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

1999 ◽  
Vol 276 (4) ◽  
pp. R929-R934 ◽  
Author(s):  
Anitha Vijayan ◽  
Samuel C. Franklin ◽  
Terry Behrend ◽  
Marc R. Hammerman ◽  
Steven B. Miller
Keyword(s):  
Renal Function ◽  
Growth Factor ◽  
Side Effects ◽  
Glomerular Filtration ◽  
Controlled Trial ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Improved Function ◽  
Double Blinded ◽  
End Stage

There is no pharmacological treatment to increase the glomerular filtration rate in end-stage renal disease (ESRD). The administration of 100 μg/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 μg ⋅ 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.

Insulin-like growth factor I preserves renal function postoperatively

1997 ◽  
Vol 272 (2) ◽  
pp. F257-F259 ◽  
Author(s):  
S. C. Franklin ◽  
M. Moulton ◽  
G. A. Sicard ◽  
M. R. Hammerman ◽  
S. B. Miller
Keyword(s):  
Intensive Care Unit ◽  
Renal Failure ◽  
Renal Function ◽  
Intensive Care ◽  
Growth Factor ◽  
Serum Creatinine ◽  
Creatinine Clearance ◽  
Renal Dysfunction ◽  
Insulin Like Growth Factor ◽  
Igf I

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.

Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep

2001 ◽  
Vol 281 (1) ◽  
pp. R318-R326 ◽  
Author(s):  
Amanda C. Marsh ◽  
Karen J. Gibson ◽  
June Wu ◽  
Phillip C. Owens ◽  
Julie A. Owens ◽  
...  
Keyword(s):  
Renal Function ◽  
Growth Factor ◽  
Plasma Renin ◽  
Sodium Reabsorption ◽  
Insulin Like Growth Factor ◽  
Adult Rats ◽  
Fetal Sheep ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 ± 1 days gestation) were infused intravenously for up to 10 days with 80 μg/h IGF-I ( n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased ( P< 0.05). However, by 4 days, GFR per kilogram had risen by 35 ± 13% ( P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ∼35% ( P < 0.005). Therefore, despite a marked increase in filtered sodium (∼30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days ( P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ∼30% more ( P = 0.05) and contained ∼75% more renin than control fetuses ( P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.

scholarly journals Insulin-Like Growth Factor I Plays a Role in Regulating Erythropoiesis in Patients with End-Stage Renal Disease and Erythrocytosis

1999 ◽  
Vol 10 (2) ◽  
pp. 315-322
Author(s):  
LEE-YUNG SHIH ◽  
JENG-YI HUANG ◽  
CHING-TAI LEE
Keyword(s):  
Growth Factor ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Insulin Like Growth Factor ◽  
Erythroid Progenitor ◽  
Factor I ◽  
Igf I ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

Abstract. Erythroid progenitor growth, the serum hormones that regulate erythropoiesis, and the effect of patient's serum on the growth of normal erythroid progenitors were assessed in eight patients with end-stage renal disease (ESRD) and erythrocytosis. All patients were male and had been on maintenance dialysis, they had a hematocrit >50% and/or a red blood cell count >6 × 1012/L and an arterial oxygen saturation >95%. Four had acquired cystic disease of the kidney (ACDK), and four other non-ACDK patients did not have known causes of secondary erythrocytosis after appropriate investigations and long-term follow-up. The methylcellulose culture technique was used to assay the erythroid progenitor (BFU-E/CFU-E) growth. Serum erythropoietin (EPO) and insulin-like growth factor I (IGF-I) levels were measured by RIA. Paired experiments were performed to determine the effects of 10% sera from ESRD patients and control subjects on normal marrow CFU-E growth. The numbers of EPO-dependent BFU-E in marrow and/or blood of patients with ESRD and erythrocytosis were higher than those of normal controls. No EPO-independent erythroid colonies were found. Serum EPO levels were constantly normal in one patient and elevated in three patients with ACDK; for non-ACDK patients, EPO levels were normal or low in two patients and persistently increased in one, but fluctuated in the remaining one on serial assays. There was no correlation between serum EPO levels and hematocrit values. The serum IGF-I levels in patients with ESRD and erythrocytosis were significantly increased compared with normal subjects or ESRD patients with anemia. We found an inverse correlation between serum EPO and IGF-I levels. Sera from patients with ESRD and erythrocytosis exhibited a stimulating effect on normal marrow CFU-E growth. The stimulating effect of sera from patients who had a normal serum EPO level and an elevated IGF-I level could be partially blocked by anti-IGF-I. The present study suggests that IGF-I plays an important role in the regulation of erythropoiesis in patients with ESRD and erythrocytosis who did not have an increased EPO production.

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