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R N Fine

Publications and source records attributed to R N Fine.

At least 19 recordsLinked to original sources
PubMed1995

Recombinant human growth hormone in infants and young children with chronic renal insufficiency. Genentech Collaborative Study Group.

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were < 2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n = 19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n = 11) received placebo injections. At entry into the study, the mean (+/- SD) calculated creatinine clearance was 29.2 +/- 14.3 (range 12.0-63.7) ml/min per 1.73 m2 in the rhGH-treated group and 23.3 +/- 15.1 (range 8.0-59.4) ml/min per 1.73 m2 in the placebo-treated group. The 1st year growth rate was 14.1 +/- 2.6 cm/year for the rhGH-treated group and 9.3 +/- 1.5 cm/year in the placebo-treated group (P < 0.00005). During the 2nd year of the study, the growth rate was 8.6 +/- 1.2 cm/year in the rhGH-treated group compared with 6.9 +/- 1.0 in the placebo group (P = 0.025). The delta height standard deviation score was +2.0 +/- 0.7 for the rhGH-treated group compared with -0.2 +/- 1.1 in the placebo-treated group (P < 0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1995

Do children exhibit catch-up growth post transplant: North American Pediatric Renal Transplant Cooperative Study special study.

Changes in height deficit and standard deviation score (SDS) were evaluated in 524 recipients who were growth retarded at transplantation (SDS > -2.00) and were followed for at least 2 years post transplant. At 2 years the delta SDS was 0.32 +/- 0.04 and the delta height deficit was 0.75 +/- 0.23. Therefore despite improvement in the SDS at 2 years post transplant, the change in height deficit was < 1 cm. Change in height deficit may be a better indication of "catch-up" growth following transplantation.

Adolescent↗
PubMed1995

Steady improvement in renal allograft survival among North American children: a five year appraisal by the North American Pediatric Renal Transplant Cooperative Study.

From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we have analyzed one and two year graft survival by annual cohorts for the years 1987 through 1991. For the 1987 cohort one and two year graft survival was 72% and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively. Using a proportional hazards model, and comparing the 1987 cohort to the 1991 cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of practice patterns revealed the following changes which may have been associated with this improved graft survival: (1) use of T cell induction antibody, 38% in 1987 and 67% in 1991 (P < or = 0.001); (2) the increased use of cyclosporine (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to 97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12 months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991 (P = 0.03); (4) the decreased use of random transfusions, 54% receiving > 5 transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use of younger cadaver donors between 1987 and 1991 (P < 0.001).

Antibodies, Monoclonal↗
PubMed1995

Insulin-like growth factor-1 enhances epidermal growth factor receptor activation and renal tubular cell regeneration in postischemic acute renal failure.

Growth factors such as insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and hepatocyte growth factor have been shown to accelerate the recovery from postischemic acute renal failure (ARF) with a concomitant increase in DNA synthesis. Interactions between growth factors have been demonstrated in a number of in vitro studies. This study examined the effect of exogenous IGF-1 on the DNA synthesis and EGF receptor (EGF-R) activation in postischemic rat kidneys. Thirty minutes after the relief of 30-minute total occlusion of the left renal artery in anesthetized 225 to 300 gm Sprague-Dawley rats, either IGF-1 (75 micrograms/kg) or normal saline solution (NS, 0.2 ml) was given by intravenous bolus, followed by twice daily subcutaneous injections of IGF-1 (50 micrograms/kg) or 0.2 ml NS for 4 days, respectively, in IGF-1-Tx) and NS treated (NS-Tx) groups (n = 8 each). On the day after the completion of treatment, inulin clearance (ml/kg/min) of the postischemic kidneys in the IGF-1-Tx group was significantly higher (p < 0.01) than inulin clearance of kidneys in the NS-Tx group. This was associated with improved kidney morphology. IGF-1 treatment also enhanced the labeling index of 5-bromo-2'-deoxyuridine (percent of stained tubule cells), a marker for active DNA synthesis, in the outer medulla of postischemic kidneys at 1 day and 2 days after the injury. EGF-R tyrosine phosphorylation (which reflects receptor activation) increased in postischemic kidneys in both NS-Tx (n = 5) and IGF-1-Tx (n = 3) groups 1 day after the injury as compared with nonischemic contralateral kidneys. In the IGF-1-Tx group there was also increased iodine 125-labeled EGF binding and EGF-R protein. Our results demonstrate a beneficial effect of IGF-1 on postischemic ARF. Furthermore, they suggest that EGF-R activation is involved in tubular regeneration and that IGF-1 may enhance EGF-R activation by increasing EGF-R expression.

