|Year : 2020 | Volume
| Issue : 4 | Page : 211-223
Preventive strategies and renal replacement therapies for patients with COVID-19
Department of Nephrology, Ain Shams University, Cairo, Egypt
|Date of Submission||15-Sep-2020|
|Date of Acceptance||17-Sep-2020|
|Date of Web Publication||16-Oct-2020|
Dr. Hesham Elsayed
Professor of Nephrology, Medical School Ain Shams University, Abbasia Square, Cairo
Source of Support: None, Conflict of Interest: None
The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection, A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Emphasis is placed on preparedness and prevention strategies for infection with this new COVID-19 Virus. Extracorporeal techniques can be helpful in the modulation of an immune dysregulated response, both in the severely ill and in the chronic HD patient. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes the effect is augmented when applied in a Hemodiafiltration mode, thanks for its dragging effect, on the other hand the use of superflux or Medium cut off dialyzers MCO are advantageous in removing the larger middle molecules with special respect to the cytokines release as a main cause of deterioration in those patients the use of more prolonged Hemodialysis, namely Continuous Renal Replacement Therapy (CRRT) as well the Prolonged Intermittent Renal Replacement Therapy (PIRRT) are considered best options as per its more prolongated time so compensate for the balance between production and elimination. Important issues are to improve the overall patients conditions on Maintenance Hemodialysis (MHD) in the term of maximizing the HD Dose, Nutritional support, treatment of any comorbidity as well inflammation as first step in preparedness of patients beside the strict and extensively adherent to preventive strategies that may improve the overall outcomes if they get infected with COVID-19.
Keywords: COVID-19, preventive strategies, renal replacement therapies
|How to cite this article:|
Elsayed H. Preventive strategies and renal replacement therapies for patients with COVID-19. J Egypt Soc Nephrol Transplant 2020;20:211-23
|How to cite this URL:|
Elsayed H. Preventive strategies and renal replacement therapies for patients with COVID-19. J Egypt Soc Nephrol Transplant [serial online] 2020 [cited 2021 May 17];20:211-23. Available from: http://www.jesnt.eg.net/text.asp?2020/20/4/211/298256
The worldwide outbreak of coronavirus disease (COVID-19) has demonstrated that we are all part of a small world where diffusion of contagious diseases is inevitable.
The several potential mechanisms of kidney involvement in patients with COVID-19 are multifactorial, profoundly interconnected, and affect many organs at the same time, with extensive affection to both the lungs and the kidneys, and have important implications for extracorporeal therapy using all the resources in the management of accumulating toxins related to the sepsis as well the accumulating toxins that almost are in the range of the middle molecules, necessitating the use of extracorporeal therapies that are capable of removing such big molecules.
Extracorporeal therapies have also been proposed as approaches to remove cytokines (nephrology back again). Our past and current experiences in nephrology are a cornerstone now to treat critical patients who are in need. The rationale for use of these therapies is that cytokine removal could prevent cytokines-induced organ damage and save lives for those with either acute kidney injury (AKI) and prevalent patients on maintenance hemodialysis (MHD).
Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, which is known to induce organ dysfunctions. Different therapies have been developed to address certain steps of the immune dysregulation. Most of the available blood purification devices focus on a single target, such as the endotoxin that triggers the immune cascade or the cytokine storm that causes organ damages.
As proposed by the third international consensus definition for sepsis and septic shock (Sepsis-3), sepsis should now be defined as ‘a life-threatening organ dysfunction caused by a dysregulated host response to infection.’ This new definition arises from an improvement in the understanding of sepsis pathophysiology. It also highlights the crucial role of the excessive or unbalanced host immune response during sepsis .
Sepsis induces signals that activate the leukocytes and induce the synthesis of proinflammatory and antiinflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1 (IL-1), IL-6, IL-8, and IL-10. The massive release of cytokines in the blood has been described as a ‘cytokine storm’ and is believed to be responsible for major organ dysfunctions .
Various hypotheses have been developed to explain the effects of extracorporeal therapies. First, they may decrease cytokine concentrations under a ‘toxic threshold’ to limit the local deleterious effects of cytokines . Other authors have hypothesized that because of a restored concentration gradient, the decrease in cytokine blood concentrations could promote leukocyte chemotaxis toward infected tissue where cytokine concentrations are higher .
