Disclaimer: The aim of these rapid reviews is to retrieve, appraise, summarize and update the available evidence on COVID-related health technology. The reviews have not been externally peer- reviewed; they should not replace individual clinical judgement and the sources cited should be checked. The views expressed represent the views of the authors and not necessarily those of their host institutions. The views are not a substitute for professional medical advice.

Copyright Claims: This review is an intellectual property of the authors and of the Institute of Clinical Epidemiology, National Institutes of Health-UP Manila and Asia-Pacific Center for Evidence Based Healthcare Inc.

INTRODUCTION

Kidney disease may be viewed as both a postulated risk factor for and a sequela of COVID-19 infection. Several studies have pegged the incidence rate of acute kidney injury (AKI) at 5-15%, with higher mortality observed in those with kidney damage.1-4 AKI Stage 1, Stage 2 and Stage 3 were independent risk factors for in- hospital mortality (HR 1.90 [95% CI 0.76-4.76], HR 3.51 [1.49-8.26], and HR 4.38 [2.31-8.31], respectively).4 The mechanisms resulting in AKI are likely due to cytokine release in COVID-19 causing intrarenal inflammation, increased vascular permeability, volume depletion, and cardiomyopathy.5 Some patients who develop AKI eventually require dialysis for uremia, electrolyte and acid- base balance, and fluid retention.2

Chronic kidney disease (CKD) patients who require dialysis are particularly at increased risk for contracting infection. This is thought to be because most of these patients are elderly and have comorbid conditions that are linked with worse prognosis in COVID-19 infected individuals such as cardiovascular disease and coronary artery disease, hypertension, and diabetes, among others.6,7 Recurrent physical presence at healthcare facilities and/or

dialysis centers and physical proximity of both patients and healthcare workers (HCW) alike during dialysis may provide the milieu necessary for increased disease transmission, not only from patient to patient, but from patient to HCW and subsequently, between HCWs. As different modes of dialysis entail different levels, durations, and methods of contact between healthcare workers and their patients, they might likewise impart varying levels of risk of disease transmission from patient to HCW.

This rapid review aims to answer the following questions:

1.Which dialysis method is most effective in treating acute kidney injury in COVID-19 patients?

2.What dialysis method and practices would best reduce the risk of COVID-19 transmission to healthcare workers performing dialysis on COVID-19 patients?

METHODS AND MATERIALS

Literature Search

An electronic literature search was conducted on PubMed, CENTRAL, ClinicalTrials.gov, ISRCTN Registry, and the WHO International Clinical Trials Registry Platform (ICTRP), UpToDate including Society Links, and Google for guidelines and primary studies on dialysis in COVID-19 patients until May 15, 2020. We also searched MedRxiv for pre-print articles. The following terms were used in both free text and MeSH: COVID-19, coronavirus, SARS-CoV-2, dialysis, renal replacement therapy. No language restrictions were applied. References were scanned for additional articles.

Selection and quality assessment of included studies

Articles on efficacy and safety were selected based on the following inclusion criteria:

•Population: COVID-19 patients

•Intervention: Intermittent hemodialysis [IHD], sustained low efficiency dialysis [SLED], continuous renal replacement therapy [CRRT]), peritoneal dialysis

•Primary outcome: Mortality

•Secondary outcomes: Clinical deterioration (e.g. ICU admission), length of hospital stay, time to viral clearance, transmission to healthcare workers

•Study designs: Any study design including systematic reviews, randomized controlled trials, observational studies, case reports/series, and clinical practice guidelines

Two independent reviewers assessed included studies using the Cochrane risk of bias tool for intervention/ effectiveness studies (ARV and VAT). Disagreements were arbitrated by a third reviewer (CAV). Risk of bias assessments are in Appendix A.

Data Extraction and Analysis

For included studies, the author, year of publication, study characteristics (population, interventions, outcomes, study design), and results of interest (e.g. frequency of events) were extracted.

RESULTS AND DISCUSSION

Hemodialysis vs. Peritoneal Dialysis

We found no published or ongoing clinical trials comparing hemodialysis and peritoneal dialysis among COVID-19 patients.

Intermittent vs. Continuous Renal Replacement Therapy

We found no published or ongoing clinical trials comparing intermittent dialysis, prolonged continuous intermittent dialysis (e.g. sustained low-efficiency dialysis [SLED]), and continuous renal replacement therapy (CRRT) among COVID-19 patients.

One retrospective cohort study in preprint (Yang 2020) compared COVID-19 patients on invasive mechanical ventilation who received CRRT (n=22) and those who did not (n=14). Matching between groups was not reported. Although baseline characteristics between the two groups were not statistically significant, there were more patients with cardiovascular and cerebrovascular disease in the non- CRRT group. The CRRT group also had a higher rate of use of antibiotics, antiviral, and/or antifungal agents. These differences may indicate bias in favor of the CRRT group, and so results on effectiveness needed to be interpreted with caution. The prevalence of AKI was similar in both groups (CRRT 22.7% vs. No CRRT 21.4%, p=0.929). There was no mention whether the patients who did not undergo CRRT received intermittent dialysis. CRRT was associated with reduced mortality (adjusted HR 0.324, 95% CI: 0.118, 0.893) after controlling for selected confounders (age, sex, IL-1β, IL-2 receptor, IL-6, IL-8, IL-10, TNF-α, white blood cell count, neutrophil count, lymphocyte count, hemoglobin, platelet, prothrombin time, activated partial thromboplastin time). Outcomes of the subset of patients with AKI were not reported. The low proportion of AKI in both the CRRT and the non-CRRT groups (5/22 and 3/14, respectively) as well as the study population being restricted to mechanically ventilated COVID-19 patients prevented generalization of CRRT’s efficacy.

