key: cord-346346-h09pn9sh
authors: Shaikh, Sana; Umemoto, Gonzalo Matzumura; Vijayan, Anitha
title: Management of Acute Kidney Injury in COVID-19
date: 2020-08-06
journal: Adv Chronic Kidney Dis
DOI: 10.1053/j.ackd.2020.08.002
sha: 
doc_id: 346346
cord_uid: h09pn9sh

Abstract Acute kidney injury is a common complication in hospitalized patients with COVID-19. Similar to AKI associated with other conditions such as sepsis and cardiac surgery, morbidity and mortality are much higher in patients with COVID-19 who develop AKI, especially in the intensive care unit. Management of COVID-19 associated AKI with kidney replacement therapy (KRT) should follow existing recommendations regarding modality, dose, and timing of initiation. However, patients with COVID-19 are very hypercoagulable and close vigilance to anticoagulation strategies is necessary to prevent circuit clotting. During situations of acute surge, where demand for KRT outweighs supplies, conservative measures have to be implemented to safely delay KRT. A collaborative effort and careful planning is needed to conserve dialysis supplies, to ensure that treatment can be safely delivered to every patient who will benefit for KRT.

Acute kidney injury (AKI) is well described in COVID-19 and is associated with high morbidity and mortality. In a large study of 5700 patients in a New York healthcare system, the incidence of AKI in hospitalized patients was 22%, and 3.2% required kidney replacement therapy (KRT) 1 . The risk for AKI and need for KRT is significantly higher in critically ill patients with COVID-19, with a correlation between invasive ventilation and initiation of KRT 2 . Data from other studies demonstrated an AKI incidence of 61-76% in the intensive care unit (ICU), with 26 to 45% of patients in the ICU with COVID-19 needed KRT 3, 4 . In this article we review the management of COVID-19 associated AKI, and address the complexities associated with delivery of KRT during a healthcare crisis which strained KRT and other resources across health systems on a global scale.

It is important to note that resources to perform KRT are limited, and dialysis resources were stretched thin during the pandemic. Safe and judicious non-dialytic management of AKI is of utmost importance in delaying initiation of KRT, if resources are restricted. In euvolemic patients with AKI stage I or II, a furosemide stress test may help identify those more likely progress to advanced AKI and need for KRT 5 . However, higher or escalating doses of loop diuretics should be reserved for patients with volume overload, as use of loop diuretics in patients with AKI in general is not associated with decreased need for KRT 6 . In addition, use of diuretics in euvolemic or hypovolemic patients with severe respiratory failure from COVID-19, could lead to exacerbation of the kidney injury, as it is difficult to ascertain their true volume status. If volume resuscitation is required, balanced solutions may be preferred over normal saline in patients at risk for AKI, as two recent trials have demonstrated decreased major adverse kidney events pragmatic trials compared balanced crystalloids to normal saline for volume resuscitation in the emergency room (SALT-ED trial) and the ICU (SMART trial). In the SALT-ED trial with 13, 347 patients, the incidence of MAKE with balanced solution was 4.7% vs 5.6% (adjusted OR 0.82, CI 0.70 -0.95; p =0.01). 7 In the SMART trial with 15,802 patients, the incidence of MAKE in the group administered balanced solutions was 14.3% vs 15.4% in the group that received normal saline (marginal OR 0.91, 95% CI 0.84 to 0.99, p = 0.04). 8 This is in contrast to the SPLIT (Saline vs. PlasmaLyte for Intensive Care Fluid Therapy) trial which did not demonstrate a reduction in the incidence of AKI with buffered solutions. 9 So while balanced crystalloids may not be necessary for everyone, it should be considered in in patients with hypotension, severe systemic inflammatory response, and elevated serum creatinine on presentation. 10 Regarding metabolic acidosis, the Sodium Bicarbonate to Treat Severe Acidosis in the Critically Ill study (BICAR-ICU) demonstrated that administration of intravenous bicarbonate solution in patients with critical illness reduced the need for KRT, when compared to control arm (35% vs 52%, 95% CI −26·4 to −7·0; p=0·0009). The patients receiving bicarbonate infusion also had delayed initiation of KRT (19 days vs 8 days, CI 3.9-15.6, p <0.0001) 11 . At baseline the patients had severe metabolic acidosis, with a pH of 7.15 and serum bicarbonate level of 13 mmol/L. New potassium binders have become available in the United States over the past few years. Sodium zirconium cyclosilicate (SZC) has a more rapid onset of action compared to others, and has shown to be effective in lowering potassium in multiple setting, including the emergency room 12 .