Given the pivotal role of cytokine production in sepsis, it follows that removal of these substances, through such extracorporeal therapies, may attenuate the response, particularly in the early phase of sepsis . Several hypotheses have been proposed as to the potential mechanisms underpinning potential benefit. These include cytotoxic theories including the peak concentration hypothesis whereby all inflammatory mediators are removed at a given rate, dependent on the BPT used and assuming they are filtered .
Alternatively, the cytokinetic theory proposes that cytokines are removed, thereby creating a cytokine gradient between the bloodstream and tissues allowing leukocyte-enhanced trafficking .
| Organs’ cross-talks with COVID-19|| |
COVID-19 and dialysis: why we should be worried
Some populations, such as dialysis patients, may have a very high prevalence and death rate for COVID-19, as they have concurrent factors such as combine older age, malnutrition, cardiovascular disease, diabetes, lung disease, and less efficient immune system, with the need for dialysis treatment in overcrowded settings, where many patients, nurses, physicians, and support staff are present at the same time ([Figure 1]).
The logistical aspects of MHD further increase the risk for disease transmission, such as recurrent physical presence at health care facilities and physical proximity of patients during HD. It is therefore crucial to rapidly use appropriate preventive strategies in outpatient HD facilities.
The strategies to prevent and treat patients with MHD who are at a higher risk of infection by COVID-19 are considered a priority measure to prevent the diffusion of the disease among patients as well the health care providers (HCPs) .
MHD patients might present with a wide range of symptom severity; the clinical outcomes, especially mortality rates, are dramatically high in this vulnerable patient population, reaching almost 30% .
It is noteworthy that even in MHD patients deemed to be stable and managed as outpatients, there were those whose clinical condition abruptly worsened, leading to subsequent death. This high mortality rate is far greater than that published this year and is more consistent with what would be expected in a cohort with underlying comorbidities that are associated with poor outcomes. MHD patients also had significant pulmonary complications, with high percentages of acute respiratory distress syndrome and mechanical ventilation, suggesting that MHD patients are at very high risk of COVID-19 complications and should be managed accordingly .
MHD patients usually presented a variety of symptoms, ranging from very mild to severe disease ([Figure 2]).
Efforts to coordinate appropriate prevention and control of coronavirus disease 2019 infection in outpatient hemodialysis facilities 
- Patients and HCPs should be educated on preventive and control strategies.
- Emphasize basic hygiene, such as hand and respiratory hygiene and coughing etiquette.
- Use of personal protective equipment (PPE).
- Advise patients to call ahead.
- Place signs.
- Create appropriate space.
- Implement triage protocol.
Managing patients and health care workers with symptoms or illness
- Appropriate initial care, surveying, and face masks.
- Separate room, cohorting if multiple patients.
- Separation by 6 feet in all directions.
- Routine cleaning and disinfection procedures.
- Keeping track of PPE inventory.
- Preserving PPE.
- Prioritizing PPE.
- Extended use of eye and face protection.
Using specific extracorporeal circuits and devices, heart, lungs, kidneys, and liver can be partially replaced or at least sustained during the severe phase of the syndrome. The concept is known as extracorporeal organ support.
Convection-based therapies are in particular important for systemic inflammatory response syndrome ([Figure 3]).
- HD when required for either patients on MHD or in patients with AKI: what we must change in HD prescription after COVID-19 pandemic?
- Probably what was an optional should be a must!
- Convection therapies and longer duration are major players in affected patients.
|Figure 3 Renal replacement therapy in MHD and patients with AKI. AKI, acute kidney injury; MHD, maintenance hemodialysis.|
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The type of HD should be individualized for every patient and in general ‘one size does not fit for all,’ and it depends on multifactorial process ([Figure 4]).
All preventive measures should be installed strictly to prevent the diffusion of the disease between patients as well in the medical health providers.
Algorithm for the management of dialysis patients during coronavirus disease 2019 pandemic
Depending on the local guidelines, all effort should be made to prevent transmission and diffusion of COVID-19 between patients in HD centers ([Figure 5]).
|Figure 5 Algorithm for the management of dialysis patients during COVID-19 pandemic.|
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The reasonable way is to strictly apply a triage where suspected cases could be picked up before the entry to the center dialysis rooms, and preferably when applicable, the patients should communicate directly with the center before arrival to announce for any new symptoms like fever or cough to direct the patient to the specific designated area for check of COVID-19.
