Acute Kidney Injury Review 2017
Acute Kidney Injury Review 2017
Acute Kidney Injury Review 2017
In the Clinic®
姝 2017 American College of Physicians ITC66 In the Clinic Annals of Internal Medicine 7 November 2017
7 November 2017 Annals of Internal Medicine In the Clinic ITC67 姝 2017 American College of Physicians
Diagnosis
What criteria should clinicians tion based on severity (stages)
use to define and classify AKI? and cause (Figure 2). KDIGO
AKI is a heterogeneous group of definition and staging are
conditions, with a common defi- based on the Risk, Injury, Fail-
nition (Figure 1) and classifica- ure, Loss, End-Stage Renal Dis-
ease (RIFLE) and AKI Network
(AKIN) criteria and studies on
Figure 1. Relationships and definitions of kidney diseases and disorders. risk relationships. The rationale
for defining AKI separately from
other acute kidney diseases and
disorders was to provide a
more rigorous basis for re-
search studies, clinical practice
guidelines, and public health
efforts.
AKD AKI CKD
The KDIGO definition of AKI in-
cludes a change in SCC within
2–7 days and oliguria for 6 or
more hours. The stage is defined
by the peak rise in SCC com-
pared with previous values and
nadir in urine output and is re-
Variable AKI AKD CKD NKD*
Duration Within 7 d ≤3 mo >3 mo lated to risk for complications
Functional Increase in serum AKI GFR <60 GFR ≥60 and prognosis (Figure 2). eGFR
criteria creatinine clearance OR mL/min/1.73 m2 mL/min/1.73 m2 is preferred to SCC for assessing
by ≥50% within 7 d GFR <60
OR mL/min/1.73 m2
GFR in the steady state (i.e.,
Increase in serum OR when GFR is stable) because the
creatinine clearance Decrease in GFR by
by ≥0.3 mg/dL ≥35% times baseline
coefficients for age, sex, and race
within 2 d OR in the estimating equation take
OR Increase in serum into account variation in creati-
Oliguria for ≥6 h creatinine clearance by
≥50% times baseline nine generation by muscle, inde-
Structural Not defined Marker of kidney Marker of kidney No marker of pendent of GFR (12). A 1.5-, 2.0-,
criteria damage damage for >3 mo kidney damage and 3.0-fold increase in SCC dur-
(albuminuria, (albuminuria is most
hematuria, or pyuria common)
ing steady-state conditions re-
is most common) flect a 39%, 57%, and 74% de-
crease in eGFR, respectively.
AKI = acute kidney injury; AKD = acute kidney diseases and disorders; CKD = chronic kidney However, during AKI, SCC may
disease; GFR = glomerular filtration rate; NKD = no kidney disease. be in the nonsteady state, so
* Implies no functional or structural criteria according to the definitions for AKI, AKD, or CKD.
Clinical judgment required for individual patient decision making. changes in SCC and eGFR lag
姝 2017 American College of Physicians ITC68 In the Clinic Annals of Internal Medicine 7 November 2017
At Risk Complications
Older age, comorbid conditions, CKD (decreased GFR, albuminuria) Volume overload
Electrolyte disorders
Stage 1 (hyperkalemia, metabolic acidosis,
Serum creatinine: 1.5–1.9 times baseline, or ≥0.3 mg/dL increase, or hyponatremia and hypernatremia,
KDIGO Staging and
hyperphosphatemia, hypermagnesemia)
Stage 2
Uremic complications
Serum creatinine: 2.0–2.9 times baseline, or urine output: <0.5 mL/kg/h for ≥12 h
(encephalopathy, pericarditis, pruritus, bleeding)
Stage 3 Drug toxicity
Initiation or renal replacement therapy, or serum creatinine: 3.0 times baseline, or
≥4.0 mg/dL, or urine output: <0.3 mL/kg/h for ≥24 h, or anuria for ≥12 h
sepsis; increased intra- Clinical Setting pyelonephritis; thrombotic Circulatory shock; sepsis;
abdominal pressure; renal Urinary tract symptoms; microangiopathy; cast neph- drug exposure; transient
artery stenosis; NSAID history of urolithiasis, ropathy; infarction; hypotension; hemolysis;
toxicity genitourinary tract neoplasia, atheroembolism rhabdomyolysis; tumor lysis
or retroperitoneal disease
Clinical Setting Clinical Setting Urinary Tract Findings
Signs of volume depletion Urinary Tract Findings Systemic diseases; Urine not concentrated
or overload; SIRS; severe Hydronephrosis; relief with microangiopathic hemolysis urine; RTE cells; granular
hypertension urinary catheter casts
Urinary Tract Findings
Urinary Tract Findings Hematuria with RBC casts;
Concentrated urine; no pyuria with WBC casts; RTE
RTE cells or casts cells
ATN = acute tubular necrosis; CKD = chronic kidney disease; GFR = glomerular filtration rate; NSAID = nonsteroidal anti-inflammatory drug;
RBC = red blood cell; RTE = renal tubular epithelial; SIRS = systemic inflammatory response syndrome; WBC = white blood cell.
