Doxycycline-induced acute kidney injury and left ventricular dysfunction in experimentally intoxicated calves

Myocardial, striated muscular and renal toxicity has been reported in calves after accidental doxycycline (DOX) intoxication. Myoglobinuric nephrotoxicity could be responsible for acute kidney injury (AKI) in those calves, but a direct toxic effect of DOX could also play a role. A previous experimental model of DOX overdose in calves failed to identify left ventricular (LV) dysfunction by 2D echocardiography. Two-dimensional-speckle tracking (2DST) is a more sensitive technique and could be more appropriate to detect regional LV dysfunction. To further evaluate the nephro- and the cardiotoxicity of experimental overdose of DOX in calves, 10 healthy Holstein calves were used: 5 receiving 25 mg/kg of DOX orally twice a day for 7 days, and 5 receiving a placebo. In this randomized double-blind placebo-controlled study, calves were monitored clinically. Blood, urine analyses were performed at day 0 (D0) and day 8 (D8) and echocardiography were performed at D0, day (D4) and D8 prior to postmortem examination. 2DST measurements included global and segmental peak values for radial and circumferential strains (SR, SC) and strain rates (SrR, SrC). Serum creatinine significantly increased in the DOX group compared to control at D8 ( p = 0.0269). Urinalysis and post-mortem examination confirmed lesions of acute tubulonephritis in the DOX group. LV function was impaired in the DOX group compared to control at D8 as shown by a significant decrease of average and segmental SR (all p < 0.05) and early diastolic SrC peak values for septal segments ( p = 0.0215). In calves, DOX overdose induces AKI. Systolic, and to a lesser extent diastolic, LV dysfunction were also observed. Understanding the pathophysiology of DOX overdose will help in the management of accidental cases.