20/8/2021 COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension - UpToDate

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COVID-19: Issues related to acute kidney injury,

glomerular disease, and hypertension
Authors: Paul M Palevsky, MD, Jai Radhakrishnan, MD, MS, Raymond R Townsend, MD
Section Editors: Jeffrey S Berns, MD, George L Bakris, MD
Deputy Editors: Shveta Motwani, MD, MMSc, FASN, John P Forman, MD, MSc

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jul 2021. | This topic last updated: Jul 20, 2021.

INTRODUCTION

At the end of 2019, a novel coronavirus (ie, SARS-CoV-2) was identified as the cause of a cluster
of pneumonia cases in Wuhan, a city in the Hubei Province of China. By 2020, it led to a
pandemic that has spread throughout most countries of the world. SARS-CoV-2 disease (COVID-
19) primarily manifests as a lung infection with symptoms ranging from those of a mild upper
respiratory infection to severe pneumonia, acute respiratory distress syndrome, and death.
COVID-19 disproportionately affects patients with pre-existing comorbidities, such as patients
with various types of kidney disease. All medical professionals, including nephrology clinicians,
are tasked with rapidly adjusting their practice to curtail the spread of the virus while providing
life-sustaining care to their patients.

This topic will discuss issues related to COVID-19 and delivery of nephrology care in patients
with acute kidney injury, glomerular disease, chronic kidney disease, and hypertension. Issues
related to the care of patients who have end-stage kidney disease or who are candidates for or
have a kidney transplant are discussed separately. (See "COVID-19: Issues related to end-stage
kidney disease" and "COVID-19: Issues related to solid organ transplantation".)
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Other important aspects of COVID-19 that may affect this population are discussed at length
elsewhere:

● (See "COVID-19: Epidemiology, virology, and prevention".)

● (See "COVID-19: Clinical features" and "COVID-19: Diagnosis".)

● (See "COVID-19: Infection control for persons with SARS-CoV-2 infection".)

● (See "COVID-19: Management in hospitalized adults".)

● (See "COVID-19: Myocardial infarction and other coronary artery disease issues".)

● (See "COVID-19: Questions and answers".)

● (Related Pathway(s): COVID-19: Initial telephone triage of adult outpatients.)

ACUTE KIDNEY INJURY

Patients with suspected or confirmed COVID-19 may present with acute kidney injury (AKI) as
part of their overall illness [1-6]. In a meta-analysis of approximately 13,000 mostly hospitalized
patients, the incidence of AKI was 17 percent, although the range of AKI incidence in the
included studies was broad (range 0.5 to 80 percent). Approximately 5 percent of patients
required kidney replacement therapy (KRT) [6]. The incidence seems to vary by geographic
location and proportion of critically ill patients included in each study.

While there are only limited data on temporal trends in the incidence of COVID-19-associated
AKI, early data suggest that rates of AKI have declined over the duration of the pandemic,
although the reason for these trends is unclear [7,8].

Clinical characteristics and histopathology — Kidney disease among patients with COVID-19

can manifest as AKI, hematuria, or proteinuria, and portends a higher risk of mortality [3,6,7,9-
14]. It remains unclear if AKI is largely due to hemodynamic changes and cytokine release or if
the virus also leads to direct cytotoxicity.

The reported incidence of AKI among patients with COVID-19, especially those who are
hospitalized, varies depending upon the severity of disease in the patients who are studied. In
two large observational studies of over 5000 patients hospitalized with COVID-19, AKI was
noted among 32 to 37 percent of patients [4,7]. Among patients with AKI, approximately one-
half had mild disease (1.5- to 2-fold increase in serum creatinine), and the remaining had
moderate or severe disease (more than doubling of creatinine). AKI requiring KRT was noted in
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12 to 15 percent of patients. AKI was associated with requirement for mechanical ventilation
and with a longer duration of hospitalization. Approximately one-half of the patients with AKI
did not achieve complete recovery of their kidney function by hospital discharge [7].
Independent predictors of AKI included being older, Black American, or male; having obesity,
diabetes, hypertension, cardiovascular disease, low baseline estimated glomerular filtration
rate (eGFR), or higher interleukin-6 level; or requiring mechanical ventilation or vasopressor
medications [4,7,15]. Similar findings were reported in another study [13].

