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).


CONCLUSIONS
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.
Department of Medicine, University of Colorado School of Medicine, Denver, CO 80262, USA.
Chirag R
CR
Parikh
Alkesh
A
Jani
Vyacheslav Y
VY
Melnikov
Sarah
S
Faubel
Charles L
CL
Edelstein
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D007674:Kidney Diseases / Q000652:urine; D007683:Kidney Tubular Necrosis, Acute / Q000652:urine*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D020382:Interleukin-18