Acute Kidney Injury
• AKI - an abrupt increase in serum creatinine of
at least 0.3 mg /dl or 1.5 over baseline over 48
hours (based on AKI Network Consensus 2007)
• stage 1 increase in creatinine 1.5-2 fold
• stage 2 increase in creatinine >2-3 fold
• stage 3 increase in creatinine >3 fold (or need
for dialysis or a peak Cr >4 mg/dl with at least a
0.5 mg/dl increase)
• Increased morbidity and mortality with
increasing stage
Syndromes of acute renal failure
Prerenal ARF
Intravascular volume depletion
Decreased effective blood volume (CHF,
hepatorenal, abdominal compartment
syndrome)
Altered intrarenal hemodynamics
preglomerular (afferent) vasoconstriction
postglomerular (efferent) vasodilation
Intrinsic ARF
Acute tubular necrosis
ischemic
nephrotoxic
sepsis
acute interstitial nephritis
acute glomerulonephritis
acute vascular syndromes
Postrenal ARF
AKI - incidence and risks
• Hospitalized patients – 5 to 7.5%
• ICU – 10 to 30%
• AKI – associated with increased cost or length
of hospital stay, risk of end-stage renal disease
• AKI -increased risk of death with AKI and sepsis,
trauma, cardiopulmonary bypass, burn injuries
(despite correction for comorbidities and severity
of illness) Crit Care Med 2010:261
• Hyperglycemia in hospital increases risk AKI
Creatinine interpretation
• Increased BUN/creatinine ratio – pre-renal, blood in gut,
obstruction, steroids, tetracycline
• Decreased BUN/creatinine ratio – rhabdomyolysis,
reduced protein intake
• False elevations in creatinine – ketones, trimethoprim,
cimetidine
• Rate of rise of creatinine – when daily creatinine
elevation starts to go down a clue that renal function
starting to improve
• eGFR – can not be calculated if Cr not stable
• Amputation - lower baseline creatinine
• Indicator AKI – relatively late; need renal “troponin”
Non -ICU
ICU
Diagnosis of prerenal azotemia
• Urine sediment (usually normal, without cellular
elements or abnormal casts, unless chronic
kidney disease is present)
• UNa< 15 meq/L (>20 in ATN)
• U/Pcreat> 20 (<15 in ATN)
• FeNa <1% (>1% in ATN)
• UNa/K <1/4
• BUN/creat >20
• Often remains a retrospective Dx made only
after response to a fluid challenge
Replacement fluids
• Ringers lactate - since contains K+ do not
give to oliguric patient
• ½ NS – avoid in hyponatremic patient
• 0.9 NS resuscitation fluid of choice, but
can worsen hyponatremia if SIADH
• Hydroxyethyl starch – increased incidence
of AKI (osmotic nephrosis)
• ½ NS + 1 amp NaHCO3 if very acidotic
Colloid vs crystalloid
• 7000 patients in medical and surgical ICUs in Saline vs
Albumin Fluid Evaluation (SAFE) - randomized, doubleblind trial comparing NS vs 4% human albumin. Results no difference in 28 day survival, days spent in the ICU,
days on mechanical ventilator.
• Hypoalbuminemic patients - small randomized trial in
which IV albumin improved sequential organ failure
assessment (SOFA) compared with NS.
• Spontaneous bacterial peritonitis - randomized trial
comparing antibiotics alone vs antibiotics plus IV albumin
(1.5 gm/kg immediately on diagnosis then 1 gm kg on
day 3). Results - decreased renal failure and improved
survival. Current standard of care in SBP.
Early Goal Directed Therapy
• Definition - in patients with septic shock early
intervention within the first 6 hours in the ED
• Goals - in first 6 hours MAP> 65 mmHg, CVP 8-12,
improvement in blood lactate, central venous 02
sat>70%, UO>0.5 ml/kg/hour
• ED patients transferred to ICU with SIRS & mean
creatinine 2.6 mg/dl: sBP<90 or lactate>4, central
venous 02 sat <50. Compared with control group the
EGDT group received more fluids, transfusions, and
dobutamine, but physiologic goals reached quicker;
hospital mortality reduced - 30% vs 45%
• Above protocol is the basis for Surviving Sepsis
Guidelines Clin J Am Soc Neph 2010:733
Fluid overload in AKI
• 618 critically ill patients - Clin J Am Soc Neph
2010:733
• Prospective, multicenter, observational study
• Examined the effect of fluid overload (>10%
increase in body weight).
