key: cord-0861270-w59qwilz authors: El Shamy, Osama; Munoz-Casablanca, Nitzy; Coca, Steven; Sharma, Shuchita; Lookstein, Robert; Uribarri, Jaime title: Bilateral Renal Artery Thrombosis in a Patient With COVID-19 date: 2020-11-10 journal: Kidney Med DOI: 10.1016/j.xkme.2020.07.010 sha: a2c2225c11334a4dd5752077deee986632544b6e doc_id: 861270 cord_uid: w59qwilz Reports of the incidence of acute kidney injury (AKI) in patients with COVID-19 have varied greatly from 0.5% to as high as 39%, with onset generally within 7 days from time of admission(1). The nature of the kidney insult is acute tubular necrosis, immune cell infiltration or rhabdomyolysis as demonstrated in autopsy reports(2)(,)(3). Moreover, infection with COVID-19 has been associated with coagulation abnormalities(4), as well as complement-mediated generalized thrombotic microvascular injury(5). These patients have been found to have high D-dimer, fibrin degradation product and fibrinogen values, an elevated INR, normal PTT and normal platelet counts. Renal artery thrombosis is a rare condition, the most common cause of which is atrial fibrillation. However, bilateral completely occlusive renal artery thrombosis is even rarer. We present a case of a patient with COVID-19 on systemic anticoagulation who presented with a serum creatinine of 6.04mg/dL requiring the initiation of kidney replacement therapy and was found to have bilateral renal artery thrombosis. The COVID-19 pandemic has presented the medical community and society at large with unprecedented challenges. The virus has had devastating effects on multiple organ systems. Hypercoagulability and thrombotic disease have also been observed at J o u r n a l P r e -p r o o f alarmingly high levels. The incidence of thrombotic disease in COVID-19 patients has been reportedly as high as 31% 6 . Zuo et al 7 even found that 52% of hospitalized COVID-19 patients had antiphospholipid antibodies. A rare condition seen in patients in a prothrombotic state is renal artery thrombosis. A large case series of emergency department patients revealed a prevalence of 0.02/1000 8 , whereas a series of 14,000 autopsies revealed a prevalence of 14/1000 9 . The most common cause of renal artery thrombosis is atrial fibrillation, followed by cholesterol-based emboli. The development of moderate-to-severe AKI in COVID-19 positive patients has been associated with a significant mortality risk 10, 11 . Those patients' 180-day mortality rate was 58% compared to their non-AKI counterparts at 28% 11 . Furthermore, the angiotensin-converting enzyme 2 (ACE-2) receptor -located on the surface of renal tubular cells, amongst other cells -has been identified as the receptor that SARS-CoV-2 uses to facilitate viral entry into target cells 12 . Furthermore, kidney damage has been reported in 80% of COVID-19 associated pneumonia cases 13 . The resultant increase in demand for kidney replacement therapy (KRT) has presented a challenge to medical institutions all around the world with as many as 5% of ICU patients requiring dialysis during the second week of infection 14 . We present a case of a woman in her 60s with a past medical history of paroxysmal atrial fibrillation on apixaban, hypertension, heart failure with preserved ejection fraction, and gastroesophageal reflux who presented to the Mount Sinai Hospital with a 2-day history of shortness of breath and productive cough. She was found to be in atrial fibrillation with rapid ventricular rate which resolved with intravenous diltiazem J o u r n a l P r e -p r o o f administration, as well as hypoxic respiratory failure requiring bilevel positive airway pressure. She was diagnosed with COVID-19 and was started on hydroxychloroquine, azithromycin and methylprednisolone. Her respiratory status improved and she was placed on oxygen nasal cannula as needed. Admission laboratory bloodwork was significant for a white blood cell count of 36.8 x 10 3 /µL serum creatinine of 6.04 mg/dL (last known creatinine was 0.64 mg/dL on 7/6/19), serum blood urea nitrogen of 53 mg/dL, serum lactate dehydrogenase of 2,600 U/L, and a brain natriuretic peptide 1,126 pg/mL. Urinalysis was significant for 4-10 red blood cells, 5-10 white blood cells and protein ≥ 500 mg/dL. The patient's last known urinalysis was from July 2019 and was unremarkable and negative for blood and protein. A kidney ultrasound demonstrated echogenic kidneys bilaterally with no hydronephrosis, mass or kidney stone visualized. She was started on intermittent hemodialysis via a femoral central venous catheter (CVC) prior to being transitioned to peritoneal dialysis. Both the CVC and PD catheter exit sites were complicated by consistent oozing requiring multiple daily dressing changes. The patient's peritoneal fluid was blood tinged for the first 2 days, and her hemoglobin remained stable at 13.6 g/dL. Her hemoglobin then dropped to 5.5 g/dL over the following 43 hours. A multiphase contrast enhanced computed tomography angiogram of the abdomen and pelvis was performed. Incidentally, bilateral renal artery thrombosis ( Figure 1A ), as well as thrombosis of the proximal celiac artery with distal reconstitution were identified, with no evidence of acute arterial extravasation. Although the kidneys appeared atrophic and lobulated in contour with perinephric fat stranding, they were of similar size to her last known computer tomography with contrast of her abdomen and pelvis ( Figure 1B) . On hospital day 8, the day after the angiogram, the patient underwent elective bilateral renal artery angiogram, confirming complete occlusion of the bilateral renal arteries. Successful percutaneous bilateral renal artery aspiration thrombectomy and thrombolysis was then performed with stent placement in the right renal artery with widely patent renal arteries on completion angiogram and restoration of blood flow ( Figure 2 ). Further imaging revealed a pulmonary embolism as well as thrombotic occlusion of the left subclavian artery. A hypercoagulable work-up was undertaken (summarized in Table 1) Bowles et al 19 found that 91% of their patients who were SARS-CoV-2 positive and with a prolonged aPTT were also positive for lupus anticoagulant. In our patient, the lupus anticoagulant panel revealed an aPTT that was more prolonged than the screening aPTT performed at the same time (38.2 vs 35.2 seconds) -this is an expected variation given that the lupus anticoagulant panel plasma sample is frozen prior to testing. While we did not test for individual coagulation pathway factor levels, the normal aPTT actin factor sensitive indicates normal coagulation pathway factor levels. We acknowledge that in order to perform an accurate, reliable thrombophilia work-up, the patient in question should be off all forms of anticoagulation. However, given the clinical context, it would not be ethical to hold the anticoagulation in a patient with known atrial fibrillation who developed bilateral renal artery thromboses while on systemic anticoagulation. Renal artery thrombosis is a rare condition. Amongst patients with atrial fibrillation with peripheral arterial thromboembolic events, renal arteries are the least affected at only 2% of the cases (as opposed to the extremities -61%) 20 . Moreover, complete infarction is the most rare, typically seen after trauma or interventions involving the aorta, neither of which were the case with our patient who was also on systemic anticoagulation both prior to and during her presentation. For these reasons, we believe that it is unlikely that atrial fibrillation was the underlying etiology in this case. It was anticipated that the renal artery thrombectomy could have potentially salvaged the patient's kidney function, however, the repeated administration of iodinated contrast and the subsequent hemodynamic instability due to continued bleeding (the Kidney disease is associated with in-hospital death of patients with COVID-19 Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. medRxiv Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases The Role of Anticoagulation in COVID-19-Induced Hypercoagulability Prothrombotic Antiphospholipid Antibodies in COVID-19 Acute renal infarction. 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