Insulin-like growth factor 1 enhances renal function in a patient with chronic renal failure on peritoneal dialysis.

Insulin-like growth factor 1 (IGF1) has been shown to improve renal function in healthy subjects, as well as those with chronic renal failure. To our knowledge, IGF1 has not been shown to be efficacious in patients who were already undergoing dialysis. We present the case of a 70-year-old woman with end-stage renal disease (ESRD) and overt uremic symptoms treated with IGF1 after peritoneal dialysis was discontinued because of complications. There was a significant improvement in her inulin clearance during the course of treatment. The patient remained well and did not require dialytic support for 19 weeks. Although further data are necessary, we believe this case shows that IGF1 may be a short-term alternative to dialysis in patients with ESRD.

Insulin-like growth factor I improves renal function in patients with end-stage chronic renal failure.

There is no pharmacological treatment to increase the glomerular filtration rate in end-stage renal disease (ESRD). The administration of 100 microgram/kg of insulin-like growth factor (IGF) I twice a day to patients with ESRD increases inulin clearance. However, its effect is short-lived and IGF-I has major side effects when given this way. To assess whether the use of a lower intermittent dose of IGF-I would effect sustained improved function with tolerable side effects we performed 1) a prospective open-labeled 24-day trial in which we enrolled five patients and 2) a 31-day randomized, double-blinded, placebo-controlled trial in which we enrolled 10 patients. Patients with ESRD [creatinine clearance of <15 ml. min-1. (1.73 m2)-1] and scheduled to initiate renal replacement therapy received subcutaneous IGF-I, 50 microgram. kg-1. day-1, or vehicle. Treatment with IGF I resulted in significantly increased glomerular filtration rates (inulin clearances) during the 3rd and 4th wk of therapy in both prospective and double-blinded studies. Vehicle had no effect. No patient required discontinuation of drug secondary to side effects. We conclude that IGF-I effects sustained improvement of renal function (clearances comparable to those generally achieved by dialysis) in patients with ESRD and is well tolerated.

Recombinant human insulin-like growth factor-I (IGF-I) therapy decreases plasma leptin concentration in patients with chronic renal insufficiency.

OBJECTIVE: To determine the relationship between plasma leptin and insulin-like growth factor-I (IGF-I) levels in healthy subjects and patients with chronic renal insufficiency at baseline, and during administration of recombinant human IGF-I in the renal impaired patients. SUBJECTS: 20 healthy subjects (six men, 14 women, age: 42.7 +/- 3.2 y) and nine subjects with chronic renal insufficiency (five men, four women, age: 53.6 +/- 3.7 y). INTERVENTION: Daily s.c. injection of recombinant human IGF-I (50 micrograms/kg) for 24 d. MEASUREMENTS: Fasting plasma levels of leptin, IGF-I, growth hormone, C-peptide, glucagon and IGF binding proteins by specific radioimmunoassays at baseline in all subjects and serially during IGF-I therapy in the renal impaired subjects. RESULTS: Baseline leptin levels were correlated with body mass index (BMI, R = 0.72, P = 0.0001) but not IGF-I levels (R = 0.02). During IGF-I therapy, plasma IGF-I levels increased from 128 +/- 17.4 ng/ml at baseline to 250 +/- 36.8 ng/ml on day 3 (P = 0.003) and 323 +/- 61.6 ng/ml on day 24 (P = 0.01), whereas leptin levels declined: 24.4 +/- 10.3 ng/ml (baseline), 19.5 +/- 6.2 ng/ml (day 3, P = 0.028), and 17.2 +/- 4.9 ng/ml (day 24, P = 0.05). CONCLUSION: Basal plasma leptin and IGF-I levels are not correlated; however, chronic administration of recombinant IGF-I is associated with an early and sustained decrease in plasma leptin levels. IGF-I may have an inhibitory effect on leptin secretion in humans.

Insulin-like growth factor I preserves renal function postoperatively.

Deterioration of renal function, which can lead to postoperative renal failure, is a complication of surgery involving the suprarenal aorta and surgery involving the renal arteries. Fifty-four patients who were at risk for developing this complication were enrolled in a double-blind, randomized, placebo-controlled trial of insulin-like growth factor (IGF-I) as a therapeutic agent to prevent the decline in renal function. The primary end point was the incidence of renal dysfunction, defined as a reduction of the glomerular filtration rate (creatinine clearance) at each of three measurements over 72 h. IGF-I (100 microg/kg subcutaneously every 12 h for 6 doses) or placebo was administered on admission to the intensive care unit immediately postoperatively. IGF-I- and placebo-treated groups were well matched for sex, age, type of surgery, renal ischemic time during surgery (ischemic index), baseline creatinine clearance, and baseline serum creatinine. No patient in the study developed acute renal failure postoperatively. IGF-I was well tolerated. A smaller proportion of patients in the IGF-I group had a postoperative decline in renal function (22%) than in the placebo-treated group (33%). There were no significant differences in levels of serum creatinine at time of discharge, length of hospital stay, length of intensive care unit stay, length of intubation, or incidence of dialysis or death. Our findings establish the feasibility and potential utility for the use of IGF-I to reduce the incidence of postoperative renal dysfunction in high-risk patients.

Prophylaxis with diphenylhydantoin and phenobarbital in alumina-gel monkey model. II. Fourth-month follow-up period: seizure, EEG, blood and behavioral data.

This study, a 4-month follow-up period of a 12-month treatment study by the present authors, was concerned with the permanent effects of treatment with diphenylhydantoin and phenobarbital in the alumina-gel monkey model. Whereas the 8 drug animals during withdrawal increased their seizure frequency, duration, and severity, those 4 animals having received 120 mg/kg/day DPH in weeks 6-12 had one-half the number of seizures of the 4 placebo monkeys in the follow-up period. The other 4 drug animals who had continued to receive 60 mg/kg/day DPH during those weeks had two to four times the number of seizures of the placebo group during posttreatment. (All drug monkeys received 80 mg/kg/day of DPH from weeks 13-52 and 6 mg/kg/day of phenobarbital throughout the 12-month treatment period). The results reaffirm the problems of drug withdrawal and the importance of altering seizure mechanisms with sufficiently high doses of efficacious anticonvulsants rather than merely treating epileptic manifestations at lower doses.