Treatment Practice Of Kidney Failure Caused By Coronavirus Disease 2019 (COVID-19)
Mar 15, 2022
For more information:ali.ma@wecistanche.com
COVID-19: The Kidneys Tell a Tale
Lii Chan, Judy Hindi, and Girish N. Nadkarni
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health emergency. Though originally described as a respiratory virus, SARS-CoV-2 has Related Articles, p.190 and p.204 now been shown to have multiorgan involvement. Chronic kidney disease (CKD) has emerged as a risk factor for adverse outcomes. In this issue of AJKD, Ng et al²and Flythe et al explore the association of the spectrum of kidney disease with outcomes in patients hospitalized with COVID-19 (Coronavirus disease 2019).
Although initial reports from China revealed a low incidence(5%-10%)of acute kidney injury(AKI), subsequent articles documented a far greater incidence of AKI (acute kidney injury) in hospitalized patients with COVID-19 (Coronavirus disease 2019)' (Fig 1).In a follow-up study of hospitalized patients with COVID-19 (Coronavirus disease 2019) from the Northwell Health system, Ng et al found that 40% of hospitalized patients admitted with COVID-19 (Coronavirus disease 2019) developed AKII (acute kidney injury). Although not discussed in this article, urinalysis suggested causes other than acute tubular injury. In general, kidney biopsies have shown varied histopathology, including acute glomerulonephritis and acute tubular injury.
Regardless of pathophysiology, COVID-19 (Coronavirus disease 2019)-associated AKII (acute kidney injury) is associated with increased mortality. Ng et al found these rates to be 46.4% in those not requiring kidney replacement therapy (KRT) and as high as 79.3%in those requiring KRT. At discharge,69% of patients who required KRT and 74% of patients with AKII (acute kidney injury) not requiring KRT had kidney recovery. What remains to be elucidated is the long-term consequences of COVID-19 (Coronavirus disease 2019)-associated AKI (acute kidney injury). Of those who did not recover kidney function or those who were discharged with a continued requirement for KRT, how many of those patients ultimately recover? Conversely, for those who recovered, what proportion of those patients will have incident CKD (Chronic kidney disease)?

Coronavirus disease 2019 (COVID-19) affects patients with kidney disease
Click to Cistanche tubulosa powder for acute kidney injury
Evaluation and treatment of AKII (acute kidney injury) in COVID-19 (Coronavirus disease 2019) patients is similar to AKII (acute kidney injury) in non-COVID-19 (Coronavirus disease 2019) patients, with supportive measures being the cornerstone of management. Hyperkalemia is common in patients hospitalized with COVID-19 (Coronavirus disease 2019), likely due to high cell turnover similar to a hypercatabolic state and reduced kidney function. Given the possibility of a limited supply of dialysis during a pandemic surge,' the use of potassium binders in addition to other temporizing measures may help delay KRT necessity.
Approximately 19% of hospitalized patients with COVID-19 (Coronavirus disease 2019)-associated AKII (acute kidney injury) will require KRT." During the pandemic and the consequent surge in patients requiring KRT, several challenges have led to reduced dialysis capacity, including nursing staff shortages, personal protective equipment shortages during the initial phases, and shortages of dialysis machines and supplies.
Intermittent hemodialysis (HD) remains the preferred option in hemodynamically stable patients, whereas continuous KRT(CKRT)is the modality of choice for hemodynamically unstable patients.° To accommodate the increased patient volume, intermittent HD treatments have often been shortened, with the use of slow continuous ultrafiltration devices and potassium binders between sessions. If CKRT is available, treatments with higher flow rates may be used to provide adequate clearance while allowing the machines to be used on multiple patients a day.'Prolonged intermittent KRT has been used in hemodynamically unstable patients in facilities without CKRT capabilities or if demand has outstripped supply. It remains to be determined whether any of these measures had an impact on patient outcomes.