• Those with fluid overload had more respiratory
failure, mechanical ventilation, and sepsis.
• Those with AKI and fluid overload had increased
mortality at 30 and 60 days and at hospital
discharge (corrected for severity of illness).
AKI fluid overload
• 7000 patients with acute lung injury
• Prospective randomized trial comparing conservative
and liberal fluid management for 7 days.
• The conservative group received more furosemide and
fewer fluid boluses, gained 7 kg less. No difference in
mortality but conservative group less days on vent, less
time in the ICU, and trend for lower need for dialysis.
• the CVP in the aggressive group was 12 at the start of
the study and remained 12 despite the 7 kg weight gain
whereas it went from 12 to 8 in the conservative group
Clin J Am Soc Neph 2010:733
AKI - use of dopamine or diuretics
• Low dose dopamine – does not reduce the
incidence of AKI, the need for RRT or improve
the outcome in AKI. Is associated with increased
myocardial 02 demand and increased incidence
of atrial fib
• Diuretics - can sometimes convert oliguric to
non oliguric but no data that shorten duration of
AKI, reduce need for RRT, or improve overall
outcomes. But can help control volume overload.
Abdominal compartment syndrome
• World Congress on ACS defined a normal intraabdominal pressure (IAP) to be between 5-7 mmHg in
critically ill patients, elevated to be >8 mmHg, and intraabdominal hypertension to be >12
• Abdominal compartment syndrome (ACS) – intraabdominal pressure>20 mmHg associated with organ
failure in one or more organs
• The renal insufficiency results from decreased renal
perfusion and correlates with the severity of the
increased intra-abdominal pressure and a decreased
abdominal perfusion pressure (Mean arterial pressure –
intra-abdominal pressure)
Measurement of intra-abdominal
pressure
• Clamp drainage tube of Foley catheter
• Instill 50 mL of sterile water into the
bladder via the aspiration port
• Measure pressure using a transducer
attached to an 18 gauge needle inserted
into the aspiration port (transducer should
be zeroed at the level of the pubic
symphysis)
Abdominal compartment syndrome
systemic effects
• Cardiac - decreased cardiac output,
increased CVP, PCWP, SVR
• Pulmonary – increased intra-thoracic and
airway pressures, decreased pa02,
increased paCO2
• GI – decreased splanchnic perfusion
• Renal - reduced renal perfusion, GFR and
urine output
ACS - causes and treatment
• Settings - trauma patient who requires massive
volume resuscitation; mechanical limitations of
the abdominal wall (tight surgical closures or
scarring after burn injuries); intra-abdominal
inflammation with fluid sequestration (eg.
bowel obstruction, pancreatitis, and peritonitis).
• Treatment - Abdominal decompression:
Paracentesis if massive ascites, surgical
decompression may be required
Cardio-renal syndrome
• As opposed to hepato-renal syndrome is not renal
dysfunction due to cardiac disease but includes vice
versa and also divides the responses into acute and
chronic.
• While creatinine is a better indicator of renal function the
BUN in CHF correlates better with mortality.
• The BUN also correlates much better with Na+ – high
BUN and low Na+ suggest pre renal state and
stimulation of the renin-angiotensin system and ADH.
• Many patients admitted with CHF are not very
edematous. Average weight loss in CHF hospitalization
is only several kgs with many patients not losing any
weight. So the notion of all CHF admissions being due to
fluid overload is simplistic. In many patients it seems to
be more related to preceding increase in systemic BP or
pulmonary hypertension
Acute decompensated HF (ADHF)
and intra-abdominal hypertension
•
•
•
•
•
•
40 consecutive patients admitted to CHF unit for ADHF
Age 59 +/- 6
LVEF 19 +/- 8
Baseline Cr 2 +/- 0.8
Baseline IAP 8 +/- 2 with 24 having high IAP
Elevated IAP associated with worsening renal function
during that admission p=0.0009
• Intensive medical Rx improved hemodynamics and renal
function in those with high IAP
• Strong correlation between reduction in IAP and
improved renal function seen in those with high IAP but
neither changes in IAP or renal function correlated with
hemodynamic changes
JACC 2008:300
ADHF response to reduction IAP
• 9 consecutive pts that were volume overloaded
with ADHF and elevated IAP refractory to
intensive medical therapy
• All had progressive elevation in serum creatinine
and worsening in IAP with IV loop diuretics
• Within 12 hours after paracentesis 5.3 L or UF 1.