In suspected cases, doing renal function tests and electrolyte with clinical judgment is essential to determine the urgency of the need of the HD or the postpone till results of COVID-19 laboratory and radiological findings are available.
| Suspected cases|| |
Take an electrolyte panel to see whether dialysis is immediately needed, or that this can be postponed until the results of the nasopharyngeal swab PCR and computer-aided tomography of the chest are known .
- Early recognition and isolation of individuals with respiratory infection.
- Facilities should implement sick leave policies that are nonpunitive, flexible, and consistent with public health policies that allow ill health care personnel (HCP) to stay home. HCP should be reminded to not report to work when they are ill.
- Facilities should identify patients with signs and symptoms of respiratory infection (e.g. fever and cough) before they enter the treatment area.
- Instruct patients to call ahead to report fever or respiratory symptoms, so the facility can be prepared for their arrival or triage them to a more appropriate setting (e.g. an acute care hospital).
- Patients should inform staff of fever or respiratory symptoms immediately upon arrival at the facility (e.g. when they check in at the registration desk).
- Patients with symptoms of a respiratory infection should put on a facemask at check-in and keep it on until they leave the facility.
- Facilities should provide patients and HCP with instructions about hand hygiene, respiratory hygiene, and cough etiquette.
- Instructions should include how to use face masks, how to use tissues to cover nose and mouth when coughing or sneezing, how to dispose of tissues and contaminated items in waste receptacles, and how and when to perform hand hygiene.
- Post signs at clinic entrances with instructions for patients with fever or symptoms of respiratory infection to alert staff, so appropriate precautions can be implemented.
- Facilities should have supplies positioned close to dialysis chairs and nursing stations to ensure adherence to hand and respiratory hygiene and cough etiquette. These include tissues and no-touch receptacles for disposal of tissues and hand hygiene supplies (e.g. alcohol-based hand sanitizer).
- Patient placement: facilities should have space in waiting areas for ill patients to sit separated from other patients by at least 6 feet.
- Medically stable patients might opt to wait in a personal vehicle or outside the health care facility where they can be contacted by mobile phone when it is their turn to be seen.
- Patients with respiratory symptoms should be brought back to an appropriate treatment area as soon as possible to minimize time in waiting areas.
- Facilities should maintain at least 6 feet of separation between masked, symptomatic patients and other patients during dialysis treatment. Ideally, symptomatic patients would be dialyzed in a separate room (if available) with the door closed.
- If a separate room is not available, the masked patient should be treated at a corner or end-of-row station, away from the main flow of traffic (if available). The patient should be separated by at least 6 feet from the nearest patient (in all directions).
- Health care workers should be trained for dealing with all cases under PPE according to individual case scenario.
When COVID-19 is suspected or confirmed in a patient receiving HD at the facility, the following additional measures apply :
- The health department should be notified about the patient.
- 1 HCP should follow the Interim Infection Prevention and Control Recommendations for Patients with Confirmed Coronavirus Disease 2019 (COVID-19) or Persons Under Investigation for COVID-19 in health care settings. This includes recommendations on PPE. Routine cleaning and disinfection are appropriate for COVID-19 in dialysis settings. Any surface, supplies, or equipment (e.g. dialysis machine) located within 6 feet of symptomatic patients should be disinfected or discarded.
Minimize patient exposure 
- Encourage patients, and their care giver if needed, to use their own transport, and to travel alone to the dialysis unit when possible.
- Minimize time in the waiting area by:
- Careful scheduling.
- Encouraging patients not to arrive early.
- Texting patients when you are ready to see them, so that they can wait outside, for example, in their car.
- If a patient is COVID-19 negative and has symptoms.Ensure that other explanations for the symptoms have been considered and treated.
- At subsequent assessment, retest the patient if there is still a clinical suspicion of COVID-19.
- Outlining restrictions to the dialysis unit to those staff and visitors essential to the delivery of the service.
- Educate your patient how to stay safe at home.
- Educate patients’ relatives how to protect themselves from COVID-19.
- Encourage patients not to use public transportation if possible? If not, use all protection tools, for example, face mask and gloves.
- Patients’ entrance and exit should not be in groups, leaving about 6 feet (1.8 m2) spacing in between.
- Meals should not be allowed on session, and only allow controlled snacks, for example, small candy to prevent hypoglycemia.
- Washing hands upon entry and before leaving the center.
- Patients never share their personal belongings.
- On praying do not use carpets, only pray while seated .
- Pass route for entering hospital and dialysis unit:
- The pick-up and drop-off should not be shared with other dialysis patients.
