Oral Acyclovir Induced Acute Kidney Injury

Acyclovir is an antiviral medication often used to treat outbreaks of herpes in children. Acyclovir has an exceptional safety profile; there is a possibility that it might induce severe nephrotoxicity in rare cases. In this report, we present the case of a 17-year-old girl with acute renal injury as a side effect of using acyclovir. The patient was admitted for three days due to drug-induced AKI, which was reversed by discontinuing the afflicted medicine (acy -clovir), initiating appropriate hydration with intravenous normal saline 0.9%, and refraining from any nephrotoxic medications. Following up a week later, the patient was asymptomatic and had normal kidney function. Therefore, it is critical to use acyclovir correctly to avoid possibly fatal consequences.


INTRODUCTION
Acyclovir is now the most effective treatment for several herpes viruses, such as herpes encephalitis (Balfour H. H., 1984;YY., 1984), varicella zoster virus (VZV), or herpes simplex virus (HSV) infections in children with compromised immune systems. In addition, high-dose intravenous acyclovir to combat viral infections may be beneficial (YY., 1984). The adverse effects of acyclovir are well-known; nonetheless, most people do not consider it. The most prevalent underlying mechanism that acyclovir may generate is crystal nephropathy, which is reported to have the adverse side effect of inducing acute renal injury (AKI). It is hypothesized that the mechanism that causes the damage is the precipitation and crystallisation of the medicine inside the renal tubules, which results in obstruction and perhaps cellular necrosis (Izzedine, 2005;Mason, 2008). Patients with acyclovir-induced acute kidney injury have a fast reduction in their renal function and an increase in their blood creatinine level. This usually occurs between 12 and 48 hours after administering the medicine (Yildiz C, 2013;Zhang Y, 2016). Appropriate diagnosis and management of AKI caused by acyclovir are necessary for an effective prognosis (Zhang Y, 2016). In this report, we present a case of a 17-year-old girl who developed an acute kidney injury as a side effect of acyclovir in the management of herpes zoster infection.

METHODOLOGY Case Presentation
Seventeen years old female with known epilepsy was admitted to our hospital. She was diagnosed five years ago with epilepsy and started on treatment for a few weeks with poor compliance due to medication side effects. She has a five-day history of skin rash affecting her upper back and right shoulder (itchy, vesicular, painful, and affecting a dermatomal distribution of cervical 4,5 and 6) associated with nausea and vomiting at the time of admittance in another facility. During that period, she was started on acyclovir 800 mg orally three times daily for the diagnosis of herpes zoster infection, Diclofenac sodium 50 mg twice and levetiracetam 500 mg orally every 12 hours. Unfortunately, she was discharged one day before her current presentation to our hospital. She also gave a history of reduced urine output. Upon arrival, she was vitally stable and afebrile, weighted 60 kg with normal capillary refill time but dry mucous membranes. Systemic examination, apart from mild epigastric tenderness, was reported as unremarkable. Neurological examination revealed unremarkable results, including motor, sensory, cranial nerves, and cerebellar functions, and no photophobia or neck stiffness. Chest X-ray and ultrasound abdomen were unremarkable. CT head done earlier showed mucosal thickening and retention cyst of left maxillary sinuses. Her laboratory results showed creatinine of 202wµ mol/L, normal electrolytes and pH 7.33, and HcO3 18 mEq/L, lactate 0.8 mmol/L. She was admitted as having acute kidney injury, probably drug-induced, using the Naranjo algorithm of adverse drug reaction. The patient was admitted for three days as drug-induced AKI, and the culprit drug (acyclovir) was stopped with the initiation of proper hydration with normal intravenous saline 0.9% and avoiding all nephrotoxic medications. She was started on metoclopramide 10 mg intravenous when needed, pantoprazole 40 mg intravenous once daily, and paracetamol 1 gm for pain control, daily renal function tests showed improvement of kidney functions, and she was tolerant of oral intake. Upon follow-up a week later, a patient had normal kidney functions and was asymptomatic.

DISCUSSION
Nephropathy caused by oral acyclovir is uncommon and only manifests itself at very high doses (more than 500 mg/m2) when the medication is used by patients whose volume status has significantly reduced (Perazella., 1999).
It is critical to know the possible nephrotoxicity for the patients being treated with acyclovir. Our patient had an acute kidney injury while taking oral acyclovir and other nephrotoxic drugs and being volume depleted, but her creatinine improved when acyclovir stopped Therefore, acyclovir crystalluria and subsequent intrarenal obstruction and nephropathy would be the most plausible explanation for the observed renal injury, even if the crystals were undetected on regular urine analysis.
In individuals with underlying volume depletion and renal insufficiency, acyclovir dosage should be lowered.
To avoid crystallisation and eventual tubular blockage, gradual medication infusion over 1-2 hours, appropriate fluid replenishment, and introduction of high urine flow rates (100-150 ml/h) should be recommended (Brigden et al., 1982;Sawyer et al., 1988). Renal function should be monitored regularly in patients receiving high-dose intravenous acyclovir in patients diagnosed with renal impairment at any dosage level. Common symptoms include unusual sickness, nausea, abdominal discomfort, vomiting, and muscle twitching while receiving treatment (Wade JC, 1983). When serum creatinine levels rise, acyclovir must be managed to be discontinued. Hydration should be maintained during therapy to ensure a high urine flow (Gunness P, 2010). If no improvement is observed in patients with renal function soon after discontinuing acyclovir, other causes of renal toxicity should be sought. Treatment may be maintained at a lower dose for secondary infections that respond to acyclovir while a renal function is closely monitored. Since volume contraction may go undiagnosed in outpatients treated with acyclovir, they are more susceptible to acyclovirinduced kidney damage (Chawla, 2017).

CONCLUSION
It is concluded that to prevent morbidity, acute kidney injury must be diagnosed as soon as possible (Ratan., 2003). Since acyclovir is frequently prescribed for renal transplantation, patients with herpes simplex virus and herpes zoster infections, and patients with Neurological viral infections, therefore, practitioners must be aware of the associated risk, side effects, and how drug-related issues might be addressed.

Ethical Approval
Ethical approval for this study was obtained from Mediclinic Al Jowhara Hospital (Reference number: UHN: 1238416). All procedures performed in the study involving the patient were by the ethical standards of the governmental guidelines and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.