Growth hormone aggravates glomerular sclerosis in the remnant kidney of 5/6 nephrectomized uremic rats

Background Our study evaluated the influence of short-term growth hormone treatment on the remnant kidney in 5/6 nephrectomized uremic rats Methods Twenty male Sprague-Dawley rats were divided into 4 groups: sham-operated control rats (SC, n=4); sham-operated rats treated with recombinant human growth hormone (SGH, n=4); uremic (5/6 nephrectomized) control rats (UrC, n=6); and uremic rats treated with recombinant human growth hormone (UrGH, n=6). Total food intake, food efficiency, average daily food intake per 100 g body weight, weight gain, increase in body length, creatinine clearance, and kidney weight per 100 g body weight were measured. Glomerular tuft area was determined, and the severity of glomerular sclerosis was scored. Insulin-like growth factor-I was localized in the kidneys by immunostaining. Results Weight gain, increase in body length, food efficiency, and food intake per unit body weight were greatest in the SGH group; in UrGH animals, food efficiency and food intake per unit body weight were significantly higher than those in UrC rats. Creatinine clearance in uremic rats was significantly reduced compared with that in sham-operated animals. There was no difference in the ratio of kidney weight to body weight among the groups. The average glomerular area was greatest, and the glomerular sclerosis index was highest, in the UrGH group. No insulin-like growth factor-I could be identified in the glomeruli. Conclusions Growth-hormone treatment augmented daily food intake, and the more rapid progression to glomerular sclerosis in hormone-treated uremic rats is probably due mainly to increased daily protein intake. This study was partly presented at both the 38th Annual Meeting of the Japanese Society of Nephrology and the Sixth Asian Pacific Congress of Nephrology     

Somatic and renal effects of growth hormone in rats with chronic renal failure

Recombinant human growth hormone (rhGH) has been widely used to improve growth in children with chronic renal failure (CRF). However, there has been great concern that GH may aggravate renal disease and hasten the progression to end-stage renal failure. We therefore investigated the effect of prolonged administration of rhGH at various doses on somatic growth and renal function and structure in rats with CRF, divided into four groups based on rhGH dose (vehicle, 0.4, 2.0, and 10.0 IU/day). rhGH was administered subcutaneously daily for 8 weeks. The mean growth was significantly greater in rats treated with high-dose rhGH (10.0 IU) than those treated with low-dose rhGH (P = 0.0089) or vehicle (P = 0.0011). Body weight gain increased in parallel with body length (Creatinine clearance at the end of the experiment was significantly lower in rats on high or medium-dose rhGH than those on low-dose rhGH and controls (P <0.05). The glomerular sclerosing index was greater in rats treated with higher doses of rhGH. There were significant differences between rats treated with high-dose rhGH and controls (P = 0.0144) and also between rats on medium-dose rhGH and controls (P = 0.0065). Although there was no significant difference, rats treated with higher doses of rhGH tended to excrete more protein. Renal insulin-like growth factor-I (IGF-I) content and circulating IGF-I and IGF-II levels did not significantly differ among groups. We conclude that: (1) GH improves somatic growth failure in rats with CRF, but prolonged administration of GH dose-dependently induces deterioration in renal function and structure and (2) this effect was induced neither via circulating IGF-I and IGF-II nor by local production of IGF-I, but seems to be direct. Received June 7, 1996; received in revised form and accepted November 19, 1996     

Growth hormone prevents steroid-induced growth depression in health and uremia.

Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normalized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed.     

