Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19).

BACKGROUND AND OBJECTIVES: AKI in coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality. The objective of this study was to identify the kidney histopathologic characteristics of deceased patients with diagnosis of COVID-19 and evaluate the association between biopsy findings and clinical variables, including AKI severity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our multicenter, observational study of deceased patients with COVID-19 in three third-level centers in Mexico City evaluated postmortem kidney biopsy by light and electron microscopy analysis in all cases. Descriptive and association statistics were performed between the clinical and histologic variables. RESULTS: A total of 85 patients were included. Median age was 57 (49-66) years, 69% were men, body mass index was 29 (26-35) kg/m2, 51% had history of diabetes, 46% had history of hypertension, 98% received anticoagulation, 66% were on steroids, and 35% received at least one potential nephrotoxic medication. Severe AKI was present in 54% of patients. Biopsy findings included FSGS in 29%, diabetic nephropathy in 27%, and arteriosclerosis in 81%. Acute tubular injury grades 2-3 were observed in 49%. Histopathologic characteristics were not associated with severe AKI; however, pigment casts on the biopsy were associated with significantly lower probability of kidney function recovery (odds ratio, 0.07; 95% confidence interval, 0.01 to 0.77). The use of aminoglycosides/colistin, levels of C-reactive protein and serum albumin, previous use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, antivirals, nonsteroid anti-inflammatory drugs, and anticoagulants were associated with specific histopathologic findings. CONCLUSIONS: A high prevalence of chronic comorbidities was found on kidney biopsies. Nonrecovery from severe AKI was associated with the presence of pigmented casts. Inflammatory markers and medications were associated with specific histopathologic findings in patients dying from COVID-19.

The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease.

AIM: Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. METHODS: Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (n = 166) and validated (n = 170). RESULTS: Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (P < 0.01) compared with non-ICU patients: alanine aminotrasnferase (ALT) 225.4 ± 341.2 vs. 41.3 ± 41.1, aspartate aminotransferase (AST) 325.3 ± 382.4 vs. 52.8 ± 47.1, lactic dehydrogenase (LDH) 764.6 ± 401.9 vs. 461.0 ± 185.6, D-dimer (DD) 7765 ± 9109 vs. 1871 ± 4146, and age 58.6 ± 12.7 vs. 49.1 ± 12.8. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (sensitivity = 0.797 and specificity = 0.391, c - statistic = 0.74; 95%IC: 0.62-0.86, P < 0.001), to predict the risk of need admission to ICU (OR = 5.8; 95% CI: 2.2-15.4, P = 0.001), was constructed. Validation cohort: in 170 different patients, the AAD model < 2.75 (c - statistic = 0.80 (95% CI: 0.70-0.91, P < 0.001) adequately predicted the risk (OR = 8.8, 95% CI: 3.4-22.6, P < 0.001) to be admitted in the ICU (27 patients, 15.95%). CONCLUSIONS: The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease.

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19.

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current pandemic, can have multi-organ impact. Recent studies show that liver injury could be a manifestation of the disease, and that liver disease could also be related to a worse prognosis. Our aim was to compare the characteristics of patients with severe coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 who required intubation versus stable hospitalized patients to identify the early biochemical predictive factors of a severe course of COVID-19 and subsequent requirement for intubation, specifically in Mexican. METHODS: This was an observational case-control study nested in a cohort study. Complete medical records of patients admitted for confirmed COVID-19 at a tertiary level center in Mexico City were reviewed. Clinical and biochemical data were collected, and the characteristics of patients who required invasive mechanical ventilation (IMV) (cases) were compared with stable hospitalized patients without ventilation (controls). RESULTS: We evaluated 166 patients with COVID-19 due to SARS-CoV-2 infection; 114 (68.7%) were men, the mean age was 50.6 ± 13.3 years, and 27 (16.3%) required IMV. The comparative analysis between cases and controls showed (respectively) significantly lower blood oxygen saturation (SpO2) (73.5 ± 12.0% vs. 83.0 ± 6.8%, P < 0.0001) and elevated alanine aminotransferase (ALT) (128 (14-1123) IU/L vs. 33 (8-453) IU/L, P = 0.003), aspartate aminotransferase (AST) (214 (17-1247) vs. 44 (12-498) IU/L, P = 0.001), lactic dehydrogenase (LDH) (764.6 ± 401.9 IU/L vs. 461.0 ± 185.6 IU/L, P = 0.001), and D-dimer (3463 (524-34,227) ng/mL vs. 829 (152-41,923) ng/mL, P = 0.003) concentrations. Patients in the cases group were older (58.6 ± 12.7 years vs. 49.1 ± 12.8 years, P=0.001). Multivariate analysis showed that important factors at admission predicting the requirement for IMV during hospitalization for COVID-19 were AST ≥250 IU/L (odds ratio (OR) = 64.8, 95% confidence interval (CI) 7.5-560.3, P < 0.0001) and D-dimer ≥ 3500 ng/mL (OR = 4.1, 95% CI 1.2-13.7, P=0.02). CONCLUSIONS: Our study confirms the importance of monitoring liver enzymes in hospitalized patients with COVID-19; seriously ill patients have significantly elevated AST and D-dimer concentrations, which have prognostic implications in the SARS-CoV-2 disease course.