Influence of growth hormone on whole body and regional soft tissue composition in adult patients on hemodialysis. A double-blind, randomized, placebo-controlled study.

BACKGROUND: Many adult patients in chronic hemodialysis exhibit malnourishment and muscle wasting, which in some may be due partly to blockage of the biological action of growth hormone and the somatomedines. Growth hormone (GH) promotes protein synthesis, and long-term treatment with growth hormone has induced an augmentation in lean body-mass (LBM) in normal elderly persons, in persons with GH deficiency as well as growth improvement in uremic children. The purpose of this study was to evaluate the effect of long-term GH treatment on soft tissues in hemodialyzed patients by dual-energy X-ray absorptiometry (DXA) with special regard to the improvement in lean body mass and fat mass (FM). DESIGN: The study was double-blinded, randomized, and placebo-controlled. Twenty enfeebled patients in chronic hemodialysis were treated by subcutaneous injections of biosynthetic human GH (4 IU/m2 per day) or placebo, given every evening for 6 months. Soft tissues as LBM and FM, were measured by DXA scan, and height, and weight were recorded before, and after 6 months treatment. Serum concentration of insulin-like growth factor (IGF-I) and type III collagen N-terminal propeptide (PIIINP) were analyzed at baseline and after 2, 4 and 6 months. RESULTS: Six months of GH therapy induced a total FM reduction of 3.05 +/- 0.75 kg (mean +/- SEM) (p < 0.001) (n = 9) corresponding to 25% of the total fat mass. The reduction in fat was most marked at the trunk, i.e. 1.39 +/- 0.41 kg (p < 0.001) corresponding to 40% of the total FM reduction. Total LBM increased by 3.14 +/-0.41 kg (p < 0.001) in the GH group. Regional changes for arm, truncus and leg in GH group amounted to 0.22 +/- 0.06 kg (p < 0.001), 1.64 +/- 0.37 kg (p < 0.001) and 0.51 +/- 0.06 kg (p < 0.001), respectively. In contrast, total body weight remained unchanged. Serum IGF-I increased from 199 +/- 14.8 microg/l to 527 +/- 111 microg/l (p < 0.0001) at month 6, and the serum PIIINP from 7.8 +/- 1.3/microg/l to 14.3 +/- 2.1 microg/l (p < 0.001) in the GH-treated group. In the placebo group (n = 11) there were no significant changes in FM, LBM or PIIINP while serum IGF-I decreased from 285 +/- 36 microg/l to 219 +/- 35 microg/l (p < 0.01) after 6 months treatment. CONCLUSIONS: Six months of GH therapy to patients with chronic renal failure resulted in marked changes of the soft tissue with an increase in LBM, and reduction of FM particularly at the trunk. The data imply that GH-induced changes in body composition are maintained with long-term therapy. Very few side-effects of GH treatment were observed, and no serious ones were encountered, though the dosage were 2 to 3 times higher than the one given to GH-insufficient, non-uremic persons, and the serum IGF-I concentrations during treatment equalized those seen in acromegalia. This indicates the existence of a reduced biological effect of GH and IGF-I in uremic persons.

Changes in cardiac muscle mass and function in hemodialysis patients during growth hormone treatment.

