The Association between COVID-19 Infection and Kidney Damage in a Regional University Hospital.

Background and Objectives: Kidneys are one of the main targets for SARS-CoV-2. Early recognition and precautionary management are essential in COVID-19 patients due to the multiple origins of acute kidney injury and the complexity of chronic kidney disease management. The aims of this research were to investigate the association between COVID-19 infection and renal injury in a regional hospital. Materials and Methods: The data of 601 patients from the Vilnius regional university hospital between 1 January 2020 and 31 March 2021 were collected for this cross-sectional study. Demographic data (gender, age), clinical outcomes (discharge, transfer to another hospital, death), length of stay, diagnoses (chronic kidney disease, acute kidney injury), and laboratory test data (creatinine, urea, C-reactive protein, potassium concentrations) were collected and analyzed statistically. Results: Patients discharged from the hospital were younger (63.18 ± 16.02) than those from the emergency room (75.35 ± 12.41, p < 0.001), transferred to another hospital (72.89 ± 12.06, p = 0.002), or who died (70.87 ± 12.83, p < 0.001). Subsequently, patients who died had lower creatinine levels on the first day than those who survived (185.00 vs. 311.17 µmol/L, p < 0.001), and their hospital stay was longer (Spearman's correlation coefficient = -0.304, p < 0.001). Patients with chronic kidney disease had higher first-day creatinine concentration than patients with acute kidney injury (365.72 ± 311.93 vs. 137.58 ± 93.75, p < 0.001). Patients with acute kidney injury and chronic kidney disease complicated by acute kidney injury died 7.81 and 3.66 times (p < 0.001) more often than patients with chronic kidney disease alone. The mortality rate among patients with acute kidney injury was 7.79 (p < 0.001) times higher than among patients without these diseases. Conclusions: COVID-19 patients who developed acute kidney injury and whose chronic kidney disease was complicated by acute kidney injury had a longer hospital stay and were more likely to die.

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial.

BACKGROUND: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. METHODS: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to <60 mL/min per 1·73 m2 and ≥60 mL/min per 1·73 m2) and urine protein excretion at screening (≤1·75 g/day and >1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. FINDINGS: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. INTERPRETATION: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. FUNDING: Travere Therapeutics.

Serum cystatin C and inflammatory factors related to COVID-19 consequences.

BACKGROUND: Besides impaired respiratory function and immune system, COVID-19 can affect renal function from elevated blood urea nitrogen (BUN) or serum creatinine (sCr) levels to acute kidney injury (AKI) and renal failure. This study aims to investigate the relationship between Cystatin C and other inflammatory factors with the consequences of COVID-19. METHODS: A total of 125 patients with confirmed Covid-19 pneumonia were recruited in this cross-sectional study from March 2021 to May 2022 at Firoozgar educational hospital in Tehran, Iran. Lymphopenia was an absolute lymphocyte count of less than 1.5 × 109/L. AKI was identified as elevated serum Cr concentration or reduced urine output. Pulmonary consequences were evaluated. Mortality was recorded in the hospital one and three months after discharge. The effect of baseline biochemical and inflammatory factors on odds of death was examined. SPSS, version 26, was used for all analyses. P-vale less than 0.05 was considered significant. RESULTS: The highest amount of co-morbidities was attributed to COPD (31%; n = 39), dyslipidemia and hypertension (27%; n = 34 for each) and diabetes (25%; n = 31). The mean baseline cystatin C level was 1.42 ± 0.93 mg/L, baseline creatinine was 1.38 ± 0.86 mg/L, and baseline NLR was 6.17 ± 4.50. Baseline cystatin C level had a direct and highly significant linear relationship with baseline creatinine level of patients (P < 0.001; r: 0.926). ). The average score of the severity of lung involvement was 31.42 ± 10.80. There is a direct and highly significant linear relationship between baseline cystatin C level and lung involvement severity score (r = 0.890, P < 0.001). Cystatin C has a higher diagnostic power in predicting the severity of lung involvement (B = 3.88 ± 1.74, p = 0.026). The mean baseline cystatin C level in patients with AKI was 2.41 ± 1.43 mg/L and significantly higher than patients without AKI (P > 0.001). 34.4% (n = 43) of patients expired in the hospital, and the mean baseline cystatin C level of this group of patients was 1.58 ± 0.90 mg/L which was significantly higher than other patients (1.35 ± 0.94 mg/L, P = 0.002). CONCLUSION: cystatin C and other inflammatory factors such as ferritin, LDH and CRP can help the physician predict the consequences of COVID-19. Timely diagnosis of these factors can help reduce the complications of COVID-19 and better treat this disease. More studies on the consequences of COVID-19 and knowing the related factors will help treat the disease as well as possible.

