Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure

Raimund Hirschberg, Joel Kopple, Pamela Lipsett, Ernest Benjamin, Joseph Minei, Timothy E Albertson, Mark Munger, Michael Metzler, Gary Zaloga, Michael Murray, Stephen Lowry, John Conger, Wade McKeown, Michael O'Shea, Robert Baughman, Kenneth Wood, Marilyn Haupt, Roger Kaiser, Hank Simms, David WarnockWarren Summer, Raymond Hintz, Brian Myers, Kathrine Haenftling, William Capra, Marilyn Pike, Hans Peter Guler

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

Background. Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. Methods. Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430) ml/24 hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary endpoint was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. Results. During the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo- treated patients died during the 28 days after the onset of treatment. Conclusions. rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.

Original languageEnglish (US)
Pages (from-to)2423-2432
Number of pages10
JournalKidney International
Volume55
Issue number6
DOIs
StatePublished - 1999

Fingerprint

Insulin-Like Growth Factor I
Acute Kidney Injury
Multicenter Studies
Clinical Trials
Placebos
Creatinine
Recovery of Function
Glomerular Filtration Rate
Urea
Ultrafiltration
Urine
Transferrin
Kidney
Albumins
Serum
Iothalamic Acid
Injections
APACHE
Renal Replacement Therapy
Mortality

Keywords

  • Comorbidity in ARF
  • Hemodynamics
  • Ischemia
  • Nephrotoxicity
  • Protein catabolism

ASJC Scopus subject areas

  • Nephrology

Cite this

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure. / Hirschberg, Raimund; Kopple, Joel; Lipsett, Pamela; Benjamin, Ernest; Minei, Joseph; Albertson, Timothy E; Munger, Mark; Metzler, Michael; Zaloga, Gary; Murray, Michael; Lowry, Stephen; Conger, John; McKeown, Wade; O'Shea, Michael; Baughman, Robert; Wood, Kenneth; Haupt, Marilyn; Kaiser, Roger; Simms, Hank; Warnock, David; Summer, Warren; Hintz, Raymond; Myers, Brian; Haenftling, Kathrine; Capra, William; Pike, Marilyn; Guler, Hans Peter.

In: Kidney International, Vol. 55, No. 6, 1999, p. 2423-2432.

Research output: Contribution to journalArticle

Hirschberg, R, Kopple, J, Lipsett, P, Benjamin, E, Minei, J, Albertson, TE, Munger, M, Metzler, M, Zaloga, G, Murray, M, Lowry, S, Conger, J, McKeown, W, O'Shea, M, Baughman, R, Wood, K, Haupt, M, Kaiser, R, Simms, H, Warnock, D, Summer, W, Hintz, R, Myers, B, Haenftling, K, Capra, W, Pike, M & Guler, HP 1999, 'Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure', Kidney International, vol. 55, no. 6, pp. 2423-2432. https://doi.org/10.1046/j.1523-1755.1999.00463.x
Hirschberg, Raimund ; Kopple, Joel ; Lipsett, Pamela ; Benjamin, Ernest ; Minei, Joseph ; Albertson, Timothy E ; Munger, Mark ; Metzler, Michael ; Zaloga, Gary ; Murray, Michael ; Lowry, Stephen ; Conger, John ; McKeown, Wade ; O'Shea, Michael ; Baughman, Robert ; Wood, Kenneth ; Haupt, Marilyn ; Kaiser, Roger ; Simms, Hank ; Warnock, David ; Summer, Warren ; Hintz, Raymond ; Myers, Brian ; Haenftling, Kathrine ; Capra, William ; Pike, Marilyn ; Guler, Hans Peter. / Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure. In: Kidney International. 1999 ; Vol. 55, No. 6. pp. 2423-2432.
@article{a4e132cc6ed548618b251c5e1df41c10,
title = "Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure",
abstract = "Background. Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. Methods. Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35{\%} of patients) and hypotension or hemodynamic shock (42 and 27{\%} of patients). At baseline, the mean (± SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430) ml/24 hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary endpoint was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. Results. During the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo- treated patients died during the 28 days after the onset of treatment. Conclusions. rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.",
keywords = "Comorbidity in ARF, Hemodynamics, Ischemia, Nephrotoxicity, Protein catabolism",
author = "Raimund Hirschberg and Joel Kopple and Pamela Lipsett and Ernest Benjamin and Joseph Minei and Albertson, {Timothy E} and Mark Munger and Michael Metzler and Gary Zaloga and Michael Murray and Stephen Lowry and John Conger and Wade McKeown and Michael O'Shea and Robert Baughman and Kenneth Wood and Marilyn Haupt and Roger Kaiser and Hank Simms and David Warnock and Warren Summer and Raymond Hintz and Brian Myers and Kathrine Haenftling and William Capra and Marilyn Pike and Guler, {Hans Peter}",
year = "1999",
doi = "10.1046/j.1523-1755.1999.00463.x",
language = "English (US)",
volume = "55",
pages = "2423--2432",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure

AU - Hirschberg, Raimund

AU - Kopple, Joel

AU - Lipsett, Pamela

AU - Benjamin, Ernest

AU - Minei, Joseph

AU - Albertson, Timothy E

AU - Munger, Mark

AU - Metzler, Michael

AU - Zaloga, Gary

AU - Murray, Michael

AU - Lowry, Stephen

AU - Conger, John

AU - McKeown, Wade

AU - O'Shea, Michael

AU - Baughman, Robert

AU - Wood, Kenneth

AU - Haupt, Marilyn

AU - Kaiser, Roger

AU - Simms, Hank

AU - Warnock, David

AU - Summer, Warren

AU - Hintz, Raymond

AU - Myers, Brian

AU - Haenftling, Kathrine

AU - Capra, William

AU - Pike, Marilyn

AU - Guler, Hans Peter

PY - 1999

Y1 - 1999

N2 - Background. Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. Methods. Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430) ml/24 hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary endpoint was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. Results. During the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo- treated patients died during the 28 days after the onset of treatment. Conclusions. rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.

AB - Background. Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. Methods. Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430) ml/24 hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary endpoint was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. Results. During the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo- treated patients died during the 28 days after the onset of treatment. Conclusions. rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.

KW - Comorbidity in ARF

KW - Hemodynamics

KW - Ischemia

KW - Nephrotoxicity

KW - Protein catabolism

UR - http://www.scopus.com/inward/record.url?scp=0032991586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032991586&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.1999.00463.x

DO - 10.1046/j.1523-1755.1999.00463.x

M3 - Article

C2 - 10354291

AN - SCOPUS:0032991586

VL - 55

SP - 2423

EP - 2432

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 6

ER -