Recovery after Critical Illness and Acute Kidney Injury

Anitha Vijayan ,1 Emaad M. Abdel-Rahman,2 Kathleen D. Liu,3 Stuart L. Goldstein,4 Anupam Agarwal ,5
Mark D. Okusa,2 and Jorge Cerda ,6 for the AKI!NOW Steering Committee

Abstract
AKI is a common complication in hospitalized and critically ill patients. Its incidence has steadily increased over
the past decade. Whether transient or prolonged, AKI is an independent risk factor associated with poor short-
and long-term outcomes, even if patients do not require KRT. Most patients with early AKI improve with 1
Division of
conservative management; however, some will require dialysis for a few days, a few weeks, or even months. Nephrology,
Approximately 10%–30% of AKI survivors may still need dialysis after hospital discharge. These patients have a Department of
Medicine, Washington
higher associated risk of death, rehospitalization, recurrent AKI, and CKD, and a lower quality of life. Survivors University in St. Louis,
of critical illness may also suffer from cognitive dysfunction, muscle weakness, prolonged ventilator St. Louis, Missouri
2
dependence, malnutrition, infections, chronic pain, and poor wound healing. Collaboration and communication Division of
among nephrologists, primary care physicians, rehabilitation providers, physical therapists, nutritionists, nurses, Nephrology and Center
for Immunity,
pharmacists, and other members of the health care team are essential to create a holistic and patient-centric care
Inflammation, and
plan for overall recovery. Integration of the patient and family members in health care decisions, and ongoing Regenerative Medicine,
education throughout the process, are vital to improve patient well-being. From the nephrologist standpoint, University of Virginia,
assessing and promoting recovery of kidney function, and providing appropriate short- and long-term follow-up, Charlottesville, Virginia
3
are crucial to prevent rehospitalizations and to reduce complications. Return to baseline functional status is the Division of
Nephrology,
ultimate goal for most patients, and dialysis independence is an important part of that goal. In this review, we Department of
seek to highlight the varying aspects and stages of recovery from AKI complicating critical illness, and propose Medicine and Critical
viable strategies to promote recovery of kidney function and dialysis independence. We also emphasize the need Care Medicine,
for ongoing research and multidisciplinary collaboration to improve outcomes in this vulnerable population. Department of
Anesthesia, University
CJASN 16: 1601–1609, 2021. doi: https://doi.org/10.2215/CJN.19601220 of California, San
Francisco, San
Francisco, California
Introduction failure, surgical complications, and sepsis. The 4
Division of
AKI is a major complication among hospitalized post–intensive care syndrome is a well-recognized Nephrology and
patients, especially in intensive care units (ICUs). entity that afflicts a significant percentage of the survi- Hypertension,
Approximately 50% of critically ill patients may University of Cincinnati
vors of critical illness (10). The post-ICU syndrome
College of Medicine
develop AKI (1). AKI is associated with significant can be a result of the underlying medical condition, and Cincinnati
morbidity and mortality, and the severity of kidney ICU-associated delirium, and ICU-acquired myopathy Children’s Hospital
injury is a determinant of short-term and long-term and weakness (11). A prolonged stay in the ICU is Medical Center,
outcomes (2,3). On discharge from the hospital, survi- associated with significant debilitation after hospitali- Cincinnati, Ohio
5
Division of
vors of critical illness and AKI still face significant zation, and has a negative effect on long-term out- Nephrology,
challenges as they slowly recover mental, emotional, comes. One study that evaluated 109 survivors of Nephrology Research
and physical well-being. Long-term consequences of acute respiratory distress syndrome revealed that and Training Center,
AKI include persistent kidney dysfunction and higher these patients have significant functional limitation University of Alabama
likelihood for CKD and kidney failure (4–6). Even at Birmingham,
even at 1 year posthospitalization, mostly from mus-
Birmingham, Alabama
mild AKI is associated with significant risk for persis- culoskeletal damage and pulmonary complications 6
Department of
tent deterioration in kidney function at 90 days (7). (12). Early mobilization in the ICU can significantly Medicine, Albany
Patients with AKI requiring dialysis at the time of dis- decrease the severity of muscle weakness and may Medical College,
charge are a particularly vulnerable group (8). In addi- help to reduce length of ICU stay (13,14). On dis- Albany, New York
tion to their multiple comorbidities, dialysis- charge, survivors of critical illness benefit from family
Correspondence:
dependent patients with AKI must cope with the chal- engagement and patient-centered care whether they Dr. Anitha Vijayan,
lenges of undergoing KRT in outpatient dialysis facili- are discharged to home or a rehabilitation facility (15). Division of
ties that typically care for patients with kidney failure. Active measures to prevent further kidney injury and Nephrology,
Such facilities may not yet be well set up to care for promote recovery of kidney function are vital, as dial- Washington University
patients with a good chance of functional recovery (9). in St. Louis, St. Louis,
ysis dependence at hospital discharge poses signifi-
MO 63110. E-mail:
cant challenges to patients’ daily lives, and is a barrier avijayan@wustl.edu
to appropriate physical and psychologic rehabilitation
Recovery from Critical Illness therapy and meaningful family and social interac-
Patients with AKI are often recovering from a pro- tions. Measures to promote recovery of kidney func-
longed stay in the ICU, complicated by multiorgan tion include: avoidance of nephrotoxins, optimization

