Experimental Endourology Antioxidant Signal and Kidney Injury Molecule-1 Levels in Shockwave Lithotripsy Induced Kidney Injury Namık Kemal Hatipog ˘lu, MD, 1 Osman Evliyaog ˘lu, MD, 2 Birgu ¨l Is xık, PhD, 2 Mehmet Nuri Bodakc ¸i, MD, 1 Yas xar Bozkurt, MD, 1 Ahmet Ali Sancaktutar, MD, 1 Haluk So ¨ ylemez, MD, 1 Murat Atar, MD, 1 Necmettin Penbegu ¨l, MD, 1 Muharrem Yu ¨ nce, MD, 2 and Mansur Dag ˘ gulli, MD 1 Abstract Purpose: Shockwave lithotripsy (SWL) induces acute kidney injury (AKI) that extends from the papilla to the outer cortex by causing ischemia and the production of nephrotoxic agents. Direct ischemic damage and the generation of free radicals cause injury to the proximal tubular cells. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is upregulated in proximal tubular cells after ischemic or nephrotoxic injury and is not expressed in healthy kidneys. We evaluated the extent of free radical production in response to SWL by measuring urinary total antioxidant capacity (TAC) and total oxidant status (TOS). Furthermore, we inves- tigated the severity of SWL-induced kidney injury by measuring KIM-1 expression levels. Patients and Methods: The study population comprised 30 patients who were carefully selected and 30 age and sex matched control subjects. All patients received the same SWL procedure. Midstream urine samples were collected from patients before SWL and at 120 minutes after SWL. Urine KIM-1 levels were measured by enzyme-linked immunosorbent assay, and TAC and TOS were measured via spectrophotometry. Results: Mean levels of TAC (2.88 – 0.56 mmolTxEq/L),TOS (8.27 – 1.57 lmolH 2 O 2 Eq/L), and KIM-1 (0.55 – 0.08 ng/mL) before SWL were not significantly different from mean TAC, TOS, and KIM-1 levels mea- sured from the control group at 2.81 – 0.42 mmolTxEq/L, 10.73 – 1.4 lmolH 2 O 2 Eq/L, and 0.51 – 0.07 ng/mL, respectively. Two hours after SWL, mean urine TAC levels (2.81 – 0.85 mmolTxEq/L, P = 0.02) were decreased and mean KIM-1 expression (0.85 – 0.11 ng/mL, P = 0.01) was significantly increased, but there was no significant difference in mean TOS levels (11.24 – 1.9 lmolH 2 O 2 Eq/L, P = 0.627) compared with the control group. Conclusions: The increased burden of free radical oxidants in the setting of decreasing antioxidant capacity may be one of the initial indicators of AKI after SWL. Moreover, KIM-1 demonstrates great potential as an early and noninvasive biomarker of SWL-induced kidney injury. Introduction K idney stones £ 2 cm in the upper urinary tract are managed by extracorporeal shockwave lithotripsy (SWL). 1,2 SWL is safe and relatively noninvasive in compari- son with other treatment modalities such as percutaneous nephrolithotomy and retrograde intrarenal surgery. 3 In ad- dition, more than 90% of kidney stones diagnosed in adults might be suitable candidates for SWL management, which has a high success rate. 3,4 Although many benefits are at- tributed to this treatment, there are risks associated with this procedure. SWL may induce acute kidney injury (AKI) by causing vessel rupture and bleeding, inflammation, and he- modynamic impairment. 2,5 Moreover, once renal injury re- solves, a scar may develop. 5 The extent of damage to the kidney by SWL is evaluated by several parameters. Previous studies revealed that there were no significant discrepancies in renal function tests including glomerular filtration rate, serum creatinine, and electrolyte levels between subjects who did and did not receive SWL. 6–8 Nevertheless, many studies continue to investigate how to best quantify the effect of acute insults to the kidney by evaluating various noninvasive biomarkers of renal injury. 9,10 The current literature suggests that the most effective biomarkers of renal damage are kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein, and interleukin-18 (IL- 18). 10 KIM-1 is a transmembrane protein that is upregulated in proximal tubule cells after ischemic or nephrotoxic AKI. 10 Ichimura and associates 11 reported that KIM-1 expression Departments of 1 Urology and 2 Biochemistry, Faculty of Medicine, Dicle University, Diyarbakır, Turkey. JOURNAL OF ENDOUROLOGY Volume 28, Number 2, February 2014 ª Mary Ann Liebert, Inc. Pp. 224–228 DOI: 10.1089/end.2013.0535 224