ABSTRACT
Background: ACE2 is a component of the renin-angiotensin system(RAS) that mainly degrades angiotensin II to angiotensin(1-7). It is expressed in renal tubular cells. Lung type 2 alveolar cells also express ACE2 where it acts as a receptor for SARS-CoV-2, which is responsible for the current coronavirus disease 2019(COVID-19) pandemic. A controversy raised regarding the use of RAS blockers in COVID-19 patients despite its demonstrated efficacy in cardiovascular disease. We studied the effect of ramipril on ACE2 expression in experimental diabetes. Methods: 12 weeks old diabetic db/db mice were given ramipril(8 mg/Kg/day) or vehicle during 8 weeks. db/m mice were used as controls. ACE2 expression and enzymatic activity were studied in kidney, heart and lung. Results: In non-treated db/db, ACE2 mRNA expression was increased in kidney(p<0.0001) and ramipril treatment reversed this effect. In heart, ACE2 expression decreased in db/db when compared to db/m(p=0.028) and ramipril had no effect. We found no differences in lung. ACE2 enzymatic activity was increased 23% in kidney and 22% in lung of db/db mice when compared to db/m. Ramipril treatment decreased ACE2 activity 25% in the lung and 13% in the kidney when compared to untreated db/db. In the heart, ACE2 activity tended to decrease in db/db mice when compared to db/m, and increased with ramipril, but did not exceed the cardiac ACE2 activity of the db/m. Conclusions: ACE2 is increased in the kidney and in the lung, and decreased in the heart of diabetic mice. Ramipril treatment restores ACE2. Our results suggest that diabetes and hypertension may per se be risk factors for COVID-19 and not the treatment with ACE inhibitors, which may exert a protective effect on COVID-19 infection.
ABSTRACT
Background: COVID-19 is a novel coronavirus currently at the centre of a global pandemic, and patients with cardiovascular risk factors such as hypertension and diabetes are at risk of a serious complication such as hospitalization and death. Chronic kidney disease (CKD) increased cardiovascular risk and >90% of CKD patients presented hypertension. The prognosis and lethality of COVID-19 in patients with biopsy-proven kidney disease has not been previously studied. Methods: Data included patients who underwent a kidney biopsy at the Vall d'Hebron Hospital between January 2013 and February 2020 with diagnostic confirmation and those with high clinical suspicion of SARS-CoV-2 infection during the period from March to May 2020. Results: Of 553 patients, 39(7%) were diagnosed with SARS-CoV2 infection. The mean age was 63.4±15 years. 48.7% were male, 31 hypertension, 19 diabetic, 12 obese and 18 patients had lung disease. The renal histological diagnosis of glomerulonephritis with extracapillary proliferation in 10.3%, allergic interstitial nephritis in 10.3 %, secondary GSFS in 8.5% and diabetic nephropathy in 10.3%. 4 patients were on hemodialysis and 6 had a kidney transplant. Creatinine before infection was 1.52mg/ dL±0,66. 17 patients were under immunosuppressive treatment (14 with prednisone, 8 mycophenolate, 6 tacrolimus, 1 rituximab). 26 patients had confirmation of SARS-CoV2 infection with RT PCR obtained from nasopharyngeal swab. 22 patients required hospital admission [average hospital stay was 16 days±11], of which 4 in the ICU and 6 (15%) died. 15 patients received lopinavir/ritornavir;23 patients, azithromycin;20 patients, hydroxychloroquine;6 patients, tocilizumab;9 patients, intravenous corticosteroids. 11 patients presented impaired renal function, of which 3 were transplanted and 8 with CKD. CKD patients under RAS blockade had less mortality than patients without RAS blockade treatment (29% vs 0%, p=0.014). Conclusions: COVID-19 was diagnosed in 7% of our CKD patients with kidney biopsy. The mortality was 15%, lower than the reported in hemodialysis patients. RAS blockade is not exerting a deleterious effect in our CKD patients with COVID-19 infection, suggesting that they should not be withdrawn.