www.cjasn.org Vol 16 October, 2021 Copyright © 2021 by the American Society of Nephrology 1601
1602 CJASN
of hemodynamics, judicious ultrafiltration, and avoidance
of hypotension, especially during KRT.
Recovery of Kidney Function
There is no single consensus definition for recovery of
kidney function after AKI. Recovery can be broadly
defined as partial or complete, depending on the degree of
improvement in kidney function (16). It has been suggested
that “complete recovery” denotes improvement in eGFR to
within 90% of baseline value (17,18). This degree of recov-
ery of kidney function probably occurs in only a minority
of patients, usually those with milder forms of AKI (17).
Patients who recover kidney function tend to be younger
and have higher kidney function and fewer comorbid con-
ditions at baseline (19,20). For example, a 25-year-old man
with previously normal kidney function who had rhabdo-
myolysis and AKI after a motor vehicle accident, but did
not require KRT, is more likely to have complete recovery
of kidney function than a 75-year-old with underlying
CKD in the same scenario (20). Patients who progress from
AKI to acute kidney disease after 7 days of nonrecovery
may have partial or complete kidney function recovery
over the subsequent 90 days (21). After 90 days, patients
with persistent kidney function are considered to have
CKD, and those who remain dialysis dependent after 90
days are considered to have kidney failure. Achieving dial-
ysis independence after 90 days is exceedingly rare (22).
Timing of recovery, as it relates to the onset of AKI, also
has significant prognostic implications (23,24). Early recov-
ery of kidney function can occur within days of onset of
AKI, usually in the hospital itself, and delayed recovery of
kidney function can occur weeks to even months later.
Early recovery of kidney function is associated with excel-
lent long-term prognosis, compared with those who never
recover kidney function (23,25). In one study of 16,968
patients with stage 2 or 3 AKI, patients in early recovery
had a 90.2% 1-year survival compared with those who
never recovered kidney function (39.2% 1-year survival) or
who had relapse of AKI (41.9% 1-year survival) (25). In a
recent study of .47,000 patients, recovery of kidney func-
tion within 4 days of AKI was associated with lower risk
for persistent kidney dysfunction when compared with
longer recovery periods (23).
Predicting recovery from AKI has important implications
regarding decisions such as frequency of dialysis sessions
or cessation of dialysis (26). Functional biomarkers (serum
creatinine [SCr] or cystatin C) and/or damage biomarkers
(kidney injury molecule-1, neutrophil gelatinase-associated
lipocalin, interleukin-18, tissue inhibitor of metallopro-
tease-2/insulin-like growth factor binding protein-7, etc.)
have been investigated in predicting kidney function
recovery and/or risk of persistent AKI (27). There are com-
plexities and confounding variables associated with these
studies (definition of recovery, duration of ICU stay, sever-
ity of AKI, and preexisting CKD) that limit conclusive evi-
dence for their utility as predictors of recovery from AKI
(28). Loss of muscle mass during critical illness may deem
SCr even less sensitive as a marker of kidney function. Cre-
atinine clearances are not routinely performed in critically
ill patients even in early stages of kidney recovery.
Although some studies have shown a significant associa-
tion between biomarkers such as neutrophil gelatinase-
associated lipocalin (NGAL) (29), plasma proenkephalin–A
(30), and urinary C-C motif chemokine ligand 14 (31) and
recovery of kidney function, these show variable rates of
false positivity, and limited value over usual markers, clini-
cal score, or kinetic change in SCr concentrations (28). As
recommended by the Acute Disease Quality Initiative
(ADQI) 16 and 23 Workgroups, additional studies in well-
designed clinical trials assessing the value of clinical risk
scores, biomarkers, imaging, and functional studies will be
needed to determine the utility of these tools (21,27).
Posthospitalization Care of AKI Patients
In the posthospitalization management of a patient after
critical illness and/or AKI, various factors must be consid-
ered, including: timing of follow-up; whether follow-up
should be with a nephrologist, a primary care physician,
or both; coordination of care among various medical serv-
ices; communication with outpatient physicians; manage-
ment of dialysis-dependent AKI patients in outpatient
facilities; and patient perspective and social implications.
The appropriate timing of follow-up after discharge from