8 L there was a significant reduction in IAP from
13 to 7 and improvement in Cr from 3.4 to 2.4
but no change in hemodynamics
J Card Failure 2008:508
ESCAPE
• Evaluation Study of CHF And Pulmonary artery
catheterization Effectiveness
• In 433 patients compared hemodynamic
monitoring with PAC vs CVP in ADHF
• Renal dysfunction (eGFR <60) either baseline or
worsening renal function (Cr increment >0.3)
both shown to be associated with adverse
outcomes during treatment of CHF.
• No correlation between baseline hemodynamics
or change in hemodynamics and worse renal
function - so poor forward flow does not account
for development of worse renal function
Rx of edema with ultrafiltration
• Aggressive diuresis causes aldosterone and
renin to increase in the CHF patient
• Renin and aldosterone may have negative
effects on cardiac and vascular function
counteracting the benefit of volume removal.
• Ultrafiltration can remove significant volume in
CHF and may not stimulate the renin
angiotensin system as much as diuretics
• High dose diuretics – in retrospective studies in
in acute Rx CHF associated with increased
mortality JAMA 2002:2547
Ultrafiltration
• Peripheral line - double lumen 6 or 7 French
• Blood pump and filter (CHF solutions device) with a
blood flow of 40-50 cc/min
• Medical floor not ICU
• Disposables - very expensive
• Systemic heparin
• Remove up to 4-8 kg per day.
• No change in concentration of BUN, creatinine, K+, etc
• UNLOAD - trial comparing UF vs IV diuretics in CHF: UF
removed more volume than furosemide, patients
discharged a little sooner and less likely to be readmitted
within 30 days (because their renin-angiotensin system
had not been activated?)
Diagnostic criteria for hepatorenal
syndrome
• Chronic or acute hepatic disease with advanced
hepatic failure and portal hypertension
• Creatinine > 1.5 mg/dL progressing over days/weeks.
• The absence of other apparent causes for the renal
disease - shock, bacterial infection, nephrotoxic drugs,
and the absence of US evidence of obstruction or
parenchymal renal disease.
• Urine RBCs < 50 cells/HPF and protein excretion less
than 500 mg/day.
• Lack of improvement in renal function after volume
expansion with IV albumin (1 g/kg body weight per
day up to 100 g/day) for at least 2 days, DC of
diuretics.
• Urine Na<10
Hepatorenal syndrome
• Type 1 - doubling of serum creatinine to a level greater
than 2.5 mg/dL or reduction of the creatinine clearance
by 50% or more to a value < 20 mL/min over a duration
of 2 weeks, usually in hospitalized patients, no inciting
agent.
• Type 2 - moderate and stable reduction in GFR,
insidious onset and slow progression of renal
insufficiency in the setting of refractory ascites, better
prognosis than type 1
• 5 randomized trials of splanchnic vasoconstricting
agents (terlipressin or noradrenaline) plus albumin all
demonstrated improved renal function and mortality
benefit in responders. Crit Care Med 2010:261
ATN causes
• Nephrotoxic
contrast
aminoglycosides
myoglobin, hemoglobin
• Ischemic
cardiopulmonary arrest
profound hypotension
unwitnessed arrhythmia
• Septic – often multifactorial
ATN - Recovery of renal function
• In contrast to the heart and brain, where
ischemic injury results in permanent cell loss,
the kidney is able to completely restore its
structure and function after acute ischemic or
toxic injury.
• The recovery from tubular necrosis involves
the dedifferentiation and proliferation of
remaining viable tubular epithelial cells
followed by reestablishment of cellular polarity,
normal histologic appearance, and physiologic
function.
Diagnosis of ATN
• Urine sediment (in patient with high pre-test
probability of ATN the presence of renal tubular
epithelial cells or granular casts is confirmatory
for ATN, but may be a relatively late sign) Clin J
Am Soc Neph 2008:1615
• UNa >20 in ATN
• U/Pcreat <15 in ATN
• FeNa >1% in ATN
• BUN/creat <20
Contrast media
• High-osmolal contrast media (osmolality
1500–1800 mOsm/kg) are first generation
agents.
