Cardiovascular Journal of Africa: Vol 27 No 3 (May/June 2016)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016 128 AFRICA
Cardiovascular Topics
Iloprost as an acute kidney injury-triggering agent in
severely atherosclerotic patients
Mehtap Erkmen Uyar, Piril Yucel, Sena Ilin, Zeynep Bal, Saliha Yildirim, Ahmet Senol Uyar, Tankut Akay,
Emre Tutal, Siren Sezer
Abstract
Background: Iloprost, a stable prostacyclin analog, is used
as a rescue therapy for severe peripheral arterial disease
(PAD). It has systemic vasodilatory and anti-aggregant
effects, with severe vasodilatation potentially causing organ
ischaemia when severe atherosclerosis is the underlying cause.
In this study, we retrospectively analysed renal outcomes after
iloprost infusion therapy in 86 patients.
Methods: Eighty-six patients with PAD who received iloprost
infusion therapy were retrospectively analysed. Clinical and
biochemical parameters were recorded before (initial, Cr1),
during (third day, Cr2), and after (14th day following the
termination of infusion therapy, Cr3) treatment. Acute
kidney injury (AKI) was defined according to KDIGO guide-
lines as a ≥ 0.3 mg/dl (26.52 μmol/l) increase in creatinine
levels from baseline within 48 hours.
Results: Cr2 (1.46 ± 0.1 mg/dl) (129.06 ± 8.84 μmol/l) and Cr3
(1.53 ± 0.12 mg/dl) (135.25 ± 10.61 μmol/l) creatinine levels
were significantly higher compared to the initial value (1.15
± 0.6 mg/dl) (101.66 ± 53.04 μmol/l). AKI was observed in
36 patients (41.86%) on the third day of iloprost infusion.
Logistic regression analysis revealed smoking and not using
acetylsalicylic acid as primary predictors (p = 0.02 and p =
0.008, respectively) of AKI during iloprost treatment. On
the third infusion day, patients’ urinary output significantly
increased (1813.30 ± 1123.46 vs 1545.17 ± 873.00 cm 3) and
diastolic blood pressure significantly decreased (70.07 ± 15.50
vs 74.14 ± 9.42 mmHg) from their initial values.
Conclusion: While iloprost treatment is effective in patients
with PAD who are not suitable for surgery, severe systemic
vasodilatation can cause renal ischaemia, resulting in non-
oliguric AKI. Smoking, no acetylsalicylic acid use, and lower
diastolic blood pressure are the clinical risk factors for AKI
during iloprost treatment.
Keywords: iloprost, acute kidney injury, severe atherosclerosis
Submitted 20/11/14, accepted 14/6/15
Cardiovasc J Afr 2016; 27: 128–133
DOI: 10.5830/CVJA-2015-051
Iloprost is a stable epoprostenol (prostacyclin, PGI2) analog that
mimics the effects of prostacyclin in the microvascular blood
flow, namely, inhibition of platelet aggregation, leukocyte–vessel
interaction and vasodilatation.1,2 A superior chemical stability
confers iloprost with a longer half-life than that of prostacyclin,
giving it an advantage as a therapeutic agent for the treatment
of many cardiovascular and pulmonary diseases.3 Iloprost also
inhibits platelet aggregation and leukocyte activation, and leads
to vasodilatation in ischaemic tissue after ischaemia/reperfusion
(I/R) injury.4,5 Iloprost is used as a rescue therapy for patients
with severe obstructive peripheral arterial disease (PAD) who
cannot tolerate surgery.
Renoprotective effects of iloprost have been reported in
contrast-induced nephropathy and I/R injury. 6 In these cases,
iloprost infusion was administered either at a low dose or
for a short duration, causing vasodilation without systemic
hypotension.7,8 On the other hand, during rescue therapy for
severe atherosclerosis, its use may lower blood pressure,9 leading
to tissue ischaemia, renal hypoperfusion and acute kidney injury. 10
Because of iloprost’s hypotension-inducing potent systemic
vasodilatory effect, several potential safety issues should
be considered in these patients.11 This ischaemia-triggering
hypoperfusion effect of iloprost may cause organ dysfunction,
such as acute kidney injury, especially in patients with
co-morbidities. On the basis of the systemic hypotensive effect of
iloprost and our clinical experience of patients with acute kidney
injury under iloprost treatment, we retrospectively analysed the
effects of iloprost infusion therapy on renal outcomes in 86
patients.
Department of Internal Medicine, Baskent University,
Ankara, Turkey
Mehtap Erkmen Uyar, MD,
Piril Yucel, MD
Sena Ilin, MD
Zeynep Bal, MD
Saliha Yildirim, MD
Department of Anesthesiology, Ulucanlar Eye Education
and Research Hospital, Ankara, Turkey
Ahmet Senol Uyar, MD
Department of Cardiovascular Surgery, Baskent University,
Ankara, Turkey
Tankut Akay, MD
Department of Nephrology, Baskent University, Ankara,
Turkey
Emre Tutal, MD
Siren Sezer, MD