hospital depends on several aspects such as severity of
AKI, presence of comorbidities, dialysis dependence on
discharge, and whether patients are discharged to home
versus intermediary facilities such as skilled nursing facili-
ties and long-term acute care hospitals. Patients with sig-
nificant kidney dysfunction may need to be seen as soon
as 1–2 weeks post hospital discharge, whereas those who
have less severe AKI may not need follow-up for up to 12
weeks after discharge (17). An inpatient nephrology con-
sultation, involvement of the nephrologist in discharge
planning, and measurement of SCr and proteinuria at the
time of hospital discharge will be helpful in deciding the
timing of outpatient follow-up. A dedicated clinic for
follow-up of patients with AKI has been established at
some centers, but more data are needed before this can be
widely recommended (32).
As stated earlier, patients with AKI follow different tra-
jectories, ranging from mild AKI with recovery early in the
course of the hospitalization, to dialysis dependence requir-
ing outpatient dialysis at discharge (Figure 1). Interdisci-
plinary coordination of care and discharge communication
are crucial to ensure appropriate postdischarge nephrology
follow-up, because patients are frequently discharged to
intermediary facilities (skilled nursing facilities, long-term
acute care hospitals) and may be lost to follow-up. The
presence of a serious complication such as AKI is
frequently missing in discharge summaries, and, there-
fore, the physician managing the patient postdischarge
will not know it occurred and cannot ensure appropriate
post-AKI follow-up. Greer and colleagues audited the doc-
umentation of AKI at hospital discharge in 75 randomly
selected patients and noted that only 44% of physician dis-
charge summaries documented a diagnosis of AKI and
even fewer listed the cause of AKI (43%) and its course
(31%). Even more concerning, only 13% documented AKI-
specific patient instructions and only 6% had follow-up
treatment plans (33). Quality improvement projects have
CJASN 16: 1601–1609, October, 2021
AKI requiring KRT
KRT at Partial or complete
discharge kidney recovery
KRT at KRT at
intermediary outpatient dialysis
facility facility
Death
Partial or complete Normalization of
kidney recovery kidney function
Figure 1. | Clinical course of patients who develop AKI in the hospital. Patients who develop AKI in the hospital may have complete or
partial recovery of kidney function in the hospital or after discharge. Those patients who do not recover kidney function in the hospital
may need ongoing KRT at an intermediary facility or outpatient dialysis facility. Patients with AKI are at risk for progression to CKD and
readmission to the hospital.
demonstrated that documentation of AKI-specific informa-
tion in after-visit summaries can be improved through a
systematic, educational initiative. In a single-center quality
improvement initiative in the United Kingdom, compliance
of documentation with AKI-specific information improved
from 22% to 92% at the end of a 12-month period and was
sustained for up to 14 months after conclusion of the pro-
ject (34). This quality improvement project was conducted
in only a small representative sample, so it is unclear if the
improvement in documentation translated to improvement
in overall postdischarge patient care.
Patients with AKI are at high risk for all-cause readmis-
sion within 30 days after discharge (35). One large health
care database analysis with approximately 150,000 patients
from 197 hospitals in Canada revealed that approximately
20% of patients required readmission and about 10% were
seen in the emergency room within 30 days after discharge
(35). Patients with AKI had a higher likelihood for read-
mission compared with those without AKI (hazard ratio
[HR] 1.53; 95% confidence interval [95% CI], 1.50 to 1.57).
This study suggests that early follow-up for patients with
AKI may be beneficial in preventing readmissions or emer-
gency room visits. For patients who have achieved dialysis
independence at discharge or never required KRT, Van-
massenhove and colleagues designed a postdischarge
follow-up algorithm (36). They proposed that patients who
had complete recovery of kidney function (return of eGFR
to within 90% of baseline) before discharge should be seen
in approximately 3 months, whereas those with incom-
plete recovery of kidney function should be seen within 3
weeks of discharge. Harel and colleagues demonstrated
that those who had severe AKI needing temporary,
in-hospital KRT and who had nephrology evaluation