Intermittent administration of parathyroid hormone (1-37) improves growth and bone mineral density in uremic rats

BACKGROUND: Parathyroid hormone (PTH) is secreted in a pulsatile fashion. Continuous infusion of PTH(1-84) resulted in a net decrease in trabecular bone volume. Differential effects have been reported following an intermittent application of PTH. We investigated the effects of a continuous infusion and of an intermittent (2 times daily subcutaneously) administration of PTH(1-37) on growth and bone mineral density (BMD) in healthy and uremic rats. METHODS: Two-stage subtotal nephrectomy was performed on 130 g female Sprague-Dawley rats. PTH(1-37) or solvent was administered through minipumps in sham-operated and uremic rats (60 microg/kg x day for 2 weeks). The effect of intermittent administration was tested with a subcutaneous injection of solvent: 30 microg/kg PTH(1-37) two times per day, 100 pmol calcitriol (C)/kg two times per day, or both. The length (snout-tailtip) and BMD were measured at the start of uremia and at sacrifice. BMD was measured by peripheral quantitative computer tomography at the proximal tibia, 6 and 12 mm distal of the kneejoint space. Femur bone morphology was assessed by x-rays, and calcium content was measured by atomic absorption spectrophotometry. RESULTS: Length gain was not altered by the continuous infusion of PTH. In contrast, it was significantly increased by intermittent PTH (control solvent 5.35 +/- 0.37 cm vs. control PTH 6.19 +/- 0.47 cm; uremia solvent 4.78 +/- 0.20 cm vs. uremia PTH 6.17 +/- 0.36 cm; P < 0.05). Intermittent PTH but not C increased BMD in uremic rats (Delta total BMD 134 + 13.3 vs. 76.3 +/- 11.5 mg/mL; P < 0.05). X-rays revealed increased bone mass following treatment with PTH but not with C. Uremia decreased bone calcium content (64 +/- 0.3 vs. 73. 3 +/- 2.5 mg/mL), which was normalized by PTH (80 +/- 3.6 mg/mL, P < 0.05) but not by C (69 +/- 1.9 mg/mL). CONCLUSION: Pulsatile administration of PTH does not adversely affect, but improves longitudinal growth independent of concomitant treatment with C. At the same time PTH increases BMD and the calcium content of bone.     

Post graft development of short children treated with growth hormone before kidney graft

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6±1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3.5±1.4 years. During treatment, mean height increased from –3.0±0.9 standard deviation score (SDS) to –1.9±1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1.2±0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5±0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: –0.5±0.4 SDS in patients grafted at early stages of puberty (P2–P3) and –0.15±0.9 SDS in patients grafted at late stages of puberty (P4–P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children. Received: 23 July 1998 / Revised: 8 December 1998 / Accepted: 13 December 1998     

Improvement of growth and food utilization by human recombinant growth hormone in uremia

We compared growth rate, food conversion ratio and morphology of the growth zone in female Sprague-Dawley rats with subtotal nephrectomy or sham operation. Both groups were either given vehicle or 1.4 IU/day recombinant human growth hormone (GH) by s.c. osmotic minipump, or 2.5 IU twice daily intraperitoneally for 14 or 20 days, respectively. Compared to uremic rats infused with vehicle, infusion of GH significantly (P less than 0.01) improved growth; that is, it increased gain of weight (delta 27.0 +/- 7.7 g vs. 11.6 +/- 4.9 g) and length (delta 1.8 +/- 0.3 cm vs. 1.12 +/- 0.44 cm) in ad libitum fed uremic rats. This was accompanied by increased food utilization ratio (0.146 vs. 0.065 g weight gain per g food intake). A similar increment of growth and food utilization ratio was also observed in GH versus solvent infused controls, either pairfed as for the uremic animals or fed ad libitum. Despite administration of GH, growth was not completely restored to normal in uremic animals. Circulating immunoreactive IGF I was not significantly increased by GH infusion in either uremic animals or controls. Histological analyses of the proximal tibia showed increased rate of longitudinal growth, as evaluated by tetracyclin-labeling, and increased volumetric density of primary spongiosa with unchanged width of primary spongiosa trabecules when GH was infused in uremic animals. The data suggest that growth impairment in the uremic rat is partially responsive to GH, and this is not accompanied by an increase of circulating IGF I. Therapeutic trials with recombinant GH in uremic children appear justified.     

