Renal tubular dysfunction in COVID-19 patients

Aroca-Martínez, Gustavo; Avendaño-Echavez, Lil; García, Carlos Tiscar; Ripoll, Daniela; Dianda, Daniela; Cadena-Bonfanti, Andrés; Musso, Carlos Guido

doi:10.1007/s11845-022-02993-0

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…A specific kidney proximal tubular dysfunction (Fanconi syndrome) associated with SARS-CoV-2 infection has been reported to be the primum movens of COVID-19 associated AKI [ 7 ] and is associated with poor prognosis [ 6 ]. In accordance with previous studies [ 5–7 ], approximately half of our patients had Fanconi syndrome; however, its occurrence poorly predicted AKI and persistent AKI. Like HIV, SARS-CoV-2 attacks the kidney in different ways [ 28 ].…”

Section: Discussionsupporting

confidence: 92%

“…Although specific kidney diseases have been reported, such as collapsing glomerulopathy, acute tubular necrosis appears to be the predominant renal pathology [ 4 ]. Several studies have highlighted kidney proximal tubular dysfunction in COVID-19 patients [ 5–7 ] and have suggested that it could precede AKI [ 7 ]. Thus, tubular dysfunction could play a critical role by facilitating an early prediction of COVID-19-associated AKI, as a urinary biomarker of kidney damage or stress [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

Larcher,

Bargnoux,

Badiou

et al. 2023

Renal Failure

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Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan–Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55–74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22–47) and median BMI: 25.7 kg/m 2 (IQR, 23.3–30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491–0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535–0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01–1.06, p = 0.005) and BMI (HR = 1.07, 95%CI: 1.00–1.14, p = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00–1.06, p = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20–12.5, p = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

Larcher,

Bargnoux,

Badiou

et al. 2023

Renal Failure

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“…To investigate the impact of COVID-19 infection on kidney specific cell targets, we integrated transcriptomic datasets from urine sediments and kidney organoids along with urine and plasma proteomic datasets. While previous studies have shown that PT cells are the main target of COVID-19 associated kidney injury 59, 60 , in this study we further identify that the cells in the juxtamedullary nephron such as LOH, DCT, CNT and PC may also be significantly impacted early due to infection. Functional overlap analysis showed that ECM homeostasis, coagulation, and degradation pathways were highly dysregulated across all four datasets.…”

Section: Discussionmentioning

confidence: 55%

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury

Anandakrishnan,

Yi,

Sun

et al. 2024

Preprint

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COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

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“…They also reported the association between renal proximal tubular dysfunction and hypophosphatemia incidence [26]. Moreover, in a recent study on 41 COVID-19-infected patients without AKI or CKD, the authors reported a remarkable renal electrolyte loss related to renal tubular dysfunction [34].…”

Section: Discussionmentioning

confidence: 93%

Hypophosphatemia in Coronavirus Disease 2019 (COVID-19), Complications, and Considerations: A Systematic Review

Fakhrolmobasheri

Vakhshoori

Heidarpour

et al. 2022

BioMed Research International

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Coronavirus disease 2019 (COVID-19) has various manifestations on different body organs, including the lungs, heart, kidneys, and central nervous system. However, the frequency of electrolyte abnormalities, especially hypophosphatemia, is still debated in this pandemic. Our main aim in this review is to evaluate the frequency and complications of hypophosphatemia in COVID-19-infected individuals. A systematic literature review was performed in Web of Science, Scopus, PubMed, EMBASE, and Cochrane electronic databases with the combination of different keywords till October 2021. We recruited all relevant published records (including cross-sectional and case-control studies as well as editorials and brief reports) assessing hypophosphatemia among patients with COVID-19 infection. After assessing all 928 recruited records and discarding duplicates, 4 records met the inclusion criteria. Three articles were further included during a manual search of the literature. Overall, the included studies reported 1757 subjects (males: 51.3%), with the mean age ranging from 37.2 ± 13.6 years to 65.9 ± 13.9 years. Hypophosphatemia prevalence has been reported from 7.6% to 19.5%. Patients with the severe status of COVID-19 had a higher prevalence of low serum phosphate levels than those with moderate infection. This review indicates that hypophosphatemia might be categorized as a complication in clinical settings during the COVID-19 pandemic, requiring a high clinical suspicion to implement appropriate diagnostic and therapeutic interventions to prevent life-threatening outcomes. However, it needs to be more elucidated by further studies whether hypophosphatemia in severe COVID-19 is directly related to COVID-19 or is just a complication of severe illness.

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Renal tubular dysfunction in COVID-19 patients

Cited by 8 publications

References 23 publications

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury

Hypophosphatemia in Coronavirus Disease 2019 (COVID-19), Complications, and Considerations: A Systematic Review

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