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Kidney Injury in Critically Ill Patients with COVID-19 – From Pathophysiological Mechanisms to a Personalized Therapeutic Model Cover

Kidney Injury in Critically Ill Patients with COVID-19 – From Pathophysiological Mechanisms to a Personalized Therapeutic Model

The Journal of Critical Care Medicine
Volume 9 (2023): Issue 3 (July 2023)
By: Cosmin Balan,  Tudor Ciuhodaru and  Serban-Ion Bubenek-Turconi  
Open Access
|Jul 2023

Figures & Tables

Fig. 1.

Pathophysiology of AKI in COVID-19. AKI arises from multiple intricated mechanisms, including 1) glomerulo-tubular injuries secondary to potentially direct viral cytopathic effects, 2) an inadequate immune response, initially localized to the lungs and later becoming systemic, 3) a ubiquitous process of thrombotic microangiopathy referred to as “microCLOTS,” and 4) a complex heart-lung interaction that requires active and individualized therapeutic intervention. Endothelial dysfunction is an all-pervasive driver of organ dysfunction. There is inadequate activation of RAAS, leading to both immediate and long-term renal consequences such as glomerular dysfunction, inflammation, fibrosis, and vasoconstriction. The initiation of IPPV has hemodynamic repercussions dependent on lung mechanics: 1) in the L subphenotype (i.e., normal lung elastance), the gradient that ensures venous return (MSFP - CVP) is reduced, mimicking hypovolemia; 2) in the H subphenotype (i.e., increased lung elastance), an increased TPP along with other pulmonary and extrapulmonary factors (e.g., hypoxemia, hypercapnia, microthrombosis in pulmonary and cardiac capillaries, hypervolemia), contribute to the development of pulmonary artery hypertension and acute cor pulmonale. A reduced MPP is the end result of all hemodynamic derangements. This may involve a decrease in MAP with or without a decrease in CO, an increase in CVP, or both. Medications can have aggravating consequences. An adequate hemodynamic and respiratory support should avoid fluid overload, reduce vasopressor doses, and optimize MPP and systemic tissue perfusion.
Pathophysiology of AKI in COVID-19. AKI arises from multiple intricated mechanisms, including 1) glomerulo-tubular injuries secondary to potentially direct viral cytopathic effects, 2) an inadequate immune response, initially localized to the lungs and later becoming systemic, 3) a ubiquitous process of thrombotic microangiopathy referred to as “microCLOTS,” and 4) a complex heart-lung interaction that requires active and individualized therapeutic intervention. Endothelial dysfunction is an all-pervasive driver of organ dysfunction. There is inadequate activation of RAAS, leading to both immediate and long-term renal consequences such as glomerular dysfunction, inflammation, fibrosis, and vasoconstriction. The initiation of IPPV has hemodynamic repercussions dependent on lung mechanics: 1) in the L subphenotype (i.e., normal lung elastance), the gradient that ensures venous return (MSFP - CVP) is reduced, mimicking hypovolemia; 2) in the H subphenotype (i.e., increased lung elastance), an increased TPP along with other pulmonary and extrapulmonary factors (e.g., hypoxemia, hypercapnia, microthrombosis in pulmonary and cardiac capillaries, hypervolemia), contribute to the development of pulmonary artery hypertension and acute cor pulmonale. A reduced MPP is the end result of all hemodynamic derangements. This may involve a decrease in MAP with or without a decrease in CO, an increase in CVP, or both. Medications can have aggravating consequences. An adequate hemodynamic and respiratory support should avoid fluid overload, reduce vasopressor doses, and optimize MPP and systemic tissue perfusion.

Fig. 2.

Echocardiography as a tool to diagnose, monitor and treat cardiocirculatory collapse.
Echocardiography as a tool to diagnose, monitor and treat cardiocirculatory collapse.