In another study of over 3000 critically ill adults with COVID-19, 21 percent developed severe
AKI requiring KRT within two weeks of admission to the intensive care unit (ICU) [16]. The 28-
day mortality among such patients was approximately 50 percent; risk factors for death
included older age, oliguria, and admission to a hospital with relatively limited ICU resources.
Of those patients who survived to discharge, 34 percent were KRT-dependent at the time of
discharge and more than one-half of those patients were still KRT-dependent by two months. It
is unclear if the KRT dependence is related to the severity of critical illness or to the specific
pathophysiology related to COVID-19. Long-term outcomes among patients requiring KRT in
the setting of COVID-19 have not been studied.

One study compared the incidence of AKI among hospitalized patients with and without COVID-
19 [17]. The incidence of AKI was higher among the 2600 patients who had COVID-19 compared
with over 19,500 patients who were hospitalized for other reasons (31 versus 18 percent). This
higher incidence of AKI could not be explained by differences in the traditional risk factors for
AKI between the groups. COVID-19 remained associated with a higher rate of AKI despite
controlling for demographic variables, comorbidities, frequency of hypotension, selected
laboratory results (eg, complete blood count, baseline eGFR), and use of nephrotoxic
medications, vasopressors, or mechanical ventilation (adjusted hazard ratio 1.40, 95% CI 1.29-
1.53). Markers of inflammation, such as C-reactive protein and ferritin, appeared to be higher
among patients who had COVID-19 compared with those who did not have COVID-19. However,
the comparison of AKI between groups controlling for these inflammatory markers was not
possible because only a few patients without COVID-19 had these checked during their
hospitalization. In another study that compared outcomes among patients with similar baseline
comorbidities who were hospitalized either for influenza or COVID-19, those with COVID-19 had
AKI at a higher frequency (41 versus 29 percent) and greater severity (stage 3 AKI in 26 versus 6
percent) [18]. In addition, the 90-day mortality was higher among patients who had COVID-19
compared with those who had influenza (35 versus 9 percent). These findings raise questions
about the various mechanisms of AKI among patients with COVID-19.

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Kidney histopathology was examined in an autopsy series of 42 patients who died with COVID-
19 [19]. Mean age of the patients included was 72 years (range, 39 to 97 years); 88 percent were
over the age of 60 years. Comorbidities, such as hypertension (73 percent), diabetes (42
percent), coronary artery or cerebrovascular disease (32 percent), obesity (31 percent), and
chronic kidney disease (29 percent) were common; only two patients had no underlying
comorbidities. AKI (mostly stage 3) was noted among 31 of 33 patients. Most patients (62
percent) exhibited varying degrees of acute tubular necrosis (ATN), one had collapsing focal
segmental glomerulosclerosis (FSGS), and many had sequelae of their medical comorbidities
(eg, hypertensive nephrosclerosis).

ATN was also the predominant kidney pathologic finding in other studies [3,20-24]. Glomerular
lesions were reported in a minority of patients with COVID-19. In addition, COVID-19 may also
be associated with renal infarction [25-30]. (See 'COVID-19 associated glomerular disease' below
and "Renal infarction", section on 'Etiology and pathogenesis'.)  

Whether SARS-CoV-2 causes a direct kidney infection remains controversial [31]. The presence
of virus-like particles have been reported in the kidneys of patients with COVID-19 [23,32].
However, these may instead be endosomal subcellular structures (eg, clathrin-coated vesicles
and multivesicular bodies) [33]. Ultrastructural in-situ hybridization used in some studies has
confirmed presence of viral RNA [34] or viral proteins [10] in kidney tissue. Other studies have
failed to demonstrate the presence of virus in the kidney [19,20].

