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

• Published in: American journal of kidney diseases Vol. 43; no. 3; pp. 405 - 414
• Main Authors: PARIKH, Chirag R, JANI, Alkesh, MELNIKOV, Vyacheslav Y, FAUBEL, Sarah, EDELSTEIN, Charles L
• Format: Journal Article
• Language: English
• Published: Orlando, FL Elsevier 01-03-2004
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers - urine; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-18 - urine; Kidney Diseases - urine; Kidney Tubular Necrosis, Acute - urine; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Human; Urine; Acute tubular necrosis; Nephrology; delayed graft function; Interleukin-18 (IL-18); Graft; Marker; acute tubular necrosis (ATN); Delay; Urology; Interleukin 18
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2003.10.040

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