- Entering and exiting with other patients at the same time should be avoided.
- The route, mode, and time of transport of dialysis personnel should be fixed.
How should facilities monitor or restrict dialysis facility staff? 
- The same screening performed for patients should be performed for facility staff.
- Dialysis staff who have signs and symptoms of a respiratory infection should not report to work. Facilities should implement sick leave policies that are nonpunitive, flexible, and consistent with public health policies that allow ill staff members to stay home.
- Any staff member who develops signs and symptoms of a respiratory infection, should follow the following procedures:
- Immediately stop work (if working), put on a facemask, and self-isolate at home.
- Inform the facility administrator, and collect information on individuals, equipment, and locations the person came in contact with.
- Contact and follow the local health department recommendations for next steps (e.g. testing, locations for treatment).
- The medical waste from confirmed or suspected patients with COVID-19 infection should be considered as infectious medical wastes and disposed accordingly.
- The health department should be notified in instances of suspected or confirmed COVID-19 infection.
- All the family members living with dialysis patients must follow all the precautions and regulations given to patients to prevent person-to-person and within family transmission of the COVID-19, which include body temperature measurement, good personal hygiene, handwashing, and prompt reporting of potentially sick people.
- Dialysis patients, who have a family member or care giver subject to ‘basic quarantine,’ can have dialysis as usual in accordance during the 14-day period.
- Once the family members or care giver of dialysis patients have been converted to a confirmed case, the patient’s identity should be upgraded and treated in a designated area with check for a confirmatory test for COVID-19.
Hemodailysis prescriptions in regular hemodialysis patients
According to the Egyptian HD guidelines:
- All patients should receive their regular HD sessions in both duration and frequencies.
- It is advisable to use the high-flux dialysis membranes.
- Always individualize therapy according to patient needs.
- Cytokine storms associated with elevated levels of IL-6, IL-18, and interferon gamma are associated with more severe disease and higher mortality .
- Extracorporeal therapies using high-volume hemofiltration or adsorption to decrease cytokine levels may theoretically be expected to confer benefit.
- Acute peritoneal dialysis (PD).
- Use of acute PD can be lifesaving and should be used as and when required and, in the setting, where HD facility is not available. Health care worker should use all precautions while initiating acute PD and discard used consumables properly.
Acute kidney injury management with COVID-19-positive patients 
- Dialysis procedures, in chronic HD patients and in patients with AKI, are at risk of transmission and dissemination of COVID-19 for multiple procedural and logistical aspects.
- Indications to start renal replacement therapy (RRT) are similar to other patients with AKI.
- Continuous renal replacement therapy (CRRT) filter changes can be performed every 72 h or at longer intervals per institution protocols.
- After treatment, dialysis equipment should be cleaned with a disinfectant as per CDC and manufacturer’s recommendations.
- The equipment should be disinfected before removed from the room.
- Some institutions may require additional cleaning before machine can be used for another patient.
- All disposable RRT machine equipment (tubing/filter sets, CRRT solutions bags, etc.) should be discarded as directed by hospital infection control and policy.
Continuous renal replacement therapy and slow low-efficiency dialysis in ICU 
- The preferred modality for RRT in critically ill patients is CRRT or slow low-efficiency dialysis (SLED) and other terminologies.
- In ICUs where ICU nurses are all trained and competent on the use of CRRT, HD nurses do not need to have direct contact with patients, thereby limiting health care staff exposure.
- Patient fluid removal rate will depend on various factors and may be regulated by ICU physicians, if patients are undergoing CRRT or SLED.
- If patient surge overwhelms CRRT capacity at an institution, consideration should be given to using CRRT machines for prolonged intermittent treatments (e.g. 10 h instead of continuous) with higher flow rates (e.g. 40–50 ml/kg/h) and then using the machine for another patient, after terminal cleaning.
- For dialysis, treatment of patients hospitalized should be in dedicated spaces or rooms, and use of monitors for continuous techniques (CRRT).
- Management modalities of the session defined by the nephrologist based on the clinical complexity.
- No contraindications to the use of intermittent or SLED techniques if the logistical conditions allow it with the use of portable osmosis.
- Currently, there is no scientific evidence of the need for dedicated dialysis monitors; thorough cleaning/disinfection of the equipment at the end of the session.
Continuous renal replacement therapy
- CRRT is beneficial to maintain volume balance, hemodynamics, and to allow plenty of nutritional support.