With limited personnel and dialysis resources during surges, acute peritoneal dialysis (PD) saw a resurgence because it helped bypass machine shortages and coagulopathy/vascular access issues, as well as reduce patient/nursing contact time. PD catheters placed by experienced personnel can be used within 24 to 48 hours of placement. The use of PD has questionable success rates in patients with acute respiratory distress syndrome treated with prone positioning. Studies of long-term outcomes of patients treated with acute PD and comparison of outcomes with HD are currently pending.
It rapidly became apparent that critically ill patients with COVID-19 (Coronavirus disease 2019) were hypercoagulable, which posed yet another challenge: clotting of vascular access and dialyzers/lines. Many institutions implemented therapeutic anticoagulation strategies; however, there are no universally used protocols.
Given the high comorbid condition burden of patients with CKD (Chronic kidney disease) and kidney failure, we anticipated COVID-19 (Coronavirus disease 2019) to have a devastating impact on these vulnerable patients. Several studies in the United States reported mortality of up to 30%
Flythe et al used the STOP-COVID database, a multi-center study of more than 4,000 critically ill patients admitted to an intensive care unit, to compare the clinical course of patients with and without pre-existing kidney disease and evaluate outcomes in patients with pre-existing kidney disease both nondialysis CKD (Chronic kidney disease) and kidney failure treated with dialysis. Although 12% of patients had pre-existing CKD (Chronic kidney disease), only 3% of patients had been receiving maintenance dialysis. Inflammatory marker patterns were inconsistent, with some higher in non-dialysis patients with KRT, several challenges have led to reduced dialysis capacity, including nursing staff shortages, personal protective equipment shortages during the initial phases, and shortages of dialysis machines and supplies.

Intermittent hemodialysis (HD) remains the preferred option in hemodynamically stable patients, whereas continuous KRT(CKRT)is the modality of choice for hemodynamically unstable patients.° To accommodate the increased patient volume, intermittent HD treatments have often been shortened, with the use of slow continuous ultrafiltration devices and potassium binders between sessions. If CKRT is available, treatments with higher flow rates may be used to provide adequate clearance while allowing the machines to be used on multiple patients a day.'Prolonged intermittent KRT has been used in hemodynamically unstable patients in facilities without CKRT capabilities or if demand has outstripped supply. It remains to be determined whether any of these measures had an impact on patient outcomes.
With limited personnel and dialysis resources during surges, acute peritoneal dialysis (PD) saw a resurgence because it helped bypass machine shortages and coagulopathy/vascular access issues, as well as reduce patient/nursing contact time. PD catheters placed by experienced personnel can be used within 24 to 48 hours of placement. The use of PD has questionable success rates in patients with acute respiratory distress syndrome treated with prone positioning. Studies of long-term outcomes of patients treated with acute PD and comparison of outcomes with HD are currently pending.
It rapidly became apparent that critically ill patients with COVID-19 (Coronavirus disease 2019) were hypercoagulable, which posed yet another challenge: clotting of vascular access and dialyzers/lines. Many institutions implemented therapeutic anticoagulation strategies; however, there are no universally used protocols.
Given the high comorbid condition burden of patients with CKD (Chronic kidney disease) and kidney failure, we anticipated COVID-19 (Coronavirus disease 2019) to have a devastating impact on these vulnerable patients. Several studies in the United States reported mortality of up to 30%

Treatment of kidney failure caused by COVID-19 (Coronavirus disease 2019)
Flythe et al used the STOP-COVID database, a multi-center study of more than 4,000 critically ill patients admitted to an intensive care unit, to compare the clinical course of patients with and without pre-existing kidney disease and evaluate outcomes in patients with pre-existing kidney disease both nondialysis CKD (Chronic kidney disease) and kidney Btreated with dialysis. Although 12% of patients had pre-existing CKD (Chronic kidney disease), only 3% of patients had been receiving maintenance dialysis. Inflammatory marker patterns were inconsistent, with some higher in non-dialysis patients with CKD and patients with kidney failure, and others lower. Kidney disease remained an independent risk factor for in-hospital mortality, with a 28-day in-hospital mortality of 51% in those with kidney failure receiving dialysis, 49% in nondialysis CKD (Chronic kidney disease), and 35% in those without pre-existing kidney disease.
Regrettably, this study highlighted "renalism,"10 demonstrating that patients with CKD (Chronic kidney disease) (including those with kidney failure)received experimental treatments half as often as patients without kidney disease. Given the high mortality rate, clinical trials need to enroll this at-risk group.
Patients receiving in-center HD are at a particularly higher risk for contracting SARS-CoV-2 infection due to frequent health care encounters. Patients with kidney Bare less likely to have classic COVID-19 (Coronavirus disease 2019) symptoms compared with patients with and without CKD (Chronic kidney disease). Interestingly, they were more likely to present with altered mental status, highlighting the need for vigilant screening given the concern for"silent spread."A recent study estimates that 10% of dialysis patients have had COVID-19 (Coronavirus disease 2019), even though they represented only 3% of the critical care population in this study.
Several professional societies have issued guidelines to limit outbreaks in dialysis units. However, specific guidelines differ based on logistics, available trained personnel, and personal protective equipment.
Immediate screening tests and isolation of patients or staff who had dose contacts with cases are effective at preventing the further spread of the infection. Although difficult to achieve in the midst of a pandemic, home modalities, which can use telemedicine platforms and reduce exposure, should be encouraged.
Since SARS-CoV-2 emerged nearly 1 year ago, the scientific community has rallied together to ensure the dissemination of knowledge regarding COVID-19 (Coronavirus disease 2019). Although we have learned a great deal about COVID-19 (Coronavirus disease 2019) and kidney disease, much remains to be elucidated, including long-term outcome studies and models for the identification of patients at high risk for AKII (acute kidney injury) and mortality. New reports have described inequalities in social determinants of health affecting COVID-19 (Coronavirus disease 2019) outcomes and these need to be focused on for research. However, much work still lies ahead(Fig 1). Although COVID-19 (Coronavirus disease 2019) is terrifying, it behooves us to remember words attributed to Marie Curie, "Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less."13(p36)

