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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 4  |  Page : 172-178

Coronavirus disease 2019 and the kidney


Department of Nephrology, Manipal Hospital, Bengaluru, Karnataka, India

Date of Submission01-May-2020
Date of Decision04-Jul-2020
Date of Acceptance07-Jul-2020
Date of Web Publication23-Oct-2020

Correspondence Address:
Dr. Ravi Jangamani
Department of Nephrology, Manipal Hospital, Hal Airport Road, Bengaluru - 560 017, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_33_20

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  Abstract 


Coronavirus disease 2019 (COVID-19) is a highly contagious infection caused by severe acute respiratory syndrome coronavirus-2, primarily manifesting as acute respiratory illness but can affect multiple organs. The COVID-19 individuals have varied renal manifestations which includes acute kidney injury, proteinuria, and hematuria. The involvement of kidneys indicates the severity of illness and is one of the determinants of mortality. The individuals with chronic kidney diseases (CKD), on dialysis and with kidney transplantation are at higher risk of severe COVID-19 infection due to the poor immune response and a high prevalence of comorbidities. Here, we review the effects of COVID-19 on kidneys and its management in CKD, dialysis, and kidney transplantation individuals.

Keywords: COVID-19, dialysis, kidney injury, kidney transplantation, severe acute respiratory syndrome coronavirus-2


How to cite this article:
Jangamani R, Thirumal C, Sundar S. Coronavirus disease 2019 and the kidney. APIK J Int Med 2020;8:172-8

How to cite this URL:
Jangamani R, Thirumal C, Sundar S. Coronavirus disease 2019 and the kidney. APIK J Int Med [serial online] 2020 [cited 2020 Nov 26];8:172-8. Available from: https://www.ajim.in/text.asp?2020/8/4/172/298934




  Introduction Top


Novel coronavirus disease 2019 (COVID-19) is a newly discovered highly contagious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. It primarily manifests as mild flu-like illness to severe acute respiratory syndrome, but can affect multiple organs such as kidneys, heart, digestive tract, blood, and nervous system.[1] Older age and comorbidities such as hypertension, diabetes, neutrophilia, and other organ dysfunction are risk factors for SARS and death.[2] Individuals with kidney diseases and transplantation are also at high risk for COVID-19. Here, we review the involvement of kidneys in COVID-19, prevention and the management of COVID-19 in individuals with kidney diseases. Given the quickly changing dynamics of the current outbreak, the guidelines for prevention and management may need to be updated and revised.


  Epidemiology Top


The rapidly spreading outbreak of COVID-19 first emerged in Wuhan, China, in December 2019. It has been declared as a global pandemic. Given the evolving nature of the disease outbreak, solid epidemiological data on COVID-19 are still lacking. In India, 182,143 confirmed cases and 5164 deaths were reported till May 31, 2020 with a fatality rate of 2.83%.[3]

The doubling of epidemic size for every 7.4 days, suggested a high human-to-human[4] transmission by respiratory droplet inhalation and by contact. Aerosol transmission is also possible in case of protracted exposure to elevated aerosol concentrations in closed spaces.


  Microbiology of Virus and Pathogenesis Top


SARS-CoV-2 is a positive-sense single stranded RNA virus with a crown-like appearance due to the presence of spike glycoproteins (S-protein) on the envelope [Figure 1]. It has been identified as bat origin belonging to the beta-coronavirus genus of Coronaviridae family.[5]
Figure 1: Structure of severe acute respiratory syndrome coronavirus-2

Click here to view


SARS-CoV-2 entry starts with the binding of the S-proteintoACE-2 on the epithelial cells. A host type-2 transmembrane serine protease (TMPRSS2) and endosomal low pH facilitates cell entry by endocytosis and then it replicates. This results in recruitment of inflammatory cells releasing interleukin-6 (IL-6). IL-6 activates the cytokine release syndrome leading to multiorgan dysfunction and ARDS.[5],[6]

Apart from lungs, angiotensin-converting enzyme 2 (ACE2) expression has been reported in other organs such as kidneys, heart, and gut, leading to SARS-CoV-2 infection.