Prognostic potential of creatinine and Cystatin C in COVID-19 - a retrospective cohort study from Karolinska University Hospital.

Acute kidney injury (AKI) is common in COVID-19 and is diagnosed using relative serum creatinine increase. Estimated GFR (eGFR) is a more accurate measure of glomerular filtration due to compensation for age and sex. Serum Cystatin-C, less affected by non-renal factors than creatinine, may further improve renal function estimation and add prognostic information. Our aim is to investigate the importance of a calculated eGFR in relation to creatinine as well as the value of Cystatin-C in patients with severe COVID-19. This study is a retrospective cohort study investigating levels and trends of routine laboratory parameters combined with clinical data from 286 consecutive patients with severe COVID-19 from Karolinska University Hospital. AKI developed in 38% of the patients and 15% were treated with hemodialysis. Mortality in the AKI group was 42% compared to 5% in the non-AKI group. At admission, eGFR, but not creatinine, was significantly associated with AKI development, need of intubation and mortality. Moreover, discrepant results between eGFR creatinine (eGFRCR) and eGFR Cystatin-C (eGFRCYS) was common in the ICU patients compared to non-ICU patients and related to outcome. In addition, we found that daily median Cystatin-C levels during the hospital stay were correlated to neutrophil count. eGFRCR was found to be an overall better prognostic marker than creatinine regarding AKI development and prognosis in severe COVID-19. Fulfillment of Shrunken pore syndrome criteria indicated a higher mortality risk. Cystatin-C may be related to neutrophil count, which could be a clue to the discrepant eGFR results.

Prognostic significance of early acute kidney injury in COVID-19 patients requiring mechanical ventilation: a single-center retrospective analysis.

Acute kidney injury (AKI) is associated with impaired outcomes in critically ill COVID-19 patients. However, the prognostic significance of early AKI is poorly described. We aimed to determine whether AKI on admission to the intensive care unit (ICU) and its development within the first 48 h predict the need for renal replacement therapy (RRT) and increased mortality. An analysis of 372 patients with COVID-19 pneumonia requiring mechanical ventilation without advanced chronic kidney disease from 2020 to 2021 was performed. The AKI stages on ICU admission and Day 2 were determined using adapted KDIGO criteria. The early development of renal function was assessed by the change in AKI score and the Day-2/Day-0 creatinine ratio. Data were compared between three consecutive COVID-19 waves and with data before the pandemic. Both ICU and 90-day mortality (79% and 93% vs. 35% and 44%) and the need for RRT increased markedly with advanced AKI stage on ICU admission. Similarly, an early increase in AKI stage and creatinine implied highly increased mortality. RRT was associated with very high ICU and 90-day mortality (72% and 85%), even surpassing that of patients on ECMO. No difference was found between consecutive COVID-19 waves, except for a lower mortality in the patients on RRT in the last omicron wave. Mortality and need for RRT were comparable in the COVID-19 and pre-COVID-19 patients, except that RRT did not increase ICU mortality in the pre-COVID-19 era. In conclusion, we confirmed the prognostic significance of both AKI on ICU admission and its early development in patients with severe COVID-19 pneumonia.

Urine Output and Mortality in Patients Resuscitated from out of Hospital Cardiac Arrest.