- Improve the clearance efficiency of medium and small molecular toxins and maintain body temperature.
- CRRT is highly indicated in patients with AKI who are suspected to have high levels of cytokines and hemodynamic instability.
According to ERA/EDTA 2020 
- Patients with COVID-19 are reported to have a high risk of thromboembolic events and, therefore, several centers use higher dosages of thrombosis prophylaxis than usual (often double dose).
Slow low-efficiency dialysis and intermittent hemodialysis
If CRRT is unavailable.
- Theoretically use hemodiafiltration (HDF) with a dialyzer capable of removing cytokines identified by membrane SC values (SC of myoglobin >0.5).
- Use more prolonged sessions to overcome the continuous cytokine production (balance between production and removal).
- Control drug doses accordingly.
If HDF is not available, use SLED technique with the same dialysis membrane above.
In presence of our inability to obtain instantaneous monitoring of biological levels of cytokines, the reasonable approach is to promote a nonspecific removal assuming that those cytokines with the highest concentration will be removed in higher amount .
Cytokines’ molecular weight
- IL-6 homodimer 19–26 kD.
- IL-7 monomer 25 kD.
- IL-8 homodimer 16 kD.
- IL-10 homodimer 20.5 kD.
- IL-11 monomer 19 kD.
- IL-12 heterodimer 35 kD.
- IL-16 homotetramer 56 kD.
- IL-17A 35 kD.
- IL-18 heterodimer 22.3 kD.
- IL-19 monomer 20.5 kD.
- TNF-a homotrimer 26 kD.
HD management is a key in COVID-19-infected patients. High-flux dialysis membrane with a myoglobin SC more than 0.5 is recommended for maximum dialysis efficiency ([Figure 6]).
|Figure 6 Approach in dialysis mode and doses according to clinical conditions.|
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HD dose will depend on two main factors: convection volume and duration of sessions ([Figure 7]).
|Figure 7 Factors affecting the dose of hemodialysis. HCO, high cutoff; MCO, medium cutoff.|
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Convection volumes are directly related to solute flux depending on the dialysis membrane used and the techniques .
- High-flux dialysis: 4–8 l (internal HDF).
- Low-efficiency HDF:<15 l in postdilutional mode.
- High-efficiency HDF >23 l in postdilutional mode.
Is it the correct time to use high-performance dialysis membranes? (albumin removal to <3 g/session).
High-performance membrane (HPM) is a classification used in Japan to identify hollow fiber dialyzers with an advanced level of performance .
The criteria for HPM include the following:
- Excellent biocompatibility.
- Effective clearance of target solute.
- Pore size larger than conventional HD membranes, thus promoting the removal of protein-bound uremic toxins and middle to large molecular-weight solutes.
- HPM should also have a high molecular weight cutoff and a sharp cutoff curve ([Figure 8]).
|Figure 8 Dialysis membranes cutoff during MCO and high-flux dialysis. MCO, medium cutoff.|
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Dialysis with patients with acute kidney injury 
Depending of the availability of the modality and/or trained personnel, the available modalities for RRT are as follows:
- Prolonged intermittent renal replacement therapy (PIRRT) or SLED with high-flux filters (preferred removal of cytokines).
- Intermittent hemodialysis (IHD) with high-flux filters.
- PD, automated peritoneal dialysis, or intermittent peritoneal dialysis. The use of acute PD can be lifesaving and should be considered when required, and in the setting where HD facility is not available.
Accumulating evidence suggests that a delayed RRT initiation is safe.
Loop diuretics may be used in the management of volume overload, per treating physician’s discretion.
If there is a lack of dialysis and/or ICU nurses, nondialysis or non-ICU nurses may be recruited to monitor patients undergoing RRT, under the supervision of an ICU or dialysis nurse.
PD in an automated mode could be also used in some centers.
Accumulating evidence of endothelial injury with COVID-19 is responsible a part for both kidney and the lung injuries .
Dialysis modality with the safest way for the biocompatibilities of the whole system is a must ([Figure 9]).
Avoiding impurities and other factors that may increase body response to the extracorporeal circuits are selected.
- The use of CRRT with specific adjustments for patients with COVID-19, and the possible use of cytokine removal strategies, ideally in patients with early signs of hyperinflammation and cytokine release syndrome.
Flux and solute permeability cut off=SC 0.1
After decades of experiences in RRT in critically ill patients in ICU, in sepsis, multiple trauma, etc.