within 90 days postdischarge had lower 2-year mortality
Recovery after Acute Kidney Injury, Vijayan et al. 1603
AKI in the hospital
AKI not requiring KRT
In-hospital death
Partial Complete
kidney recovery kidney recovery
Clinic follow-up
Recurrent AKI or Development
rehospitalization for of CKD
other causes
compared with those who did not have nephrology
follow-up (15.5% versus 18.9%; HR 0.76; 95% CI, 0.62 to
0.93) (37). Patients with AKI during their hospitalization
are at high risk for recurrent AKI necessitating rehospitali-
zation (38). Recurrent AKI usually occurs in patients with
other comorbidities—malignancy, liver disease, or heart
failure. It is plausible that close follow-up and manage-
ment of AKI patients after initial hospitalization may
decrease their risk for recurrent AKI.
The ADQI consensus statement recommends that health
systems develop a structure and process for follow-up of
patients with AKI, instituting appropriate monitoring meas-
ures to assess for recovery and to prevent further kidney
injury (39). At a minimum, we recommend that during each
ambulatory visit, a basic metabolic panel and urine albumin-
to-creatinine ratio be obtained to assess kidney function and
the degree of proteinuria, respectively. The frequency of the
ambulatory visits will depend on the severity of AKI, under-
lying CKD, and other comorbidities, because patients with
more severe and complex illnesses will need to be evaluated
on a more frequent basis. The Assessment, Serial Evaluation,
and Subsequent Sequelae in Acute Kidney Injury study,
which matched 769 patients who had AKI in the hospital
with those who did not have AKI, documented that higher
urine albumin-to-creatinine ratio at the 3-month posthospi-
talization visit was associated with a significant risk for pro-
gression of kidney disease (40). On the basis of SCr, an esti-
mation of GFR using the Modification of Diet in Renal
Disease or Chronic Kidney Disease Epidemiology Collabora-
tion formula can be performed if SCr is in a steady state.
These equations are not reliable in the setting of AKI with
frequent fluctuations of SCr. Caution must also be used in
using these equations with extremes of age, body mass
index, and muscle mass. A review of medications should
1604 CJASN
be performed at each visit to ensure appropriate medication
dosing in the setting of kidney dysfunction, and to
discontinue those that are potentially nephrotoxic, e.g., non-
steroidal anti-inflammatory medications. Blood pressure and
volume status assessment should be performed, with judi-
cious use of renin-angiotensin-aldosterone system (RAAS)
blockers and diuretics. Combination of nonsteroidal anti-
inflammatory medications, diuretics (including potassium-
sparing diuretics), and RAAS blockers is associated with
higher risk for AKI, as may be the sacubitril/valsartan com-
bination (41,42). The BP target for patients within the 90-day
window after AKI is unclear, but hypotension with resultant
renal hypoperfusion should be avoided. If kidney function
remains stable, reinitiation or de novo initiation of RAAS
blockers should be considered, but the exact timing of start-
ing these drugs remains controversial. A large retrospective
cohort study demonstrated that a prescription of either
angiotensin-converting enzyme inhibitor or angiotensin
receptor blocker within 180 days of discharge after AKI was
associated with lower mortality (39.2% versus 50.6%;
adjusted HR 0.85; 95% CI, 0.81 to 0.89). However, it was also
associated with higher risk for hospitalization for AKI, vol-
ume overload, and hyperkalemia (5.8% versus 5.2%; HR
1.31; 95% CI, 1.15 to 1.49) (43). Other large retrospective
cohort studies have not demonstrated a higher risk for hos-
pitalizations with reinitiation or continuation of RAAS
blockers after AKI (44,45), and one even suggested better
survival among patients started on RAAS blockers versus
the nonusers (46). A large prospective interventional trial is
needed to confirm or refute the potential benefit, and appro-
priate timing, of initiating angiotensin-converting enzyme
inhibitor and angiotensin receptor blocker after hospitaliza-
tion complicated by AKI. Until then, these medications
should be prescribed on the basis of cardiovascular risk fac-
tors and other indications.
There is considerable debate as to whether patients with
AKI in the hospital require follow-up with nephrologists or
general practice physicians. This probably depends on the
severity of AKI and other comorbidities. As stated earlier,
patients with dialysis-dependent AKI who have only a
brief duration of KRT in the hospital have better outcomes