7 November 2017 Annals of Internal Medicine In the Clinic ITC69 姝 2017 American College of Physicians
姝 2017 American College of Physicians ITC70 In the Clinic Annals of Internal Medicine 7 November 2017
7 November 2017 Annals of Internal Medicine In the Clinic ITC71 姝 2017 American College of Physicians
姝 2017 American College of Physicians ITC72 In the Clinic Annals of Internal Medicine 7 November 2017
absence of hematuria, pyuria, tal protein are preferred for eval- tions in critically ill pa-
tients: association with
uation of kidney disease in adults mortality rates and RRT.
renal tubular epithelial cells, and Clin J Am Soc Nephrol.
(12), but both may be helpful in
granular and cellular casts (Ap- 2015;10:21-8. [PMID:
the evaluation of AKI. Loss of al- 25376761]
pendix Table 1, available at 30. Miller TR, Anderson RJ,
bumin in the urine is a marker of Linas SL, et al. Urinary
Annals.org). If obstruction is sus-
glomerular damage and occurs diagnostic indices in
pected, ultrasonography of the acute renal failure: a
in most parenchymal kidney dis- prospective study. Ann
kidneys is warranted, with a Intern Med. 1978;89:47-
eases other than ATN. Total pro-
postvoiding image of the blad- 50. [PMID: 666184]
teinuria in the absence of albu- 31. Muriithi AK, Nasr SH,
der if symptoms occur during Leung N. Utility of urine
minuria is a marker of increased eosinophils in the diag-
urination (Appendix Table 1) nosis of acute interstitial
production or impaired tubular
(28). We generally obtain a urine nephritis. Clin J Am Soc
reabsorption of low-molecular- Nephrol. 2013;8:1857-
culture, since urinary tract infec- 62. [PMID: 24052222]
weight serum proteins (light- 32. Wald R, Bell CM, Nisen-
tion can be a cause of AKI (pye-
chain proteinuria or tubular pro- baum R, et al. Interob-
lonephritis or ATN associated server reliability of urine
teinuria, respectively). The urine sediment interpretation.
with sepsis) or may complicate Clin J Am Soc Nephrol.
dipstick is more sensitive to albu-
other causes. Additional tests min than other serum proteins;
2009;4:567-71. [PMID:
19261816]
are required to assess complica- the albumin-to-creatinine ratio 33. Perazella MA, Coca SG,
Kanbay M, Brewster UC,
tions, systemic diseases or dis- and protein-to-creatinine ratio Parikh CR. Diagnostic
eases in other organ systems, provide a quantitative assess-
value of urine micros-
copy for differential diag-
and hemodynamic status in criti- ment, but urine creatinine excre- nosis of acute kidney
injury in hospitalized
cally ill patients. tion decreases when SCC in- patients. Clin J Am Soc
Nephrol. 2008;3:1615-9.
Tests of urine concentration were creases, which may cause a [PMID: 18784207]
initially proposed for the evalua- falsely elevated albumin-to- 34. Chawla LS, Bellomo R,
Bihorac A, et al; Acute
tion of oliguric AKI to distinguish creatinine or protein-to- Disease Quality Initiative
creatinine ratio. Workgroup 16. Acute
decreased kidney perfusion from kidney disease and renal
recovery: consensus
ATN (14, 30). They are also useful Red blood cells and white blood report of the Acute Dis-
in nonoliguric AKI due to these cells may be detected in unspun
ease Quality Initiative
(ADQI) 16 Workgroup.
and other causes. The glomerular urine with a dipstick (heme or Nat Rev Nephrol. 2017;
13:241-257. [PMID:
filtrate is isotonic with plasma; con- leukocyte esterase reagent pads, 28239173]
centration of the urine requires in- respectively) and quantified with 35. Bellomo R, Vaara ST,
Kellum JA. How to im-
tact tubular function. Concentration a manual or automated cell coun- prove the care of patients
of the urine in the setting of AKI indi- with acute kidney injury
ter. We do not recommend rou- [Editorial]. Intensive Care
cates decreased kidney perfusion tine testing for urine eosinophils Med. 2017;43:727-729.