Patiromer is also approved for treatment of hyperkalemia, but the onset of action is prolonged when compared to SZC (7 hours vs.1 hour) and therefore may not be suitable for immediate correction of hyperkalemia 13, 14 . Escalating dosages of intravenous loop diuretics in patients with volume overload, intravenous sodium bicarbonate solution in patients with severe metabolic acidosis, and use of rapid acting potassium binders like sodium zirconium cyclosilicate for Continuous kidney replacement therapy (CKRT) is the recommended modality for management of AKI in patients with hemodynamic instability 20 . KDIGO recommends an effluent flow rate of 20-25 ml/kg/hour. Depending on the mechanism of clearance, CKRT can be delivered as continuous venovenous hemofiltration (CVVH) (convective clearance), continuous venovenous hemodialysis (CVVHD) (diffusive clearance), and continuous venovenous hemodiafiltration (CVVHDF) (combination of both). Convective clearance is not superior to diffusive clearance and in fact, maybe associated with higher rates of filter clotting due to higher filtration fraction 21 .

We recommend using the available modality at each institution. In the setting of a demand vs.

resource imbalance due to a surge in patient volumes, consideration should be given to conservation of dialysate and replacement fluids, by reducing flow rates to 15 ml/kg/hour, once metabolic control has been achieved.

Prolonged intermittent kidney replacement therapy (PIKRT) is a hybrid therapy that provides KRT for an extended time but on an intermittent basis 22 . PIKRT can be used as a substitute for CKRT or IHD. When HD machine is used for PIKRT, it is usually referred to as sustained low efficiency dialysis (SLED). SLED offers the option to use HD machine to provide KRT to hemodynamically unstable patients, and in most institutions that perform SLED, one-on-one hemodialysis nursing is not required. This alleviates the pressure for dialysis nursing support in the times of an acute surge of patients. SLED is often performed for 8-12 hours, with lower blood and dialysate flow rates. In our, as well as other institutions, CKRT machines that have an effluent drain line are utilized for PIKRT, as the drain line reduces nursing workload, who otherwise will need to change the effluent bag every one to two hours. PIKRT allows one CKRT machine to be used for 2-3 patients, depending on the duration of treatment. Provision of PIKRT in this manner allows multiple patients to be treatment with one CKRT machine, thereby J o u r n a l P r e -p r o o f preventing delays in timely delivery of KRT, which can occur during a surge of patients at individual hospitals, if adequate number of CKRT machines are not available. Another option for PIKRT is to alternate one machine between 2 patients every 24 hours 23 .

Intermittent hemodialysis (IHD) is the traditional modality for providing KRT in patients who are hemodynamically stable. Based on the ATN study, KDIGO and KDOQI recommends provision of IHD 3 times/week, with a delivered single pool Kt/Vurea of 1.3 per session 20, 24, 25 . Providing IHD to a COVID-19 patient may require one-on-one dialysis nursing support, whether in the ICU or on the general hospital floor. This increases exposure for the nursing staff and creative maneuvers have been implemented at hospitals to reduce nursing time in the room. Strategies proposed to conserve resources, and decrease exposure include decreasing duration of treatments, decreasing frequency of dialysis to twice a week and telemonitoring (e.g. use of baby monitors or tablets to visualize patients from outside the room). (Table 1) . Consideration for patient safety should be paramount when implementing any resource conservation and exposure reduction measures. Reducing time and/or frequency of HD treatments for an extended period can result in uremia and metabolic disturbances and patients should be carefully monitored for manifestations of inadequate dialysis.

