Original investigation: transplantation
Urinary actin, interleukin-6, and interleukin-8 may predict sustained arf after ischemic injury in renal allografts

https://doi.org/10.1016/S0272-6386(03)00206-3Get rights and content

Abstract

Background:

Cellular damage and inflammation after ischemia contribute to sustained acute renal failure (ARF).

Methods:

To quantify cellular damage and inflammation in postischemic ARF and identify markers of renal functional outcome, urine specimens from 40 renal allograft recipients, including 30 cadaveric (9 “sustained ARF” and 21 “recovery” subjects) and 10 living donor allografts (“LD”), were analyzed for actin, γ-glutamyl transpeptidase (GGTP), lactate dehydrogenase (LDH), interleukin–6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) during the first posttransplant week.

Results:

On day 0, urinary actin, GGTP, IL-6, and IL-8 were elevated in recipients destined to have sustained ARF compared with those destined to recover. Median values per gram of urine creatinine in the sustained ARF, recovery, and LD groups were 263.9, 0.0, and 0.0 μg for actin; 5000.0, 892.9, and 5555.6 U for GGTP; 193.1, 27.2, and 10.5 ng for IL-6; and 382.0, 17.8, and 18.5 ng for IL-8, respectively. In contrast, urinary LDH and TNF-α increased in recipients with recovering function compared with those who had sustained ARF. The corresponding median values were 36.7 and 16.3 U (recovery versus sustained ARF) for LDH, and 18.4 and 7.6 ng (LD versus sustained ARF) for TNF-α. Computational analyses using the Receiver Operating Characteristic Curve found that elevated urinary actin, IL-6, and IL-8 on day 0 were strong predictors of sustained ARF, where the calculated areas under the curve were 0.75, 0.91, and 0.82, respectively.

Conclusion:

Increased urinary actin, IL-6, and IL-8 may be useful markers for the prediction of sustained ARF after ischemia.

Section snippets

Subjects

The subjects comprised 30 consecutive consenting recipients of a cadaveric renal allograft (CAD), and 10 recipients of a living donor kidney (LD) who never had an episode of acute rejection or other medical and surgical complications during the first 2 posttransplant weeks. Informed consent was obtained for a postoperative study of renal allograft function and damage approved previously by Indiana University-Purdue University in Indianapolis and Clarian Institutional Review Boards. Patient age

Clinical features

Clinical characteristics of the allografts and patient population are summarized in Table 1. Gender and age distribution of patients were similar in the cadaveric allograft groups displaying sustained ARF and recovery and the living donor group. Total and warm ischemic times did not differ significantly between sustained ARF and recovery groups (1,706.2 ± 146.5 versus 1,664.4 ± 53.1 min and 34.8 ± 2.0 versus 36.9 ± 1.3 min, respectively).

Renal function

Subjects were classified into the sustained ARF or

Discussion

Clinical parameters that are obtained easily and reliably and reflect the ongoing pathophysiologic status of the kidney may facilitate improved management and decrease morbidity and mortality in ARF. In this study, we analyzed daily urine samples from recipients of a renal allograft to determine potential markers of renal injury and inflammation. Ischemic insult to the kidney often results in damage to cells of nephron and renal vasculature. Cells are lost through the processes of necrosis and

Acknowledgements

The authors thank Serafina K. Salamo, Stacy Vulgamott, and Seok-Min Hong for technical assistance.

References (67)

  • T. Hirano et al.

    Biological and clinical aspects of interleukin 6

    Immunol Today

    (1990)
  • F. Kayama et al.

    Cadmium-induced renal damage and proinflammatory cytokinesPossible role of IL-6 in tubular epithelial cell regeneration

    Toxicol Appl Pharmacol

    (1995)
  • R.J. Stewart et al.

    Biological control of the tumor necrosis factor and interleukin-1 signaling cascade

    Am J Kidney Dis

    (1995)
  • L. Baud et al.

    Production of tumor necrosis factor by rat mesangial cells in response to bacterial lipopolysaccharide

    Kidney Int

    (1989)
  • M.R. Shalaby et al.

    Endotoxin, tumor necrosis factor-alpha, and interleukin 1 induce interleukin 6 production in vivo

    Clin Immunol Immunopathol

    (1989)
  • T. Wada et al.

    Detection of urinary interleukin-8 in glomerular diseases

    Kidney Int

    (1994)
  • E.M. Levy et al.

    The effect of acute renal failure on mortality—A cohort analysis

    JAMA

    (1996)
  • H. Rabb

    Evaluation of urinary markers in acute renal failure

    Curr Opin Nephrol Hyperten

    (1998)
  • N.E. Tolkoff-Rubin et al.

    Diagnosis of tubular injury in renal transplant patients by a urinary assay for a proximal tubular antigen, the adenosine-deaminase-binding protein

    Transplantation

    (1986)
  • M. Taman et al.

    Increased urinary hepatocyte growth factor excretion in human acute renal failure

    Clin Nephrol

    (1997)
  • S. Di Paolo et al.

    Renal expression and uriary concentration of EGF and IL-6 in acutely dysfunctioning kidney transplanted patients

    Nephrol Dial Transplant

    (1997)
  • B. Li et al.

    Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine

    N Engl J Med

    (2001)
  • N. Schwartz et al.

    Ischemia activates actin depolimerizing factorRole in proximal tubule microvillar actin alterations

    Am J Physiol

    (1999)
  • S.L. Ashworth et al.

    Ischemic injury induces ADF relocalization to the apical domain of rat proximal tubule cells

    Am J Physiol Renal Physiol

    (2001)
  • B.A. Molitoris

    Ischemia-induced loss of epithelial polarityPotential role of the actin cytoskeleton

    Am J Physiol

    (1991)
  • B.A. Molitoris et al.

    Ischemia-induced loss of epithelial polarity. Role of the tight junction

    J Clin Invest

    (1989)
  • P. White et al.

    Coincident microvillar actin bundle disruption and perinuclear actin sequestration in anoxic proximal tubule

    Am J Physiol

    (2000)
  • O. Kwon et al.

    Ischemia induces alterations of actin filaments in renal vascular smooth muscle cells

    Am J Physiol Renal Physiol

    (2002)
  • W. Kuhne et al.

    Disintegration of cytoskeletal structure of actin filaments in energy-depleted endothelial cells

    Am J Physiol

    (1993)
  • Z. Albert et al.

    Histochemical demonstration of gamma-glutamyl transpeptidase

    Nature

    (1961)
  • G.G. Glenner et al.

    Histochemical demonstration of gamma-glutamyl transpeptidase-like activity

    J Histochem Cytochem

    (1962)
  • C.J. Danpure

    Lactate dehydrogenase and cell injury

    Cell Biochem Function

    (1984)
  • Cited by (0)

    This study was supported by Department of Medicine, Indiana University School of Medicine.

    View full text