The kidney involvement in COVID-19 varies from hematuria, proteinuria to acute kidney injury (AKI). Targeting of ACE2 by SARS-CoV-2 results in angiotensin dysregulation, innate and adaptive immune pathway activation, and hypercoagulation to result in organ injury and AKI. Organ crosstalk between the injured lungs, the heart, and the kidney may further propagate kidney injury. Furthermore, virus particles were reported to be present in renal endothelial cells, indicating viremia as a possible cause of endothelial damage and thrombotic microangiopathy to AKI.[7] In addition, SARS-CoV-2 can directly infect the renal tubular epithelium and podocytes through an ACE2-dependent pathway and cause mitochondrial dysfunction, acute tubular necrosis, proteinuria, and rarely collapsing glomerulopathy.[8],[9]

AKI appears to involve a complex process driven by virus-mediated injury, cytokine storm, and AngII pathway activation, dysregulation of complement, hypercoagulation and microangiopathy interacting with common and known risk factors for AKI such as dehydration, sepsis, shock, rhabdomyolysis, and nephrotoxic drugs [Figure 2].[10]
Figure 2: Pathogenesis of kidney injury in coronavirus disease 2019[7]

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  Clinical Presentation Top


The incubation period is between 2 and 14 days after exposure, with most cases occurring within 5 days after exposure.[4],[11] The COVID-19 presentations varies from mild flu-like illness to severe acute respiratory illness with multiorgan dysfunction. The overall case-fatality rate (CFR)[12] was 2.3%. The CFR was more in aged above 70 years (22.8%), in critical cases (49%) and with preexisting comorbidities.


  Renal Manifestations in Coronavirus Disease 2019 Infection Top


Renal manifestations in COVID-19 infection vary from AKI needing dialysis to asymptomatic proteinuria and hematuria. AKI was common among critically ill patients withCOVID-19, affecting approximately 20%–40% of patients admitted to intensive care according to experience in Europe and the USA.[13],[14] Furthermore, the overall burden of AKI inCOVID-19 might be underestimated, as creatinine values at admission might not reflect true preadmission baseline kidney function, and previous serum creatinine values might not be readily available.[15] Around 20% of patients admitted to an intensive care unit with COVID-19 require renal replacement therapy (RRT) at a median of 15 days from illness onset. Early detection of AKI is done by monitoring urine output and creatinine. There was a dose dependent relationship between AKI stages and death, with an excess risk of mortality by at least 4 times among those with stage 3 AKI.[16],[17]

Cheng et al .[17] found the presence of proteinuria and hematuria in 44% and 26.7% cases, respectively, on admission. Collapsing glomerulopathy has also been described in COVID-19.[9]


  Coronavirus Disease 2019 in Chronic Kidney Disease and Immune Mediated Kidney Disease Top


The patients with chronic kidney diseases (CKD) and immune-mediated kidney diseases should be regarded as at risk to experience a more severe disease of COVID-19 due to impaired host defenses and use of immunosuppression drugs. The Relapse of severe Nephrotic syndrome results in further impairment of host defenses through hypogammaglobulinemia, thrombophilia, and volume overload predisposing to the risk for COVID-19. The fever or other classical symptoms may not be seen in these patients as compared to general population. COVID-19 infection is to be considered when a patient with immune-mediated kidney disease presents with a “flare.”[18]


  Coronavirus Disease 2019 in Dialysis Patients Top


The dialysis patients are having an elevated risk of severe COVID-19 infection due to the poor immune response and a high prevalence of comorbidities among them. The COVID-19 infection presents particular challenges for patients on dialysis; in particular, for those on in-center hemodialysis (HD). Patients on home HD and peritoneal dialysis have lesser risk of infection as they will not be exposed to hospital environment. The initial data from HD center at Renmin Hospital, Wuhan University,[19] showed patients on HD with COVID-19 had less lymphopenia, lower serum levels of inflammatory cytokines, and milder clinical disease than other patients with COVID-19 infection. This is probably due to the reduced function of the immune system and decreased cytokine storms in dialysis patients. In another study at New York City, medical center showed that the presentation of the patients on dialysis with COVID-19 was similar to that of the general population but they had poor outcomes with 75% mortality among those requiring mechanical ventilation.[20]