BACKGROUND: Limited data exist regarding urine output (UO) as a prognostic marker in out-of-hospital-cardiac-arrest (OHCA) survivors undergoing targeted temperature management (TTM). METHODS: We included 247 comatose adult patients who underwent TTM after OHCA between 2007 and 2017, excluding patients with end-stage renal disease. Three groups were defined based on mean hourly UO during the first 24 h: Group 1 (<0.5 mL/kg/h, n = 73), Group 2 (0.5-1 mL/kg/h, n = 81) and Group 3 (>1 mL/kg/h, n = 93). Serum creatinine was used to classify acute kidney injury (AKI). The primary and secondary outcomes respectively were in-hospital mortality and favorable neurological outcome at hospital discharge (modified Rankin Scale [mRS]<3). RESULTS: In-hospital mortality decreased incrementally as UO increased (adjusted OR 0.9 per 0.1 mL/kg/h higher; p = 0.002). UO < 0.5 mL/kg/h was strongly associated with higher in-hospital mortality (adjusted OR 4.2 [1.6-10.8], p = 0.003) and less favorable neurological outcomes (adjusted OR 0.4 [0.2-0.8], p = 0.007). Even among patients without AKI, lower UO portended higher mortality (40% vs 15% vs 9% for UO groups 1, 2, and 3 respectively, p < 0.001). CONCLUSION: Higher UO is incrementally associated with lower in-hospital mortality and better neurological outcomes. Oliguria may be a more sensitive early prognostic marker than creatinine-based AKI after OHCA.

Immunogenicity and safety of two-dose SARS-CoV-2 vaccination via different platforms in kidney transplantation recipients.

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes.

Background: Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. Methods: We used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. Results: Increased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.

On-admission and dynamic trend of laboratory profiles as prognostic biomarkers in COVID-19 inpatients.

This large-scale study aimed to investigate the trend of laboratory tests of patients with COVID-19. Hospitalized confirmed and probable COVID-19 patients in three general hospitals were examined from March 20, 2020, to June 18, 2021. The confirmed and probable COVID-19 patients with known outcomes and valid laboratory results were included. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to select admittance prognostic features. Parallel Pairwise Comparison of mortality versus survival was used to examine the trend of markers. In the final cohort, 11,944 patients were enrolled, with an in-hospital mortality rate of 21.8%, mean age of 59.4 ± 18.0, and a male-to-female ratio of 1.3. Abnormal admittance level of white blood cells, neutrophils, lymphocytes, mean cellular volume, urea, creatinine, bilirubin, creatine kinase-myoglobin binding, lactate dehydrogenase (LDH), Troponin, c-reactive protein (CRP), potassium, and creatinine phosphokinase reduced the survival of COVID-19 inpatients. Moreover, the trend analysis showed lymphocytes, platelet, urea, CRP, alanine transaminase (ALT), and LDH have a dissimilar trend in non-survivors compared to survived patients. This study proposed a novel approach to find serial laboratory markers. Serial examination of platelet count, creatinine, CRP, LDH, and ALT can guide healthcare professionals in finding patients at risk of deterioration.

IL-6 at the center of cytokine storm: Circulating inflammation mediators as biomarkers in hospitalized COVID-19 patients.