Acute Kidney Injury↗
PubMed1992

Extended recombinant human growth hormone treatment after renal transplantation in children.

Recombinant human growth hormone (rhGH) was administered to 13 pediatric renal allograft recipients, ages 7.6 to 17.7 yr, who were 14 to 92 months posttransplant and growth retarded as manifested by either a standard deviation (SD) more negative than -2.00 or a height velocity index of less than 25%. The rhGH was given either daily or thrice weekly (0.375 mg/kg/wk) for a period of 12 to 36 months. Growth velocity increased from 2.7 +/- 2.1 SD for the 12-month period before the initiation of treatment of 6.3 +/- 2.9 SD (P less than 0.00005) and 5.2 +/- 2.9 SD (P less than 0.02) after 12 and 24 months of treatment, respectively. Although individual recipients had improvement in their SD scores, the mean values did not increase despite the increased growth velocity. Except for a 0.5-yr increase over 24 months in two recipients, the bone age did not increase at a rate greater than the increase in chronologic age. Four rejection episodes occurred in two recipients during rhGH treatment--an incidence not greater than that which occurred during a comparable time interval before the initiation of treatment. The calculated creatinine clearance declined from 66 +/- 26 SD mL/min/1.73 m2 at the initiation of treatment to 55 +/- 30 SD mL/min/1.73 m2 at 24 months and 52 +/- 28 SD mL/min/1.73 m2 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Renal ultrasound abnormalities in children with end-stage liver disease--reversal by liver transplantation.

Ultrasound (US) imaging of the kidneys was performed in 43 pediatric patients with end-stage liver disease evaluated for orthotopic liver transplantation. Renal size was increased in 8 patients (19%) and echogenicity of the kidneys was increased in 12 patients (28%). In 12 patients studied after liver transplantation, US revealed normal renal size in all and increased echogenicity in only 2 patients shortly after transplantation. Normalization of renal US findings was also found in 2 patients studied before and after liver transplantation. The glomerular filtration rate varied from 65 to 225 ml/min per 1.73 m2 in 5 patients with abnormal US, and from 74 to 116 ml/min per 1.73 m2 in 3 patients with normal US. Nephromegaly and increased echogenicity on renal US are frequent in children with end-stage liver disease and appear to be mostly reversible by liver transplantation.

Adolescent↗
PubMed1991

Improved cadaveric renal transplant outcome in children.

We analyzed the results of 165 pediatric cadaver renal transplants performed at the University of California at Los Angeles to identify the factors which are linked to improved allograft survival. Both univariate life-table analysis and the Cox proportional hazard model were used. The use of a sequential immunosuppressive regimen (P less than 0.001) and kidneys from donors of more than 6 years of age (P less than 0.001) were found to be the factors having the most influence on primary graft survival. The sequential regimen was the only factor favorably influencing retransplants. With sequential therapy 1- and 2-year actuarial graft survival rates were 94% and 91% in primary transplants, and 82% and 70% in retransplants. Medication noncompliance exerted a large negative effect on transplant outcome. Of 70 recipients who had been on cyclosporine for at least 6 months, 50% evidenced noncompliance. Sixty-four percent of adolescents were noncompliant. Thirteen percent of the recipients lost their graft because of noncompliance. We conclude that good results can be obtained with cadaver renal transplants in children with a sequential immunosuppressive regimen and the use of kidneys from adolescent and adult donors. Noncompliance is a great barrier to long-term success in pediatric transplantation.

