Covid-19 and acute kidney injury in hospital: summary of NICE guidelinesBMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1963 (Published 26 May 2020) Cite this as: BMJ 2020;369:m1963
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COVID-19 associated acute kidney injury (AKI) has been reported in different countries1 2 and I agree that early detection and diagnosis with AKI in COVID-19 is essential for effective healthcare management in terms of the high risk for mortality of this comorbidity. I also agree that limited clinical knowledge is available to assist the management3. However, other information could be utilized to guide this effort.
The COVID-19-causing coronavirus SARS-CoV-2 utilizes the two human host cell surface receptors ACE2 and TMPRSS2 to enter cells4, initiating its infection. In other words, low levels of the receptor expression may attenuate the infection and in contrast, high level expression may become a hotspot of infection. In humans, no study has been done whether individuals with high receptor expressions are more vulnerable to SARS-CoV-2 but in mice, only the human ACE2 makes the animal vulnerable5, supporting the view that these receptors regulate the vulnerability. The question is why kidney is super-sensitive to the infection in selected patients with COVID-19?
Large variation in kidney receptor concentration is observed. I have examined many COVID-19 injured organs including lung, kidney, liver and heart for tissue density of these receptors and found that kidney has the highest density of these receptors among the examined organs. Kidney also is the organ with the largest variation in the receptor levels among individuals. More interestingly some individuals have high density for both receptors in their kidneys, suggesting that those individuals, once infected, are more likely to develop AKI.
Family history, genetic tests or renal biopsy thus may help assess whether subjects of interest have high levels of the coronaviral receptors, becoming an option for early detection or diagnosis with risk for AKI in COVID-19.
1. Fanelli V, Fiorentino M, Cantaluppi V, et al. Acute kidney injury in SARS-CoV-2 infected patients. Critical care (London, England) 2020;24(1):155. doi: 10.1186/s13054-020-02872-z [published Online First: 2020/04/18]
2. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ (Clinical research ed) 2020;368:m1091. doi: 10.1136/bmj.m1091 [published Online First: 2020/03/29]
3. Selby NM, Forni LG, Laing CM, et al. Covid-19 and acute kidney injury in hospital: summary of NICE guidelines. BMJ (Clinical research ed) 2020;369:m1963. doi: 10.1136/bmj.m1963 [published Online First: 2020/05/28]
4. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020 doi: 10.1016/j.cell.2020.02.052 [published Online First: 2020/03/07]
5. Bao L, Deng W, Huang B, et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 2020 doi: 10.1038/s41586-020-2312-y [published Online First: 2020/05/08]
Competing interests: No competing interests
I read with interest the summary of NICE guidelines for the prevention and management of acute kidney injury (AKI) in COVID-19 patients (1). The authors highlight the role of hypovolemia in the development of AKI and the importance of fluid management. They mention that the aim should be to "achieve and maintain optimal fluid status" but do not provide clear guidance on how to achieve that goal, nor define what they mean by “optimal fluid status”. The authors suggest that clinical examination and the use of heart rate, blood pressure, and pulmonary edema may help to assess fluid status. I believe that the assessment of volume status may be much more complex in COVID-19 patients.
First, these patients are septic, and a high pulse rate or a low blood pressure may simply reflect fever and systemic vasodilation. Pulmonary edema, a major cause of mechanical ventilation and intensive care unit (ICU) admission, is rather due to pulmonary capillary leak than to fluid overload. Second, dynamic predictors of fluid responsiveness, often used in critically ill patients to guide fluid management, are difficult to interpret, when not impossible to use. For instance, in emergency departments and on hospital wards, the pleth variability index (a quantification of the respiratory variation in the pulse oximetry waveform), or the inferior vena cava collapsibility (estimated by ultrasound techniques), do not help to predict fluid responsiveness. Indeed, in spontaneously breathing patients with acute respiratory failure, they depend more on respiratory efforts than on the volume status (2). In the ICU, where most patients are mechanically ventilated and have a radial arterial catheter, the arterial pulse pressure variation (PPV), easy to measure, could be used to guide fluid management. However, in the context of protective mechanical ventilation with low tidal volume, although a high PPV (>13%) is highly suggestive of hypovolemia, a low PPV cannot exclude it (3).
So, what could be done to rationalize fluid administration? First, we can mimic the effects of a fluid challenge with a passive leg raising (PLR) maneuver (4). In hypovolemic patients, PLR induces significant changes in stroke volume (SV, measured by a cardiac output monitor), in the velocity time integral (VTI) of the left ventricular outflow tract (measured by echo-Doppler), in the peripheral perfusion index (PI, measured by pulse oximetry) and in PPV (measured from any arterial waveform) (5). In the context of pulmonary edema, the PLR has the major advantage to provide information without the need to administer a single drop of fluid (4). The alternative to the PLR maneuver is the mini-fluid challenge that consists in the quick administration of a small volume of fluid (100 ml in a few minutes). Both the PLR and the mini-fluid challenge can be used in mechanically ventilated and in spontaneously breathing patients. During mechanical ventilation, the end-expiratory occlusion test (transient interruption of mechanical ventilation), the tidal volume challenge (transient increase in tidal volume) and the lung recruitment maneuver (transient increase in airway pressure) can be used as well to detect changes in SV, VTI, PI and PPV and unmask an hypovolemic state (5).
In summary, I agree with Selby et al. (1) that detecting and correcting hypovolemic states is key to prevent AKI in COVID-19 patients. However, I believe that clinicians cannot simply rely on clinical examination to detect hypovolemia and need actionable guidelines to rationalize fluid therapy.
1. Selby et al. BMJ 2020; 369:m1963
2. Michard & Shelley. Should we monitor pulsus paradoxus via pulse oximetry in COVID-19 patients with acute respiratory failure? Am J Respir Crit Care Med, in press
3. Michard et al. Applicability of pulse pressure variation: how many shades of grey? Crit Care 2015; 19 :144
4. Monnet & Teboul. Passive leg raising: five rules, not a drop of fluid! Crit Care 2015; 19:18
5. Michard. Toward precision hemodynamic management. Crit Care Med 2017; 45:1421-23
Competing interests: No competing interests