key: cord-0874973-w6topyk9 authors: Abdelbary, Asmaa A.; Alharafsheh, Ahmad E.; Ahmed, Afif; Nashwan, Abdulqadir J. title: Favipiravir‐induced nephrotoxicity in a patient with COVID‐19: A case report date: 2021-08-15 journal: Clin Case Rep DOI: 10.1002/ccr3.4539 sha: 46c04f943f111278c826486fc6d9628d4849eb2a doc_id: 874973 cord_uid: w6topyk9 This report describes a case of 45 years old male patient who tested positive for COVID‐19 presented to the emergency department on March 2021 complaining of fever, cough, runny nose, and shortness of breath. The patient denied any history of nausea or diarrhea who has eventually developed favipiravir‐induced nephrotoxicity. This report describes a case of 45-year-old male patient who tested positive for COVID-19 presented to the emergency department on March 2021 complaining of fever, cough, runny nose, and shortness of breath. The patient denied any history of nausea or diarrhea who has eventually developed favipiravir-induced nephrotoxicity. COVID-19 (caused by SARS-COV-2) has rapidly spread worldwide through close human interactions or the spilled respirational material (cough and sneeze) of the infected people resulting in a pandemic throughout China, as well as other countries throughout the world. 1 Acute kidney injury (AKI) is prevalent among patients admitted with SARS-COV-2 infections. 2 Many published studies had addressed this issue as poor clinical outcomes and prognosis accompany it. The mechanism and pathophysiology of renal involvement in SARS-COV-2 infection are unclear. Still, some published literature are justifying it by having COVID-19 related causes such as direct injury to the kidney tissue from the entry of the virus through the receptor angiotensin-converting enzyme ACE2, which is highly expressed in the kidney or non-COVID specific mechanisms like hypovolemia, hemodynamic instability, or sometimes nephrotoxic medications. [3] [4] [5] Favipiravir is an orally administered antiviral nucleotide analog. 6 It inhibits RNA polymerase, which targets both viral shedding and loads with subsequent reduction in mortality and intubation in patients affected with COVID-19. 7 It is one of the primary medications that have been used in the treatment protocol of confirmed COVID-19 mild-to-moderate pneumonia cases in the state of Qatar. Generally, favipiravir is well tolerated with a good safety profile, and the main reported ADRs are GIT side effects and elevation in both ALT and AST. 6 Favipiravir did not show a nephrotoxic effect on animal studies. Favipiravir is actively excreted through the renal route, and its serum concentration is expected to increase by twofold to threefold in patients with eGFR of 30-50 ml/min; however, data are lacking and insufficient about the need for renal dosing calculation or adjustment. 8 Clinical trials are excluding patients with severe renal impairment. Favipiravir had shown efficacy in treating COVID-19 pneumonia on some ESRD patients who are maintained on hemodialysis. 9 The drug data basis and monographs are only recommending general caution about worsening renal parameters and kidney functions; however, they lack data about adequate dose adjustments based on current kidney or liver functions. TA is 45-year-old male obese patient (body mass index [BMI] = 35) known case of hypertension (HTN) for more than 10 years controlled on amlodipine 10 mg daily, chronic kidney disease (CKD) with a history of proteinuria (Baseline Srcr 177 mmol/L with calculated Clcr =51 ml/min) Old CVA (Left Basal Ganglia ICH 2016 with right hemiparesis maintained on baclofen 10 mg TID), presented to the emergency department on March 13, 2021 complaining of fever, cough, runny nose, and shortness of breath. The patient denied any history of nausea or diarrhea. He has positive COVID-19 PCR with an average CT = 29, Temp = 37, a chest X-ray showed mild infiltrates on Lt side blood results on admission are shown on ( Table 1) . The patient was started on COVID-19 Medication as per our protocol. favipiravir 1600mg bid received on March 14, 2021 then 600mg bid for total 7 days (received only one day March 15, 2021) , ceftriaxone 2gm IV daily for 7 days, and dexamethasone 8mg IV daily for 10 days. We found the patient to have an abrupt elevation on his Src from the baseline admission by 2.7-fold approximately 48 hours after starting favipiravir reaching 489µmol/l with accepted urine output 1.3-1.5 L (see Figure 1 ); nephrologist was consulted who had ordered for ultrasound kidneys, ureters, and bladder (USG KUB) which showed normal size bilateral kidneys with evidence of chronic parenchymal medical disease as well as autoimmune workup (C3, C4, ANA, anti-GBM) which all came negative to rule out autoimmune kidney disease. Serum creatinine and renal parameters showed trending down after stopping favipiravir until reaching baseline of 169 Mmol/L with adequate renal output also; the patient showed features of resolving respiratory failure; trending down inflammatory markers and successful oxygen weaning off. The AKI improved within 12-24 hours after favipiravir discontinuation, demonstrating a timely association of favipiravir and the abrupt elevation of renal parameters (nephrotoxicity). Drug-induced nephrotoxicity is defined by "the presence of any kidney injury caused directly or indirectly by medication". 10 It is common among hospitalized patients, the third main cause of AKI, and anti-infectives had been shown to be one of the most common drug classes associated with it. 11 Favipiravir had been widely used as an effective antiviral for the management of COVID-19 pneumonia since it was declared as a pandemic last December 2019. Favipiravir had shown better therapeutic responses on COVID-19 pneumonia in terms of disease progression and viral clearance. 12 In another randomized, controlled, open-label multicenter trial, favipiravir was found to significantly improve the latency to relief for pneumonia symptoms like pyrexia and cough. 13 According to Nasa and colleagues, 14 there was a case report published early this year of two COVID-19 pneumonia male patients (38 and 51 years old) with normal kidney functions at baseline who had developed non-oliguric AKI approximately 48hours after receiving favipiravir on the same dose like that mentioned above. This AKI had improved 24-48 hours after stopping favipiravir and this to a certain extent coincident with the abovementioned findings of our patient apart from that our patient is a known case of CKD. The presence of CKD was a risk factor of favipiravirinduced nephrotoxicity and AKI in our reported patient case; however in the absence of documented nephrotoxicity in the drug leaflet and monograph, clinicians may choose to still prescribe the medication in those patients with stable CKD if the anticipated benefit outweighs the highlighted harm and with close monitoring of kidney functions especially that favipiravir had demonstrated an efficacy against COVID-19 patient with ESRD undergoing maintenance hemodialysis. 15 The health care professional need to be very careful of any new adverse events with all the medications used to treat COVID-19 pneumonia as enough evidence from the literature does not support them. The AKI needs a comprehensive review for all possible underlying etiologies and causes before correlating it to COVID-19. 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Favipiravir-induced nephrotoxicity in a patient with COVID-19: A case report