Acute Kidney Injury in Critical Care COVID-19 Patients on Invasive Mechanical Ventilation: The Potential Preventive Role of Dexamethasone

Abstract Background: A high incidence of acute kidney injury (AKI) has been reported in coronavirus disease 2019 (COVID-19) patients in critical care units and those undergoing invasive mechanical ventilation (IMV). The introduction of dexamethasone (DXM) as treatment for severe COVID-19 has improved mortality, but its effects in other organs remain under study. Objective: The objective of this study was to evaluate the association between DXM and AKI in COVID-19. Methods: In this prospective observational cohort study, we evaluated the incidence of AKI in critically ill COVID-19 patients undergoing mechanical ventilation, and the association of DXM treatment with the incidence, severity, and outcomes of AKI. The association between DXM treatment and AKI was evaluated by multivariable logistic regression. The association of the combination of DXM treatment and AKI on mortality was evaluated by Cox-regression analysis. Results: We included 552 patients. AKI was diagnosed in 311 (56%), of which 196 (63%) corresponded to severe (stage 2 or 3) AKI, and 46 (14.8%) received kidney replacement therapy. Two hundred and sixty-seven (48%) patients were treated with DXM. This treatment was associated to lower incidence of AKI (Odds Radio 0.34, 95% Confidence intervals [CI] 0.22-0.52, p < 0.001) after adjusting for age, body mass index, laboratory parameters, SOFA score, and vasopressor use. DXM treatment significantly reduced mortality in patients with severe AKI (HR 0.63, 95%CI 0.41-0.96, p = 0.032). Conclusions: The incidence of AKI is high in COVID-19 patients under IMV. DXM treatment is associated with a lower incidence of AKI and a lower mortality in the group with severe AKI.

Characteristics and outcomes of a Hispanic lupus nephritis cohort from Mexico.

OBJECTIVES: To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico. METHODS: We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival. RESULTS: The median age of the study cohort was 29 years (IQR 23-37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48-118) and 24 h-uPCR was 3.4 g/g (IQR 1.9-5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years. CONCLUSION: Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.

The first-year course of urine MCP-1 and its association with response to treatment and long-term kidney prognosis in lupus nephritis.

OBJECTIVES: The present study aims to assess the course of uMCP-1 and its association with response to therapy and long-term kidney function in a prospective cohort of adults who received a kidney biopsy for suspicion of active lupus nephritis (LN). METHODS: Subjects were segregated into a histologically active LN group and a histologically chronic LN group. Both groups were followed for > = 36 months and urine were collected at flare, 3, 6, and 12 months of follow-up. The association between the course of uMCP-1, response to treatment, and progression to 30% loss of the eGFR was evaluated by linear mixed models for repeated measures. RESULTS: A kidney biopsy was performed on 125 subjects. In 114, the report was consistent with histologically active LN; in 11, with histologically chronic LN. Urine MCP-1 levels were significantly higher in the active LN than in the chronic LN group. Urine MCP-1 levels correlated with the histological findings of cellular crescents, endocapillary hypercellularity, interstitial inflammation, glomerular sclerosis, interstitial fibrosis, and tubular atrophy. The mean estimates of uMCP-1 at flare were higher in the non-response group than in the complete response group, and decreased in the complete/partial response groups by the third month, while they remained elevated in the non-response group. The mean estimates for uMCP-1 were higher at LN flare and remained elevated in patients who progressed to loss of 30% of the eGFR, while they decreased in patients with stable kidney function. CONCLUSION: The first-year course of uMCP-1 is associated with response to therapy and kidney survival in LN. Key Points •Urine MCP-1 levels differentiate histologically-active lupus nephritis from histologically-chronic lupus nephritis •Urine MCP-1 levels decrease by 3 months of therapy in subjects with a favorable response whose kidney function remains stable long-term •Urine MCP-1 levels remain elevated during the first year of therapy in subjects the will later lose kidney function.

Acute Kidney Injury in Critical Care COVID-19 Patients on Invasive Mechanical Ventilation: The Potential Preventive Role of Dexamethasone.