INTRODUCTION: The management of hospitalized COVID-19 patients depends largely on controlling the intensified inflammatory response known as the cytokine storm. Candidate inflammatory cytokines can serve as new biomarkers for the management of hospitalized COVID-19 patients. METHODS: Patients (80) were recruited into three groups: room air (RA), oxygen (OX) and mechanical ventilator (MV). Blood analysis was performed for RBC, WBC, Hb, Platelets, serum albumin and creatinine, INR, PTT, and hematocrit. ELISA was used to quantify a panel of inflammatory mediators including GM-SCF, IFN-α, IFNγ, IL-1ß, IL-1R, IL-2, IL-2Ra, IL-6, IL-8, IL-10, IL-12p70, IL-13, MCP-1, MIP-1a, and TNF-α. Correlations between laboratory results and the levels of circulating inflammation mediators were investigated. RESULTS: Patients on MV had low RBC, Hb, albumin, and HCT and high WBC count, PTT, and INR when compared to RA and OX groups. A statistical positive correlation was found between WBC and the levels of IL-6 and MCP-1. RBCs correlated negatively with IL-6 and IL-10 and positively with IL-8. Higher TNF-α correlated with lower platelet counts while higher levels of IL-1Rα and IL-10 were associated with lower Hb levels. Increases in IFN-γ and TNF-α were indicative of compromised kidney functions as creatinine levels increased significantly. Most significant correlations were found between IL-6 and lab results, showing positive correlation with WBC and INR, and negative correlation with RBC, albumin, and HCT. CONCLUSIONS: Having the most significant correlations, IL-6 high levels in mechanically ventilated patients were shown to affect laboratory results, and, therefore, is suggested as a severity biomarker of COVID-19.

[Poor prognostic factors in patients hospitalized for COVID-19].

BACKGROUND: The clinical spectrum of COVID-19 varies from no or mild symptoms to pneumonia with fatal complications. The aim of the study was to find predictors of mortality and admission in the intensive care unit (ICU) in patients hospitalized for COVID-19. METHODS: Retrospective study of a cohort of patients admitted for COVID-19 between March 2020 and February 2021. Demographic, clinical, radiological and laboratory variables were described at admission. Independent predictors of mortality and ICU admission were identified by means of backward stepwise logistic regression and described in terms of odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: A total of 883 patients were included, 51.8% men with a mean age of 68; 1.8% readmissions. 17.6% of patients died (n=154). The independent predictors of mortality were age (OR=1.071; 95%CI: 1.046-1.095), percentage of oxygen saturation (SatO2) (OR=0.938; 95%CI: 0.903-0.974), diastolic blood pressure (DBP, OR= 0.972; 95%CI: 0.955-0.989), creatinine (OR=1.516; 95%CI: 1.088-2.113), INR (OR=1.199; 95%CI: 1.012-1.419) and sodium (OR=1.082; 95%CI: 1.037-1.128). Eight percent of patients were admitted to ICU; the independent predictors were: male sex (OR=2.079; 95%CI: 1.099-3.935), age (OR=0.960; 95%CI: 0.942-0.979), SatO2 (OR=0.925; 95%CI: 0.889-0.962), creatinine (OR=1.551; 95%CI: 1.118-2.152) and C-reactive protein (CRP, OR=1.003; 95%CI: 1.000-1.007). CONCLUSION: The identification of independent predictors of mortality (age, SatO2, DBP, creatinine, INR, sodium) and ICU admission (sex, age, SatO2, creatinine, and CRP) allowed for the stratification of patients to adapt clinical care protocols to these findings, thereby improving medical decisions.

Acute kidney injury in patients with COVID-19: a retrospective cohort study from Switzerland.