Experiences from resource-limited countries have shown adequate metabolic and fluid control with acute peritoneal dialysis (PD) in AKI 26, 27 . Under usual circumstances, acute PD is not utilized in US and other developed countries for adult patients with AKI, because regulation of ultrafiltration and metabolic control is superior with CKRT in hemodynamically unstable patients.

However, due to acute surge during the pandemic in NY, acute PD was implemented in few hospitals, due to shortages in extracorporeal KRT consumables, fluids and nursing 28 .

A bedside catheter placement of a cuffed peritoneal dialysis catheter is preferred for patients who are critically ill 29 . Automated cycler use and extension tubing to keep the machine outside the patient's room can limit exposure to healthcare workers. An average-sized adult can usually tolerate 2-liter (L) exchanges, however, reduced volume should be considered for the initial few exchanges to decrease risk of peri-catheter leaks. To maximize efficiency of acute PD, an exchange time of 1-2 hours should be used. Assuming a 2L exchange volume with 60-minute exchange time, UF of about 1.2 -3.6 L/day can be achieved with 1.5%, 2.4 -7.2 L/day with 2.5% and 7.2 -9.6 L/day with 4.25%. As such, for patients with severe pulmonary edema, initial rapid in-out exchanges using 4.25% can be considered 29 . Theoretically, high volume peritoneal dialysis (HVPD) may impair diaphragmatic movement, increase intra-abdominal pressure, and worsen respiratory mechanics. However, one single center study showed no effect of HVPD on pulmonary compliance although the study excluded patients with FiO2 > 70% and PEEP > 10 cm H20 30 . In patients requiring prone positioning, PD may not be feasible but successful delivery has been described in small studies 31 .

Adequate central venous access is imperative to provide sufficient blood flows during KRT.

Hemodialysis catheter length (15-16 cm for right internal jugular (IJ), 19-20 cm for left IJ, 24 cm for femoral) and location must be carefully selected, as inappropriate catheter length can lead to inadequate blood flows which leads to increased filter clotting 32 . The right IJ is the preferred access for KRT as this offers a direct path for the catheter tip to be placed at preferred locationthe junction of the superior vena cava and right atrium. There is some controversy whether the second choice should be the L IJ or the femoral vein. The femoral vein site may be associated with higher risk for infections and blood flows may be affected in patients who need to be proned for ventilation. The left IJ can provide inadequate blood flow, especially when shorter catheters are inadvertently placed 33 . In the setting of a surge, physicians not familiar with hemodialysis catheters may be responsible for placing catheters in patients with COVID-19. A cheat sheet with appropriate information related to hemodialysis catheters is a useful tool to distribute in the COVID ICUs. In patients with end stage kidney disease, a single-center study has described the use of arteriovenous fistula and arteriovenous graft for CKRT, but this practice is largely limited due to intricacies with patient monitoring, dialysis and ICU nursing coordination and risk of extravasation 34 . In patients on extracorporeal membrane oxygenation (ECMO), unless restricted by high ECMO flow, CKRT can be performed via the circuit after default CKRT access alarms are reset to accommodate the higher pressures via the ECMO circuit 35 .