Recombinant human growth hormone overcomes the growth-suppressive effect of methylprednisolone in uraemic rats

Paediatric renal allograft recipients frequently manifest growth retardation because of suboptimal graft function and/or concomitant corticosteroid treatment. To determine if the growth-suppressive effects of methylprednisolone (MP) could be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH) under conditions of normal and reduced renal function, the following animal model was set up. Female uraemic Sprague-Dawley rats (140 g) together with pairfed and ad libitum-fed control animals were treated with 6 mg/kg per day MP with or without 10 IU/kg per day rhGH. MP suppressed linear growth and weight gain by 43% and 63%, respectively in ad libitum-fed normal control animals; the suppression was more pronounced in uraemic animals (57% and 107%, respectively). The suppressive effects were independent of food intake. The food conversion ratio (weight gain/food intake) was diminished to one-third in control and to more than one-tenth in uraemic animals. Concomitant treatment with rhGH completely reversed the suppression of length gain and weight gain (total body and muscle) and normalized the food conversion ratio. We concluded that rhGH can completely reverse the catabolic effects of corticosteriods under conditions of normal or reduced renal function. The data provide a reasonable rationale for prospective controlled studies on the use of rhGH treatment in paediatric kidney transplant recipients with growth failure.     

Plasma renin activity as a marker for growth failure due to sodium deficiency in young rats

We evaluated the effect of feeding diets of varying sodium content on growth and plasma renin activity (PRA) in young rats. In the first study, four groups of rats were offered 10 g/100 g body weight per day of diets containing either 0.005%, 0.015%, 0.03%, or 0.3% sodium; weight gain per day of each rat was followed for 10–14 days and PRA was then measured. A control group was fed a sodium-replete tryptophan-deficient diet which caused protein calorie malnutrition and inhibited growth. Weight gain (g/day) among the rats on the sodium-deficient diets varied directly (r=0.81,P<0.001) and PRa inversely (r=–0.82,P<0.001) with dietary sodium content. PRA varied inversely with weight gain (r=–0.84,P<0.001). Insulin-like growth factor-1 (IGF-1), which is depressed in calorie-deficient growth failure, was depressed in all the rats on the low-sodium intakes relative to ad libitum-fed controls, but did not vary in relation to dietary sodium or weight gain within those groups. In rats fed the trytophandeficient diet, both IGF-1 and weight gain were severely depressed; PRA was normal. In the second study, rats in each of two groups were pair fed, the diet containing either 0.03% or 0.3% sodium matched to rats fed the 0.005% sodium diet; weight gain was followed for 28 days. Both length and weight gain were retarded; PRA again varied inversely with dietary sodium content and with weight gain. We conclude that sodium-deficient diets retard growth in proportion to the degree of dietary sodium deficiency. PRA, but not IGF-1, is a marker for growth retardation due to sodium deficiency.     

Recombinant human growth hormone treatment of children on hemodialysis

Forty-two children, aged 2–21.5 years on hemodialysis with a height below –2.0 standard deviation score (SDS) for age, were selected to receive recombinant human growth hormone (rhGH) therapy at 17 French centers. Of the 42 children, 36 were prepubertal and 8 were in early puberty (testicular volume between 4 and 8 ml for boys, breast development B2 or B3 in girls). All received 1 IU/kg per week by daily subcutaneous injection for 1–5 years. The year before rhGH therapy served as a control period. During the 1st year of treatment, mean growth velocity increased from 3.5 to 7.0 cm/year (P <0.0001) and was always over 2.5 cm/year. This velocity allowed a catch-up growth of +0.5 height SDS. Neither weight nor the body mass index varied compared with the pretreatment year. No change was observed in urea, creatinine, or glucose tolerance. The mean increment in bone age was 0.9 years. The mean growth velocity decreased over subsequent years (P <0.0001), but remained higher than the prestudy velocity. A significant negative correlation was observed during the 1st year between the increase in growth velocity and the prestudy velocity (P <0.0001), with the least gain in patients who had the best spontaneous velocity. Pubertal status had no influence on response to rhGH. No significant side effects were observed during the 103 treatment-years. Five patients developed secondary hyperparathyroidism and 1 suffered from acute pancreatitis, but the relationship with rhGH therapy remains uncertain. rhGH therapy appears indicated for children on hemodialysis, even though the potential benefits appear somewhat lower for those with a spontaneous growth velocity over 6 cm/year. Received April 18, 1997; received in revised form October 23, 1997; accepted October 28, 1997     