BACKGROUND: Data about patients in Europe with corona virus disease-2019 (COVID-19) and acute kidney injury (AKI) are scarce. We examined characteristics, presentation and risk factors of AKI in patients hospitalised with COVID-19 in a tertiary hospital in Switzerland. METHODS: We reviewed health records of patients hospitalised with a positive nasopharyngeal polymerase chain reaction test for SARS-CoV2 between 1 February and 30 June 2020, at the University Hospital of Basel. The nadir creatinine of the hospitalisation was used as baseline. AKI was defined according the KDIGO guidelines as a 1.5× increase of baseline creatinine and in-hospital renal recovery as a discharge creatinine <1.25× baseline creatinine. Least absolute shrinkage and selection operator (LASSO) regression was performed to select predictive variables of AKI. Based on this a final model was chosen. RESULTS: Of 188 patients with COVID-19, 41 (22%) developed AKI, and 11 (6%) required renal replacement therapy. AKI developed after a median of 9 days (interquartile range [IQR] 5-12) after the first symptoms and a median of 1 day (IQR 0-5) after hospital admission. The peak AKI stages were stage 1 in 39%, stage 2 in 24% and stage 3 in 37%. A total of 29 (15%) patients were admitted to the intensive care unit and of these 23 (79%) developed AKI. In-hospital renal recovery at discharge was observed in 61% of all AKI episodes. In-hospital mortality was 27% in patients with AKI and 10% in patients without AKI. Age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 1.01­1.08; p = 0.024), history of chronic kidney disease (aOR 3.47, 95% CI 1.16­10.49;p = 0.026), C-reactive protein levels (aOR 1.09, 95% CI 1.03­1.06; p = 0.002) and creatinine kinase (aOR 1.03, 95% CI 1.01­1.06; p = 0.002) were associated with development of AKI. CONCLUSIONS: AKI is common in hospitalised patients with COVID-19 and more often seen in patients with severe COVID-19 illness. AKI is associated with a high in-hospital mortality.

Impact of ACE2 and TMPRSS2 Expression in Patients With Preeclampsia.

BACKGROUND/AIM: As maternal morbidity and mortality during pregnancy have increased during the COVID-19 pandemic, studies on pregnancy-related complications from SARS-CoV-2 infection are being actively conducted. Considering that pregnant women with COVID-19 may develop a preeclampsia (PE)-like syndrome, it is necessary to differentiate it from PE because true PE can result in an unfavorable perinatal outcome during a hasty delivery. MATERIALS AND METHODS: We investigated the protein expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) in placental samples from 42 normotensive (n=9) and PE (n=33) patients without SARS-CoV-2 infection. We isolated placental trophoblast cells from normotensive and PE patients without evidence of SARS-CoV-2 infection to determine the mRNA and protein expression levels of TMPRSS2 and ACE2. RESULTS: High ACE2 cytoplasmic expression in extravillous trophoblasts (EVTs) was correlated with lower fibrin deposition (p=0.017). In comparison with high nuclear TMPRSS2 expression, low nuclearTMPRSS2 expression in endothelial cells (ECs) was positively correlated with PE (p=0.005), significantly higher systolic blood pressure (p=0.006), and higher urine protein-to-creatinine ratio (p=0.022). In contrast, high cytoplasmic TMPRSS2 expression in fibroblasts (FBs) was correlated with higher urine protein-to-creatinine ratio (p=0.018). Trophoblast cells extracted from PE placental tissue showed lower mRNA levels for both ACE2 and TMPRSS2. CONCLUSION: TMPRSS2 nuclear expression in ECs and cytoplasmic expression in FBs of the placenta may be related to a trophoblast-independent PE mechanism, and TMPRSS2 could be a new biomarker to discriminate actual PE from a PE-like syndrome associated with COVID-19.

Profiling Covid-19 patients with respect to level of severity: an integrated statistical approach.

A full understanding of the characteristics of Covid-19 patients with a better chance of experiencing poor vital outcomes is critical for implementing accurate and precise treatments. In this paper, two different advanced data-driven statistical approaches along with standard statistical methods have been implemented to identify groups of patients most at-risk for death or severity of respiratory distress. First, the tree-based analysis allowed to identify profiles of patients with different risk of in-hospital death (by Survival Tree-ST analysis) and severity of respiratory distress (by Classification and Regression Tree-CART analysis), and to unravel the role on risk stratification of highly dependent covariates (i.e., demographic characteristics, admission values and comorbidities). The ST analysis identified as the most at-risk group for in-hospital death the patients with age > 65 years, creatinine [Formula: see text] 1.2 mg/dL, CRP [Formula: see text] 25 mg/L and anti-hypertensive treatment. Based on the CART analysis, the subgroups most at-risk of severity of respiratory distress were defined by patients with creatinine level [Formula: see text] 1.2 mg/dL. Furthermore, to investigate the multivariate dependence structure among the demographic characteristics, the admission values, the comorbidities and the severity of respiratory distress, the Bayesian Network analysis was applied. This analysis confirmed the influence of creatinine and CRP on the severity of respiratory distress.