There is growing evidence of endothelial activation causing a hypercoagulable state, leading to higher incidence of thrombotic complications in patients with COVID-9 36 . In addition to deep vein thrombosis and pulmonary embolism, clotting of extracorporeal circuits is a major concern, as this leads to significant blood loss, and excessive loss of KRT filters. Unless there is a contraindication to anticoagulation, we recommend that every COVID-19 patient starting CKRT or PIKRT receive anticoagulation per institution protocol. (Figure 1 ) If initial anticoagulation strategy is not effective, then an alternative plan will need to be implemented. At our center, systemic unfractionated heparin is administered to all COVID-19 patients on CKRT (target activated partial thromboplastin time of 60-90 seconds). If patients develop bleeding or other complications from unfractionated heparin, we use regional citrate anticoagulation (RCA), based on our existing policy. In some centers, RCA is the first line option for anticoagulation for CKRT. 37, 38 RCA is a complicated and nursing intensive technique, and we do not recommend hasty implementation of an RCA protocol in the setting of a surge, as this can lead to significant adverse events 37 . Other centers have used other anticoagulation methods such as low molecular weight heparin and direct thrombin inhibitors for CKRT. Involvement of pharmacists to establish appropriate anticoagulation protocol is important to ensure adequate dosing and prevent errors.

Hemoperfusion (HP) involves non-specific removal of cytokines by an extracorporeal membrane and has been proposed as a complementary therapeutic option in patients with COVID-19 and multiorgan dysfunction. In the current crisis, the Food and Drug Administration (FDA) has granted emergency use authorization to 3 different apheresis and cartridge systems.

Hemoadsorption devices have been shown to remove cytokines such as IL-6, but this may not translate to improved patient outcomes 39 . The most robust evidence available for use of HP in septic shock showed no change in mortality or any other parameter when compared to a sham HP group 40 . At this time we do not recommend use of these devices in the treatment of critically ill patients with COVID-19. However, clinical trials evaluating the effect of these devices and filters on patient outcomes should be considered.

The pandemic and associated surge of patients posed a significant strain on dialysis resources and hospital personnel across the globe 38 . Similar to a patient who requires mechanical ventilation for respiratory failure to sustain life, a patient with AKI or ESKD requires KRT.

However, unlike ventilators, there is no national stockpile of KRT machines and filters in the United States. Dialysate, and replacement fluids are perishable and cannot be stockpiled.

Hospitals had to institute changes to conserve resources and protect personnel. (Table 1 

Management of patients with COVID-19 associated AKI is generally similar to patients with AKI associated with other etiologies such as sepsis. Conservative management of volume overload, metabolic acidosis, and hyperkalemia can be attempted before considering initiation of KRT. In patients with COVID-19, KRT, especially CKRT and PIKRT is associated with high rate of circuit clotting and anticoagulation should be initiated at the start of KRT. Delivery of KRT during a pandemic with acute influx of hospitalized patients poses significant challenges, and careful planning is required to provide safe and effective KRT to every patient who needs it. * Use citrate anticoagulation only if an existing protocol is available at the institution. Implementation of citrate anticoagulation protocol requires careful advanced planning, and education of physicians and nurses to prevent adverse events. We do not recommend initiation of a new regional citrate anticoagulation during acute surge.

J o u r n a l P r e -p r o o f 

Acute kidney injury (AKI) is well described in COVID-19 and is associated with high morbidity and mortality. In a large study of 5700 patients in a New York healthcare system, the incidence of AKI in hospitalized patients was 22%, and 3.2% required kidney replacement therapy (KRT) 1 . The risk for AKI and need for KRT is significantly higher in critically ill patients with COVID-19, with a correlation between invasive ventilation and initiation of KRT 2 . Data from other studies demonstrated an AKI incidence of 61-76% in the intensive care unit (ICU), with 26 to 45% of patients in the ICU with COVID-19 needed KRT 3, 4 . In this article we review the management of COVID-19 associated AKI, and address the complexities associated with delivery of KRT during a healthcare crisis which strained KRT and other resources across health systems on a global scale.