The equipment, devices, and the manpower are essentially the same.
It should be noted that patients with COVID-19 requiring RRT may have increasing possibilities of extracorporeal circuit clotting.
Extracorporeal treatments do not compromise the experimental antibody-based therapies used in COVID-19, such as tocilizumab, intravenous immunoglobulins, and convalescent plasma administration.
Neither hemodialysis filters nor hemadsorption cartridges remove antibodies, as their size (e.g. 150 kDa for immunoglobulin G) far exceeds the upper size of molecules that can be removed with RRT (around 60 kD).
Proposed cytokines’ MW is shown in [Figure 10].
CRRT and SLED in the ICU
Modalities used will depend on the availability of staff and equipment and the clinical complexity of the case.
- CVVHDF before and/or after dilution with a prescribed dose of 25–30 ml/kg/h.
- In the presence of a cytokine storm, higher doses may be required.
- The dose should be regularly reassessed to determine if treatment goals are being met.
- CRRT is beneficial for maintenance of volume balance, hemodynamic stability, and to allow adequate nutritional support. It will improve the clearance efficiency of medium and small molecular toxins and can maintain body temperature. CRRT is particularly indicated in patients with AKI who are suspected to have high levels of cytokines and with hemodynamic instability.
- If a patient surge overwhelms the CRRT capacity at an institution, consideration should be given to using CRRT machines for prolonged intermittent treatments (e.g. 10 h instead of continuous) with higher flow rates (e.g. 40–50 ml/kg/h) and then using the machine for another patient, after terminal cleaning as per instituional policies.
- The use of prolonged intermittent or SLED techniques is an accepted choice and preferred for its easier use and experiences.
- If the logistical conditions require SLED, It is noninferior to continuous therapies. High-flux (sieving coefficient for myoglobin >0.5) membranes are essential if available in this context.
A guide for standard operating procedure for SLED ([Figure 11]).
|Figure 11 Standard operating procedure with SLED. SLED, slow low-efficiency dialysis.|
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The preferred modality for RRT in critically ill patients is CRRT or SLED and other hybrid treatments (PIRRT).
CRRT is a commonly initiated treatment in the ICU.
Indications for CRRT include AKI with metabolic acidosis, hyperkalemia, excessive uremia, or refractory fluid overload as in other causes for AKI.
SLED is efficient as CRRT using higher SC dialyzer membranes.
Continuous renal replacement therapy versus slow low-efficiency dialysis and outcome in patients with acute kidney injury
There are various modalities of in-hospital RRT that are in use today, but the critically ill patient imposes the additional challenge of serious hemodynamic instability, which limits RRT options. The advent of CRRT permitted the treatment of hemodynamically unstable AKI with tolerance for ultrafiltration, excellent control of azotemia, and potentially less ongoing or repeated renal ischemia. The introduction of SLED, which uses lower flow rates than conventional IHD, improves convenience by restricting therapy time while still allowing for a similar hemodynamic tolerability to CRRT. Additionally, SLED is operationalized with IHD equipment and does not require prepackaged replacement solution(s). Cost savings thus accrued have resulted in the promotion of SLED utilization in many centers . In a systemic review and a meta-analysis, 1564 patients from 18 studies were included. The meta-analysis results indicated no statistically significant difference in primary outcome, overall proportion of renal recovery (risk ratio 0.87, 95% confidence interval (CI) 0.63–1.20, I2=66%). No significant difference was observed for the secondary outcome of time to renal recovery (mean difference 1.33, 95% CI 0.23–2.88, I2=0%). Statistically, SLED was marginally favored over CRRT for the secondary outcome of mortality (risk ratio 1.21, 95% CI 1.02–1.43, I2=47%) .
SLED is an intermittent hybrid renal replacement modality in between conventional IHD and CRRT. The choice of modality depends on the availability thereof and on the experience of the doctor who prescribes the modality of treatment. However, the clinical experience is that approximately two-thirds of IHD sessions in critically ill patients are not well tolerated, requiring the use of continuous techniques .
Inevitably the question arises whether kidney replacement therapy should be approached differently in the acute care setting. If cytokine storm is contributing to disease severity in COVID-19 infection, in theory, convective-based clearance may be superior for the removal of large cytokines, when compared with diffusion-based modalities. The dialysis modality has been informed by the acuity of illness, with CRRT or SLED reserved for patients who are too sick to tolerate conventional IHD. In the absence of data clearly demonstrating the superiority of one modality over another, choice of dialysis modality should be informed foremost by resources readily available and for which local clinical expertise lies .