Long-term results of rhGH treatment in children with renal failure: experience of the French Society of Pediatric Nephrology

Few publications have described the long-term effects of recombinant human growth hormone (rhGH) in uremic patients. This study reports the results of rhGH therapy at the end of treatment and at adult age in 178 French patients. At enrollment, 63 patients were under conservative treatment (CT), 40 under hemodialysis (HD), and 75 had a functioning renal transplant (RT). Under rhGH treatment, height velocities (HV) significantly increased in all patients, but the effect was significantly better in the CT group. The HV gain (HV under rhGH-HV before treatment) was similar in all three groups. Increases in HV allowed height standard deviation scores (SDS) catch up, and this effect persisted over a 5-year period. SDS height at the completion of treatment was significantly related to group (best in CT) and response to treatment during the first year. Data on adult height was available for 102 patients. Mean adult height was 162.2 cm in men and 152.9 cm in women, and 46% were > −2 SDS for height. Adult height SDS was correlated with height SDS and spontaneous HV before treatment and effect of treatment. Analysis of adult height in the 49 patients who entered the protocol with a height SDS between −2 and −3 (the current recommendation for rhGH use) revealed that 65% had an adult-height SDS >−2. These adult heights were significantly better if compared with historical cohorts of patients not treated by rhGH; rhGH significantly improves the adult-height prognosis of uremic patients suffering from growth retardation. Early rhGH administration during CT gives better height SDS at both the end of rhGH therapy and in adulthood. Members of the French Society of Pediatric Nephrology: J.L. André, A. Bensman, E. Bérard, J.P. Bertheleme, F. Bouissou, B. Boudailliez, F. Brou, M. Broyer, A. Burguet, G. Champion, P. Cochat, M. Dehennault, G. Deschênes, P. Desprez, R. Dumas, M. Fischbach, M. Foulard, M.T. Freycon, M.F. Gagnadoux, S. Gié, G. Guest, C. Guyot, G. Landthaler, M.P. Lavocat, C. Loirat, M.A. Macher, D. Morin, C. Mousson, P. Niaudet, H. Nivet, J.B. Palcoux, G. Picon, B. Roussel, M. Tsimaratos     

Acidosis prevents growth hormone-induced growth in experimental uremia

The effects of 2 weeks of a daily injection (2 IU/day) of recombinant human growth hormone (GH) were studied in young (60-g) growing rats in two experiments. Experiment 1 was performed in uremic animals (mean plasma creatinine 65–71 mol/l) who were either acidotic (mean bicarbonate 11.5 mmol/l) or had acidosis corrected (mean bicarbonate 26 mmol/l) by addition of sodium bicarbonate to the diet. Experiment 2 used rats with normal renal function (plasma creatinine 25 mol/l) who were either non-acidotic but restricted to the dietary intake of uremic rats or rendered acidotic by ammonium chloride. GH induced an increase in body weight and length in nonacidotic uremic (+33% and +41%) and in non-acidotic food-restricted (+13% and +42%) rats, associated with an increased rate of protein synthesis and little change in plasma insulin-like growth factor 1 (IGF 1). In both acidotic rat groups, GH altered none of the parameters studied. Thus: (1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats and (2) the increment of growth rate does not depend on a rise in plasma IGF 1.     

