Urinary Interleukin-18 Is a Marker of Human Acute Tubular Necrosis

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.