Figure 1. Timeline of coronavirus disease 2019 (COVID-19) scientific discoveries and future directions, with special emphasis on the kidney and the unanswered questions for kidney disease and COVID-19.
Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; FDA, US Food and Drug Administration;
HD, hemodialysis; KF, kidney failure; pt, patient; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WHO, World Health Organization.
References
1. Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19 (Coronavirus disease 2019).Nat Med.2020;26(7):1017-1032.
2. Na JH. Hirsch JS, Hazan A, et al Outcomes among patients hospitalized with COMD-19 and acute kidney injury. Am J Kidney Dis. 2021;77(2):204-215.
3. Flythe JE, Simon MM, Tugman MJ, et al. Characteristics and outcomes of individuals with pre-existing kidney disease and
COVD-19 admitted to intensive care units in the United States. Am J Kidney Dis.2021;77(2):190-203.
4. Chan L, Chaudhary K, Saha A, et al.AKII (acute kidney injury) in hospitalized patients with COMD-19 [published online ahead of print September 3, 2020]. J Am Soc Nephrol.
5. Reddy YNV, Walensky RP, Mendu ML, Green N, Reddy KP. Estimating shortages incapacity to deliver continuous kidney replacement therapy during the COVID-19 (Coronavirus disease 2019) pandemic in the United States. Am J Kidney Dis.2020;76(5):696-709.e1.
6. Adapa S,Aeddula NR,Konala VM.COVID-19 (Coronavirus disease 2019) and renal failure: challenges in the delivery of renal replacement therapy. J Clin Med Res. 2020;12(5):276-285.
7. The Division of Nephrology, Columbia University Vagelos College of Physicians Working Group.Disaster response to the COVD-19 pandemic for patients with kidney disease in New York City. J Am Soc Nephrol. 2020;31(7):1371-1379.
8. Srivatana V, Aggarwal V, Finkelstein FO, Naliayan M, Crabtree JH, Perl J. Peritoneal dialysis for acute kidney injury treatment in the United States: brought to you by the COVD-19 pandemic. Kidney360.2020;1(5):410-415.
9. Shankaranarayanan D, Muthukumar T, Barbar T, et al. Anticoagulation strategies and filter life in COVD-19 patients receiving continuous renal replacement therapy: a single-center experience [pubished online ahead of print September 17.2020]
10. Chertow GM, Normand S-LT, McNeil BJ."Renalsm": inappropriately low rates of coronary angiography in elderly individuals with renal insufficiency. J Am Soc Nephrol.2004;15(9):2462-2468.
11. LiS-Y,Tang YS,Chan Y-J,Tarng D-C.Impact of the COVID-19 (Coronavirus disease 2019) pandemic on the management of patients with end-stage renal disease. J Chin Med Assoc.2020:83(7);628-633.000356.
12. Cho JH, Kang SH, Park HC, et al. Hemodialysis with cohort isolation to prevent secondary transmission during a COVID-19 (Coronavirus disease 2019) outbreak in Korea.JAm Soc Nephrol.2020;31(7):1398-1408.
13. Seaborg GT. Need we fear our nuclear future? Bull Atomic Scientists. 1968;24(1);36-42.





