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Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

ABSTRACT: Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Using measurements of ∼4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

SUBMITTER: Paranjpe I

PROVIDER: S-EPMC9460972 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

Paranjpe Ishan I Jayaraman Pushkala P Su Chen-Yang CY Zhou Sirui S Chen Steven S Thompson Ryan R Del Valle Diane Marie DM Kenigsberg Ephraim E Zhao Shan S Jaladanki Suraj S Chaudhary Kumardeep K Ascolillo Steven S Vaid Akhil A Kumar Arvind A Kozlova Edgar E Paranjpe Manish M O'Hagan Ross R Kamat Samir S Gulamali Faris F FF Kauffman Justin J Xie Hui H Harris Joceyln J Patel Manishkumar M Argueta Kimberly K Batchelor Craig C Nie Kai K Dellepiane Sergio S Scott Leisha L Levin Matthew A MA He John Cijiang JC Suarez-Farinas Mayte M Coca Steven G SG Chan Lili L Azeloglu Evren U EU Schadt Eric E Beckmann Noam N Gnjatic Sacha S Merad Miram M Kim-Schulze Seunghee S Richards Brent B Glicksberg Benjamin S BS Charney Alexander W AW Nadkarni Girish N GN

medRxiv : the preprint server for health sciences 20220829

Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Using measurements of ∼4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437 ...[more]

PMID: 36093350

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Project description:BackgroundWe aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children.MethodsSequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days.ResultsIn 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED.ConclusionsAKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes.Trial registrationNCT01987921.ImpactWhat is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.

Project description:ImportanceAn association between serum creatine kinase (CK) levels and the risk of kidney failure in patients with exertional rhabdomyolysis (ERM) has been suggested. However, the actual incidence of AKI in hospitalized patients with ERM along with the contributing cofactors that may increase the risk of AKI have rarely been investigated.ObjectivesTo examine the incidence of kidney injury in hospitalized patients with ERM and to identify additional cofactors that might contribute to the development of kidney injury in patients with ERM.Design, setting, and participantsThis retrospective cohort study was conducted in a diverse community population of patients 18 years or older with ERM who were hospitalized across Kaiser Permanente Northern California between January 1, 2009, and December 31, 2019. Patients were initially identified through electronic screening for all-cause rhabdomyolysis admissions, followed by manual medical record reviews to verify their eligibility for the study. The diagnosis of AKI and chronic kidney disease (CKD) was determined using KDIGO (Kidney Disease Improving Global Outcomes) criteria and confirmed by medical record review. Data analysis was performed from October 1, 2023, to January 31, 2024.ExposuresHistory of strenuous physical exercise before hospitalization for ERM.Main outcome and measuresDevelopment of AKI, CKD, and compartment syndrome and number of deaths.ResultsAmong 3790 patients hospitalized for rhabdomyolysis between 2009 and 2019 in Kaiser Permanente Northern California, 200 (mean [SD] age, 30.5 [8.5] years; 145 [72.5%] male) were confirmed to have ERM via medical record review. Seventeen patients (8.5%) developed AKI, none developed CKD, 1 (0.5%) developed compartment syndrome, and there were no fatalities. There was no association between serum CK levels and the risk of AKI. However, the risk of AKI was significantly higher in patients with ERM who used nonsteroidal anti-inflammatory drugs (NSAIDs) before admission (11 of 17 with AKI [64.7%] vs 40 of 183 without AKI [21.9%], P < .001) or experienced dehydration (9 of 183 without AKI [52.9%] vs 9 of 17 with AKI [4.9%], P < .001). This analysis suggests that eliminating preadmission NSAID use and dehydration could reduce the risk of potential AKI in patients with ERM by 92.6% (95% CI, 85.7%-96.1%) in this population.Conclusions and relevanceThe findings of this cohort study of hospitalized patients with ERM suggest that serum CK elevation alone is insufficient as an indicator of AKI in patients with ERM. Concurrent risk factors, such as NSAID use or dehydration, may be associated with AKI development in patients with ERM.

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Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

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Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

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