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

Author(s):  
Ishan Paranjpe ◽  
Pushkala Jayaraman ◽  
Chen-Yang Su ◽  
Sirui Zhou ◽  
Steven Chen ◽  
...  

AbstractAcute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using longitudinally collected biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Using longitudinal 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 upregulated and 40 downregulated proteins 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 longitudinal 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.

Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhubin Lun ◽  
Jin Liu ◽  
Liwei Liu ◽  
Jingjing Liang ◽  
Guanzhong Chen ◽  
...  

Background. Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation. Methods. We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24–72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan–Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality. Results. The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02–1.74, P = 0.038 ) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65–1.31, P = 0.633 ) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention. Conclusions. Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain

Abstract Background and Aims Renal function recovery after acute kidney injury (AKI) is associated with patient outcomes. The study objectives were to assess the patterns of AKI recovery within 6 months following discharge for AKI and subsequent incidence of chronic dialysis. Method A retrospective cohort of 234,867 hospitalized adult patients was examined for AKI between January 1, 2010, and December 31, 2017 in the largest healthcare delivery system in Taiwan. Renal function recovery at 3- and 6-month post discharge, incident chronic kidney disease and chronic dialysis initiation were analyzed over 7 years of follow-up. Renal recovery was defined by &lt; 1.5× baseline SCr (prior to the hospitalization). Independent associations between renal function recovery patterns and renal outcomes was assessed by Cox proportional hazard model controlling for potential confounders, and subdistribution hazard ratio (SHR) with [95% CI] was analysed for competing risk of early death. Results Among 3 months AKI survivors (n=24,132), 14.28% (n=3,430) did not recovery back to baseline, and 16% of recovery did not sustain. Three distinct renal function recovery continuums at 6 months post hospital discharge were: persistent non-recovery (10.18%), non-recovery (14.33%), and recovery (75.5%). Comparing to survivors without AKI (n=50,387), the impact of renal recovery continuum on chronic dialysis initiation varied by patient’s baseline renal disease (SHR was 2.82 [95%CI, 2.42-3.28] in CKD, and 0.8 [95%CI, 0.27-2.38] for non-CKD. Persistent non-recovery was significantly associated with a greater increased risk of chronic dialysis than non-recovery in any patients with AKI. Comparing to patients with sustained AKI recovery, risk of CKD onset increased 5-fold in persistent non-recovery and 3-fold risk in non-recovery. Conclusion The continuum of AKI recovery post 6 months is associated with increased risk of chronic dialysis, particularly in patients with baseline CKD. These study results suggested that patients ever with AKI should receive close renal function monitoring for post-discharge management.


2020 ◽  
Author(s):  
Joana Gameiro ◽  
Filipe Marques ◽  
José António Lopes

Abstract The incidence of acute kidney injury (AKI) has increased in the past decades. AKI complicates up to 15% of hospitalizations and can reach up to 50–60% in critically ill patients. Besides the short-term impact of AKI in patient outcomes, several studies report the association between AKI and adverse long-term outcomes, such as recurrent AKI episodes in 25–30% of cases, hospital re-admissions in up to 40% of patients, an increased risk of cardiovascular events, an increased risk of progression of chronic kidney disease (CKD) after AKI and a significantly increased long-term mortality. Despite the long-term impact of AKI, there are neither established guidelines on the follow-up care of AKI patients, nor treatment strategies to reduce the incidence of sequelae after AKI. Only a minority of patients have been referred to nephrology post-discharge care, despite the evidence of improved outcomes associated with nephrology referral by addressing cardiovascular risk and risk of progression to CKD. Indeed, AKI survivors should have specialized nephrology follow-up to assess kidney function after AKI, perform medication reconciliation, educate patients on nephrotoxic avoidance and implement strategies to prevent CKD progression. The authors provide a comprehensive review of the transition from AKI to CKD, analyse the current evidence on the long-term outcomes of AKI and describe predisposing risk factors, highlight the importance of follow-up care in these patients and describe the current therapeutic strategies which are being investigated on their impact in improving patient outcomes.


2021 ◽  
pp. ASN.2020111665
Author(s):  
Cal Robinson ◽  
Nivethika Jeyakumar ◽  
Bin Luo ◽  
Ron Wald ◽  
Amit Garg ◽  
...  

Background Acute kidney injury (AKI) is common during pediatric hospitalizations and associated with adverse short-term outcomes. However, long-term outcomes among survivors of pediatric AKI who received dialysis remain uncertain. Methods To determine the long-term risk of kidney failure (defined as receipt of chronic dialysis or kidney transplant) or death over a 22-year period for pediatric survivors of dialysistreated AKI, we used province-wide health administrative databases to perform a retrospective cohort study of all neonates and children (aged 0-18 years) hospitalized in Ontario, Canada, from April 1, 1996, to March 31, 2017, who survived a dialysis-treated AKI episode. Each AKI survivor was matched to four hospitalized pediatric comparators without dialysis-treated AKI, based on age, sex, and admission year. We reported the incidence of each outcome and performed Cox proportional hazards regression analyses, adjusting for relevant covariates. Results We identified 1688 pediatric dialysis-treated AKI survivors (median age 5 years) and 6752 matched comparators. Among AKI survivors, 53.7% underwent mechanical ventilation and 33.6% had cardiac surgery. During a median 9.6-year follow-up, AKI survivors were at significantly increased risk of a \ composite outcome of kidney failure or death versus comparators. Death occurred in 113 (6.7%) AKI survivors, 44 (2.6%) developed kidney failure, 174 (12.1%) developed hypertension, 213 (13.1%) developed chronic kidney disease (CKD), and 237 (14.0%) had subsequent AKI. AKI survivors had significantly higher risks of developing CKD and hypertension versus comparators. Risks were greatest in the first year after discharge and gradually decreased over time. Conclusions Survivors of pediatric dialysis-treated AKI are at higher long-term risks of kidney failure, death, CKD, and hypertension, compared with a matched hospitalized cohort.