  Coronavirus Disease 2019 in Kidney Transplant Recipients Top


Kidney transplant recipients are at higher risk for COVID-19 due to immunosuppression and other comorbidities, in particular diabetes and hypertension.[21] They had less fever as an initial symptom with lower CD3, CD4, and CD8 cell counts but deteriorate rapidly compared to persons with Covid-19 in the general population. The kidney transplant recipients with Covid-19 had a very high early mortality of 28% as compared to 1%-5% among general population with Covid-19.[22]


  Diagnosis of Coronavirus Disease 2019 Top


The diagnosis of COVID-19 is mainly based on epidemiological factors (history of contact), clinical manifestations, and laboratory examination-reverse transcriptase polymerase chain reaction (RT-PCR) for virus, chest computed tomography.

RT-PCR detects SARS-CoV-2 RNA in Bronchoalveolar lavage (93%), sputum (72%), nasal swabs (63%), pharyngeal swabs (32%), feces (29%), and blood (1%).[23],[24] Single positive test should be confirmed by a second RT-PCR assay targeting a different SARS-CoV-2 gene.

COVID-19 rapid test useful for screening which qualitatively detects immunoglobulin G (IgG) and immunoglobulin M antibodies to SARS-CoV-2 in human whole blood, serum, and plasma samples.

Kidney involvement in COVID-19 is assessed by monitoring urine output, urine analysis, creatinine, renal imaging, and renal biopsy whenever needed.


  Management of Coronavirus Disease 2019 Top


The current World Health Organization (WHO) and center for disease control and prevention states that the therapeutic strategies to deal with COVID-19 are only supportive and prevention aimed at reducing transmission in the community.[25],[26]

The cases with mild disease are managed by home isolation and with symptomatic treatment. The severe and critically ill cases need to be admitted and managed in COVID-19 designated hospitals. Patients need to be kept in isolation till the respiratory samples turns out to be negative.

The main principles of managing critically ill COVID-19 cases include optimization of intravascular volume status, ventilator support, prevention of secondary infections, prevention of vascular thrombosis and use of extra corporeal therapies in cases with multi-organ dysfunction.

There is no proven specific effective antiviral drug available for COVID-19 at present. The currently available drugs which can be potentially used for treatment of COVID-19 are summarized in [Table 1]. The WHO recommends anti-viral therapeutics should be used only in approved, randomized controlled trials. The role of convalescent plasma therapy is also to be proven.
Table 1: The drugs which can be beneficial in coronavirus disease-19

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  Management of Acute Kidney Injury in Coronavirus Disease 2019 Top


Given the high incidence of kidney involvement in COVID-19, it is important to consider all available treatment options to support kidney function.


  Clinical Management Top


In critically ill patients, avoidance of nephrotoxins, regular monitoring of serum creatinine and urine output, consideration of hemodynamic monitoring, and optimization of intravascular volume help to reduce the occurrence and severity of AKI in COVID-19.[27] Mitigation of volutrauma and barotrauma through the application of lung-protective ventilation lowers the risk of new or worsening AKI by limiting ventilation-induced hemodynamic effects and the cytokine burden on the kidney.[28],[29] Another important option is to adjust fluid balance according to volume responsiveness and tolerance assessment as most of them are dehydrated at the time of admission. This strategy aims to restore normal volume status to avoid volume overload and reduce the risk of pulmonary edema, right ventricular overload, congestion, and subsequent AKI.


  Renal Replacement Therapy and Extracorporeal Support Top


If conservative management fails, RRT should be considered in patients with volume overload, refractory hyperkalemia, and metabolic acidosis. In patients with COVID-19 and AKI, early initiation of RRT and sequential extracorporeal organ support (ECOS) seem to provide adequate organ support and prevent progression of disease severity [Figure 3].[30],[31]
Figure 3: The management of acute kidney injury necessitating renal replacement therapy in patients with coronavirus disease 2019[31]

Click here to view


Continuous RRT (CRRT) is the preferred modality in hemodynamically unstable patients with COVID-19. The right jugular vein is the preferred insertion site, as the catheter exit site and anchoring remain visible after prone positioning. CRRT should be delivered with a minimum dose of 20–25 mL/kg/h.[27] Adequate anticoagulation for the extracorporeal circuit must be tailored to the needs of individual patients as there is hypercoagulable state is often observed in severely ill COVID-19 cases. The use of high cutoff or medium cutoff membranes in Continuous Veno-Venous Hemodialysis (CVVHD) may help to increase cytokine removal.[32]

Slow low efficiency dialysis can be done in hemodynamically unstable patients whenever CRRT is not available.

