Urinary interleukin-18 is a marker of human acute tubular necrosis

Am J Kidney Dis. 2004 Mar;43(3):405-14. doi: 10.1053/j.ajkd.2003.10.040.


Background: Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice.

Methods: IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied.

Results: Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 +/- 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 +/- 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 +/- 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 +/- 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 +/- 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 +/- 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 +/- 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 +/- 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 +/- 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009).

Conclusion: IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / urine
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-18 / urine*
  • Kidney Diseases / urine
  • Kidney Tubular Necrosis, Acute / urine*
  • Male
  • Middle Aged


  • Biomarkers
  • Interleukin-18