It is important to note that resources to perform KRT are limited, and dialysis resources were stretched thin during the pandemic. Safe and judicious non-dialytic management of AKI is of utmost importance in delaying initiation of KRT, if resources are restricted. In euvolemic patients with AKI stage I or II, a furosemide stress test may help identify those more likely progress to advanced AKI and need for KRT 5 . However, higher or escalating doses of loop diuretics should be reserved for patients with volume overload, as use of loop diuretics in patients with AKI in general is not associated with decreased need for KRT 6 . In addition, use of diuretics in euvolemic or hypovolemic patients with severe respiratory failure from COVID-19, could lead to exacerbation of the kidney injury, as it is difficult to ascertain their true volume status. If volume resuscitation is required, balanced solutions may be preferred over normal saline in patients at risk for AKI, as two recent trials have demonstrated decreased major adverse kidney events pragmatic trials compared balanced crystalloids to normal saline for volume resuscitation in the emergency room (SALT-ED trial) and the ICU (SMART trial). In the SALT-ED trial with 13,347 patients, the incidence of MAKE with balanced solution was 4.7% vs 5.6% (adjusted OR 0.82, CI 0.70 -0.95; p =0.01). 7 In the SMART trial with 15,802 patients, the incidence of MAKE in the group administered balanced solutions was 14.3% vs 15.4% in the group that received normal saline (marginal OR 0.91, 95% CI 0.84 to 0.99, p = 0.04). 8 This is in contrast to the SPLIT (Saline vs. PlasmaLyte for Intensive Care Fluid Therapy) trial which did not demonstrate a reduction in the incidence of AKI with buffered solutions. 9 So while balanced crystalloids may not be necessary for everyone, it should be considered in in patients with hypotension, severe systemic inflammatory response, and elevated serum creatinine on presentation. 10 11 . At baseline the patients had severe metabolic acidosis, with a pH of 7.15 and serum bicarbonate level of 13 mmol/L. New potassium binders have become available in the United States over the past few years. Sodium zirconium cyclosilicate (SZC) has a more rapid onset of action compared to others, and has shown to be effective in lowering potassium in multiple setting, including the emergency room 12 .

Patiromer is also approved for treatment of hyperkalemia, but the onset of action is prolonged when compared to SZC (7 hours vs.1 hour) and therefore may not be suitable for immediate correction of hyperkalemia 13, 14 . Escalating dosages of intravenous loop diuretics in patients with volume overload, intravenous sodium bicarbonate solution in patients with severe metabolic acidosis, and use of rapid acting potassium binders like sodium zirconium cyclosilicate for hyperkalemia can potentially delay KRT and conserve valuable resources in the setting of a surge 5, 11, 12, 15, 16 .

KRT during acute surge in the hospitals has been extremely challenging, as institutions Continuous kidney replacement therapy (CKRT) is the recommended modality for management of AKI in patients with hemodynamic instability 20 . KDIGO recommends an effluent flow rate of 20-25 ml/kg/hour. Depending on the mechanism of clearance, CKRT can be delivered as continuous venovenous hemofiltration (CVVH) (convective clearance), continuous venovenous hemodialysis (CVVHD) (diffusive clearance), and continuous venovenous hemodiafiltration (CVVHDF) (combination of both). Convective clearance is not superior to diffusive clearance and in fact, maybe associated with higher rates of filter clotting due to higher filtration fraction 21 .

We recommend using the available modality at each institution. In the setting of a demand vs.

resource imbalance due to a surge in patient volumes, consideration should be given to conservation of dialysate and replacement fluids, by reducing flow rates to 15 ml/kg/hour, once metabolic control has been achieved.