Evaluation of AKI in hospitalized patients — In patients with suspected or confirmed COVID-

19 who develop AKI, an emphasis should be placed on optimization of volume status to exclude
and treat prerenal (functional) AKI while avoiding hypervolemia, which may worsen the
patient's respiratory status.

The evaluation for other AKI etiologies should be undertaken in a manner similar to other
critically ill patients with AKI. As an example, manual urine sediment examination should be
performed, if appropriate, since urine samples are not considered to be highly infectious.

Management of AKI in hospitalized patients

Patients with dialysis-requiring AKI — The indications for KRT for AKI remain the same
regardless of the COVID-19 status of any given patient. Alterations in KRT management that
might be undertaken during the COVID-19 outbreak, particularly during a surge in cases,
include the following:

● Patients with COVID-19 and AKI who require KRT should be co-localized on a floor or ICU,
when possible. Co-localization within adjacent rooms can enable one dialysis nurse to
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simultaneously deliver dialysis to more than one patient. If a patient is in a negative-

pressure isolation room, then one hemodialysis nurse will need to be dedicated for the care
of that patient in a 1:1 nurse-to-patient ratio.

● If at all possible, patients with suspected or confirmed COVID-19 who are not critically ill
but who have AKI requiring KRT should be dialyzed in their isolation room rather than
being transported to the inpatient dialysis unit.

● Continuous kidney replacement therapy (CKRT) remains preferred among critically ill
patients with AKI. Even among patients who are hemodynamically stable and could tolerate
intermittent hemodialysis (IHD), CKRT or prolonged intermittent kidney replacement
therapy (PIKRT; also called sustained low-efficiency dialysis or SLED) should be performed
instead, depending upon machine and staffing availability. This is because CKRT or PIKRT
can be managed without 1:1 hemodialysis nursing support. This would potentially help
minimize wastage of personal protective equipment and limit exposure among
hemodialysis nurses.

● CKRT machines can either be placed inside an isolation room as per standard practice or
outside the room with the use of extended tubing. Placing the machine outside of the room
minimizes the need for repeated entry to troubleshoot and manage the machine, and
therefore reduces wastage of personal protective equipment. However, extended tubing is
a scarce resource. In addition, use of extended tubing requires additional tubing
connections and increases the likelihood that tubing will become disconnected. Extended
tubing also decreases the sensitivity of pressure alarms to detect disconnection of the
venous lines and potentially increases the risk of clotting due to the longer tubing length.  

● If CKRT capacity at an institution is overwhelmed, CKRT machines can be used to deliver

prolonged intermittent treatments (eg, 10 hours rather than continuous) with higher flow
rates (eg, 40 to 50 mL/kg/hour). Alternatively, the machine can be rotated between patients
every 24 hours or whenever the circuit clots, so that use of new filter sets is minimized. This
will enable the CKRT machine to become available sooner for care of another patient after
terminal cleaning.

● Institutions facing scarcity of replacement fluid for CKRT can lower the delivered dose to 15
mL/kg/hour from the standard 20 to 25 mL/kg/hour, especially among patients who are not
hypercatabolic. One institution developed a real-time tracking system to account for and
plan redistribution of scarce replacement fluid [35].

When supplies of commercially prepared replacement fluid are exhausted, institutional

pharmacies may develop their own replacement fluid by mixing all of the following (in a
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sterile fashion) [36]:

• 1 L of 0.9 percent saline with potassium chloride as needed

• 1 L of 5 percent dextrose water with 150 mEq sodium bicarbonate
• 1 L of 0.9 percent saline with 1 g magnesium chloride
• 1 L of 0.9 percent saline with 1 g calcium chloride

This will yield a 4 L solution containing 153 mEq/L sodium, 37.5 mEq/L bicarbonate, 2.6
mmol/L magnesium, 2.25 mmol/L calcium, and a variable amount of potassium.

Other methods for preparation of dialysate solutions have been formulated at the
Cleveland Clinic and Johns Hopkins Hospital [37] in the United States and Guy's and St
Thomas' National Health Service Foundation Trust in the United Kingdom [38].