Acute peritoneal dialysis can be lifesaving and should be used as and when required and in the setting, where hemodialysis facility is not available.

Hemoperfusion with sorbent cartridges might prevent cytokine induced kidney damage in early phase of cytokine storm. These treatments might be indicated in special cases in which immunodysregulation is evident, inflammatory parameters or cytokines are elevated and other supportive therapies are failing or insufficient.[32]

Extracorporeal carbon dioxide removal might help to avoid progression of clinical severity in cases with severe respiratory acidosis, increased need for vasopressors and AKI.[33]

Extracorporeal membrane oxygenator (ECMO) is useful in cases with cardiomyopathy and severe alveolar damage leading to severe AKI. When RRT is carried out in conjunction with ECMO, RRT should be performed through venous access independent of the ECMO circuit to minimize clot formation in the latter.[30] Whenever there is paucity of sites for direct cannulation, the RRT outflow should be connected to the preoxygenator limb of the ECMO circuit, as the oxygenator can serve as a protective barrier and minimize risk of systemic gas embolism in the lungs.

Sequential extracorporeal therapies[30],[32],[34] such as endotoxin removal, cytokine removal and immunomodulation, ECOS for various organs should be considered according to the current evidence or pathophysiological rationale.

Neither hemodialysis filters nor hemadsorption cartridges remove antibodies, as their size (e.g., 150 kDa for IgG) far exceeds the upper size of molecules that can be removed with RRT or hemadsorption (around 60 kDa).


  Measures to Prevent Coronavirus Disease 2019 Transmission Top


Preventive measures are the current strategy to limit the spread of COVID-19. The WHO and other organizations have advised use of face mask, social distancing, and frequent hand washing as the main preventive measures.

The National Taskforce for COVID-19 constituted by the Indian Council of Medical Research recommends the use of hydroxychloroquine for prophylaxis of SARS-CoV-2 infection for asymptomatic health-care workers. The prophylactic dose of hydroxychloroquine is 400 mg twice a day on day 1, followed by 400 mg once weekly for the next 7 weeks; to be taken with meals.


  Recommendations for the Management of Immune-Mediated Kidney Diseases during Coronavirus Disease 2019 Pandemic Top


  • Update the vaccination status of each patient
  • Replace office visits with telephone or video consultations
  • Kidney biopsies should only be performed in urgent cases such as severe nephrotic syndromes and rapidly progressive renal failure
  • Newly diagnosed patients require an individual risk-benefit assessment of whether to start or stop an immunosuppressive treatment regimen based on disease progress, biopsy findings, kidney function, level of proteinuria, and comorbidities during the pandemic[18]
  • Viral screening before initiating immunosuppressive therapy at least excludes silent COVID-19
  • Do not stop treatment with Renin-Angiotensin System (RAS) inhibitors[35]
  • Patients with COVID-19 may benefit from hospitalization, adjusting their immunosuppressive therapy, stress-dose hydrocortisone, monitoring of drug levels and dose adjustments according to excretory kidney function
  • Be aware of possible rise in drug levels of calcineurin inhibitors when an individual is on treatment for COVID-19 with hydroxychloroquine and antiviral drugs.