Dialysis Methods to Prevent Transmission to Healthcare Workers

To our knowledge, there are no published or ongoing trials comparing one dialysis method to another in terms of preventing transmission of COVID-19 from a patient to the healthcare worker.

Guideline Recommendations

Effective dialysis method for COVID-19 patients with AKI

Clinical guidelines from both the US Centers for Disease Control (CDC) and Prevention and the Ministry of India make no preference for dialysis modality for COVID-19 patients with AKI, and state that the decision depends on a patient’s clinical status.9,10 In addition, the CDC states that the facility’s resources should be considered when choosing between intermittent hemodialysis (IHD) and CRRT.

Dialysis methods to prevent COVID-19 transmission to healthcare workers

The American Society of Nephrology recommends CRRT over IHD for critically ill patients with COVID-19 who need dialysis because it requires only minimal contact between the HCW and the patient, thereby decreasing the risk for transmission.11 IHD may still be performed for critically ill patients if CRRT is not available or if the institution has limited experience with its use, provided that strict infection control protocols are adhered to.11, 12

Two studies briefly mentioned recommendations on the type of peritoneal dialysis preferred to curb infection. Lai, Wang, and Guo (2020) suggested to adjust treatment of patients on continuous ambulatory peritoneal dialysis (CAPD) such that they can use the machines for automatic peritoneal dialysis (APD) to lessen the risk of contact infection.13 On the other hand, Wilkie and Davis (2020) preferred CAPD over APD in patients undergoing dialysis for the first time as the former will result to lesser catheter problems due to less critical flow rates and decreased future demand for APD machines.14

There were twenty-one descriptive publications that described the experiences in dialysis centers in Italy, Belgium, Spain, USA, Taiwan, and China.13-33 Proposed strategies to prevent transmission of COVID-19 within these centers included the following:

•Healthcare workers should be trained and regularly updated on infection control measures through various media and platforms.

•Pre-dialysis triaging and strict entrance screening of symptoms should be enforced.

•Arrangement of transportation for suspected and confirmed patients with use of appropriate PPE and vehicle sanitation should be done. Ambulance transport to and from the hemodialysis center can also be coordinated.

•Standard infection prevention and control measures should be observed:

Strict hand-hygiene

Proper distancing between patients and HCWs, as well as between HCWs in the workplace at all times

Appropriate use of PPEs by both patients (surgical masks) and HCWs

Proper disposal of infectious wastes

Standard disinfection of environment and equipment including dialysis machines after use

•Facilities should have proper ventilation, areas conducive for enough physical distancing, airborne infection isolation rooms, and written plans for triaging patients. Monitoring systems such as temperature surveillance and checking of symptoms should be in place.

•Opening of additional shifts and optimizing scheduling system to reduce congestion in waiting rooms.

•Suspected or confirmed cases should be cohorted along with assigned medical personnel; suspected and confirmed patients should undergo dialysis preferably in a separate room and during the last shift of the day. Alternatively, a specific shift can be designated for COVID-positive patients only. Avoid changing dialysis units and shifts to avoid cross-contamination.

•Isolation and transfer of suspected and confirmed patients to fever clinics and quarantine centers, respectively.

•Designation of particular hospitals as dialysis centers for confirmed patients.

•Self-monitoring by both the patient and the HCW for symptoms, followed by strict self-isolation if symptomatic, should be observed.

•Acquisition of prescriptions, solutions, and caps by relatives or caregivers of patients on peritoneal dialysis instead of patients themselves

•Usage of telehealth for home dialysis patients. Monitoring of patients on peritoneal dialysis can be done over the phone or via online platforms.

•Collaboration with laboratory and courier companies to do home visits for patient’s laboratory test needs and delivery of medications, respectively.

•Staying at home while off dialysis and deferral of hospitalization unless required.

•If possible, do transitioning of patients to home dialysis (i.e. peritoneal dialysis).

These measures are consistent with the recommendations

of the US Center for Disease Control (CDC), American Society of Nephrology (ASN), International Society of Nephrology (ISN), Centers for Medicare and Medicaid Services (CMS), the European Dialysis (EUDIAL) Working Group of the European Renal Association- European Dialysis and Transplant Association (ERA- EDTA), the Korean Society of Nephrology, the Chinese Society of Nephrology, the Taiwan Society of Nephrology, and the Philippine Society of Nephrology.9,11, 34-40

CONCLUSION

Very low-quality evidence suggests that CRRT may reduce mortality among COVID-19 patients on invasive mechanical ventilation. Further studies are needed to confirm this finding. Available guidelines recommend weighing clinical indications and institutional resources in selecting a dialysis modality for the COVID-19 patient with AKI. The ASN recommends the use of CRRT for critically ill patients with COVID-19 to minimize the risk of possible transmission, if this option is available.

We found no ongoing trials comparing various renal replacement methods. Deciding on a dialysis modality should be tailored to the patient’s clinical status while maximizing available resources and minimizing potential exposure to other patients and healthcare workers.

Guidelines uniformly recommend strict adherence to standard infection prevention and control measures within dialysis centers to minimize the risk of exposure of patients and HCWs to COVID-19.

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