Prolonged intermittent kidney replacement therapy (PIKRT) is a hybrid therapy that provides KRT for an extended time but on an intermittent basis 22 . PIKRT can be used as a substitute for CKRT or IHD. When HD machine is used for PIKRT, it is usually referred to as sustained low efficiency dialysis (SLED). SLED offers the option to use HD machine to provide KRT to hemodynamically unstable patients, and in most institutions that perform SLED, one-on-one hemodialysis nursing is not required. This alleviates the pressure for dialysis nursing support in the times of an acute surge of patients. SLED is often performed for 8-12 hours, with lower blood and dialysate flow rates. In our, as well as other institutions, CKRT machines that have an effluent drain line are utilized for PIKRT, as the drain line reduces nursing workload, who otherwise will need to change the effluent bag every one to two hours. PIKRT allows one CKRT machine to be used for 2-3 patients, depending on the duration of treatment. Provision of PIKRT in this manner allows multiple patients to be treatment with one CKRT machine, thereby preventing delays in timely delivery of KRT, which can occur during a surge of patients at individual hospitals, if adequate number of CKRT machines are not available. Another option for PIKRT is to alternate one machine between 2 patients every 24 hours 23 .

Intermittent hemodialysis (IHD) is the traditional modality for providing KRT in patients who are hemodynamically stable. Based on the ATN study, KDIGO and KDOQI recommends provision of IHD 3 times/week, with a delivered single pool Kt/Vurea of 1.3 per session 20, 24, 25 . Providing IHD to a COVID-19 patient may require one-on-one dialysis nursing support, whether in the ICU or on the general hospital floor. This increases exposure for the nursing staff and creative maneuvers have been implemented at hospitals to reduce nursing time in the room. Strategies proposed to conserve resources, and decrease exposure include decreasing duration of treatments, decreasing frequency of dialysis to twice a week and telemonitoring (e.g. use of baby monitors or tablets to visualize patients from outside the room). (Table 1) . Consideration for patient safety should be paramount when implementing any resource conservation and exposure reduction measures. Reducing time and/or frequency of HD treatments for an extended period can result in uremia and metabolic disturbances and patients should be carefully monitored for manifestations of inadequate dialysis.

Experiences from resource-limited countries have shown adequate metabolic and fluid control with acute peritoneal dialysis (PD) in AKI 26, 27 . Under usual circumstances, acute PD is not utilized in US and other developed countries for adult patients with AKI, because regulation of ultrafiltration and metabolic control is superior with CKRT in hemodynamically unstable patients.

However, due to acute surge during the pandemic in NY, acute PD was implemented in few hospitals, due to shortages in extracorporeal KRT consumables, fluids and nursing 28 .

A bedside catheter placement of a cuffed peritoneal dialysis catheter is preferred for patients who are critically ill 29 . Automated cycler use and extension tubing to keep the machine outside the patient's room can limit exposure to healthcare workers. An average-sized adult can usually tolerate 2-liter (L) exchanges, however, reduced volume should be considered for the initial few exchanges to decrease risk of peri-catheter leaks. To maximize efficiency of acute PD, an exchange time of 1-2 hours should be used. Assuming a 2L exchange volume with 60-minute exchange time, UF of about 1.2 -3.6 L/day can be achieved with 1.5%, 2.4 -7.2 L/day with 2.5% and 7.2 -9.6 L/day with 4.25%. As such, for patients with severe pulmonary edema, initial rapid in-out exchanges using 4.25% can be considered 29 . Theoretically, high volume peritoneal dialysis (HVPD) may impair diaphragmatic movement, increase intra-abdominal pressure, and worsen respiratory mechanics. However, one single center study showed no effect of HVPD on pulmonary compliance although the study excluded patients with FiO2 > 70% and PEEP > 10 cm H20 30 . In patients requiring prone positioning, PD may not be feasible but successful delivery has been described in small studies 31 .

Adequate central venous access is imperative to provide sufficient blood flows during KRT.