CARDS phenotyping – a mechanistic overview_

CriterionCARDS subphenotype
L subphenotypeH subphenotype
Pulmonary mechanicsEL and ECW are normalEELV is normalNormal strain and stress at TV 6–8ml/kg IBWEL is increased and ECW is normalEELV is reducedIncreased strain and stress at TV 6–8ml/kg IBW
Computer TomographyAeratedGround glassNormal weightDependent atelectasisCondensationsIncreased weight
Histopathologic substratemicroCLOTSDiffuse alveolar damage
Gas exchange abnormalityV/Q mismatchDecreased fluid toleranceShuntSeverely decreased fluid tolerance
Positive pressure transmission Ppleural = Palveolar × (ECW/ET)Mainly in the pleural spacePpleural increases, so then CVP increasesMainly transpulmonaryAlveolar pressure increases, so then TPP increases, TPP = Palveolar - Ppleural
Cardiac effectsRV preload is reducedMimicking hypovolemiaRV afterload is increasedRisking acute cor pulmonale
Renal effectsDecreased arterial flowDecreased MPPDecreased arterial flowDecreased MPPVenous congestion
Respiratory strategyLow recruitment potentialAvoid open lung approachPP responsiveness is lowHigh recruitment potentialIndividualized open lung approachPP responsiveness is high
Hemodynamic strategyPrevent fluid overload.Optimize RV preloadReduce lung water.Optimize RV afterload
Hemodynamic monitoringUltrasoundTPTDPPV/SVV: useful for fluid management.UltrasoundTPTDPPV/SVV: less useful, increased rate of false negatives if used with VT < 8ml/kg IBW or of false positives if acute cor pulmonale ensues. A VT challenge helps discriminate the false negatives. Cardiac ultrasound helps discriminate the false positives.

Preventive measures in COVID-AKI

InterventionArgumentRecommendation
Renal functionStaging AKI and assessing clinical risk are epidemiological imperatives with crucial therapeutic implications.Recommend the use of serum creatinine and urine output for monitoring renal function, paying attention to limitations of both parameters.(Level of evidence: 1B)
Hemodynamic profilingInadequate tissue perfusion contributes to the worsening of organ dysfunction (e.g., kidney, lung, liver, and heart).Recommend an individualized hemodynamic strategy based on dynamic and quantitative indices of cardiovascular evaluation. (Level of evidence: 1B)
FluidsFluid composition has systemic consequences, including renal. High chloride content was associated with an increased incidence of AKI, and the use of hydroxyethyl starch derivatives in sepsis is contraindicated.Recommend the use of balanced crystalloids for initial volume resuscitation in at-risk patients or those who develop COVID-AKI, in the absence of other specific indications. (Level of evidence: 1A)
Glycemic controlInsulin resistance and hypercatabolism are frequently encountered in patients with COVID-19.Suggest the use of an intensive glycemic control strategy. (Level of evidence: 2C)
NephrotoxinsVarious nephrotoxins are commonly prescribed to patients with COVID-19.Recommend limiting exposure to nephrotoxic medications and vigilant monitoring when they cannot be avoided. (Level of evidence: 1B)
Contrast agentsThe relevance of contrast agent toxicity is uncertain.Recommend optimizing intravascular volume as the only preventive measure. (Level of evidence: 1A)
Mechanical ventilationIncreased intrathoracic pressure results in: 1) elevated central venous pressures and peripheral venous congestion; 2) sympathetic adrenergic and renin-angiotensin-aldosterone system activation; 3) mechanical disadvantage, particularly for the right ventricle; 4) renal, hepatic, and splanchnic cross-talk.Suggest the use of a protective ventilatory strategy for both the lungs and the right ventricle, individualized and continuously tailored to the patient's real-time physiology. (Level of evidence: 2C)

Potential risk factors associated with COVID-AKI

Socio-demographic risk factorsRisk factors at admissionPost-admission risk factors
Advanced age (> 70 years)Elevated viremiaNephrotoxins (e.g., contrast agents)
Diabetes mellitusLeukocytosis and lymphopeniaVasopressors
HypertensionIncreased levels of ferritin, CRP, and D-dimersMechanical ventilation
Congestive heart failureHypovolemia/dehydrationHypovolemia
ObesityMultiorgan involvementHypervolemia
Chronic kidney diseaseRhabdomyolysisMetabolic disturbances (e.g., hyperglycemia)
ImmunosuppressionExposure to ACE inhibitors, ARBs, and NSAIDsFluid imbalances (e.g., use of hydroxyethyl starch, increased chloride levels)