Changes in body composition of children with chronic renal failure on growth hormone

Body composition is altered in children with chronic renal failure (CRF) and contributes to the significant growth failure seen in these children. Recombinant human growth hormone (rhGH) has been used in the past several years to improve the somatic growth of children with CRF. To determine if the growth achieved in these children occurs concomitantly with body compositional changes, seven prepubertal (n=6) and pubertal (n=1) children with chronic renal insufficiency (n=4) and end-stage renal disease (n=3) underwent measurements of total body fat (FM), fat free mass (FFM), bone mineral density (BMD), total bone mineral mass (TBBM), total body water (TBW), and total body potassium (TBK) before and 6 months after initiation of subcutaneous recombinant human growth hormone (rhGH) at 0.35 mg/kg per week. The techniques used included dual- energy X-ray absorptiometry (for measurement of FM, BMD, and TBBM), total body potassium counting (for measurement of TBK), and deuterated water for assessment of TBW. Significant increases in both height and weight were seen following 6 months of rhGH therapy. These increases were accompanied by significant re- ductions in FM (4.4±1.4 kg vs. 3.6±1.2 kg, P=0.002) and percentage fat (18.6±3.9% vs. 14.5±3.4%, P=0.04), while FFM (17.9±3.0 kg vs. 20.7±3.6 kg, P=0.04) increased significantly as did TBBM (776±171 g vs. 844±177 g, P=0.001). Increases in TBK, a measure of body cell mass, were also seen. No difference in total BMD was observed. Thus, growth in CRF is occurring with repletion of the FFM and TBBM compartments. Despite these improvements, no change was observed in the body mass index (BMI). Measurement of BMI alone does not define the compartmental catabolic losses in FFM. Received: 20 September 1999 / Revised: 31 January 2000 / Accepted: 8 February 2000     

Involvement of low-calcium diet in the reduced bone mineral content of idiopathic renal stone formers

Summary The possibility that low-calcium intake in renal stone formers could lead to reduced bone mineral content was investigated in 123 male patients with idiopathic urolithiasis. Radius bone mineral content, (BMC) was measured by single photon absorptiometry. Two groups of patients were analyzed: group 1 (n=63) maintained on a free diet; group 2 (n=60) maintained on a low-calcium diet (350 mg/day ±20 SEM) for 3.9 years ±0.6 SEM. The two groups of patients were investigated after a standard reduction of calcium intake for at least 1 week. The urinary excretion of calcium and of hydroxyproline, and the serum alkaline phosphatase activity were higher in both groups than in normal subjects submitted to the same low-calcium diet. Both groups of stone formers showed lowered radius BMC values at 3 cm (distal) and 8 cm (proximal) above the styloid process, but distal BMC was significantly lower in group 2 than in group 1. The results suggest that low-calcium intake could worsen the already decreased BMC of idiopathic renal stone formers.     

Intensified and daily hemodialysis in children might improve statural growth

In children conventional hemodialysis does not often improve growth. We determined linear growth in five children on in-center intensified and daily hemodialysis (IDd) regimen, with a mean age of 8 years 7 months at enrolment. Four of five were on growth hormone started for a median of 28.5 months before IDd. IDd was delivered 5 to 6 times weekly, for three hours each session. Mean follow up of IDd was 18.6 months. Dropout from IDd was kidney transplantation (n=4) or transfer to another center (n=1). IDd and free diet improved appetite, thereby protein intake, was above 2 g/kg/BW. Median weekly Kt/V_urea was 9.1 (8.7 to 10.4). Predialysis phosphorus blood levels were higher at the start (2.04±0.34 mmol/L) than at end of IDd (1.39±0.41 mmol/L) without need for carbonate of calcium in four of five cases. During conventional dialysis ht SDS decreased from −0.8 to −1.44, which occurred predominantly before rhGH start. Conversion to IDd significantly increased growth velocity to a mean of 13 cm/year (10.3–18) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests the potential efficacy of IDd regimen in promising growth velocity, either directly from a higher dialysis dose or indirectly through an improved nutritional status.     

Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone

We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (±SD) rhGH treatment observation period was 19.9±5.9 months. The mean age at the start of rhGH treatment was 8.3±3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43–2.66] than in prepubertal patients (1.19, 95% CI 1.01–1.40). Increases in PTH levels were significantly different between the two groups (=1.64, 95% CI 1.16–3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.     

Results of recombinant growth hormone treatment in children with end-stage renal disease on regular hemodialysis

Children with chronic kidney disease are at high risk for growth retardation and decreased adult height. Growth hormone (GH) treatment is known to stimulate growth in children with short stature suffering from chronic kidney disease. However, the extent to which this therapy affects final adult height is not known. This study was performed on 15 patients with end-stage renal disease (ESRD) on regular hemodialysis to detect the effect of using recombinant human growth hormone (rhGH) on growth of patients with ESRD on regular hemodialysis and comparing this effect with the growth velocity in the same group without using rhGH in the year before therapy. There were eight females and seven males with mean age 10.6 ± 2.8 (range 5-14 years). For each patient, recombinant GH was given for one year, three-times weekly. The data of these 15 patients was compared with the year before treatment versus data of the same group of patients after six months and after one year of rhGH therapy. Our results showed that, in the year before therapy, height of these patients increased from a mean of 112.1 ± 11.6 cm to 112.7 ± 11.5 cm, which is a non-significant increase statistically (P >0.05) as well as clinically (mean growth velocity 0.6 cm/year), while height of these patients increased from a mean of 112.7 ± 11.5 cm at the start of therapy to 116.8 ± 11 cm after therapy for one year, which, although statically not significant (P >0.05), was of clinical significance as it makes rate of increase, i.e. the mean growth velocity, 4.1 cm/year close to the normal growth velocity, which is 5 cm/year, before puberty. rhGH therapy for patients with ESRD on regular hemodialysis is helpful in height gain and catch-up growth even when given three-times per week instead of five- or six-times per week. We recommend giving rhGH therapy as a routine supplementation to pediatric patients before epiphyseal closure.     

Effect of various protein diets on growth, renal function, and survival of uremic rats.

The effects on growth, renal function, and survival of three isocaloric diets of various protein content (14, 27, and 37 g/100 g in diets I, II, and III, respectively) were compared in uremic rats and in controls. Diet I provided the minimal requirements in all amino acids for gorwing rats. In controls fed ad lib, weight and length gain were better with high protein diets, whereas they were inversely related to the diet protein content in uremic rats. The higher the protein intake, the higher the progressive elevation of BUN and serum creatinine and the mortality rate. Because proteins were supplied by fish flour, their increase was associated with increased mineral content, and the conclusions are restricted to the use of natural proteins: a moderately restricted protein diet securing only the minimal requirements had a beneficial effect on growth and survival of rats with reduced kidney mass. Avoiding any excess in proteins from the early stage of renal disease is suggested.     

Effect of 1,25-dihydroxyvitamin D3 on intestinal glucose absorption in uremic rats

The effect of 1,25-dihydroxyvitamin D3 (1,25-D) on the absorption of glucose in the small intestine was studied in five-sixths nephrectomized uremic rats and sham-operated rats. Four weeks after the nephrectomy, the uremic animals were divided into two groups: One group was given 1,25-D (300 pmol/kg body weight/day, three times per week) intraperitoneally, and the other was left untreated. One week after the 1,25-D treatment, an in vivo glucose absorption test was performed at 00.00 h in consideration of the circadian rhythm of glucose absorption. In untreated uremic rats, the glucose absorption rate was lower than in sham-operated rats. In 1,25-D treated uremic rats, the glucose absorption rate was higher than in untreated uremic rats and not lower than in sham-operated rats. These results suggest that the absorption rate of glucose of the small intestine is reduced in uremic rats and that it is recovered on treatment with 1,25-D.     

Kidney growth and renal functions under the growth hormone replacement therapy in children

Objective: The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. Materials and methods: A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Results: Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p?0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p?0.05). Height was the most significant predictor of kidney volume in rhGH received children (p?0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p?0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p?>?0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p?0.05). Conclusions: In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.