● Circuit thrombosis during KRT occurs more frequently in patients with COVID-19 than in
other patients [39,40]. In the absence of contraindications, patients with COVID-19 should
receive anticoagulation during KRT. This can be in the form of regional anticoagulation
using unfractionated heparin or citrate, or systemic anticoagulation with unfractionated or
low-molecular-weight heparin. Based on low quality data, regional citrate anticoagulation
appears to be less effective among COVID-19 patients [39,40]; the reason for this is unclear.
Due to this potential lack of adequate efficacy and to minimize risk of other treatment
errors, institutions that have no prior experience with regional citrate anticoagulation
should avoid adopting a new citrate protocol during this crisis. Additional details regarding
anticoagulation for the hemodialysis procedure are presented separately, as is the issue of
hypercoagulability in the setting of COVID-19. (See "Anticoagulation for the hemodialysis
procedure" and "Anticoagulation for continuous kidney replacement therapy" and "COVID-
19: Hypercoagulability".)

● Where available, remote monitoring with audio and video streams should be used to
troubleshoot alarms from outside the room and to minimize the need for the dialysis nurse
or the nephrologist to enter an isolation room.

● No special provisions or methods for disposal of the CKRT effluent are necessary. This is
because neither presence of SARS-CoV-2 nor other similar viruses have been demonstrated
in the effluent.

● When available hemodialysis or CKRT machines are scarce, clinicians may need to consider
treatment of AKI with peritoneal dialysis [41-46]. Important considerations include:

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• Patients with AKI who are treated with peritoneal dialysis have similar rates of all-cause
mortality, kidney function recovery, and infectious complications compared with
patients treated with other modalities. (See "Use of peritoneal dialysis (PD) for the
treatment of acute kidney injury (AKI) in adults", section on 'Outcomes with PD for
AKI'.)

• Peritoneal dialysis requires relatively less equipment, infrastructure, and resources

relative to other forms of KRT. Nurses and clinicians can be trained expeditiously to
provide peritoneal dialysis. (See "Use of peritoneal dialysis (PD) for the treatment of
acute kidney injury (AKI) in adults", section on 'Outcomes with PD for AKI'.)

• Peritoneal dialysis can increase intra-abdominal pressure, interfere with respiratory

mechanics [47], and may theoretically worsen respiratory failure, particularly among
mechanically ventilated patients. However, it can be used among mechanically
ventilated patients when other options such as intermittent hemodialysis and CKRT are
not available. Performing peritoneal dialysis in a mechanically ventilated patient who
requires a prone position may be challenging, although one case report found it to be
feasible and safe [48]. (See "Use of peritoneal dialysis (PD) for the treatment of acute
kidney injury (AKI) in adults", section on 'Complications of PD for AKI'.)

• When peritoneal dialysis is used for management of AKI in patients with COVID-19,
automated peritoneal dialysis with a cycler should be used, if available. This minimizes
the contact between health care personnel and the patient. (See "Use of peritoneal
dialysis (PD) for the treatment of acute kidney injury (AKI) in adults", section on
'Selecting PD modalities for AKI'.)

• Similar to disposal of peritoneal dialysis effluent for patients with end-stage kidney
disease, there are a range of opinions for safe disposal of the effluent in the setting of
AKI. Data suggesting that peritoneal dialysis effluent is infectious are lacking [42]. (See
"COVID-19: Issues related to end-stage kidney disease", section on 'Hospitalized
patients'.)

● Extracorporeal hemoperfusion devices for cytokine removal, such as Cytosorb, have had no
clear role in management of sepsis prior to the COVID-19 pandemic. Due to lack of proven
benefit, we do not use Cytosorb or other similar devices among critically ill COVID-19
patients with or without dialysis-requiring AKI. (See "Investigational and ineffective
therapies for sepsis", section on 'Cytokine and endotoxin inactivation or removal'.)

The suggestions are generally consistent with CDC guidance on providing KRT in the acute care
setting.
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Patients with AKI that is not dialysis-requiring — Patients who have AKI that is not
dialysis-requiring should be managed with limited contact as much as possible. Physical
examination and ultrasound evaluations should be coordinated with the primary/consulting
teams to minimize contact, when possible.