Recommendations for the good clinical practice of RRT

RRT ComponentManagement
IndicationWhen metabolic byproducts (e.g., hyperkalemia, acidosis, hypervolemia) exceed renal clearance.An individualized approach that should consider the decreased fluid tolerance observed in patients with severe forms of COVID-19.
ModalitySelection of RRT technique depends on the metabolic and hemodynamic priorities of the patient, as well as on the local expertise and resources.CRRT benefit hemodynamically unstable or fluid overloaded patients.Reduced tolerance to intercompartmental fluid shifts favors the use of CRRT.IHD may be useful in stable hemodynamic patients with progressively favorable outcomes.
DoseCRRT: effluent rate of 25–30 ml/kg/h.IHD: ≥ 3 sessions/week, alternating days.Adjustment of effluent doses based on individual metabolic needs.Correction of effluent doses based on periods of circuit clotting and transportation outside the ICU.To protect the filter, avoid filtration fractions greater than 20%.
AnticoagulationAdjusted to coagulation status.RCA: initial dose of 4% trisodium citrate set at 3.5 mmol/L and post-filter Ca2+ at 0.25–0.35 mmol/L.HNF: initial dose set at 10–15 IU/kg/h, with a target aPTT of 60–90 seconds.LMWH: initial dose set at 3.5 mg/h, with a target residual anti-Xa activity of 0.25–0.35 IU/ml.
Vascular accessUltrasound guidance reduces costs and complications.First choice: right internal jugular vein; avoid subclavian access.
Fluid removalFunctional hemodynamic monitoring is essential for optimizing fluid removal rate.In the most basic functional hemodynamic model, the concurrent monitoring of CO, CVP, and MAP is essential. In this model, the ideal removal rate seeks to preserve stable CO and MAP levels while decreasing CVP, all without requiring an escalation of vasoactive support.Sustaining removal rates above 1.75 ml/kg/hour without a hemodynamic feedback loop may worsen hemodynamics.

AKI incidence in patients with COVID-19 disease

Author and ReferenceLocationPeriodDefinitionPatients no.Critically ill no.COVID-AKI no. (%)COVID-AKI in ICU no. (%)RRT no. (%)
Bubenek-Turconi [13]Romania25.03.2020–26.03.2021KDIGO905890582183 (24.1)2183 (24.1)453 (5)
Huang [15]Wuhan16.12.2019–02.01.2020KDIGO41133 (7.31)3 (23.08)3 (7.31)
Richardson [16]New York01.03.2020–04.04.2020KDIGO5700/2351#373523 (22.2)NR81 (3.4)
Hirsch [17]New York01.03.2020–05.04.2020KDIGO + all stages544913951993 (36.6)1060 (76)285 (5.2)
Gupta [18]USA04.03.2020–04.04.2020KDIGO stage 2/322152215952 (43)952 (43)443 (20)
Mohamed [19]Louisiana01.03.2020–31.03.2020KDIGO575173161 (28)105 (61)89 (15.5)
Schaubroeck [20]Belgium01.02.2020–31.01.2021KDIGO + all stages128612861094 (85.1)1094 (85.1)126 (9.8)
Sullivan [21]United Kingdom17.01.2020–5.12.2020KDIGO + all stages85687NR13000 (31.5)NR2198 (2.6%)
Wang [22]Wuhan01.01.2020–03.02.2020KDIGO138365 (3.62)3 (8.33)2 (1.45)
Guan [23]China11.12.2019–29.01.2020KDIGO109917312 (1.09)6 (3.47)9 (0.82)
Cao [24]Wuhan03.01.2020–01.02.2020KDIGO1021820 (19.61)8 (44.44)6 (5.88)
Zhang [25]Wuhan02.01.2020–10.02.2020KDIGO2215510 (4.52)8 (14.55)5 (2.26)
Xu [26]China01.01.2020–20.02.2020NR3557156 (15.77)21(29.58)NR
Li Z [27]China06.01.2020–21.02.2020KDIGO1936555 (28.5)43(66.15)7 (3.63)
Zheng [28]Hangzhou22.01.2020–05.03.2020KDIGO34347 (20.59)7 (20.59)5 (14.71)
Arentz [29]Seattle20.02.2020–05.03.2020KDIGO21214 (19.05)4 (19.05)NR
DOI: https://doi.org/10.2478/jccm-2023-0023 | Journal eISSN: 2393-1817 | Journal ISSN: 2393-1809
Journal RSS Feed
Language: English
Page range: 148 - 161
Submitted on: Jul 6, 2023
|
Accepted on: Jul 28, 2023
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Published on: Jul 31, 2023
Published by: University of Medicine, Pharmacy, Science and Technology of Targu Mures
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
acute kidney injury,
COVID-19,
renal replacement therapy,
acute respiratory distress syndrome,
personalized cardiocirculatory support
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Internal medicine, other,
Surgery,
Surgery, other,
Anaesthesiology,
Emergency medicine and intensive-care medicine

© 2023 Cosmin Balan, Tudor Ciuhodaru, Serban-Ion Bubenek-Turconi, published by University of Medicine, Pharmacy, Science and Technology of Targu Mures
This work is licensed under the Creative Commons Attribution 4.0 License.

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