[PMID: 28600756]
and preserved tubular function. Ab- (31). Detection of renal tubular 36. Davenport A, Anker SD,
sence of urine concentration indi- epithelial cells and granular and Mebazaa A, et al; Acute
Dialysis Quality Initiative
cates impaired tubular function. The cellular casts requires micro- (ADQI) consensus group.
ADQI 7: the clinical man-
fractional excretion of sodium and scopic examination of urine sedi- agement of the Cardio-
urea (FENa and FEurea) can be ment. Increased red or white Renal syndromes: work
group statements from
computed easily from simultaneous blood cells in the urine indicates the 7th ADQI consensus
serum and spot urine samples (Ap- conference. Nephrol Dial
a urinary tract lesion, but the Transplant. 2010;25:
pendix Table 1). Diuretic therapy presence of renal tubular epithe- 2077-89. [PMID:
20494894]
impairs sodium reabsorption more lial cells or granular or cellular 37. Facciorusso A, Chandar
than urea reabsorption, so a low casts in the sediment localizes AK, Murad MH, et al.
Comparative efficacy of
FEurea may be a more reliable test the lesion to the kidney. The di- pharmacological strate-
gies for management of
for distinguishing decreased kidney agnostic accuracy of these find- type 1 hepatorenal syn-
perfusion from ATN than a low ings has not been well-studied drome: a systematic
review and network
FENa in patients with recent diuretic (32, 33). Our interpretation is that meta-analysis. Lancet
therapy. Exacerbations of heart, the presence of renal tubular epi- Gastroenterol Hepatol.
2017;2:94-102. [PMID:
lung, or liver disease may be associ- thelial cells and granular and cel- 28403995]
7 November 2017 Annals of Internal Medicine In the Clinic ITC73 姝 2017 American College of Physicians
姝 2017 American College of Physicians ITC74 In the Clinic Annals of Internal Medicine 7 November 2017
tion is started that inhibits creati- consulting a specialist? gators. Effect of a buff-
ered crystalloid solution
nine secretion (trimethoprim or Consultation with a nephrologist vs saline on acute kidney
injury among patients in
cimetidine) or interferes with the is often unnecessary for detect- the intensive care unit:
assay for creatinine (flucytosine ing AKI. However, it should usu- The SPLIT randomized
clinical trial. JAMA.
for the creatinine iminohydrolase ally be requested for identifying 2015;314:1701-10.
[PMID: 26444692]
assay). Serum ketones interfere with the cause of AKI resulting from 48. Hewitt J, Uniacke M,
the widely used colorimetric assay something other than volume Hansi NK, Venkat-Raman
G, McCarthy K. Sodium
for creatinine. GFR, measured using depletion that resolves promptly bicarbonate supplements
for treating acute kidney
clearance of an exogenous filtration with volume repletion (Figure 2). injury. Cochrane Data-
marker, or creatinine clearance, can Consultation may also be helpful base Syst Rev. 2012:
CD009204. [PMID:
be assessed to identify misleading for identifying the cause of 22696382]
alterations in SCC or eGFR. If GFR is CKD. 49. Bellomo R, Cass A, Cole
L, et al; RENAL Study
Investigators. Calorie
intake and patient out-
comes in severe acute
Diagnosis... Decreased GFR may be due to AKI, AKD, or CKD. KDIGO kidney injury: findings
guidelines define AKI as an increase in SCC by ≥50% within 7 days or from The Randomized
Evaluation of Normal vs.
≥0.3 mg/dL (26.5 μmol/L) within 2 days, or oliguria for ≥6 hours. The Augmented Level of
stage (severity) is defined by the peak increase in SCC compared with Replacement Therapy
(RENAL) study trial. Crit
previous values and the nadir in urine output, and is related to the risk Care. 2014;18:R45.
for complications and the prognosis. The causes of AKI— decreased kid- [PMID: 24629036]
ney perfusion, obstruction of the urinary tract, parenchymal kidney dis- 50. Bellomo R, Cass A, Cole
L, et al; RENAL Study
eases other than ATN, and ATN—are grouped according to underlying Investigators. Daily pro-
pathophysiology and are the basis for specific therapy. The clinical set- tein intake and patient
outcomes in severe acute
ting, including response to IV fluid, and urinary tract findings are helpful kidney injury: findings of
in determining the cause of AKI. the randomized evalua-
tion of normal versus
augmented level of
replacement therapy
CLINICAL BOTTOM LINE (RENAL) trial. Blood Purif.
