Risk Factors of AKI in Acute Respiratory Distress Syndrome: A Time-Dependent Competing Risk Analysis on Severe COVID-19 Patients

Introduction: Acute kidney injury (AKI) is frequently observed in patients with COVID-19 admitted to intensive care units (ICUs). Observational studies suggest that cardiovascular comorbidities and mechanical ventilation (MV) are the most important risk factors for AKI. However, no studies have investigated the renal impact of longitudinal covariates such as drug treatments, biological variations, and/or MV parameters. Methods: We performed a monocentric, prospective, longitudinal analysis to identify the dynamic risk factors for AKI in ICU patients with severe COVID-19. Results: Seventy-seven patients were included in our study (median age: 63 [interquartile range, IQR: 53-73] years; 58 (75%) men). Acute kidney injury was detected in 28 (36.3%) patients and occurred at a median time of 3 [IQR: 2-6] days after ICU admission. Multivariate Cox cause-specific time-dependent analysis identified a history of hypertension (cause-specific hazard (CSH) = 2.46 [95% confidence interval, CI: 1.04-5.84]; P = .04), a high hemodynamic Sequential Organ Failure Assessment score (CSH = 1.63 [95% CI: 1.23-2.16]; P < .001), and elevated Paco2 (CSH = 1.2 [95%CI: 1.04-1.39] per 5 mm Hg increase in Pco2; P = .02) as independent risk factors for AKI. Concerning the MV parameters, positive end-expiratory pressure (CSH = 1.11 [95% CI: 1.01-1.23] per 1 cm H2O increase; P = .04) and the use of neuromuscular blockade (CSH = 2.96 [95% CI: 1.22-7.18]; P = .02) were associated with renal outcome only in univariate analysis but not after adjustment. Conclusion: Acute kidney injury is frequent in patients with severe COVID-19 and is associated with a history of hypertension, the presence of hemodynamic failure, and increased Pco2. Further studies are necessary to evaluate the impact of hypercapnia on increasing the effects of ischemia, particularly in the most at-risk vascular situations.

[1]  G. Geri,et al.  The role of acute hypercapnia on mortality and short-term physiology in patients mechanically ventilated for ARDS: a systematic review and meta-analysis , 2022, Intensive Care Medicine.

[2]  N. Powe,et al.  New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. , 2021, The New England journal of medicine.

[3]  É. Azoulay,et al.  Acute kidney injury in SARS-CoV2-related pneumonia ICU patients: a retrospective multicenter study , 2021, Annals of Intensive Care.

[4]  G. Geri,et al.  Outcome of acute kidney injury: how to make a difference? , 2021, Annals of Intensive Care.

[5]  L. Celi,et al.  Cardio-pulmonary-renal interactions in ICU patients. Role of mechanical ventilation, venous congestion and perfusion deficit on worsening of renal function: Insights from the MIMIC-III database. , 2021, Journal of critical care.

[6]  Z. Massy,et al.  The spectrum of kidney biopsies in hospitalized patients with COVID-19, acute kidney injury, and/or proteinuria , 2021, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  A. Layton,et al.  A Model of Mitochondrial O2 Consumption and ATP Generation in Rat Proximal Tubule Cells. , 2019, American journal of physiology. Renal physiology.

[8]  J. Kellum,et al.  eResearch in acute kidney injury: a primer for electronic health record research , 2019, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  Rinaldo Bellomo,et al.  Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study , 2015, Intensive Care Medicine.

[10]  Yves Cohen,et al.  Acute respiratory distress syndrome and risk of AKI among critically ill patients. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[11]  Claude Guerin,et al.  High versus low blood-pressure target in patients with septic shock. , 2014, The New England journal of medicine.

[12]  J. Fine,et al.  A competing risks analysis should report results on all cause-specific hazards and cumulative incidence functions. , 2013, Journal of clinical epidemiology.

[13]  J. Laffey,et al.  Hypercapnia: permissive and therapeutic. , 2006, Minerva anestesiologica.

[14]  Peter C Austin,et al.  Bootstrap Methods for Developing Predictive Models , 2004 .

[15]  E. Blackstone,et al.  Breaking down barriers: helpful breakthrough statistical methods you need to understand better. , 2001, The Journal of thoracic and cardiovascular surgery.

[16]  J. Laffey,et al.  Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion. , 2000, American journal of respiratory and critical care medicine.

[17]  G. Huemer,et al.  Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome. , 2000, American journal of respiratory and critical care medicine.

[18]  J. Chevrolet,et al.  Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome , 1996, Intensive Care Medicine.

[19]  J. Moxham,et al.  The effects of oxygen and dopamine on renal and aortic blood flow in chronic obstructive pulmonary disease with hypoxemia and hypercapnia. , 1995, American journal of respiratory and critical care medicine.

[20]  R. McIntyre,et al.  Cardiopulmonary effects of permissive hypercapnia in the management of adult respiratory distress syndrome. , 1994, The Journal of trauma.

[21]  K. Walley,et al.  Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs. , 1990, Circulation research.

[22]  R. Carey,et al.  Synergistic Effects of Acute Hypoxemia and Hypercapnic Acidosis in Conscious Dogs , 1983, Circulation research.