Kidney Week

Abstract: FR-PO008

Cisplatin-Induced Kidney Injury Is Transient and Associated with Short-Term Elevation of Urine Interleukin-18 in Patients with Testicular Cancer

Session Information

• AKI: Clinical, Outcomes, Trials - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• McMahon, Kelly, McGill University, Montreal, Quebec, Canada

Kelly McMahon,

• Cameron, Alan C., University of Glasgow, Glasgow, United Kingdom

Alan C. Cameron,

• White, Jeff D., Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom

Jeff D. White,

• Welsh, Paul, University of Glasgow, Glasgow, United Kingdom

Paul Welsh,

• Zappitelli, Michael, Toronto Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Michael Zappitelli,

• Touyz, Rhian, University of Glasgow, Glasgow, United Kingdom

Rhian Touyz,

• Mark, Patrick B., University of Glasgow, Glasgow, United Kingdom

Patrick B. Mark,

• Lang, Ninian N., University of Glasgow, Glasgow, United Kingdom

Ninian N. Lang,

Background

Cisplatin causes acute kidney injury (AKI) but changes in urinary AKI biomarkers are not well defined in clinical practice. We investigated short- and medium-term AKI using novel biomarkers over 9 months in patients with testicular cancer treated with cisplatin.

Methods

Prospective observational study of men with testicular cancer in 3 groups following orchiectomy: 1) surveillance; 2) adjuvant cisplatin (1-2 cycles); 3) metastatic disease with high dose cisplatin (3-4 cycles). Blood/urine was collected at 6 visits: baseline, 24h, 6 weeks, 3, 6 and 9 months for renal injury markers.

Results

27 men (median age 34y [IQR 31-40y]) were recruited: surveillance (N=10); adjuvant cisplatin (N=7); metastatic cisplatin (N=10). Urine tubular injury markers (interleukin-18 [IL-18], neutrophil gelatinase-associated lipocalin [NGAL], vascular endothelial growth factor [VEGF], kidney injury molecule-1 [KIM-1]), urine albumin/creatinine ratio (ACR) and serum cystatin C (CysC) were elevated at 24h and 6 weeks (KIM-1) post cisplatin in adjuvant and metastatic groups (all: P<0.05 vs. baseline). These normalized by 6 weeks (IL-18, NGAL, VEGF, ACR, CysC) and 3 months (KIM-1). eGFR was within normal range throughout. Urine IL-18 rose in both cisplatin groups at 24h (median [IQR]: adjuvant 24h 22.8 [16.4-34.7] vs. baseline 6.8 [5.7-15.9]; metastatic 24h 23.7 [20.1-36.1] vs. baseline 9.2 [7.2-11.9] pg/mg, P<0.05) and returned to baseline by 6 weeks.

Conclusion

Cisplatin nephrotoxicity is reversible over 3 months and is evident with use of novel biomarkers. Elevation of IL-18 supports a major inflammatory renal insult. This provides evidence to support investigation of anti-inflammatory drugs to prevent cisplatin toxicity.

Funding

• Government Support - Non-U.S.