than those with a more prolonged course of AKI (23). In a
retrospective study, Stoumpos demonstrated that of 396
patients with AKI who recovered kidney function within 1
year, only 8.8% of patients progressed to CKD after a
median of 5.3 years. The risk factors for progression to
CKD were older age and presence of diabetes mellitus and
vascular disease (47). This study implies that patients who
achieve close to complete recovery of kidney function
within 1 year may not need nephrology follow-up for an
extended period.
Patients with AKI who remain dialysis dependent at dis-
charge receive intermittent hemodialysis treatments either at
an in-center facility or at an intermediary location like a reha-
bilitation hospital. The care of the dialysis-dependent AKI
patient is fundamentally different from that of a patient with
kidney failure, and it is imperative that this distinction be
reflected in the management of the patients in the outpatient
setting. Abdel-Rahman and colleagues adopted a protocol
for care of dialysis-dependent patients with AKI in the out-
patient hemodialysis facility. Patients with dialysis-
dependent AKI were seen by a nephrologist at each dialysis
session, and ultrafiltration rate and blood pressure and vol-
ume status were closely monitored. Medications were
reviewed for their nephrotoxic potential and adverse effects.
Assessments of kidney function using 24-hour combined cre-
atinine and urea clearance were obtained weekly. Dialysis
was discontinued upon sustaining average urea and creati-
nine clearances of .15 ml/min, whereas transitioning to a
diagnosis of kidney failure was done if no signs of recovery
of kidney function were noted within 90 days. Using this
protocol, 42% of patients became dialysis independent
within 90 days (48). Longer follow-up revealed that 75% of
those who recovered kidney function remained alive or dial-
ysis independent at a median of 2.4 years (49). Hypotensive
episodes during intermittent hemodialysis are associated
with delay in kidney function recovery (50–52). It is impera-
tive that ultrafiltration rates are adjusted each session for
patients with AKI on the basis of hemodynamic and volume
status, as opposed to using a designated target weight that is
considered routine care for patients with kidney failure.
Patient-Centered Care and Education
Patients recovering from critical illness are coping with
multiple comorbidities, and their understanding of AKI
and the potential for recovery of kidney function may be
insufficient for coping with the disease (53). Many patients
who experience AKI during their hospitalization may not
be aware of its significance and its prognostic implications,
and some may not even realize that they suffered kidney
injury during their hospitalization (53). Patients and care-
givers may prioritize other aspects of their overall illness
that they deem to be more important than AKI. Intense
education and raising awareness of AKI and its consequen-
ces in the community are vital to prevent recurrent AKI,
and to promote kidney function and overall recovery. A
single-center study demonstrated that a multipronged
approach to patient understanding of AKI during the first
follow-up visit can significantly influence the patient’s
understanding of the severity of AKI and its consequences
(54). Patients, family members, and other caregivers are
under considerable stress as patients recover from their
critical illness and AKI. It is important to remember that
education and awareness need to be multidimensional and
must be targeted at all health care workers and the public.
Patients who have recovered from critical illness and AKI
have recently been heard at national meetings discussing
their harrowing experiences with outpatient care (55).
Physicians, social workers, nurses, rehabilitation personnel,
and others should understand and acknowledge the
patients’ hardships as they try to regain normalcy and
their prior quality of life (Figure 2). Nephrologists and
dialysis staff taking care of dialysis-dependent AKI
patients in the outpatient setting may not be cognizant of
the complexities of managing an AKI patient with poten-
tial for recovery of kidney function, and therefore, educa-
tion and a culture shift are required in this regard as well.
Lack of interoperability among electronic medical records
(EMR) systems, especially between outpatient dialysis
facilities and hospitals, results in information silos and
fragmented care, leading to errors in medication and
hemodialysis prescription and lack of communication
CJASN 16: 1601–1609, October, 2021 Recovery after Acute Kidney Injury, Vijayan et al. 1605