Hemodialysis catheter length (15-16 cm for right internal jugular (IJ), 19-20 cm for left IJ, 24 cm for femoral) and location must be carefully selected, as inappropriate catheter length can lead to inadequate blood flows which leads to increased filter clotting 32 . The right IJ is the preferred access for KRT as this offers a direct path for the catheter tip to be placed at preferred locationthe junction of the superior vena cava and right atrium. There is some controversy whether the J o u r n a l P r e -p r o o f Page 8 of 18 second choice should be the L IJ or the femoral vein. The femoral vein site may be associated with higher risk for infections and blood flows may be affected in patients who need to be proned for ventilation. The left IJ can provide inadequate blood flow, especially when shorter catheters are inadvertently placed 33 . In the setting of a surge, physicians not familiar with hemodialysis catheters may be responsible for placing catheters in patients with COVID-19. A cheat sheet with appropriate information related to hemodialysis catheters is a useful tool to distribute in the COVID ICUs. In patients with end stage kidney disease, a single-center study has described the use of arteriovenous fistula and arteriovenous graft for CKRT, but this practice is largely limited due to intricacies with patient monitoring, dialysis and ICU nursing coordination and risk of extravasation 34 . In patients on extracorporeal membrane oxygenation (ECMO), unless restricted by high ECMO flow, CKRT can be performed via the circuit after default CKRT access alarms are reset to accommodate the higher pressures via the ECMO circuit 35 .

There is growing evidence of endothelial activation causing a hypercoagulable state, leading to higher incidence of thrombotic complications in patients with COVID-9 36 . In addition to deep vein thrombosis and pulmonary embolism, clotting of extracorporeal circuits is a major concern, as this leads to significant blood loss, and excessive loss of KRT filters. Unless there is a contraindication to anticoagulation, we recommend that every COVID-19 patient starting CKRT or PIKRT receive anticoagulation per institution protocol. (Figure 1 ) If initial anticoagulation strategy is not effective, then an alternative plan will need to be implemented. At our center, systemic unfractionated heparin is administered to all COVID-19 patients on CKRT (target activated partial thromboplastin time of 60-90 seconds). If patients develop bleeding or other complications from unfractionated heparin, we use regional citrate anticoagulation (RCA), based on our existing policy. In some centers, RCA is the first line option for anticoagulation for CKRT. 37, 38 RCA is a complicated and nursing intensive technique, and we do not recommend hasty implementation of an RCA protocol in the setting of a surge, as this can lead to significant adverse events 37 . Other centers have used other anticoagulation methods such as low molecular weight heparin and direct thrombin inhibitors for CKRT. Involvement of pharmacists to establish appropriate anticoagulation protocol is important to ensure adequate dosing and prevent errors.

Hemoperfusion (HP) involves non-specific removal of cytokines by an extracorporeal membrane and has been proposed as a complementary therapeutic option in patients with COVID-19 and multiorgan dysfunction. In the current crisis, the Food and Drug Administration (FDA) has granted emergency use authorization to 3 different apheresis and cartridge systems.

Hemoadsorption devices have been shown to remove cytokines such as IL-6, but this may not translate to improved patient outcomes 39 . The most robust evidence available for use of HP in septic shock showed no change in mortality or any other parameter when compared to a sham HP group 40 . At this time we do not recommend use of these devices in the treatment of critically ill patients with COVID-19. However, clinical trials evaluating the effect of these devices and filters on patient outcomes should be considered.

The pandemic and associated surge of patients posed a significant strain on dialysis resources and hospital personnel across the globe 38 . Similar to a patient who requires mechanical ventilation for respiratory failure to sustain life, a patient with AKI or ESKD requires KRT.

However, unlike ventilators, there is no national stockpile of KRT machines and filters in the United States. Dialysate, and replacement fluids are perishable and cannot be stockpiled.

Hospitals had to institute changes to conserve resources and protect personnel. (Table 1) 

Management of patients with COVID-19 associated AKI is generally similar to patients with AKI associated with other etiologies such as sepsis. Conservative management of volume overload, metabolic acidosis, and hyperkalemia can be attempted before considering initiation of KRT. In patients with COVID-19, KRT, especially CKRT and PIKRT is associated with high rate of circuit clotting and anticoagulation should be initiated at the start of KRT. Delivery of KRT during a * Use citrate anticoagulation only if an existing protocol is available at the institution. Implementation of citrate anticoagulation protocol requires careful advanced planning, and education of physicians and nurses to prevent adverse events. We do not recommend initiation of a new regional citrate anticoagulation during acute surge.