The choice of RRT will depends largely on the availability, the staff, and the experiences as well. In situations where there may be insufficient CRRT machines or equipment to meet demand, it is advocated to perform PIRRT instead of CRRT, and then using the machine for another patient after appropriate cleaning .
CRRT is the most common modality of RRT used in critically ill patients. However, other RRT modalities, such as PIRRT, HD, or PD, also can be considered for critically ill patients, particularly in settings with limited availability of CRRT machines. When using PIRRT, duration of therapy is ∼6–8 h using a blood flow rate of ∼200 ml/min, dialysate flow rate of 200–300 ml/min, and ultrafiltration rate limited to less than 1 l/h .
Additional considerations for PIRRT and HD include low temperature (35.5°C) and high calcium bath (3 mmol/l) to attenuate intradialytic hypotension. If acute PD is used, cycler use is recommended, with each fill limited to 1 liter in cycles of 1.5–2 h for a total of 8–12 h to minimize risk of catheter leak contemplated .
If a patient develops indications to start RRT (or if a patient with ESKD needs a dialysis catheter for vascular access), one should insert a double-lumen internal jugular catheter (preferable).
This should be placed by a physician with the most expertise in placement of central venous catheters, for example, vascular surgeon, ICU physician, or radiology consultant.
Ultrasound-guided placement is recommended where available. Jugular catheters are more convenient where patient proning is needed to facilitate ventilation.
Renal replacement therapy and anticoagulation 
Patients with COVID-19 have a high risk of thromboembolic events, and many centers use higher dosages of thrombosis prophylaxis than usual (often double dose).
The choice of anticoagulation is based on the patient’s need for systemic anticoagulants, the risk or presence of bleeding, and the available drugs and expertise.
- Regional citrate anticoagulation, where available (cautions with liver affection).
- Systemic heparinization with unfractionated heparin.
- Treatment without using anticoagulants
Severe COVID-19 induces a hypercoagulable state in many critically ill patients, as evidenced by a markedly high rate of RRT blood circuit failures (clotting) and higher rates of venous thromboembolism. The pathophysiology of this hypercoagulable state is still unknown, but possible mechanisms include macrophage activation with cytokine release, deficiencies in fibrinolytic pathways, and endothelial injury leading to platelet activation. In this context, regional citrate anticoagulation  or systemic anticoagulation  is used exclusively or synergistically. Unfortunately, regional citrate anticoagulation has not proven to be nearly as effective in COVID-19 as in other critically ill patients. Alternatives using direct thrombin inhibitors, such as bivalirudin or argatroban, also can be considered, although data in the overall rRT population are limited. Importantly, some type of anticoagulation, regionally in the CRRT/PIRRT circuit or systemically, should be used in patients with COVID-19 on RRT unless there are contraindications, taking into consideration specific logistics available locally at each institution .
Care and disinfection of dialysis equipment
CRRT filter changes can be performed every 72 h or when clotting happens.After treatments, dialysis equipment should be disinfected according to national guidelines.
The equipment should be disinfected before being removed from the room.
Additional cleaning may be needed before the machine can be used for another patient.
Meticulous disinfection of the KRT machine surface is recommended by using registered bleach wipe products against COVID. In isolated COVID-19 units, machines will typically remain sequestered and disinfected there. If machines are to be transported back to the dialysis unit or storage, disinfection should occur before mobilization, and precautions during transport procedures should be taken .
Preparedness of hospitals to accommodate RRT requirements ([Figure 12]).
|Figure 12 Stages of preparing units to accommodate COVID-19-infected patients. CRRT, continuous renal replacement therapy. IHD only in stable patients; IHD, intermittent hemodialysis; PIRRT, prolonged intermittent renal replacement therapy.|
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Using MCO dialyzers versus OL-HDF
Removal of a wide range of molecular weights, was almost equal with the MCO dialyzer in HD treatment compared with eight high-flux dialyzers in high-volume OL-HDF without relevant changes in albumin loss. With 20 years of experience, OL-HDF technology has progressively evolved, and it can be considered a safe, fully consolidated treatment that provides many clinical advantages. Similar reduction ratios for small and middle molecules in the range 60–41 000 D for the MCO dialyzer in HD treatment compared with eight high-flux dialyzers in high-volume postdilution OL-HDF currently used in clinical practice .
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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