Nephrologists

Family members Other support

Patients recovering from AKI Primary care physicians

Outpatient dialysis and critical illness Rehabilitation physicians
nurses and staff Mental health personnel
Other specialists

Social workers
Rehabilitation personnel
Dietitians

Figure 2. | Coordination of care for patients with critical illness and AKI after discharge. Multidisciplinary care and coordination among
multiple specialties, with close involvement of patient and family, are essential for patient recovery after prolonged hospitalization compli-
cated by AKI.

between dialysis centers and other health care facilities
(56–58). Appropriate peer-to-peer and interdisciplinary
communication remains vital in the coordination of care
of patients with AKI after discharge.
Care of the Pediatric Patient
Hospitalized children are also at risk for development of
AKI, both in the ICU and on the wards. As with adults,
ICU admission, sepsis, cardiac surgery, and exposure to
nephrotoxic medications represent the most common
causes of AKI in children. One-quarter of neonates and
children admitted to an ICU develop AKI, and Kidney Dis-
ease Improving Global Outcomes stage 2 or 3 AKI is inde-
pendently associated with mortality (59,60). Thirty to 40
percent of children develop AKI after cardiac surgery (61),
and once again AKI is independently associated with poor
outcomes in these children. As with adults, the need for
KRT is associated with higher risk for mortality.
One could argue that follow-up of children who survive
an AKI episode entails a greater imperative given their lon-
ger projected lifespan compared with adults. As mentioned
above, just as in adults, follow-up has not been carried out
in a systematic manner for pediatric AKI survivors. Yet,
numerous pediatric studies have demonstrated a high prev-
alence of CKD after an AKI episode, irrespective of the cause
of AKI. For example, Garg and colleagues demonstrated in a
systematic review that 25% of children who experienced
diarrhea-associated hemolytic uremic syndrome had CKD
or proteinuria/hypertension 4 years after the episode (62).
Menon and colleagues showed that .50% of children who
experienced nephrotoxic medication–associated AKI had
evidence of CKD or proteinuria 6 months after the AKI epi-
sode (63). Importantly, none of these children had any evi-
dence of kidney injury before the AKI episode. Mammen
and colleagues found that .50% of children who survived
AKI in a pediatric ICU had evidence of CKD or kidney
injury 1 year later (64). Finally, children who suffer AKI after
1606 CJASN

Table 1. Recommendations for posthospitalization evaluation of patients with AKI

Patients Who Recover Kidney Patients Who Are Dialysis

Function in the Hospital Dependent at Discharge

Discharge planning and
communication
Outpatient follow-up
Clinical and laboratory
parameters at follow-up
Prognosis for progression to
CKD and kidney failure
Coordinate discharge planning with primary
team
Ensure appropriate follow-up with PCP and
other specialists as needed
Educate patient and family on AKI and its
current and future implications
Nephrology follow-up within 4 weeks after
discharge, depending on severity of AKI
and comorbid diseases
Assess blood pressure and volume status, SCr,
eGFR, and proteinuria at visit
Review medications and initiate or reinitiate
diuretics, ACEI, ARB, and SGLT-2 inhibitors
on the basis of comorbidities and
indications
Coordinate with other specialties regarding
mediation dosing of other agents, e.g.,
chemotherapy medications,
immunosuppressive agents, and antibiotics
Determine risk for progression to CKD and
kidney failure and arrange subsequent
follow-up
If complete recovery of kidney function and
no proteinuria on initial evaluation,
consider discharge to primary care
physician for further follow-up
Coordinate care with accepting nephrologist
and dialysis facility staff
Communicate with outpatient nephrologist
regarding prognosis for kidney function
recovery
Educate patient and family on AKI and its
current and future implications
Follow up for outpatient dialysis at a
dialysis facility per dialysis schedule
Preferably allocate in an AKI recovery
outpatient unit dedicated to promote
recovery
Assess for kidney function recovery at
weekly intervals, e.g., decreasing SCr
trends, increase in urine output
Avoid aggressive ultrafiltration to prevent
hypotensive episodes
Avoid establishing a target weight
Review medications regularly to prevent
further nephrotoxicity, and avoid side
effects from renally cleared medications
Determine risk for progression to CKD and
kidney failure and plan for long-term
dialysis or refer for transplant if poor
prognosis for kidney function recovery
If patient recovers kidney function sufficient
to discontinue dialysis, establish
nephrology clinic follow-up

