Pathogenesis of coronavirus disease 2019-associated kidney injury

Smith, Kelly D.; Akilesh, Shreeram

doi:10.1097/mnh.0000000000000708

Cited by 11 publications

(16 citation statements)

References 79 publications

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“…Collectively, our results reveal that SARS-CoV-2 can directly infect and damage kidney tubular epithelial cells in organoids derived from pluripotent stem cells ( 92 ). In this regard, kidney organoid epithelium may model features of lung epithelium in acute respiratory distress syndrome relevant to COVID-19.…”

Section: Discussionmentioning

confidence: 75%

Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations

Helms¹,

Marchianò²,

Stanaway³

et al. 2021

JCI Insight

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Kidneys are critical target organs of COVID-19, but susceptibility and responses to infection remain poorly understood. Here, we combine SARS-CoV-2 variants with genome-edited kidney organoids and clinical data to investigate tropism, mechanism, and therapeutics. SARS-CoV-2 specifically infects organoid proximal tubules among diverse cell types. Infections produce replicating virus, apoptosis, and disrupted cell morphology, features of which are revealed in the context of polycystic kidney disease. Cross-validation of gene expression patterns in organoids reflects proteomic signatures of COVID-19 in the urine of critically ill patients indicating interferon pathway upregulation. SARS-CoV-2 viral variants alpha, beta, gamma, kappa, and delta exhibit comparable levels of infection in organoids. Infection is ameliorated in ACE2–/– organoids and blocked via treatment with de novo–designed spike binder peptides. Collectively, these studies clarify the impact of kidney infection in COVID-19 as reflected in organoids and clinical populations, enabling assessment of viral fitness and emerging therapies.

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Section: Discussionmentioning

confidence: 75%

Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations

Helms¹,

Marchianò²,

Stanaway³

et al. 2021

JCI Insight

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“…Acute kidney injury in patients with COVID-19 may manifest as a range of pathophysiologic entities that may occur singly or in combination, including acute tubular, vascular, glomerular, and interstitial injury [ 3 , 4 ]. In one study, approximately one of four people hospitalized with COVID-19 experienced acute kidney injury [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…One hypothesized mechanism involves inflammation that is local and systemic, and subsequent cytokine (that is tumor necrosis factor (TNF)-α) release, which leads to injury of the endothelial system and coagulopathy, as well as activation of the renin–angiotensin system [ 3 , 5 ]. Underlying genetic mechanisms have been reported such as occurrence of COVID-19-associated glomerulopathy in those with certain apolipoprotein L1 genotypes [ 4 ]. In this case report, the subject’s renal biopsy sample histopathology had negative SARS-CoV-2 immunostaining.…”

Section: Discussionmentioning

confidence: 99%

Acute kidney injury due to myoglobin cast nephropathy in the setting of coronavirus disease 2019-mediated rhabdomyolysis: a case report

et al. 2022

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Background We present this case of coronavirus disease 2019-associated acute kidney injury with rhabdomyolysis—with noteworthy renal biopsy findings demonstrating myoglobin cast nephropathy—to add to the limited literature on coronavirus disease 2019-related acute kidney injury and rhabdomyolysis. Case presentation A 67-year-old Caucasian man presented to our hospital with 3 weeks of malaise and decreased oral intake and several days of abnormal taste, poor appetite, decrease urine output, gastrointestinal symptoms, and myalgias, and was ultimately diagnosed with coronavirus disease 2019. His hospital course was complicated by acute kidney injury and, upon workup of his renal failure, was diagnosed with myoglobin cast nephropathy due to coronavirus disease 2019-mediated rhabdomyolysis. Ultimately, his renal function improved following hydration back to his baseline 6 weeks after his initial diagnosis of coronavirus disease 2019. Conclusions Given our limited knowledge of manifestations of coronavirus disease 2019, it is important to have a more in-depth understanding of the spectrum of disease of coronavirus disease 2019, which can affect various organ systems, including the kidney, and the manifestations of end-organ damage associated with it. We present this case to highlight a rarely reported finding of myoglobin cast nephropathy due to coronavirus disease 2019-mediated rhabdomyolysis.

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“…AKI is reportedly a frequent pattern in patients dying from COVID-19 (15,(35)(36)(37)(38), with acute tubular injury being the most common morpho-pathologic finding in kidney autopsies (37)(38)(39). Furthermore, ACE-2 and TMPRSS2 are highly expressed in proximal tubules, where SARS-CoV-2 particles could be detected postmortem in the respective podocytes from COVID-19 patients (40), hinting that the novel coronavirus can directly target the kidneys (7,10,34,41).…”

Section: Interpretation Of Findingsmentioning

confidence: 99%

A Prospective Study on Risk Factors for Acute Kidney Injury and All-Cause Mortality in Hospitalized COVID-19 Patients From Tehran (Iran)

et al. 2022

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BackgroundSeveral reports suggested that acute kidney injury (AKI) is a relatively common occurrence in hospitalized COVID-19 patients, but its prevalence is inconsistently reported across different populations. Moreover, it is unknown whether AKI results from a direct infection of the kidney by SARS-CoV-2 or it is a consequence of the physiologic disturbances and therapies used to treat COVID-19. We aimed to estimate the prevalence of AKI since it varies by geographical settings, time periods, and populations studied and to investigate whether clinical information and laboratory findings collected at hospital admission might influence AKI incidence (and mortality) in a particular point in time during hospitalization for COVID-19.MethodsHerein we conducted a prospective longitudinal study investigating the prevalence of AKI and associated factors in 997 COVID-19 patients admitted to the Baqiyatallah general hospital of Tehran (Iran), collecting both clinical information and several dates (of: birth; hospital admission; AKI onset; ICU admission; hospital discharge; death). In order to examine how the clinical factors influenced AKI incidence and all-cause mortality during hospitalization, survival analysis using the Cox proportional-hazard models was adopted. Two separate multiple Cox regression models were fitted for each outcome (AKI and death).ResultsIn this group of hospitalized COVID-19 patients, the prevalence of AKI was 28.5% and the mortality rate was 19.3%. AKI incidence was significantly enhanced by diabetes, hyperkalemia, higher levels of WBC count, and blood urea nitrogen (BUN). COVID-19 patients more likely to die over the course of their hospitalization were those presenting a joint association between ICU admission with either severe COVID-19 or even mild/moderate COVID-19, hypokalemia, and higher levels of BUN, WBC, and LDH measured at hospital admission. Diabetes and comorbidities did not increase the mortality risk among these hospitalized COVID-19 patients.ConclusionsSince the majority of patients developed AKI after ICU referral and 40% of them were admitted to ICU within 2 days since hospital admission, these patients may have been already in critical clinical conditions at admission, despite being affected by a mild/moderate form of COVID-19, suggesting the need of early monitoring of these patients for the onset of eventual systemic complications.

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Pathogenesis of coronavirus disease 2019-associated kidney injury

Cited by 11 publications

References 79 publications

Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations

Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations

Acute kidney injury due to myoglobin cast nephropathy in the setting of coronavirus disease 2019-mediated rhabdomyolysis: a case report

A Prospective Study on Risk Factors for Acute Kidney Injury and All-Cause Mortality in Hospitalized COVID-19 Patients From Tehran (Iran)

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