Differences in management of AKI among patients with COVID-19 may include limited use of
intravenous fluids. Most patients with COVID-19 characterized by pneumonia have variable
degree of oxygen requirements and/or airway control. Fluid resuscitation goals are
understandably conservative as per various acute respiratory distress syndrome criteria. Thus,
fluid resuscitation should be individualized and based on trackable objective measures (eg,
inferior vena cava collapse on ultrasound).

GLOMERULAR DISEASE

COVID-19 associated glomerular disease — Glomerular lesions were reported in a minority of

patients with COVID-19, with collapsing focal segmental glomerulosclerosis (FSGS), also called
COVID-associated nephropathy (COVAN), being the most common. Such patients present with
nephrotic-range proteinuria and acute kidney injury (AKI) [9,11,24,49-53]. Similar to HIV-
associated nephropathy, COVAN occurred exclusively in Black individuals, and a high proportion
tested possessed high-risk APOL1 genotypes [24,53]. (See "Collapsing focal segmental
glomerulosclerosis not associated with HIV infection", section on 'Genetic factors'.).

Thrombotic microangiopathy is another uncommon finding among patients who develop AKI
and nephrotic-range proteinuria [24]. There are case reports of other glomerular diseases
associated with COVID-19, including antineutrophil cytoplasmic antibody (ANCA)-associated
vasculitis [54], anti-glomerular basement membrane antibody disease [55], and IgA
nephropathy [56].

COVID-19 vaccine-associated glomerular disease — Both de novo glomerular disease and

relapse of pre-existing glomerular disease have been reported shortly after administration of
COVID-19 messenger RNA (mRNA) vaccines (Moderna mRNA-1273 and Pfizer-BioNTech
BNT162b2) [57-69]. (See "COVID-19: Vaccines to prevent SARS-CoV-2 infection".)

However, these are overall rare and a causal link with the COVID-19 vaccine is not firmly
established. Our approach to COVID-19 vaccination among patients with glomerular disease is
discussed below. (See 'COVID-19 vaccination in patients with glomerular disease' below.)

The following de novo glomerular diseases have been described following COVID-19
vaccination:
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● IgA nephropathy [57,58]

● Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis [57]
● Minimal change disease [59-62,70]
● Anti-glomerular basement membrane (anti-GBM) nephritis [58]

In addition, a relapse of the following glomerular diseases has been reported following COVID-
19 vaccination:

● IgA nephropathy [63-65]

● Minimal change disease [66-68]
● Primary membranous nephropathy [69]
● Complement-mediated thrombotic microangiopathy (C-TMA) [71]

Modifications to the management of pre-existing glomerular disease — Patients with

glomerular disease who are treated with immunosuppressive therapies may be at a heightened
risk of infections (COVID-19 or other infections). However, there are no rigorous studies to guide
pandemic-related modifications to the treatment of glomerular disease. We modify the
immunosuppressive therapy in some patients with glomerular disease depending upon their
risk of progression to end-stage kidney disease and the local transmission of COVID-19 [72].

Among patients who are at low risk of acquiring COVID-19 because of limited community
transmission and their ability to self-isolate (eg, ability to work from home and have limited or
no interaction with outsiders), we continue with their previously planned treatment for their
glomerular disease. Additionally, we reinforce the risks and benefits of undergoing
immunosuppressive therapy in the context of the pandemic to ensure adherence to strict
isolation while on treatment.  

Among patients who are at risk of acquiring COVID-19 due to regional transmission rates and
other factors (eg, inability to quarantine because of their occupation), we take the following
approach:

● If the patient's glomerular disease is being treated with calcineurin inhibitors or

hydroxychloroquine, no treatment modification is necessary (these drugs do not increase
the risk of COVID-19).