PCP, primary care physician; SCr, serum creatinine; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor
blocker; SGLT-2, sodium-glucose cotransporter 2.

cardiac surgery are at higher risk of CKD 5 years later, as
evidenced by decreased GFR or persistence of elevated uri-
nary concentrations of novel biomarkers (65,66). These stud-
ies are confounded by an ascertainment bias, in that the data
were available from patients who had kidney function
assessment as part of clinical care, and not in a prospective
systematic fashion. As a result, an AKI survivor clinic was
developed at two centers to follow AKI survivors prospec-
tively (67). This program also educated patients and their
caregivers regarding avoidance of nephrotoxic medications
and discussed their history of AKI during evaluation for
future surgical procedures.
Recovery from Critical Illness and AKI Secondary to
Coronavirus Disease 2019
Coronavirus disease 2019 (COVID-19)–associated AKI
came to the forefront of nephrology issues in 2020, and
numerous papers have outlined the pathophysiology,
course of illness, and recovery after AKI. One study from
New York documented a 50% in-hospital mortality among
1825 patients with AKI, and, of the survivors, 35% had per-
sistent acute kidney disease on discharge (68). Similar data
showing very low rates of recovery of kidney function after
COVID-19–associated AKI were reported from other cen-
ters (69,70). The lower rate of recovery of kidney function
after COVID-19 probably reflects the overall severity of
AKI and underlying comorbidities such as diabetes
mellitus, hypertension, and obesity, along with possible
direct kidney involvement from the severe acute respira-
tory syndrome coronavirus 2 virus itself (71). Long-term
prognoses such as progression to advanced CKD and kid-
ney failure among patients with COVID-19–associated AKI
remain guarded. A cohort study of 1612 patients with AKI
noted that GFR declined by 11.3 ml/min per 1.73 m2 faster
in patients with COVID-19–associated AKI as compared
with AKI from other causes, even after adjustment for
other baseline comorbidities and severity of AKI (72).
COVID-19 patients also require comprehensive care after
discharge as they experience significant physical and men-
tal health disturbances for several weeks after hospitaliza-
tion (H. Weerahandi et al., unpublished observations).
Summary
In summary, recovery from critical illness and AKI fol-
lows a prolonged and winding course and imposes a sig-
nificant toll on patients and caregivers. An interdisciplin-
ary, well-established, collaborative approach is needed to
improve the care and experiences of AKI patients after dis-
charge from the hospital. Our recommendations on appro-
priate follow-up of patients with AKI after discharge are
outlined in Table 1. Patients with AKI undergoing dialysis
at outpatient dialysis facilities should have closer and AKI-
specific monitoring to assess for and promote kidney func-
tion recovery. Prospective data collection on the
CJASN 16: 1601–1609, October, 2021
management of dialysis-dependent patients with AKI in
outpatient dialysis facilities will help us to understand and
outline the best practices required to care for this popula-
tion. The National Institutes of Health has placed emphasis
on research in this area, specifically to test interventions to
reduce posthospitalization complications and morbidity in
patients with stage 2 and 3 AKI (55). The request for pro-
posals for the Caring for Outpatients after Acute Kidney
Injury was recently announced (https://grants.nih.gov/
grants/guide/rfa-files/RFA-DK-20-012.html). Research foc-
using on better definition of recovery of kidney function,
precise predictors of outcomes, patient and caregiver per-
spectives, timely interventions, and optimal postdischarge
care will have a positive effect on the care of patients with
AKI.
Disclosures
E.M. Abdel-Rahman reports receiving research funding from
Covance and serving as a member of the Kidney Health Initiative.
