An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.

Abstract

OBJECTIVES:

The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD).

PATIENTS AND METHODS:

In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis.

RESULTS:

The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI.

CONCLUSIONS:

In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury.

• Authors: Louis Y A Chai, Mihai G Netea, Bee Choo Tai, Lay Wai Khin, Alieke G Vonk, Boon Wee Teo, Haran T Schlamm, Raoul Herbrecht, J Peter Donnelly, Peter F Troke, Bart-Jan Kullberg
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 68 Issue 7 Pg. 1655-9 (Jul 2013) ISSN: 1460-2091 [Electronic] England
• PMID: 23557927 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• IL10 protein, human
• IL6 protein, human
• Interleukin-6
• Interleukin-8
• Interleukin-10
• Amphotericin B

Topics

• Acute Kidney Injury (chemically induced, immunology)
• Adult
• Aged
• Amphotericin B (administration & dosage, adverse effects)
• Antifungal Agents (administration & dosage, adverse effects)
• Female
• Humans
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Male
• Middle Aged
• Serum (chemistry)