Management of COVID-19 in special populations with kidney disease
=================================================================

* Yeshwanter Radhakrishnan
* Mohamed Hassanein
* Brian Stephany

## ABSTRACT

Although the literature is limited, early evidence suggests that patients with chronic kidney disease, end-stage kidney disease, and kidney transplant recipients are at increased risk for severe COVID-19 disease and death. Hence, management should focus on both infection prevention and treatment. There is currently a lack of evidence and guideline recommendations on optimal management of immunosuppression in kidney transplant recipients with COVID-19 infection. This article focuses on the prevention and management of COVID-19 in patients with chronic kidney disease, patients with end-stage kidney disease on home hemodialysis and peritoneal dialysis, and kidney transplant recipients.

## COVID-19 AND CHRONIC KIDNEY DISEASE

The prevalence of COVID-19 in patients with chronic kidney disease (CKD) is currently unknown. However, patients with CKD may be at risk for severe COVID-19 disease.1 Chronic kidney disease was associated with an increased risk of severe COVID-19 disease in a meta-analysis of 4 studies that included 1,389 patients with COVID-19, although individual studies did not show any association.1 COVID-19 in patients with CKD is also associated with increased mortality.2 Thus, management should focus on both infection prevention and treatment.

The most effective measures to reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include social distancing, limiting human interaction, and prioritizing outings. When caring for patients with stable CKD, physicians should minimize hospital and clinic visits and face-to-face encounters by performing telemedicine visits that are compliant with current Health Insurance Portability and Accountability Act regulations.3 Patients can be triaged by nursing providers before the visit to assess the need for an in-person visit. Disease prevention strategies such as the use of personal protective equipment as recommended by the Centers for Disease Control and Prevention or local authorities, physical distancing, and practicing hand hygiene should be continued in outpatient and specialty clinics.4

Early in the pandemic, there was concern about the use of renin-angiotensin system (RAS) inhibitors increasing patients suseptibilty to SARS-CoV-2 infection. RAS inhibitors were thought to possibly upregulate expression of angiotensin-converting enzyme 2 thus increasing susceptibility to SARS-CoV-2 infection. However, multiple studies have demonstrated that the use of RAS inhibitors are not associated with an increased risk of SARS-CoV-2 infection. Therefore, RAS inhibitors should not be discontinued when being used in patients with stable CKD.3

In May 2020, the US Food and Drug Administration issued an emergency use authorization for remdesivir, a DNA/RNA polymerase inhibitor, to treat patients with COVID-19. There is limited evidence on the use of remdesivir in patients with CKD as the clinical trials excluded patients with a glomerular filtration rate (GFR) less than 30 mL/min/1.73m2. There is a concern for mitochondrial toxicity since it is a DNA/RNA polymerase inhibitor and toxicity from the accumulation of sulfobutylether-b-cyclodextrin carrier that the drug is compounded with, in patients with kidney disease.5 However, clinical trials for Ebola and COVID-19 did not report an increased risk of renal adverse events. Thus, remdesivir should not be used in patients with COVID-19 and a GFR less than 30 mL/min/1.73m2 unless the benefits outweigh the risks.5

Dexamethasone lowered the 28-day mortality rate in hospitalized patients with COVID-19 who were on invasive mechanical ventilation or required supplemental oxygen support.6 Though patients with severe kidney impairment (ie, GFR less than 30 mL/min/1.73m2) were enrolled in the dexamethasone trial, a lack of subgroup analyses confirming this benefit in the CKD population is yet to be published. Despite the lack of subgroup analyses, dexamethasone can still be used in patients with CKD provided the risk-benefit ratio is taken into consideration.

## COVID-19 AND END-STAGE KIDNEY DISEASE

Although not necessarily surprising, early evidence has emerged suggesting that patients with end-stage kidney disease (ESKD) on hemodialysis (HD) and peritoneal dialysis (PD) are more likely to develop COVID-19 complications such as acute respiratory distress syndrome, arrhythmias, shock, and acute cardiac injury along with a higher risk of mortality.7,8

### Patients with ESKD on home-based dialysis modalities

Data from the United Kingdom Renal Registry and Ontario Renal Network have shown that patients receiving PD and home HD have a lower risk of acquiring COVID-19 infection than patients receiving center-based HD.9 Thus, a robust home HD program can minimize patients’ and healthcareworkers’ exposure to COVID-19 while still providing effective dialysis for patients with ESKD. Education of healthcare workers and patients with ESKD on advances in COVID-19, use of personal protective equipment, and infection control measures should continue to be implemented. Patients on PD should have at least 2 weeks of dialysis supplies. Home visits by healthcare workers should be avoided except for emergencies and patients with disabilities.10 For patients using automated PD systems, remote management platforms should be used to assess and monitor PD sessions. For patients on home HD, real-time monitoring of vital signs and treatment data can be performed by HD technicians who can also help patients troubleshoot or answer questions.11 Thomas and colleagues showed that monthly blood sampling was not associated with a lower risk of death when compared to sampling every 6 weeks.12 Based on this study, we recommend that the home dialysis team should work with ESKD patients to decide if a more spaced-out surveillance blood work is appropriate.