● However, among other patients at risk of acquiring COVID-19, we modify our approach as
follows:

• For patients who are not yet on immunosuppressive therapy for their glomerular
disease, we postpone treatment among the following groups:

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- Patients with membranous nephropathy who have uncomplicated nephrotic

syndrome and preserved estimated glomerular filtration rate (eGFR)

- Patients with IgA nephropathy who do not have features associated with a high
risk of progression (eg, heavy proteinuria, impaired eGFR, or crescents on
histopathology)

- Patients who have glomerular diseases for which it is unclear that

immunosuppressive therapy is beneficial (eg, infection-related glomerular disease)

• For patients who were initiated on immunosuppressive therapy before the pandemic
and who are not yet in remission, an individual risk-benefit assessment is needed
regarding continuation of such therapy. According to institutional policies,
arrangements should be made for administration of necessary intravenous (IV)
infusions at home rather than in an institutional infusion center. In addition, when
possible, IV infusions should be changed to equivalent oral alternatives. As examples:

- IV cyclophosphamide could be changed to either oral cyclophosphamide or oral

mycophenolate mofetil

- IV pulse methylprednisolone could be changed to either oral high-dose prednisone

or oral methylprednisolone

In patients who have glomerular diseases for which there is no widely accepted
immunosuppressive strategy (eg, glucocorticoid-resistant FSGS), we avoid cytotoxic
drugs (eg, cyclophosphamide), rituximab, and antimetabolites (eg, mycophenolate
mofetil).

• For patients who were initiated on immunosuppressive therapy before the pandemic
and who are already in remission, we lower the doses of their immunosuppressive
medication to a minimum level that will maintain remission. Among patients who have
been in remission for >12 months, we favor immediate cessation of antimetabolites,
such as mycophenolate mofetil or azathioprine, and avoidance of maintenance
rituximab infusions.

• For patients with glomerular disease who are receiving immunosuppressive therapy
that includes antimetabolites and who have suspected or confirmed COVID-19, we
discontinue antimetabolites for 7 to 10 days after symptom onset. In addition, among
patients who are on long-term glucocorticoids and who require hospitalization for
moderate to severe COVID-19, we also administer stress-dose glucocorticoids. Patients

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with nephrotic-range proteinuria who receive hydroxychloroquine or azithromycin for

treatment of COVID-19 should have an electrocardiogram performed to check the
corrected QT interval. This is because patients with nephrotic syndrome can have a low
ionized calcium.

• For patients with glomerular disease who are enrolled in research studies that entail
having kidney biopsies purely for research purposes (rather than for clinical decision-
making), such biopsies should be postponed or cancelled.

COVID-19 vaccination in patients with glomerular disease — Our approach to COVID-19

vaccination depends upon the timing of onset of the glomerular disease (or relapse) and the
vaccination status of the patient (unvaccinated or partially vaccinated) (see 'COVID-19 vaccine-
associated glomerular disease' above and "COVID-19: Vaccines to prevent SARS-CoV-2
infection"):

● Glomerular disease onset before vaccination – Among patients who have a glomerular
disease with onset prior to COVID-19 vaccination, we ask that they proceed with COVID-19
vaccination without delay, even if they are on immunosuppressive therapy. For patients
whose immunosuppressive therapy consists of rituximab and for whom delaying therapy
would be safe, we administer rituximab four to six weeks after completion of the COVID-19
vaccination series. Other relevant pandemic-related treatment modifications are discussed
above. (See 'Modifications to the management of pre-existing glomerular disease' above.)

● Glomerular disease onset after vaccination – Among patients who develop glomerular
disease (de novo or relapse) that is temporally associated with the COVID-19 vaccine, it is
possible that the second dose of the vaccine will adversely impact their kidney function. The
decision to proceed with the second dose (of the two-dose vaccines) for such patients
should be based upon shared decision-making with the patient. The discussion of risks and
benefits of vaccination should be individualized in context of the patient's type and severity
of glomerular disease and whether or not they are in remission by the time of the
scheduled second dose [73]. As examples, patients with minimal change disease who
achieve remission or those with self-limited IgA nephropathy could receive the second dose
of vaccine. Conversely, patients with ANCA vasculitis, C-TMA, or anti-GBM disease should
likely not receive the second dose.

