key: cord-0750936-m4s3gtmk authors: Bascuñana., Arturo; Mijaylova., Antonia; Vega, Almudena; Macías, Nicolás; Verde, Eduardo; Rodríguez-Ferrero, Maria Luisa; Delgado, Andrés; Carbayo, Javier; Goicoechea, Marian title: Thrombotic Microangiopathy in a Kidney Transplant Patient With COVID-19 date: 2020-12-10 journal: Kidney Med DOI: 10.1016/j.xkme.2020.09.014 sha: c2e95c5f70f7b87db7c79c22b019f6e28502c33a doc_id: 750936 cord_uid: m4s3gtmk Kidney transplant recipients are at increased risk of infection, including COVID-19, given ongoing immunosuppression. In individuals with COVID-19, complications including thrombosis and endothelial dysfunction, portend worse outcomes. In this report, we describe a kidney transplant recipient who developed severe thrombotic microangiopathy (TMA) with low platelet count (12 x 109 /L), anemia (7.5g/dL with 7% schistocytes on peripheral blood smear) and severe acute kidney injury concurrent with COVID-19. The clinical course improved following plasma exchange. Given this presentation, we hypothesize that COVID-19 triggered TMA. Many systemic complications associated with COVID-19 have been described. There is a complex relationship between COVID-19 infection and pathological activation of immune cells, with not only inflammatory pathway activation and the presence of cytokine storm but also endothelial injury, dysfunction and microthrombotic pathway activation. We describe a kidney transplant patient with COVID-19 infection who developed a severe thrombotic microangiopathy (TMA) in the setting of acute infection. The patient is a man in his 40s who is 9 years status post cadaveric donor kidney transplant; kidney failure was secondary to Liddle syndrome with mutation of gene SCNN1B. The patient was maintained on an immunosuppression regimen of tacrolimus, everolimus and prednisone. There was no previous history of rejection, and he had no history of donor specific antibodies. At his most recent follow-up assessment, one month before admission, his serum creatinine was 1.75 mg/dL, estimated glomerular filtration rate (eGFR) was 42 mL/min, serum tacrolimus level was 5.3 ng/mL and everolimus 3.6 ng/mL, with normal urinalysis. He presented with fever (maximum noted of 38ºC at home), dyspnea, diarrhea and abdominal pain for one week. On initial examination, his temperature was 37ºC, blood pressure 122/60 mmHg, pulse 90 beats per minute, and oxygen saturation 93% (ambient air); he had bibasilar crackles and appeared volume depleted. Laboratory results are summarized in table 1. The main findings were lymphopenia, thrombocytopenia, high serum C-reactive protein and D-dimer, acute kidney injury with metabolic acidosis and the presence of epithelial and granular casts on urinalysis. Anemia was not present. Thoracic radiography showed an interstitial pulmonary infiltrate on basal right lung. A J o u r n a l P r e -p r o o f nasopharyngeal swab followed by reverse transcription polymerase chain reaction (RT-PCR) assessment confirmed the diagnosis of COVID-19 infection. The course of the patient's symptoms and treatments are summarized in Figure 1 . We initiated supportive treatment with oxygen therapy and volume repletion, and started empiric treatment with hydroxychloroquine and azithromycin. We initially reduced tacrolimus dose and discontinued everolimus. Two days later, the tacrolimus level remained elevated and we discontinued all immunosuppression. On the third hospital day, the patient had high levels of pancreatic enzymes without abdominal pain, diarrhea or other gastrointestinal symptoms, with subsequent normalization on the following days. On hospital day nine, he had an elevated high sensitivity cardiac troponin I, without chest pain and with a normal electrocardiogram and normal biventricular function on echocardiogram; he was presumptively diagnosed with myocarditis related to COVID-19. His respiratory status subsequently worsened, and a chest radiograph revealed new bilateral pulmonary infiltrations; he started methylprednisolone bolus (2 mg/Kg/day) for seven days and oxygen supplementation was increased. On hospital day eleven, a diagnosis of TMA was made based on the following findings: anemia with hemoglobin level of 7.5g/dL, thrombocytopenia with platelet count of 12 x 10 9 /L, reticulocytosis, elevated lactate dehydrogenase (LDH), 7% schistocytes on peripheral blood smear, negative direct and indirect coombs test, undetectable haptoglobin, and acute kidney injury with serum creatinine peaking at 8.79 mg/dL. An ADAMTS 13 activity of 68% excluded TTP. There was no presence of bacteria pathogens on stool culture or urinary antigen S. pneumoniae. Serologic tests for HIV, HVC, parvovirus B19 were negative and CMV and EBV serologies were negative. Immunological studies, including antinuclear antibody, anti-double strand DNA, antiphospholipid antibodies, complement, and immunoglobulin levels, were normal. To treat TMA, the patient received five sessions of plasma exchange with fresh frozen plasma replacement, and two hemodialysis sessions were necessary. Subsequently serum creatinine decreased to 2.5 mg/dL, and there was no evidence of further hemolysis. Immunosuppressive treatment was reintroduced. On hospital day 23, the patient developed chest pain accompanied by elevated of high sensitivity cardiac troponin I. He was diagnosed with an acute myocardial infarction and successfully treated with angioplasty of the right coronary artery. He was discharged on hospital day 36 with recovery of kidney function and normalized platelet count. Multiple complications related to COVID-19 infection have been described Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China A pneumonia outbreak associated with a new coronavirus of probable bat origin A Novel Coronavirus from Patients with Pneumonia in China Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany First Case of 2019 Novel Coronavirus in the United States Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease Acute pulmonary embolism and COVID-19 pneumonia: a random association? Thrombotic microangiopathy associated with parvovirus B 19 infection after renal transplantation Cytomegalovirus-induced thrombotic microangiopathy after renal transplant successfully treated with eculizumab: case review of the literature Cyclosporine and tacrolimus-associated thrombotic microangiopathy Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression Renal histopathological analysis fo 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020 Targeting complement in severe coronavirus disease 2019 to address microthrombosis