### Patients with ESKD on in-center hemodialysis

Infection control measures to reduce the risk of COVID-19 infection should be continued in all dialysis facilities. Patients must be instructed and triaged by phone calls to determine if they have been in close contact with individuals with COVID-19 or have COVID-19 symptoms before they arrive for their dialysis sessions.13 Although screening for COVID-19 symptoms with temperature checks is controversial, this practice continues to be implemented in our institution. Testing protocols for patients and staff at dialysis units should be implemented upon arrival at the dialysis center if it does not have the resources to triage patients beforehand. Patients with COVID-19 can be assigned to HD units dedicated only to COVID-19–positive patients.3 Routine disinfection of dialysis equipment and supplies should be implemented in all facilities. Appropriate use and preservation of personal protective equipment by providers to prevent shortage when caring for patients with and without COVID-19 is recommended in US Centers for Disease Control and Prevention guidelines. These interventions should help minimize the exposure of patients and healthcare workers in HD units to COVID-19.

### COVID19 and kidney transplant recipients

Many transplant centers temporarily halted activity during the initial stages of the pandemic. However, kidney transplantation has resumed at high rates throughout the country because the competing risk of waitlist mortality outpaced the risk of COVID-19 infection as a newly transplanted patient. Screening of donors and recipients prior to kidney transplant surgery is recommended.3

Kidney transplant recipients (KTRs) are particularly vulnerable to higher morbidity and mortality in the setting of COVID-19 infection due to the higher incidence of comorbid conditions compared to the general population as well as a depressed immune state.3,14 In a prospective study consisting of 1,216 KTRs, the incidence of COVID-19 infection was found to be 5% with a mortality rate of 24% among COVID-19–positive patients compared to a mortality rate ranging from 1% to 5% in the general population.14 Fever is the most common reported symptom of COVID-19 in KTRs, followed by cough, dyspnea, and gastrointestinal symptoms; some patients present with mild or atypical symptoms such as conjunctivitis and a normal white blood cell count.14–17 Thus, mild and atypical symptoms should prompt testing for COVID-19 in KTRs.

There is currently a lack of evidence and guideline recommendations on optimal management of COVID-19 infection in KTRs. In ambulatory recipients with COVID-19, the immunosuppression regimen is continued without any changes. For inpatient recipients with mild COVID-19 and no supplemental oxygen requirements, we recommend reducing the dose of mycophenolate mofetil while maintaining the rest of the immunosuppression regimen. If inpatient KTRs develop severe COVID-19 infection requiring supplemental oxygen, dexamethasone or remdesivir, or both, we discontinue mycophenolate mofetil while continuing the calcineurin inhibitors but targeting a lower trough level (eg, tacrolimus trough level 4–6 ng/mL). Telemedicine with remote monitoring of kidney transplant recipients should be continued to reduce exposure to COVID-19. Table 1 summarizes the key recommendations provided throughout this article.

View this table:
[TABLE 1](http://www.ccjm.org/content/early/2020/12/01/ccjm.87a.ccc067/T1)

TABLE 1 
Summary of recommendations for COVID-19 in special patient populations with kidney disease

## DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

## Footnotes

*   Disclaimer: The statements and opinions expressed in COVID-19 Curbside Consults are based on experience and the available literature as of the date posted. While we try to regularly update this content, any offered recommendations cannot be substituted for the clinical judgment of clinicians caring for individual patients.

*   Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.

## REFERENCES

1.  Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Int Urol Nephrol 2020; 52(6):1193–1194. doi:10.1007/s11255-020-02451-9
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1007/s11255-020-02451-9&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=32222883&link_type=MED&atom=%2Fccjom%2Fearly%2F2020%2F12%2F01%2Fccjm.87a.ccc067.atom) 

2.  Gansevoort R.T., Hilbrands L.B. CKD is a key risk factor for COVID-19 mortality. Nat Rev Nephrol 2020; 16:705–706. [doi.org/10.1038/s41581-020-00349-4](http://doi.org/10.1038/s41581-020-00349-4)
    
    

3.  Hassanein M, Radhakrishnan Y, Sedor J, et al. COVID-19 and the kidney. Cleve Clin J Med 2020; 87(10):619–631. doi:10.3949/ccjm.87a.20072
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiY2Nqb20iO3M6NToicmVzaWQiO3M6OToiODcvMTAvNjE5IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

4.  Ajaimy M, Melamed ML. COVID-19 in Patients with Kidney Disease. Clin J Am Soc Nephrol 2020; 15(8):1087–1089. doi:10.2215/CJN.09730620
    
    [FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiY2xpbmphc24iO3M6NToicmVzaWQiO3M6OToiMTUvOC8xMDg3IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

5.  Adamsick ML, Gandhi RG, Bidell MR, et al. Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19. J Am Soc Nephrol 2020; 31(7):1384–1386. doi:10.1681/ASN.2020050589
    