  Management of Patients on Dialysis during Coronavirus Disease 2019 Pandemic Top


The Chinese Society of Nephrology,[36] the Taiwan Society of nephrology,[37] and the American Society of Nephrology/Centers for Disease Control[38] have recently developed guidelines for dialysis units during the COVID-19 outbreak. The Indian Ministry of Health and Family Welfare[39] has also given its guidelines. A summary of these guidelines is provided below:

Guidelines for dialysis center and staff

  1. Posters/notices should be placed at waiting areas highlighting symptoms of COVID-19 infection and on preventive measures
  2. Entrance control-identification and shunting of people at risk of infection, thermal screening, hand washing, wearing proper (surgical or N95) masks throughout the dialysis process, machine disinfection, environmental cleanliness, good air conditioning, and ventilation conditions, should be instituted
  3. A fixed working team consisting of dialysis physicians, nursing staff and technologists should receive training in updated clinical knowledge of epidemic COVID-19 and preventive measures. The team's health status should be monitored
  4. Do not touch patients or use stethoscope unless essential
  5. The health department should be notified in instances of suspected or confirmed COVID-19 infection.


Guidelines for patient

  1. All patients should have their temperature monitored on arrival for dialysis
  2. Patients and accompanying persons should be given hands-free hand sanitizer and mask while entering the dialysis room
  3. Patients who have fever or respiratory symptoms should call their dialysis unit before arrival, be assessed in fever clinic and should be screened for COVID-19 infection. Patients with suspected COVID-19 infection should receive “Fixed Dialysis Care Model” as below during the 14-day period of quarantine


  1. Patients should continue hemodialysis at the original hemodialysis center and not change to another center
  2. Do not change dialysis shifts and caregiver staff to avoid cross contamination and infection
  3. Dialysis to be done in the last shift of the day
  4. The pick-up and drop-off should not be shared with other dialysis patients
  5. Patients should not be in close proximity, with a space of at least 6 feet between patients; with good ventilation
  6. All staffs should undertake full protection with personal protection equipment-long-sleeved waterproof isolation clothing, hair caps, goggles, gloves, and medical masks (surgical mask grade or above). Hand hygiene should be strictly implemented
  7. Equipment that may come into contact with patients or potentially contaminated material should be disinfected according to standard protocols
  8. Home hemodialysis or peritoneal dialysis is preferable
  9. Patients on peritoneal dialysis disinfect used bags and tubes with 1% sodium hypochlorite before disposing in the sealed bag. The fluid also to be disinfected before flushing.



  Management of Kidney Transplantation during Coronavirus Disease 2019 Pandemic Top


The Indian Society of Organ Transplantation has given following guidelines for transplantation, on March 26, 2020.

Guidelines for transplant centers

  • The living donor transplant program may be temporarily suspended in line with the MoHFW's advisory. However, if transplant is being done in view of emergency medical need of recipient, then adequate caution should to be taken
  • It should be done only at the center where facilities for the management of COVID-19 patients are available
  • The pre-, peri-, and post-transplant areas, including the operation theaters and the staffs need to be specifically ear marked for this purpose.


Guidelines for donors

  • Donors with a history of international travel or contact with confirmed case of COVID-19 in last 14 days should NOT be accepted
  • Routine COVID-19 (SARS-CoV-2) viral testing should be undertaken in all potential donors within 72 h prior to donation
  • Confirmed Covid-19-positive case should not be accepted as donor
  • Donors who have recovered from COVID-19 at least 28 days ago should be used only with caution on case to case basis.


Guidelines for recipients

  • Similar to the general population, transplant recipients should also strictly follow the preventive measures
  • Recipients with stable graft function and adequate drug supply can avoid routine follow-up visits to transplant hospitals
  • There is no consensus regarding modification in the immunosuppressive regimen of transplant recipients with COVID-19. The dose adjustment has to balance the infection control and the organ rejection. However, there is overall agreement of stopping anti-metabolite drugs and decrease calcineurin inhibitors by 50% in recipients with severe COVID-19 infection. Steroid should be continued on same doses.



  Conclusions Top


The COVID-19 pandemic represents the greatest global public health crisis of this generation. Kidney involvement seems to be frequent in this infection, and AKI is an independent predictor of mortality. Individuals with CKD and kidney transplantation are at higher risk for COVID-19. The management of patients on dialysis who have been suspected to have contact with COVID-19 should be carried out according to strict protocols to minimize risk to other patients and health-care personnel. At present, there is no standardized treatment or vaccine available for COVID-19. Hence, containment and prevention are the best option available.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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