SARS-CoV-2 renal tropism associates with acute kidney injury.
Ontology highlight
ABSTRACT:
SUBMITTER: Braun F
PROVIDER: S-EPMC7431179 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
SARS-CoV-2 renal tropism associates with acute kidney injury.
Braun Fabian F Lütgehetmann Marc M Pfefferle Susanne S Wong Milagros N MN Carsten Alexander A Lindenmeyer Maja T MT Nörz Dominik D Heinrich Fabian F Meißner Kira K Wichmann Dominic D Kluge Stefan S Gross Oliver O Pueschel Klaus K Schröder Ann S AS Edler Carolin C Aepfelbacher Martin M Puelles Victor G VG Huber Tobias B TB
Lancet (London, England) 20200817 10251
Similar Datasets
Project description:Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2+ or TMPRSS2+ renal tubular cells, whereas the RNAscope® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient's condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.
| S-EPMC8201778 | biostudies-literature
Project description:Neutrophils have been suggested mediators of organ dysfunction in COVID-19. The current study investigated if systemic neutrophil activity, estimated by human neutrophil lipocalin (HNL) concentration in peripheral blood, is associated with acute kidney injury (AKI) development. A total of 103 adult patients admitted to intensive care, with PCR-confirmed SARS-CoV-2 infection, were prospectively included (Clinical Trials ID: NCT04316884). HNL was analyzed in plasma (P-HNL Dimer) and in whole blood (B-HNL). The latter after ex vivo activation with N-formyl-methionine-leucine-phenylalanine. All patients developed respiratory dysfunction and 62 (60%) were treated with invasive ventilation. Sixty-seven patients (65%) developed AKI, 18 (17%) progressed to AKI stage 3, and 14 (14%) were treated with continuous renal replacement therapy (CRRT). P-HNL Dimer was higher in patients with invasive ventilation, vasopressors, AKI, AKI stage 3, dialysis, and 30-day mortality (p < 0.001-0.046). B-HNL performed similarly with the exception of mild AKI and mortality (p < 0.001-0.004). The cohort was dichotomized by ROC estimated cutoff concentrations of 13.2 µg/L and 190 µg/L for P-HNL Dimer and B-HNL respectively. Increased cumulative risks for AKI, AKI stage 3, and death were observed if above the P-HNL cutoff and for AKI stage 3 if above the B-HNL cutoff. The relative risk of developing AKI stage 3 was nine and 39 times greater if above the cutoffs in plasma and whole blood, respectively, for CRRT eight times greater for both. In conclusion, systemically elevated neutrophil lipocalin, interpreted as increased neutrophil activity, was shown to be associated with an increased risk of severe AKI, renal replacement therapy, and mortality in COVID-19 patients with respiratory failure.
| S-EPMC8464787 | biostudies-literature
Project description: Not available
| S-EPMC7240771 | biostudies-literature
Project description:BackgroundAcute Kidney Injury (AKI) is a frequent complication of severe SARS-CoV-2 infection. Multiple mechanisms are involved in COVID-19-associated AKI, from direct viral infection and secondary inflammation to complement activation and microthrombosis. However, data are limited in critically-ill patients. In this study, we sought to describe the prevalence, risk factors and prognostic impact of AKI in this setting.MethodsRetrospective monocenter study including adult patients with laboratory confirmed SARS-CoV-2 infection admitted to the ICU of our university Hospital. AKI was defined according to both urinary output and creatinine KDIGO criteria.ResultsOverall, 100 COVID-19 patients were admitted. AKI occurred in 81 patients (81%), including 44, 10 and 27 patients with AKI stage 1, 2 and 3 respectively. The severity of AKI was associated with mortality at day 28 (p = 0.013). Before adjustment, the third fraction of complement (C3), interleukin-6 (IL-6) and ferritin levels were higher in AKI patients. After adjustment for confounders, both severity (modified SOFA score per point) and AKI were associated with outcome. When forced in the final model, C3 (OR per log 0.25; 95% CI 0.01-4.66), IL-6 (OR per log 0.83; 95% CI 0.51-1.34), or ferritin (OR per log 1.63; 95% CI 0.84-3.32) were not associated with AKI and did not change the model.ConclusionIn conclusion, we did not find any association between complement activation or inflammatory markers and AKI. Proportion of patients with AKI during severe SARS-CoV-2 infection is higher than previously reported and associated with outcome.
| S-EPMC7471244 | biostudies-literature
Project description:Acute kidney injury (AKI) associates with higher in-hospital mortality, but whether it also associates with increased long-term mortality is unknown, particularly after accounting for residual kidney function after hospital discharge. We retrospectively analyzed data from US veteran patients who survived at least 90 d after discharge from a hospitalization. We identified AKI events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 d before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). Among the 864,933 hospitalized patients in the study cohort, we identified 82,711 hospitalizations of patients with AKI. In the study population of patients who survived at least 90 d after discharge, 17.4% died during follow-up (AKI 29.8%, without AKI 16.1%). The adjusted mortality risk associated with AKI was 1.41 (95% confidence interval [CI] 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 d after discharge. Long-term mortality risk is highest among the most severe cases of AKI.
| S-EPMC2834549 | biostudies-literature
Project description:Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.
| S-EPMC5487594 | biostudies-literature
Project description:The kidney is comprised of heterogeneous cell populations that function together to perform a number of tightly controlled, complex and interdependent processes. Renal endothelial cells contribute to vascular tone, regulation of blood flow to local tissue beds, modulation of coagulation and inflammation, and vascular permeability. Both ischemia and sepsis have profound effects on the renal endothelium, resulting in microvascular dysregulation resulting in continued ischemia and further injury. In recent years, the concept of the vascular endothelium as an organ that is both the source of and target for inflammatory injury has become widely appreciated. Here we revisit the renal endothelium in the light of ever evolving molecular advances.
| S-EPMC4476528 | biostudies-other
Project description:Pre-renal acute kidney injury (AKI) is assumed to represent a physiological response to underperfusion. Its diagnosis is retrospective after a transient rise in plasma creatinine, usually associated with evidence of altered tubular transport, particularly that of sodium. In order to test whether pre-renal AKI is reversible because injury is less severe than that of sustained AKI, we measured urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), ?-glutamyl transpeptidase, IL-18, and kidney injury molecule-1 (KIM-1)) at 0, 12, and 24?h following ICU admission. A total of 529 patients were stratified into groups having no AKI, AKI with recovery by 24?h, recovery by 48?h, or the composite of AKI greater than 48?h or dialysis. Pre-renal AKI was identified in 61 patients as acute injury with recovery within 48?h and a fractional sodium excretion <1%. Biomarker concentrations significantly and progressively increased with the duration of AKI. After restricting the AKI recovery within the 48?h cohort to pre-renal AKI, this increase remained significant. The median concentration of KIM-1, cystatin C, and IL-18 were significantly greater in pre-renal AKI compared with no-AKI, while NGAL and ?-glutamyl transpeptidase concentrations were not significant. The median concentration of at least one biomarker was increased in all but three patients with pre-renal AKI. Thus, the reason why some but not all biomarkers were increased requires further study. The results suggest that pre-renal AKI represents a milder form of injury.
| S-EPMC3365288 | biostudies-literature
Project description:Background and objectivesAKI 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, & measurementsOur 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.ResultsA 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.ConclusionsA 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.
| S-EPMC8259494 | biostudies-literature
Project description:BackgroundHospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern.MethodsSecondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators.ResultsOverall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds.ConclusionsSARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.
| S-EPMC8831033 | biostudies-literature