Background: A high incidence of acute kidney injury (AKI) has been reported in coronavirus disease 2019 (COVID-19) patients in critical care units and those undergoing invasive mechanical ventilation (IMV). The introduction of dexamethasone (DXM) as treatment for severe COVID-19 has improved mortality, but its effects in other organs remain under study. Objective: The objective of this study was to evaluate the association between DXM and AKI in COVID-19. Methods: In this prospective observational cohort study, we evaluated the incidence of AKI in critically ill COVID-19 patients undergoing mechanical ventilation, and the association of DXM treatment with the incidence, severity, and outcomes of AKI. The association between DXM treatment and AKI was evaluated by multivariable logistic regression. The association of the combination of DXM treatment and AKI on mortality was evaluated by Cox-regression analysis. Results: We included 552 patients. AKI was diagnosed in 311 (56%), of which 196 (63%) corresponded to severe (stage 2 or 3) AKI, and 46 (14.8%) received kidney replacement therapy. Two hundred and sixty-seven (48%) patients were treated with DXM. This treatment was associated to lower incidence of AKI (Odds Radio 0.34, 95% Confidence intervals [CI] 0.22-0.52, p < 0.001) after adjusting for age, body mass index, laboratory parameters, SOFA score, and vasopressor use. DXM treatment significantly reduced mortality in patients with severe AKI (HR 0.63, 95%CI 0.41-0.96, p = 0.032). Conclusions: The incidence of AKI is high in COVID-19 patients under IMV. DXM treatment is associated with a lower incidence of AKI and a lower mortality in the group with severe AKI.

Community- and Hospital-Acquired Acute Kidney Injury in COVID-19: Different Phenotypes and Dismal Prognosis.

INTRODUCTION: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. METHODS: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. RESULTS: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49-70] vs. 50 years [IQR 43-61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1-4] vs. 1 point [IQR 0-2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53-11.3), hypertension (OR 1.55, 95% CI 1.01-2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02-1.32), and SOFA score (OR 2.19, 95% CI 1.87-2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1-126), elevated troponin I (OR 1.95, 95% CI 1.01-3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02-1.08). DISCUSSION/CONCLUSIONS: CA-AKI and HA-AKI portend an adverse prognosis in CO-VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.

Alternative complement pathway activation in thrombotic microangiopathy associated with lupus nephritis.

INTRODUCTION/OBJECTIVE: Thrombotic microangiopathy (TMA) in systemic lupus erythematosus is a rare manifestation associated with activation of the complement system. This study aimed to compare plasma and urine complement activation products between patients with active lupus nephritis (aLN) and those with acute TMA plus concomitant active LN (aTMA+aLN). METHODS: Plasma and urine samples were obtained from 20 patients with aTMA+aLN, 20 patients with aLN matched by the histological activity index, 5 patients with chronic TMA, 20 patients with inactive LN, and 10 kidney donors. Complement fragments C3a, C4a, C4d, Ba, C5a, C5bC9, and factor H were determined by ELISA; and kidney C4d deposition was detected by immunohistochemistry. Patients were followed for > 12 months and complement activation products re-measured after treatment in 10 aTMA+aLN patients. RESULTS: Both aTMA+aLN and aLN groups had increased circulating C3a, Ba, and C5bC9; and decreased circulating C3, C4, C4a, C4d, and factor H. Urinary C3a, C5a, Ba, and C5bC9 were higher in patients with aTMA+aLN than in aLN. After treatment, levels of circulating C3, C4, and factor H increased; while levels of urinary C3a, C5a, Ba, and C5bC9 decreased in patients with aTMA+aLN. These changes were observed at each aTMA episode in two patients studied during repeated TMA episodes. There was no difference in C4d deposition in glomerular capillaries, tubular basement membrane, peritubular capillaries, and arterioles between patients with aLN and those aTMA+aLN. CONCLUSIONS: Circulating and urine complement activation products suggest that thrombotic microangiopathy associated with LN is mediated through activation of the alternative complement pathway. Key Points • Immune-complex kidney disease in systemic lupus erythematosus (SLE) is associated with activation of the classical, lectin, and alternative complement pathways • Indirect evidence from measurement of circulating and urinary complement pathway activation products suggests that renal acute thrombotic microangiopathy in SLE is mediated by activation of the alternative complement pathway • C4d kidney immunohistochemistry may be positive in both immune complex nephritis and thrombotic microangiopathy. Therefore, it is not a specific marker of renal thrombotic microangiopathy in SLE.