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

Cosmin Balan
Cosmin Balan
, 
Tudor Ciuhodaru
Tudor Ciuhodaru
 oraz 
Serban-Ion Bubenek-Turconi
Serban-Ion Bubenek-Turconi
   | 31 lip 2023
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Article Category: Review
Data publikacji: 31 lip 2023
Zakres stron: 148 - 161
Otrzymano: 06 lip 2023
Przyjęty: 28 lip 2023
DOI: https://doi.org/10.2478/jccm-2023-0023
Słowa kluczowe
© 2023 Cosmin Balan et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

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.

Criterion CARDS subphenotype
L subphenotype H subphenotype
Pulmonary mechanics EL and ECW are normalEELV is normalNormal strain and stress at TV 6–8ml/kg IBW EL is increased and ECW is normalEELV is reducedIncreased strain and stress at TV 6–8ml/kg IBW
Computer Tomography AeratedGround glassNormal weight Dependent atelectasisCondensationsIncreased weight
Histopathologic substrate microCLOTS Diffuse alveolar damage
Gas exchange abnormality V/Q mismatchDecreased fluid tolerance ShuntSeverely decreased fluid tolerance
Positive pressure transmission Ppleural = Palveolar × (ECW/ET) Mainly in the pleural spacePpleural increases, so then CVP increases Mainly transpulmonaryAlveolar pressure increases, so then TPP increases, TPP = Palveolar - Ppleural
Cardiac effects RV preload is reducedMimicking hypovolemia RV afterload is increasedRisking acute cor pulmonale
Renal effects Decreased arterial flowDecreased MPP Decreased arterial flowDecreased MPPVenous congestion
Respiratory strategy Low recruitment potentialAvoid open lung approachPP responsiveness is low High recruitment potentialIndividualized open lung approachPP responsiveness is high
Hemodynamic strategy Prevent fluid overload.Optimize RV preload Reduce lung water.Optimize RV afterload
Hemodynamic monitoring UltrasoundTPTDPPV/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

Intervention Argument Recommendation
Renal function Staging 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 profiling Inadequate 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)
Fluids Fluid 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 control Insulin resistance and hypercatabolism are frequently encountered in patients with COVID-19. Suggest the use of an intensive glycemic control strategy. (Level of evidence: 2C)
Nephrotoxins Various 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 agents The relevance of contrast agent toxicity is uncertain. Recommend optimizing intravascular volume as the only preventive measure. (Level of evidence: 1A)
Mechanical ventilation Increased 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 factors Risk factors at admission Post-admission risk factors
Advanced age (> 70 years) Elevated viremia Nephrotoxins (e.g., contrast agents)
Diabetes mellitus Leukocytosis and lymphopenia Vasopressors
Hypertension Increased levels of ferritin, CRP, and D-dimers Mechanical ventilation
Congestive heart failure Hypovolemia/dehydration Hypovolemia
Obesity Multiorgan involvement Hypervolemia
Chronic kidney disease Rhabdomyolysis Metabolic disturbances (e.g., hyperglycemia)
Immunosuppression Exposure to ACE inhibitors, ARBs, and NSAIDs Fluid imbalances (e.g., use of hydroxyethyl starch, increased chloride levels)

Recommendations for the good clinical practice of RRT

RRT Component Management
Indication When 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.
Modality Selection 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.
Dose CRRT: 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%.
Anticoagulation Adjusted 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 access Ultrasound guidance reduces costs and complications.First choice: right internal jugular vein; avoid subclavian access.
Fluid removal Functional 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 Reference Location Period Definition Patients no. Critically ill no. COVID-AKI no. (%) COVID-AKI in ICU no. (%) RRT no. (%)
Bubenek-Turconi [13] Romania 25.03.2020–26.03.2021 KDIGO 9058 9058 2183 (24.1) 2183 (24.1) 453 (5)
Huang [15] Wuhan 16.12.2019–02.01.2020 KDIGO 41 13 3 (7.31) 3 (23.08) 3 (7.31)
Richardson [16] New York 01.03.2020–04.04.2020 KDIGO 5700/2351# 373 523 (22.2) NR 81 (3.4)
Hirsch [17] New York 01.03.2020–05.04.2020 KDIGO + all stages 5449 1395 1993 (36.6) 1060 (76) 285 (5.2)
Gupta [18] USA 04.03.2020–04.04.2020 KDIGO stage 2/3 2215 2215 952 (43) 952 (43) 443 (20)
Mohamed [19] Louisiana 01.03.2020–31.03.2020 KDIGO 575 173 161 (28) 105 (61) 89 (15.5)
Schaubroeck [20] Belgium 01.02.2020–31.01.2021 KDIGO + all stages 1286 1286 1094 (85.1) 1094 (85.1) 126 (9.8)
Sullivan [21] United Kingdom 17.01.2020–5.12.2020 KDIGO + all stages 85687 NR 13000 (31.5) NR 2198 (2.6%)
Wang [22] Wuhan 01.01.2020–03.02.2020 KDIGO 138 36 5 (3.62) 3 (8.33) 2 (1.45)
Guan [23] China 11.12.2019–29.01.2020 KDIGO 1099 173 12 (1.09) 6 (3.47) 9 (0.82)
Cao [24] Wuhan 03.01.2020–01.02.2020 KDIGO 102 18 20 (19.61) 8 (44.44) 6 (5.88)
Zhang [25] Wuhan 02.01.2020–10.02.2020 KDIGO 221 55 10 (4.52) 8 (14.55) 5 (2.26)
Xu [26] China 01.01.2020–20.02.2020 NR 355 71 56 (15.77) 21(29.58) NR
Li Z [27] China 06.01.2020–21.02.2020 KDIGO 193 65 55 (28.5) 43(66.15) 7 (3.63)
Zheng [28] Hangzhou 22.01.2020–05.03.2020 KDIGO 34 34 7 (20.59) 7 (20.59) 5 (14.71)
Arentz [29] Seattle 20.02.2020–05.03.2020 KDIGO 21 21 4 (19.05) 4 (19.05) NR
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Język:
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Częstotliwość wydawania:
4 razy w roku
Dziedziny czasopisma:
Medicine, Clinical Medicine, Internal Medicine, other, Surgery, Anaesthesiology, Emergency Medicine and Intensive-Care Medicine
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