"Saving lives with nirmatrelvir/ritonavir one transplant patient at a time".

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of complications from COVID-19. Nirmatrelvir/ritonavir (Paxlovid) can reduce mortality from COVID-19 but is contraindicated in patients receiving calcineurin inhibitors (CI), which depend on cytochrome p4503A (CY3PA). In this study, we aim to show the feasibility of nirmatrelvir/ritonavir administration to SOT recipients receiving CI with coordination of medication management and limited tacrolimus trough monitoring. METHODS: We reviewed adult SOT recipients treated with nirmatrelvir/ritonavir from 4/14 to 11/1/2022 and assessed for changes in tacrolimus trough and serum creatinine after therapy. RESULTS: Of 47 patients identified, 28 were receiving tacrolimus and had follow-up laboratory testing. Patients had a mean age of 55 years, 17 (61%) received a kidney transplant and 23 (82%) received three or more doses of SARS-CoV-2 mRNA vaccine. Patients had mild-moderate COVID-19 and started nirmatrelvir/ritonavir within 5 days of symptom onset. Median baseline tacrolimus trough concentration was 5.6 ng/mL (Interquartile range 5.1-6.7), while median follow-up tacrolimus trough concentration was 7.8 ng/mL (Interquartile range 5.7-11.5, p = 0.0017). Median baseline and follow-up serum creatinine levels were 1.21 mg/dL (Interquartile range 1.02-1.39) and 1.21 mg/dL (interquartile range 1.02-1.44, p = 0.3162), respectively. One kidney recipient had a follow up creatinine level >1.5 times baseline. No patients were hospitalized or died from COVID-19 in the follow up period. CONCLUSION: While administration of nirmatrelvir/ritonavir resulted in a significant increase in tacrolimus concentration, this did not result in significant nephrotoxicity. Early oral antiviral treatment in SOT recipients is feasible with medication management, even with limited tacrolimus trough monitoring.

Effect of remdesivir on adverse kidney outcomes in hospitalized patients with COVID-19 and impaired kidney function.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for mortality from COVID-19. Remdesivir has been shown to shorten time to recovery in patients with severe COVID-19. However, exclusion of patients with severe kidney function impairment in clinical trials has led to concerns about kidney safety of remdesivir in patients with pre-existing kidney disease. METHODS: Retrospective propensity score matched cohort study of hospitalized patients with COVID-19 admitted with estimated glomerular filtration rate (eGFR) between 15 - 60 mL/min/1.73m2. Remdesivir-treated patients were 1:1 matched to historical comparators admitted during the first wave of COVID-19 (between March-April 2020) prior to emergency use authorization of remdesivir using propensity scores accounting for factors predicting treatment assignment. Dependent outcomes included in-hospital peak creatinine, incidence of doubling of creatine, rate of kidney replacement therapy initiation and eGFR among surviving patients at day 90. RESULTS: 175 remdesivir-treated patients were 1:1 matched to untreated historical comparators. Mean age was 74.1 (SD 12.8), 56.9% were male, 59% patients were white, and the majority (83.1%) had at least one co-morbidity. There were no statistically significant differences in peak creatinine during hospitalization (2.3mg/dL vs. 2.5 mg/dL, P = 0.34), incidence of doubling of creatinine (10.3% vs. 13.1%, P = 0.48), and rate of kidney replacement therapy initiation (4.6% vs. 6.3%, P = 0.49) in remdesivir-treated patients versus matched untreated historical comparators, respectively. Among surviving patients, there was no difference of the average eGFR at day 90 (54.7 ± 20.0 mL/min/1.73m2 for remdesivir-treated patients vs. 51.7 ± 19.5 mL/min/1.73m2 for untreated comparators, P = 0.41). CONCLUSIONS: Remdesivir use in patients with impaired kidney function (eGFR between 15 - 60 mL/min/1.73m2) who present to the hospital with COVID-19 is not associated with increased risk of adverse kidney outcomes.