Author(s):  
Ron Wald ◽  
Ziv Harel

Recent research has provided important insights on the long-term outcomes of patients who develop acute kidney injury (AKI) in the setting of critical illness. Large epidemiologic studies have demonstrated compelling associations between episodes of AKI and progressive kidney disease and death, respectively, although such studies do not establish causality due to the potential for confounding. Whether AKI is intrinsically toxic or a mere by-product of serious comorbidities (e.g. prior chronic kidney disease, heart failure, diabetes), there is no doubt that AKI survivors are a high-risk group who would likely benefit from close post-discharge follow-up. Recent studies have shown that a minority of patients with AKI receive specialized nephrology follow-up after discharge, suggesting an opportunity for quality improvement. Emerging research is evaluating factors that predict chronic kidney disease, end-stage renal disease, and death among AKI survivors. This work will, it is hoped, suggest new targets for prevention and treatment, with the goal of enhancing the likelihood of recovery following AKI.


2016 ◽  
Vol 21 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Bethany W. Ibach ◽  
Emilie D. Henry ◽  
Peter N. Johnson

Recent reports have described increased risk of acute kidney injury (AKI) in adults receiving concomitant vancomycin and piperacillin/tazobactam, but few reports exist in children. We describe an 8-year-old girl who was admitted to the pediatric intensive care unit with respiratory distress secondary to pneumonia. She began treatment with vancomycin and piperacillin/tazobactam. She developed AKI, and piperacillin/tazobactam and vancomycin were discontinued. Following a furosemide infusion, her AKI resolved and serum creatinine returned to baseline. She later resumed piperacillin/tazobactam monotherapy for multidrug-resistant tracheitis with no evidence of AKI and was eventually discharged to a long-term care facility. The Naranjo probability scale supports a probable drug-related adverse event. Clinicians must be aware of the possibility of AKI with this combination and should monitor renal function and vancomycin concentrations vigilantly. Future prospective studies are needed to explore the incidence and clinical characteristics associated with AKI after this combination in children.


2013 ◽  
Vol 118 (4) ◽  
pp. 809-824 ◽  
Author(s):  
John F. Mooney ◽  
Isuru Ranasinghe ◽  
Clara K. Chow ◽  
Vlado Perkovic ◽  
Federica Barzi ◽  
...  

Abstract Background: Kidney dysfunction is a strong determinant of prognosis in many settings. Methods: A systematic review and meta-analysis was undertaken to explore the relationship between estimated glomerular filtration rate (eGFR) and adverse outcomes after surgery. Cohort studies reporting the relationship between eGFR and major outcomes, including all-cause mortality, major adverse cardiovascular events, and acute kidney injury after cardiac or noncardiac surgery, were included. Results: Forty-six studies were included, of which 44 focused exclusively on cardiac and vascular surgery. Within 30 days of surgery, eGFR less than 60 ml·min·1.73 m−2 was associated with a threefold increased risk of death (multivariable adjusted relative risk [RR] 2.98; 95% confidence interval [CI] 1.95–4.96) and acute kidney injury (adjusted RR 3.13; 95% CI 2.22–4.41). An eGFR less than 60 ml·min·1.73 m−2 was associated with an increased risk of all-cause mortality (adjusted RR 1.61; 95% CI 1.38–1.87) and major adverse cardiovascular events (adjusted RR 1.49; 95% CI 1.32–1.67) during long-term follow-up. There was a nonlinear association between eGFR and the risk of early mortality such that, compared with patients having an eGFR more than 90 ml·min·1.73 m−2 the pooled RR for death at 30 days in those with an eGFR between 30 and 60 ml·min·1.73 m−2 was 1.62 (95% CI 1.43–1.80), rising to 2.85 (95% CI 2.49–3.27) in patients with an eGFR less than 30 ml·min·1.73 m−2 and 3.75 (95% CI 3.44–4.08) in those with an eGFR less than 15 ml·min·1.73 m−2. Conclusion: There is a powerful relationship between eGFR, and both short- and long-term prognosis after, predominantly cardiac and vascular, surgery.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Marc Weiner ◽  
Matteo Coen ◽  
Jacques Serratrice ◽  
Thomas A. Mavrakanas ◽  
Antonio Leidi

Abstract Background Leptospirosis is an underdiagnosed bacterial infection with nonspecific symptoms, hence, a diagnostic challenge. Identifying a case of leptospirosis in Switzerland is uncommon. Although kidney complications are frequent in severe forms, including tubular dysfunction, observing this complication is rare in our country. We report the case of a patient with leptospirosis and kidney dysfunction, which was notable for proximal tubulopathy. This case report describes the diagnosis and management of this patient’s tubular dysfunction. Case presentation A 34-year-old Caucasian male known for alcohol and drug abuse presented to our emergency department suffering from severe pain in the lower limbs, jaundice, and fever with flu-like symptoms. Physical examination was not contributory. Blood tests showed cytopenia, elevated inflammatory markers, acute kidney injury, and altered liver function tests with predominant cholestasis. Urinalysis showed proteinuria and significant glycosuria without concomitant hyperglycemia. Leptospirosis was suspected and confirmed by both positive serum polymerase chain reaction and elevated immunoglobulin M for Leptospira interrogans. The patient was treated with intravenous amoxicillin–clavulanate and doxycycline for 7 days. After antibiotic treatment, symptoms disappeared, and kidney dysfunction completely resolved. Conclusion Our case focuses on the description of leptospirosis-related acute kidney injury with proximal tubular dysfunction, which is a rare finding in Switzerland.


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