CHRONIC KIDNEY DISEASE AND HYPERTENSION

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Among patients with COVID-19, both chronic kidney disease (CKD) and hypertension are risk
factors for more severe disease [74-80]:

● In a meta-analysis of four studies and 1389 infected patients (including 273 patients with
severe disease), the prevalence of underlying CKD was more frequent among those with
severe disease (3.3 versus 0.4 percent; odds ratio 3.03, 95% CI 1.09-8.47) [77].

● In the same cohort of 1389 patients from these four studies, history of hypertension was
more common among those who had severe, as compared with nonsevere, COVID-19 (15
versus 32 percent) [77]. Similarly, in a separate cohort of 1590 hospitalized patients in
China, underlying hypertension was independently associated with severe COVID-19
(hazard ratio 1.58, 95% CI 1.07-2.32) [74]. While some studies conducted in the United
States and Italy reveal broadly consistent findings [75,76], others suggest that hypertension
is not an independent risk factor for severe COVID-19 [78].

Renin angiotensin system inhibitors — Patients receiving angiotensin-converting enzyme

(ACE) inhibitors or angiotensin receptor blockers (ARBs) should continue treatment with these
agents (unless there is an indication for discontinuation such as hyperkalemia or hypotension).
There is no evidence that stopping ACE inhibitors or ARBs reduces the severity of COVID-19 [81-
86]. This approach is supported by multiple guideline panels [87-91].

There was speculation that patients with COVID-19 who are receiving these agents may be at
increased risk for adverse outcomes [92,93]. ACE2 is a receptor for SARS-CoV-2 [94] and some,
but not all, evidence suggests that renin angiotensin system inhibitors may increase ACE2 levels
[95-98]. In addition, patients with cardiovascular disease, hypertension, and diabetes (a
disorder with a high prevalence of renin angiotensin system inhibitors-treated use) often have a
more severe clinical course in the setting of infection with SARS-CoV-2.

However, there is no evidence to support discontinuation of renin angiotensin system inhibitors

in patients diagnosed with COVID-19. The best data come from a trial of 740 hypertensive
adults hospitalized for mild or moderate COVID-19 who were taking either an ACE inhibitor or
ARB prior to hospitalization; patients were randomly assigned to continue or discontinue their
ACE inhibitor or ARB for 30 days [81]. Compared with those assigned to discontinue therapy,
those who continued taking an ACE inhibitor or ARB had statistically similar 30-day mortality
(2.8 versus 2.7 percent), need for mechanical ventilation (7.7 versus 9.6 percent), shock
requiring vasopressors (7.1 versus 8.4 percent), and median length-of-stay (five days in each
group).

The conclusions of this trial are supported by multiple, large observational studies, most of
which found no relationship between the use of ACE inhibitors or ARBs and severity of COVID-
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19 [75,76,82-86,99-101], although some suggested that these drugs may attenuate the severity
of disease [79,102-107].

In addition, studies conducted prior to the COVID-19 pandemic suggested that discontinuing
ACE inhibitors and ARBs in some patients may exacerbate underlying cardiovascular or kidney
disease and lead to increased mortality [108-110].

Dialysis access planning in advanced CKD — Patients with stage 4 or 5 CKD who are referred
for dialysis access placement should undergo these procedures as planned (and not have their
planned procedure deferred).

Although nonessential surgeries should be delayed during the COVID-19 pandemic, guidance
from the United States has clarified that placement of arteriovenous fistulas or grafts for
hemodialysis and peritoneal dialysis catheters for peritoneal dialysis are essential procedures
[111,112].

INFECTION CONTROL PRACTICES

Infection control practices specific to the care of patients with kidney disease requiring dialysis
are presented in the preceding discussions.