BACKGROUND: Adult patients with chronic renal failure (CRF) often show symptoms as fatigue, wasting, and reduced working capacity with concomitant findings of reduced cardiac performance and muscle mass. This state may in part be caused by an imbalance in the somatostatin/somatomedine axis resulting in increased catabolism. During an attempt to correct this catabolic state by administration of exogenous growth hormone, cardiac muscle mass and performance were studied. METHODS: In a double-blind, placebo-controlled 6-month study comprising 20 adult enfeebled hemodialysis patients, 9 patients were treated with a single daily subcutaneous injection of recombinant human growth hormone (rhGH) 4 IU/m2 and 11 with placebo injections. Left ventricular muscle mass (LVM) and ejection fraction (EF) were evaluated by echocardiography and the maximal working capacity (MWC) was measured by a bicycle exercise test performed before and after the treatment period. Supplementary electrocardiography (ECG) was performed before and after 6-month treatment. RESULTS: Median LVM increased significantly from 172 to 220 g (p = 0.03) in the rhGH-treated group, while an insignificant decrease was observed in the placebo group from 281 to 200 g (p = 0.3). The EF showed no significant changes in the two groups. MWC showed a slight, insignificant decrease in both groups. From ECG no significant ST deviations were found and no significant changes regarding B-Hb, blood pressure or pulse were observed in the two groups. Irregular heart rhythm aggravated in one patient during the first month of treatment with rhGH, but was overcome by a -blocking agent. CONCLUSION: The treatment with rhGH of adult chronic hemodialysis patients for 6 months increased the left ventricular mass significantly, but without any effect on ejection fraction or maximal working capacity. No electrocardiographic signs of ischemia were associated with the increasing muscle mass and only one patient developed symptoms that might relate to ischemia. No changes in B-Hb, blood pressure or pulse were observed during the treatment period.

What are the clinical benefits of correcting the catabolic state in haemodialysis patients?

In a double-blind, placebo-controlled trial of recombinant human growth hormone (rhGH) comprising 20 chronic enfeebled haemodialysed patients, the clinical benefit of daily growth hormone treatment for six months was evaluated. Nine patients (five male, four female) were treated with rhGH 4 i.u./m2/day and eleven with placebo (seven male, four female). Their mean age was 46.5 years (range 18-68). No difference in mean age was found between the groups. A significant increase in insulin-like growth factor I (IGF-I) was observed in the rhGH-treated group (200 to 527ng/ml, p = 0.01), while a decrease was noticed in the placebo group (285 to 219ng/ml, p = 0.02). S-GH did not change significantly in either group, and there were no differences between the two groups in terms of weight, haemoglobin, s-albumin, -urea or -creatinine, which all remained unchanged during the trial. Patients' lean body mass, as measured by DXA-scanning, increased significantly in the rhGH-treated group (43.4 to 46.7kg, p = 0.004), while no change was observed in the placebo group (44.9 to 45.2kg, p = 0.76). The changes in lean body mass between the two groups were significant, p = 0.001. Left ventricular muscle mass increased significantly (227 to 286g, p = 0.03) in the rhGH-treated group, but not in the placebo group (292 to 253g, p = 0.3). The changes in left ventricular muscle mass between the two groups were significant (p = 0.02). The maximal working capacity decreased slightly and insignificantly in both groups, when measured by bicycle ergometry. Isometric muscle contraction force and endurance did not change significantly in either group. Patients' opinion about the influence of the treatment on their general well-being and working capacity, evaluated blindly on a subjective scale, improved significantly in the rhGH-treated group (9.7 to 12.6, p = 0.02), while no change was experienced in the placebo group (9.9 to 10.7, p = 0.2). No difference was however demonstrable between the two groups (p = 0.4). Thus we conclude that adult patients in long-term haemodialysis treated with rhGH experienced an increase in their lean body mass and left ventricular muscle mass. This increase in muscle mass did not, however, improve muscle contraction force or endurance when measured objectively. The rhGH-treated patients nevertheless had a subjective feeling of a slight improvement in their general wellbeing.

[Carbamide kinetics in the evaluation of the therapeutic quality of hemodialysis]. / Carbamidkinetik til vurdering af behandlingskvalitet ved haemodialyse.

A urea kinetic analysis, (the Sargent and Gotch model), was applied to 62 haemodialysis patients. The protein catabolic rate was below 1 g/kg/day in 56.5% of the patients and 66.3% had a KT/V (Clearance x Time/Volume) below 1. The median KT/V was 0.90 and the median normalized protein catabolic rate was 0.95 g/kg/day. KT/V was strongly correlated to protein intake (normalized protein catabolic rate). It is concluded that urea kinetic modelling is a practical tool for assessing the dialysis adequacy and nutritional status of haemodialyzed patients.

Septicemia with Agrobacterium species from a permanent vena cephalica catheter. A case report.

A case of Agrobacterium septicemia is reported in a 47-year-old woman with disseminated adenomcarcinoma mammae and a permanent vena cephalica catheter.