    [FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiam5lcGhyb2wiO3M6NToicmVzaWQiO3M6OToiMzEvNy8xMzg0IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

6.  RECOVERY Collaborative GroupHorby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020 Jul 17:NEJMoa2021436. doi:10.1056/NEJMoa2021436
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1056/NEJMoa2021436&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=32678530&link_type=MED&atom=%2Fccjom%2Fearly%2F2020%2F12%2F01%2Fccjm.87a.ccc067.atom) 

7.  Wu J, Li J, Zhu G, et al. Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Clin J Am Soc Nephrol 2020; 15(8):1139–1145. doi:10.2215/CJN.04160320
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiY2xpbmphc24iO3M6NToicmVzaWQiO3M6OToiMTUvOC8xMTM5IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

8.  Valeri AM, Robbins-Juarez SY, Stevens JS, et al. Presentation and Outcomes of Patients with ESKD and COVID-19. J Am Soc Nephrol 2020; 31(7):1409–1415. doi:10.1681/ASN.2020040470
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiam5lcGhyb2wiO3M6NToicmVzaWQiO3M6OToiMzEvNy8xNDA5IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

9.  Brown EA, Perl J. Increasing Peritoneal Dialysis Use in Response to the COVID-19 Pandemic: Will It Go Viral? J Am Soc Nephrol 2020; 31(9):1928–1930. doi:10.1681/ASN.2020050729
    
    [FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiam5lcGhyb2wiO3M6NToicmVzaWQiO3M6OToiMzEvOS8xOTI4IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

10. Strategies regarding COVID-19 in PD patients. International Society for Peritoneal Dialysis. Accessed September 6, 2020. [http://ispd.org/strategies-covid19/](http://ispd.org/strategies-covid19/)
    
    

11. Srivatana V, Liu F, Levine DM, Kalloo SD. Early Use of Telehealth in Home Dialysis during the COVID-19 Pandemic in New York City. Kidney360 2020; 1(6):524–526. doi:10.34067/KID.0001662020
    
    [FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6OToia2lkbmV5MzYwIjtzOjU6InJlc2lkIjtzOjc6IjEvNi81MjQiO3M6NDoiYXRvbSI7czo0NDoiL2Njam9tL2Vhcmx5LzIwMjAvMTIvMDEvY2NqbS44N2EuY2NjMDY3LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

12. Thomas A, Silver SA, Perl J, et al. The Frequency of Routine Blood Sampling and Patient Outcomes Among Maintenance Hemodialysis Recipients. Am J Kidney Dis 2020; 75(4):471–479. doi:10.1053/j.ajkd.2019.08.016
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1053/j.ajkd.2019.08.016&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=31732233&link_type=MED&atom=%2Fccjom%2Fearly%2F2020%2F12%2F01%2Fccjm.87a.ccc067.atom) 

13. Ikizler TA, Kliger AS. Minimizing the risk of COVID-19 among patients on dialysis. Nat Rev Nephrol 2020; 16(6):311–313. doi:10.1038/s41581-020-0280-y
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1038/s41581-020-0280-y&link_type=DOI) 

14. Elias M, Pievani D, Randoux C, et al. COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes. J Am Soc Nephrol 2020; 31(10):2413–2423. doi:10.1681/ASN.2020050639
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiam5lcGhyb2wiO3M6NToicmVzaWQiO3M6MTA6IjMxLzEwLzI0MTMiO3M6NDoiYXRvbSI7czo0NDoiL2Njam9tL2Vhcmx5LzIwMjAvMTIvMDEvY2NqbS44N2EuY2NjMDY3LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

15. Akalin E, Azzi Y, Bartash R, et al. Covid-19 and Kidney Transplantation. N Engl J Med 2020; 382(25):2475–2477. doi:10.1056/NEJMc2011117
    
    [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1056/NEJMc2011117&link_type=DOI) 
    
    [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=32329975&link_type=MED&atom=%2Fccjom%2Fearly%2F2020%2F12%2F01%2Fccjm.87a.ccc067.atom) 

16. Columbia University Kidney Transplant Program. Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York. J Am Soc Nephrol 2020; 31(6):1150–1156. doi:10.1681/ASN.2020030375
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiam5lcGhyb2wiO3M6NToicmVzaWQiO3M6OToiMzEvNi8xMTUwIjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

17. Husain SA, Dube G, Morris H, et al. Early Outcomes of Outpatient Management of Kidney Transplant Recipients with Coronavirus Disease 2019. Clin J Am Soc Nephrol 2020; 15(8):1174–1178. doi:10.2215/CJN.05170420
    
    [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiY2xpbmphc24iO3M6NToicmVzaWQiO3M6OToiMTUvOC8xMTc0IjtzOjQ6ImF0b20iO3M6NDQ6Ii9jY2pvbS9lYXJseS8yMDIwLzEyLzAxL2Njam0uODdhLmNjYzA2Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=)