The general approach to infection control in the health care setting, in the home, and in non-
hospital institutional settings, as well as the approach to discontinuation of COVID-19
precautions and return-to-work for health care personnel, are presented in detail elsewhere.
(See "COVID-19: Infection control for persons with SARS-CoV-2 infection".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: COVID-19 – Index of
guideline topics".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
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short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: COVID-19 overview (The Basics)" and "Patient
education: COVID-19 vaccines (The Basics)")  

SUMMARY AND RECOMMENDATIONS

● SARS-CoV-2 disease (COVID-19) disproportionately affects patients with various types of

kidney disease. Nephrology clinicians are tasked with rapidly adjusting their practice to
curtail the spread of the virus while providing life-sustaining care to their patients. (See
'Introduction' above.)

● The American Society of Nephrology has issued guidelines for nephrology clinicians caring
for hospitalized patients requiring dialysis for acute kidney injury (AKI). These guidelines
continue to evolve and are frequently updated. Although policies enforced at the level of
the institution may vary, when possible, adherence to these guidelines is encouraged (see
'Patients with dialysis-requiring AKI' above):

• Patients with COVID-19 should be co-localized on a floor or intensive care unit (ICU),
when possible. Co-localization within adjacent rooms can enable one dialysis nurse to
simultaneously deliver dialysis for more than one patient. If a patient is in a negative-
pressure isolation room, then one hemodialysis nurse will need to be dedicated for the
care of that patient in a 1:1 nurse-to-patient ratio.

• When possible, patients with suspected or confirmed COVID-19 who are not critically ill
should be dialyzed in their own isolation room rather than being transported to the
inpatient dialysis unit.

• Where available, video and audio streams should be used to troubleshoot alarms from
outside the room to minimize the need for the dialysis nurse or the nephrologist to
enter an isolation room.

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• Continuous kidney replacement therapy (CKRT) is preferred among critically ill patients
in the ICU who have end-stage kidney disease (ESKD) or AKI. Even among patients who
are hemodynamically stable and who could tolerate intermittent hemodialysis, CKRT or
prolonged intermittent kidney replacement therapy (PIKRT), also called sustained low-
efficiency dialysis (SLED), should be performed instead, depending upon machine and
staffing availability. This is because CKRT or PIKRT can be managed without 1:1
hemodialysis support. This would potentially help minimize wastage of personal
protective equipment and limit exposure among hemodialysis nurses.

• If CKRT capacity at an institution is overwhelmed, CKRT machines can be used to

deliver prolonged intermittent treatments (eg, 10 hours rather than continuous) with
higher flow rates (eg, 40 to 50 mL/kg/hour). This will enable the CKRT machine to
become available sooner for care of another patient after terminal cleaning.

• When available hemodialysis or CKRT machines are scarce, clinicians may need to
consider treatment of AKI with peritoneal dialysis. (See "Use of peritoneal dialysis (PD)
for the treatment of acute kidney injury (AKI) in adults".)

● In patients with suspected or confirmed COVID-19 who develop AKI, an emphasis should be
placed on optimization of volume status to exclude and treat prerenal (functional) AKI while
avoiding hypervolemia, which may worsen the patient's respiratory status. Patients who
have AKI that is not dialysis-requiring should be managed with limited contact as much as
possible. Physical examination and ultrasound evaluations should be coordinated with the
primary/consulting teams to minimize contact, when possible. (See 'Evaluation of AKI in
hospitalized patients' above and 'Patients with AKI that is not dialysis-requiring' above.)

● Both COVID-19 and vaccination against COVID-19 may be associated with the development
of glomerular disease. In addition, due to the heightened risk of infection among
immunosuppressed patients, those who have pre-existing glomerular disease may require
modifications to their management plan during the COVID-19 pandemic. (See 'COVID-19
associated glomerular disease' above.)

● Patients receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor

blockers (ARBs) should continue treatment with these agents (unless there is an indication
for discontinuation such as hyperkalemia or hypotension). There is no evidence that
stopping ACE inhibitors or ARBs reduces the severity of COVID-19. (See 'Renin angiotensin
system inhibitors' above.)

● Patients with stage 4 or 5 CKD who are referred for dialysis access placement should
undergo these procedures as planned (and not have their planned procedure deferred).
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(See 'Dialysis access planning in advanced CKD' above.)

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