2014;37:325-34. [PMID:
25171270]
51. Cox ZL, McCoy AB, Ma-
theny ME, et al. Adverse
drug events during AKI
7 November 2017 Annals of Internal Medicine In the Clinic ITC75 姝 2017 American College of Physicians
姝 2017 American College of Physicians ITC76 In the Clinic Annals of Internal Medicine 7 November 2017
measures to remove potassium route (49). Minimal nitrogenous kidney function after
acute kidney injury in
from the body. For patients with- waste production is desirable in the elderly: a systematic
review and meta-
out oliguria, high-dose loop di- AKI; however, protein restriction analysis. Am J Kidney
uretics can be used to increase is not suggested as a means to Dis. 2008;52:262-71.
[PMID: 18511164]
urine output and potassium ex- avoid KRT. On the basis of low- 67. Heung M, Steffick DE,
cretion. For patients with oliguria, quality evidence, KDIGO guide- Zivin K, et al; Centers for
Disease Control and
sorbitol with sodium polystyrene lines recommend protein goals Prevention CKD Surveil-
lance Team. Acute kidney
sulfonate or calcium polystyrene of 0.8 –1.0 g/kg per day in non- injury recovery pattern
sulfonate resins can be used to catabolic patients, 1.1–1.5 g/kg and subsequent risk of
CKD: an analysis of Vet-
per day in patients receiving re- erans Health Administra-
induce osmotic diarrhea and fe-
nal replacement therapy, and a tion data. Am J Kidney
cal potassium losses. Most ex- Dis. 2016;67:742-52.
maximum 1.7 g/kg per day in [PMID: 26690912]
perts suggest using supplemen- 68. Wu VC, Wu CH, Huang
hypercatabolic patients or those
tal sodium bicarbonate when TM, et al; NSARF Group.
requiring continuous KRT (1, 50). Long-term risk of coro-
metabolic acidosis is severe, al- nary events after AKI. J
In critically ill patients, KDIGO Am Soc Nephrol. 2014;
though there is no high-quality
guidelines suggest insulin ther- 25:595-605. [PMID:
evidence (48). Hypernatremia 24503241]
apy targeting plasma glucose 69. Ftouh S, Thomas M;
may be encountered in AKI with Acute Kidney Injury
110 –149 mg/dL. Guideline Development
dehydration, after normal saline Group. Acute kidney
resuscitation, or when access to Patients with AKI require special injury: summary of NICE
guidance. BMJ. 2013;
water is restricted. It can usually drug dosing due to buildup from 347:f4930. [PMID:
be corrected by providing water decreased excretion and metab- 23985310]
70. Soares DM, Pessanha JF,
via enteral routes or IV hypnatric olism by the kidney as well as the Sharma A, Brocca A,
Ronco C. Delayed ne-
solutions. The management of effects of kidney failure on other phrology consultation
hyponatremia in the setting of routes of drug excretion and me- and high mortality on
acute kidney injury: a
AKI depends on its cause. In tabolism (51, 52). Estimated GFR meta-analysis. Blood
states of volume depletion, admin- is less accurate to guide dosing Purif. 2017;43:57-67.
[PMID: 27915348] doi:
istration of isotonic IV fluids is gen- in the nonsteady state than in the 10.1159/000452316
7 November 2017 Annals of Internal Medicine ITC77 姝 2017 American College of Physicians
姝 2017 American College of Physicians ITC78 Annals of Internal Medicine 7 November 2017
IntheClinic
www.kdigo.org/clinical_practice_guidelines/pdf
Tool Kit
/KDIGO%20AKI%20Guideline.pdf
Guidelines published by the International Society of
Nephrology.
www.clinicalguidelines.gov.au/portal/2481/clinical
-practice-guideline-acute-kidney-injury
2014 guideline from the National Health and Medical
Research Council of Australia.
Acute Kidney www.nice.org.uk/guidance/cg169
Injury Guidance from the National Institute for Health and Care
Excellence.