A. Agarwal reports consultancy agreements with Akebia Thera-
peutics (serving on an expert panel to review new therapeutics on
the basis of the Hypoxia Inducible Factor pathway for AKI),
Dynamed (reviewing content related to AKI for Dynamed and
reviewing updated materials prepared by the Dynamed editorial
team for AKI topics), and Reata Pharmaceuticals; ownership inter-
est in Goldilocks Therapeutics, Inc.; receiving research funding
through the Genzyme/Sanofi Fabry Fellowship Award; receiving
honoraria from Akebia Therapeutics, Emory, University of South-
ern California, and Vanderbilt; serving on the editorial boards of
the American Journal of Physiology–Renal Physiology, Kidney Interna-
tional, and Lab Investigation; serving on the advisory board of
Goldilocks Therapeutics, a New York–based company investigat-
ing delivery of drugs in the kidney using nanotechnology for acute
and chronic kidney disease; serving on the external evaluation
panel for the Kidney Precision Medicine Program; and serving
on the Advisory Board of Angion and Alpha Young, LLC. Addi-
tionally, A. Agarwal’s spouse will be President-Elect for Women in
Nephrology (2018–2019). J. Cerda reports employment with Capi-
tal District Renal Physicians, Albany Medical College, St Peter’s
Health Partners; being a shareholder in Capital District Renal
Physicians; receiving research funding from University of Ala-
bama/University of California, San Diego O’Brien Research Center
on AKI–National Institutes of Health (NIH); and serving as
Co-Chair of the International Society of Nephrology AKI Commit-
tee of the 0by25 Initiative, Chair of the American Society of
Nephrology AKI!Now Initiative, Co-Chair of the Advisory Com-
mittee of the International Society of Nephrology, member of the
ASN Online AKI Community, and Associate Director of the Inter-
national Society of Nephrology 0by25 Initiative. S.L. Goldstein
reports consultancy agreements with Baxter Healthcare, Bioporto,
Inc., CHF Solutions, Fresenius, Kaneka, Inc., La Jolla Pharmaceuti-
cals, MediBeacon, Medtronic, Otsuka, Reata, and Renibus; owner-
ship interest in MediBeacon; receiving research funding from Bax-
ter Healthcare, Bioporto, and CHF Solutions; receiving honoraria
from Baxter Healthcare and Fresenius; patents and inventions with
Vigilanz; serving as a scientific advisor or member of MediBeacon;
and serving on the speakers bureau with Baxter Healthcare and
Fresenius. K.D. Liu reports consultancy agreements with Astute
and BOA Medical; holding stock in Amgen; receiving honoraria
from the American Society of Nephrology; and serving on the edi-
torial boards of the American Journal of Respiratory and Critical Care
Recovery after Acute Kidney Injury, Vijayan et al. 1607
Medicine, the American Journal of Kidney Diseases, and CJASN. M.D.
Okusa reports receiving a research grant from the NIH and
research funding from AM Pharma/Pfizer; receiving honoraria
from UpToDate; patents and inventions with the University of Vir-
ginia Patent Office; serving as a scientific advisor or member of
AM Pharma, Janssen, and Pfizer; and other interests/relationships
with the John Bower Foundation. A. Vijayan reports consultancy
agreements with Boehringer Ingelheim, NxStage, and Sanofi;
receiving research funding from Astellas and Spectral; receiving
honoraria from Astute and Sanofi; serving as a scientific advisor or
member of NxStage; and serving as a member of the National Kid-
ney Foundation.
Funding
None.
Acknowledgments
The authors would like to acknowledge the dedication and support
of the following American Society of Nephrology (ASN) staff mem-
bers who were crucial to the mission and success of the AKI!NOW
Initiative: Ms. Susan Stark, Acting Vice President, Excellence in
Patient Care; Ms. Bonnie Freshly, Project Specialist; Ms. Kerry Leigh,
Project Specialist; and Ms. Darlene Rodgers, Nurse Clinical Consul-
tant. ASN has received a Baxter Healthcare Corporation unrestricted
educational grant to support the AKI!Now ASN initiative.
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