterified carnitine levels as well as lipids were investigated in patients undergoing regular hemodialysis (HD) treatment before and during 12 weeks of treatment with L-carnitine (1 g i.v.) at the end of each HD. The results were compared with those obtained in patients on continuous ambulatory peritoneal dialysis (CAPD; n = 15) or intermittent peritoneal dialysis (IPD; n = 3) and healthy controls (CO; n = 20). In HD patients (n = 23) total carnitine (TC) was 49.9 +/- 3.9 (CO: 46.0 +/- 2.5; NS), free carnitine (FC) was 31.6 +/- 2.8 (CO: 37.4 +/- 1.3; p less than 0.05), short-chain acylcarnitine (SCC) was 17.0 +/- 1.8 (CO: 7.2 +/- 0.9; p less than 0.0001) and long-chain acylcarnitine (LCC) was 1.2 +/- 0.2 mumol/l (CO: 0.6 +/- 0.1; p less than 0.05). FC was in the normal range in CAPD (35.6 +/- 3.2) and IPD (44.5 +/- 8.0 mumol/l) patients, whereas SCC (30.1 +/- 3.5) and LCC (2.9 +/- 0.2) levels were maximal elevated in IPD patients (11.8 +/- 0.8 and 1.5 +/- 0.2 on CAPD). Therefore, TC was higher in IPD than in CAPD patients (77.5 +/- 5.0 vs. 49.0 +/- 3.5 mumol/l). 12 weeks after L-carnitine supplementation in HD patients, TC was 313.9 +/- 22.6, FC was 207.7 +/- 12.4, SCC was 99.6 +/- 12.1 and LCC was 7.1 +/- 0.6 mumol/l. TC and FC were significantly lower in females compared with males. Total cholesterol and ketone bodies were normal, HDL cholesterol was significantly decreased before and after L-carnitine supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Study on the assay of uremic protein-binding inhibitors: furan compound and hippuric acid]

Plasma levels of 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (FA) and hippuric acid (HA) were studied in healthy subjects, uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Analysis of FA and HA in the plasma were performed by gas chromatography with capillary column. The mean value of FA in HD patients (16.7 +/- 6.1 micrograms/ml) was significantly higher than these in healthy subjects (3.6 +/- 1.0 micrograms/ml) and in patients on CAPD (4.1 +/- 3.7 micrograms/ml) (p less than 0.01). HA levels in CAPD and HD groups were higher than those in healthy controls (2.4 +/- 0.8 micrograms/ml). In addition, the values in HD patients (46.7 +/- 53.5 micrograms/ml) were more increased than those in CAPD (18.5 +/- 16.5 micrograms/ml) (p less than 0.05). Approximately 95% of total FA and 25% of HA were bound to the plasma protein. However, the plasma level of HA was significantly reduced by HD therapy, whereas that of FA was not altered. In the previous study, it was described that no effect of HD on the percent of the binding of acid drugs to the plasma protein in the uremic plasma was observed. Therefore it is supposed that FA is more involved in the binding of drugs to the plasma protein in comparison with HA. The peritoneal losses of FA and HA in CAPD were 2.3 +/- 1.3 mg/day and 276 +/- 40 mg/day, respectively. As the duration of HD became longer, plasma concentrations of FA in HD patients were more increased. In general, they were maintained to be comparatively low in patients on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term recombinant human growth hormone therapy does not modify growth hormone, thyrotropin and prolactin responses to thyrotropin-releasing hormone in adult dialysis patients.

BACKGROUND: We recently have reported the first randomized, controlled study on the effects of short-term recombinant human growth hormone (rhGH|| therapy on the nutritional status of a group of malnourished adult dialysis patients. In order to evaluate whether rhGH administration exerts any influence on GH, thyrotropin (TSH|| and prolactin (PRL|| responses to TSH-releasing hormone (TRH||, we assessed these responses before and after rhGH therapy. METHODS: GH, PRL and TSH responses to TRH before and 1 month after rhGH therapy in a group of adult dialysis patients were evaluated. Seventeen dialysis patients (11 on continuous ambulatory peritoneal dialysis/six on haemodialysis|| were studied (rhGH group, n=8; control group, n=9||. In the rhGH group, 0.2 IU/kg/day rhGH was administered subcutaneously. Each patient was tested with TRH (400 microg bolus i.v.|| on two separate occasions, just before and immediately after the treatment period. RESULTS: rhGH treatment did not modify baseline serum GH concentrations (6.6+/-2.7 vs 4.1+/-1.1 microg/l||, paradoxical GH responses to TRH (six out of eight patients||, GH peak (11.9+/-4.6 vs 11.2+/-5.3 microg/l, NS|| or area under the secretory curve of GH (GH AUC; 19.1+/-4.5 vs 12.1+/-3.1 microg/h/l||. Both basal PRL (35.5+/-7.1 vs 36.7+/-8.6 microg/l|| and TSH (2.3+/-1.1 vs 2.8+/-1.7 mU/l|| concentrations, as well as their responses to TRH stimulation (PRL peak, 59.9+/-16.6 vs 59. 5+/-11.8 microg/l; TSH peak, 6.2+/-2.6 vs 7.1+/-3.9 mU/l||, were also unaffected by rhGH therapy. CONCLUSION: These results suggest that short-term rhGH therapy does not significantly influence the magnitude of the somatotropic, lactotropic or thyrotropic response to TRH in adult dialysis patients. However, this finding has to be interpreted with caution due to the two different patient groups included in this study.     

Recombinant human erythropoietin dosage in children undergoing hemodialysis and continuous ambulatory peritoneal dialysis

The efficacy of erythropoietin (EPO) in 11 children on hemodialysis (HD) and 8 on continuous ambulatory peritoneal dialysis (CAPD) (mean age 11.8 years) was compared. The initial EPO dose was 50 U/kg s.c. once a week; the time of observation was 24 weeks. In the CAPD group, the mean hemoglobin (Hb) level increased from 7.7±0.2 to 11.2±0.6 g/dl (P< 0.001) and hematocrit (Hct) from 22.3±1.0 to 32.6±1.4% (P<0.001), while in the HD group the mean Hb rose from 7.7±0.6 to 9.3±0.8 g/dl (P<0.001) and mean Hct from 22.7±2.3 to 27.6±2.8% (P<0.001) after 12 weeks of observation. An increase in Hb to over 10 g/dl was obtained in 87.5% of children on CAPD but in only 10% on HD after 8 weeks of EPO treatment. After 12 weeks of treatment, all children on CAPD had the target Hb level of more than 10 g/dl, while 7 children on HD required increased doses of EPO (100 U/kg per week). We conclude that the EPO dose of 50 U/kg given s.c. once a week is effective for children with anemia on CAPD but is insufficient for children on HD. Received June 17, 1996; received in revised form January 24, 1997; accepted March 4, 1997