Patient Information
www.kidney.org/atoz/content/AcuteKidneyInjury
Information presented by the National Kidney foundation
for both patients and caregivers.
www.thinkkidneys.nhs.uk/aki/wp-content/uploads
/sites/2/2015/11/BKPA-RCGP-A4-Printout-Leaflet_v4
.pdf
Printable leaflet of the British Kidney Patient Association.
www.ncbi.nlm.nih.gov/pubmedhealth/PMH0071507/
Information for patients and caregivers from PubMed
Health.
www.nhs.uk/conditions/acute-kidney-injury/Pages
/Introduction.aspx
Information from the National Health Service.
7 November 2017 Annals of Internal Medicine ITC79 姝 2017 American College of Physicians
Patient Information
• Have chronic kidney disease back to normal. You may also take medicines
• Have chronic heart, lung, or liver disease to help balance your fluid levels.
• Have diabetes • In more serious cases, you may need dialysis
• Have cancer while your kidneys recover. Dialysis filters the
• Are anemic waste in your body, just as healthy kidneys do.
What Are the Symptoms? Questions for My Doctor
AKI usually has no symptoms until your kidneys • What caused my AKI?
start to fail. Kidney failure means that your kid- • Will I need dialysis?
neys can no longer properly remove waste from • Will I have permanent damage?
your body. These symptoms may occur if you • If I recover, what are the chances I'll get it
have kidney failure: again in the future?
• Feeling sleepy • Should I eat a special diet?
• Feeling sick to your stomach • Should I avoid any medications?
RBC = red blood cell; HPF = high-power field; WBC = white blood cell.
* Urine concentration assessed from urine specific gravity (concentrated > 1.020); osmolality (concentrated >500 mosm/kg);
fractional excretion of sodium (FENa) (concentrated <1%); fractional excretion of urea (FEurea) (concentrated <35%); ratio of SUN
to serum creatinine clearance (Scr) >20:1. FENa is calculated from UNa x Scr/SNa x Ucr. FEurea is calculated from UUN x Scr/SUN
x Ucr.
† Albumin and total protein assessed from dipstick (more sensitive to albumin than other proteins); albumin-to-creatinine ratio
(ACR), moderately increased 30 –300 mg/g, severely increased >300 mg/g (nephrotic range >2200 mg/g); and total protein-to-
creatinine ratio (PCR), moderately increased 150 –500 mg/g, severely increased >500 mg/g (nephrotic range >3500 mg/g).
Ranges for ACR and PCR are defined for steady-state conditions; values may be higher in acute kidney injury because urine
creatinine excretion decreases with increased Scr.
‡ Normal urine contains <5 RBC/HPF and <5 WBC/HPF.
§ Renal ultrasonography is the preferred method for evaluating hydronephrosis. Hydronephrosis may be absent in cases of
massive bleeding into the urinary tract or extensive retroperitoneal fibrosis.
ACE = angiotensin-converting enzyme; AKI = acute kidney injury; ARB = angiotensin-receptor blocker; eGFR = estimated glo-
merular filration rate; GBM = glomerular basement membrane; GFR = glomerular filration rate; Scr = serum creatinine.
Appendix Table 3. Kidney Replacement Therapies for Hemodialysis and Hemofiltration in Acute Kidney Injury
Example Solute Removal Blood Flow Rate Duration Recommended Dose
Continuous kidney
replacement
therapies
Continuous Convective 150–250 mL/min Daily for 24 h/d (minus To deliver an effluent volume
venovenous interruptions) (replacement for fluid
hemofiltration removed by ultrafiltration)
of 20–25 mL/kg per h
Continuous Diffusive
venovenous
hemodialysis
Continuous Diffusive and
venovenous convective
hemodiafiltration
Intermittent kidney
replacement
therapies
Intermittent Diffusive 200–350 mL/min Typically 3–4 times/wk, To deliver a weekly Kt/V (a
hemodialysis 4 h/session measure of urea clearance)
of 3.9
Prolonged intermittent
kidney replacement
therapies
Sustained low Diffusive 100–300 mL/min Typically daily for ≥6 h To deliver a weekly Kt/V (a
efficiency dialysis measure of urea clearance)
of 3.9
Sustained low Diffusive and
efficiency convective
diafiltration
Sustained continuous Convective
ultrafiltration
70
60 49.4
47.8
Pooled AKI-Associated
50
Mortality Rate
40
28.5
30 23.0
15.9
20
10
Studies, n 110 26 25 25 31
Patients With AKI, n 429 535 8226 42 354 42 354 6534
Error bars represent 95% CIs. AKI = acute kidney injury; KDIGO = Kidney Disease Improving Global Outcomes.