J o u r n a l P r e -p r o o f 

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Acute kidney injury in patients hospitalized with COVID-19

Acute Kidney Injury in Hospitalized Patients with COVID-19. medRxiv

Acute Kidney Injury Associated with Coronavirus Disease

Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care

Impact of furosemide on mortality and the requirement for renal replacement therapy in acute kidney injury: a systematic review and meta-analysis of randomised trials. Ann Intensive Care

Balanced Crystalloids versus Saline in Noncritically Ill Adults

Balanced Crystalloids versus Saline in Critically Ill Adults

Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial

Intravenous Fluids: Finding the Right Balance

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial

Pharmacology of new treatments for hyperkalaemia: patiromer and sodium zirconium cyclosilicate

Potassium-Binding Agents for the Clinical Management of Hyperkalemia

Clinical Pharmacology in Diuretic Use

COVID-19 and the Inpatient Dialysis Unit: Managing Resources during Contingency Planning Pre-Crisis

Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of REFERENCES

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Acute Kidney Injury Associated with Coronavirus Disease

Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care

Impact of furosemide on mortality and the requirement for renal replacement therapy in acute kidney injury: a systematic review and meta-analysis of randomised trials. Ann Intensive Care

Balanced Crystalloids versus Saline in Noncritically Ill Adults

Balanced Crystalloids versus Saline in Critically Ill Adults

Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial

Intravenous Fluids: Finding the Right Balance

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial

Pharmacology of new treatments for hyperkalaemia: patiromer and sodium zirconium cyclosilicate

Potassium-Binding Agents for the Clinical Management of Hyperkalemia

Clinical Pharmacology in Diuretic Use

COVID-19 and the Inpatient Dialysis Unit: Managing Resources during Contingency Planning Pre-Crisis

Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials

Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis

Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury

Revisiting Filtration Fraction as an Index of the Risk of Hemofilter Clotting in Continuous Venovenous Hemofiltration

Division of Nephrology CUVCoPWGNYNY. Disaster Response to the COVID-19 Pandemic for Patients with Kidney Disease in New York City

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Acute PD: Evidence, Guidelines, and Controversies(

High-volume peritoneal dialysis in acute kidney injury: indications and limitations

Peritoneal Dialysis During the Coronavirus 2019 (COVID-19) Pandemic: Acute Inpatient and Maintenance Outpatient Experiences

Peritoneal Dialysis for Acute Kidney Injury Treatment in the United States: Brought to You by the COVID-19 Pandemic

Effect of peritoneal dialysis on respiratory mechanics in acute kidney injury patients

Peritoneal dialysis in a patient receiving mechanical ventilation in prone position

Vascular access for continuous renal replacement therapy. Semin Dial

A randomized trial of catheters of different lengths to achieve right atrium versus superior vena cava placement for continuous renal replacement therapy

Safety of arteriovenous fistulae and grafts for continuous renal replacement therapy: The Michigan experience

Renal replacement therapy in critically ill patients receiving extracorporeal membrane oxygenation

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med

Regional citrate anticoagulation for RRTs in critically ill patients with AKI

Ensuring Sustainability of Continuous Kidney Replacement Therapy in the Face of Extraordinary Demand: Lessons From the COVID-19 Pandemic

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial

Effect of Targeted Polymyxin B Hemoperfusion on 28-Day Mortality in Patients With Septic Shock and Elevated Endotoxin Level: The EUPHRATES Randomized Clinical Trial

pandemic with acute influx of hospitalized patients poses significant challenges, and careful planning is required to provide safe and effective KRT to every patient who needs it.