Association of SARS-CoV-2 viral load with biochemical profile of COVID-19 patients: A nigerian experience.

Background: Kidney involvement in coronavirus disease 2019 (COVID-19) pathology has been supported by high frequency of angiotensin-converting enzyme 2 (ACE2) expression on renal cells and reports of acute kidney injury. However, the association between host viral load and kidney function is not clear. Aim: In this study, plasma levels of renal markers (urea nitrogen, creatinine, and estimated glomerular filtration rate (eGFR)) and electrolytes (sodium, potassium, chlorine, and bicarbonate) were assessed in relation to SARS-CoV-2 viral load of COVID-19 patients. Patients and Methods: This cross-sectional study involved 144 consenting COVID-19 patients admitted to the Ogun state COVID-19 isolation center between May and December 2020. All participants presented with mild respiratory symptoms and did not require ICU admission or ventilation support. Data included reverse transcriptase polymerase chain reaction (RT-PCR) cycle threshold (CT) value, blood urea nitrogen (BUN), creatinine, sodium, potassium, chlorine, bicarbonate measurements, and glomerular filtration rate. Reference intervals were used as comparators, and multiple linear regression model was fitted. Statistical significance was set at P < 0.05. Results: BUN level and creatinine were elevated in 4 (2.8%) and 42 (29.2%) patients, respectively, with lowered eGFR observed in 37 (25.7%) patients. Hyponatremia and hypokalemia were observed in 35 (24.3%) and 21 (14.6%) patients, respectively, while hypochloremia was observed in 21 (14.6%) patients. Lowered bicarbonate was observed in 29 (20.1%) patients. Linear regression showed statistically significant association (R2 = 0.340, P = 0.032) between RT-PCR CT value and eGFR (ß = 0.006, P = 0.017) as well as HCO3 (ß = -0.262, P = 0.036). Conclusion: COVID-19 patients with mild respiratory symptoms exhibited renal abnormalities, electrolytes, and acid-base imbalances which were partly associated with SARS-CoV-2 viral load.

Risk of mortality in COVID-19 patients: a meta- and network analysis.

Understanding the most relevant hematological/biochemical characteristics, pre-existing health conditions and complications in survivors and non-survivor will aid in predicting COVID-19 patient mortality, as well as intensive care unit (ICU) referral and death. A literature review was conducted for COVID-19 mortality in PubMed, Scopus, and various preprint servers (bioRxiv, medRxiv and SSRN), with 97 observational studies and preprints, consisting of survivor and non-survivor sub-populations. This meta/network analysis comprised 19,014 COVID-19 patients, consisting of 14,359 survivors and 4655 non-survivors. Meta and network analyses were performed using META-MAR V2.7.0 and PAST software. The study revealed that non-survivors of COVID-19 had elevated levels of gamma-glutamyl transferase and creatinine, as well as a higher number of neutrophils. Non-survivors had fewer lymphocytes and platelets, as well as lower hemoglobin and albumin concentrations. Age, hypertension, and cerebrovascular disease were shown to be the most influential risk factors among non-survivors. The most common complication among non-survivors was heart failure, followed by septic shock and respiratory failure. Platelet counts, creatinine, aspartate aminotransferase, albumin, and blood urea nitrogen levels were all linked to ICU admission. Hemoglobin levels preferred non-ICU patients. Lower levels of hemoglobin, lymphocytes, and albumin were associated with increased mortality in ICU patients. This meta-analysis showed that inexpensive and fast biochemical and hematological tests, as well as pre-existing conditions and complications, can be used to estimate the risk of mortality in COVID-19 patients.

Machine learning for prediction of in-hospital mortality in coronavirus disease 2019 patients: results from an Italian multicenter study.

BACKGROUND: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission. METHODS AND RESULTS: We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ±â€Š13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P < 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78). CONCLUSION: In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.