Adolescent↗
PubMed1991

Recombinant human growth hormone treatment of children following renal transplantation.

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6-30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5 +/- 2.1 vs 5.7 +/- 2.7; P less than 0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potential adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P less than 0.009) and 12 months (P less than 0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.

Adolescent↗
PubMed1991

Recombinant human growth hormone treatment of children with chronic renal failure: long-term (1- to 3-year) outcome.

Treatment of nine boys, aged 2.8-16.3 years, with growth retardation consequent to chronic renal failure (CRF), with recombinant human growth hormone (rhGH) for 12-36 months demonstrated a significant improvement in growth velocity at each 12-month interval compared with that achieved the year prior to treatment. Despite the acceleration in growth velocity the bone age did not increase more than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following the initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uremia following rhGH treatment. Currently, six of seven patients who have been treated for more than 24 months have achieved sufficient acceleration of growth velocity to attain a standard deviation score that was more positive than -2.00, and are above the 5th per centile for chronological age on the growth curve. These data indicate that rhGH treatment of growth-retarded children with CRF results in accelerated growth velocity during the 2nd and 3rd years of treatment, and demonstrate the potential for such children to achieve normal stature for chronological age despite the continued presence of renal failure.

Adolescent↗
PubMed1991

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 pair-fed 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 corticosteroids 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.

Animals↗
PubMed1991

A case report of Drash syndrome in a 46,XX female.

Progressive renal insufficiency, male pseudohermaphrotidism, and Wilms tumor are known as the triad of Drash syndrome. The renal involvement has been reported in association with Wilms tumor with or without pseudohermaphroditism. The nephropathy progresses rapidly, is unresponsive to steroids, and eventually requires dialysis. The case we report is a 46,XX phenotypic female child who had diffuse mesangial sclerosis (DMS) and developed Wilms tumor 3 years after initiating dialysis for end-stage renal disease (ESRD). Any child presenting with DMS should be considered at risk for development of Wilms tumor and should be investigated for the presence of XY gonadal dysgenesis. Once ESRD develops in such a child, prophylactic nephrectomy and possibly gonadectomy should be undertaken.

Child, Preschool↗
PubMed1991

Long-term cyclosporine A treatment of steroid-resistant and steroid-dependent nephrotic syndrome.

Eighteen patients with steroid-resistant nephrotic syndrome (SRNS) and steroid-dependent nephrotic syndrome (SDNS) were treated with cyclosporine A (CyA) (6 mg/kg/d) for 2 to 29 months. CyA levels were monitored monthly and plasma levels by Abbott TDX (Therapeutic Drug Analyzer System) fluorescence polarization immunoassay were maintained at 100 to 150 ng/mL. The corticosteroid dosage administered at the time CyA therapy was initiated was variable and was continued following CyA therapy. Six of these patients (all with SDNS and minimal change nephrotic syndrome [MCNS]) had been treated with one or more courses of cytotoxic drug therapy, and all had clinical evidence of corticosteroid toxicity after receiving corticosteroid therapy for 26 to 120 months. The corticosteroid dosage was reduced by slow tapering and was ultimately discontinued in six patients. These patients were maintained on CyA monotherapy for 7 to 21 months at a dose of 3.2 to 6.7 mg/kg/d. Following 11 to 29 months of CyA therapy, seven patients underwent an elective renal biopsy, which showed nephrotoxicity in all seven. This led to discontinuation of CyA in four patients. Following discontinuation of CyA monotherapy, all four patients relapsed within 2 to 4 months. CyA therapy did not achieve a remission in 10 patients with SRNS regardless of the presence of focal segmental glomerulosclerosis (FSGS) or MCNS on renal biopsy. In conclusion, CyA has limited effectiveness in patients with SDNS who manifest corticosteroid toxicity; however, CyA should be used cautiously because of the potential for CyA nephrotoxicity and the failure to obtain a sustained remission following discontinuation of CyA monotherapy. CyA dependence is substituted for corticosteroid dependence.

Biopsy↗
PubMed1991

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.

Animals↗