• Low-osmolal contrast media still have an
increased osmolality compared with
plasma (600–850 mOsm/kg),
• The newest nonionic radiocontrast agents
have a lower osmolality, 290 mOsm/kg,
iso-osmolal to plasma
Risk factors for contrast-induced
nephropathy
• Patient related – pre-existing renal
insufficiency, diabetes mellitus,
intravascular volume depletion, reduced
cardiac output, common
nephrotoxins(especially NSAIDs)
• Procedure related – increased dose of
radio-contrast, multiple procedures within
72 hours, intra-arterial administration, type
of radio-contrast
Prevention of contrast nephropathy
NS at a rate of 1 mL/kg per hour, begun at
least 2 and preferably 6-12 hrs prior to the
procedure, and continuing for 6-12 hrs
after contrast administration.
Isotonic sodium bicarbonate may be as or
more effective (conflicting meta-analyses)
Acetylcysteine – 600-1200 mg po BID, the
day before and the day of the procedure,
based upon its potential for benefit and low
toxicity & cost. (conflicting meta-analyses)
Hemodialysis to prevent CIN
• Routine hemofiltration or hemodialysis for
the prevention of contrast nephropathy in
patients with stage 3 and 4 CKD is not
recommended.
• More data are needed in stage 5 CKD
(Prophylactic use of hemodialysis in
patients with stage 5 CKD, can be
considered, provided that a functioning
access is already available) AJKD
2006:361
Treatment of rhabdomyolysis
• NS – early hydration may prevent severe
AKI. Must monitor for fluid overload
• NaHCO3 – to raise urine pH >6.5;
eg. I amp 1 L 1/2 NS; monitor serum pH
• Mannitol – eg. 50 cc of 20% to each L of IV
fluid to increase UO; monitor osmolarity
• Initial rate of IV fluid about 500-1000
cc/hour; goal UO >300.
• All authorities agree with vigorous
hydration but no consensus on the rate of
Indications for RRT
• Refractory fluid overload
• Hyperkalemia – eg, K+ >6.5 meq/L, rapidly rising
levels, marked EKG changes espeically if patient
oliguric or can not take kayexalate
• Marked metabolic acidosis in which are limited in
giving NAaHCO3 due to volume constraints
• Signs of uremia, such as declining mental status,
not eating, uremic pericarditis (rare)
CRRT vs intermittent hemodialysis
• A number of meta-analyses have addressed this
question. Current data do not support the
superiority of either CRRT or IHD.
• In Europe and Australia use of CRRT much
higher than in US
• Many patients during the course of AKI receive
several modalities
• Peritonal dialysis can be done also but may be
difficult to give as much dialysis, no head to
head trials showing that it is less effective
Timing of initiation of RRT
• Initiation of dialysis prior to the
development of symptoms and signs of
renal failure due to AKI is recommended.
• It is unproven whether initiation of earlier
or prophylactic dialysis offers any clinical
or survival benefit.
• If do start RRT before symptoms is no
concensus on what level of BUN or
creatinine to start
AKI - obstructive uropathy
• To cause AKI need bilateral obstruction or
obstruction of sole kidney
• Always consider in the hospitalized patient
that the Cr elevation could be bladder
dysfunction from meds, reduced LOC,
bedridden patient.
• Post-void residual by bladder scan
• Renal US - a very sensitive test, false
negatives: retroperitoneal fibrosis, early
obstruction, severe volume depletion
AKI - interstitial causes
Suspect if WBC casts, marked pyuria, on a
med that commonly causes intersitial
nephritis, hypercalcemia
Acute interstitial nephritis - most commonly
due to drugs esp antibiotics, PPI
Pyelonephritis
Acute urate nephropathy
Tumor lysis syndrome
hypercalcemia
AKI - acute glomerulonephritis
• Suspect if patient has marked proteinuria,
RBC casts, marked hematuria
• If is AKI and GN indicates possible RPGN
• Relatively urgent need for a renal biopsy
since creatinine can go up daily and may
not be completely reversible
• If seriously suspect may start steroids
before the biopsy is back
AKI – vascular causes
• Renal emboli – suspect in patient with AF
other embolic phenomenona, high LDH
• Cholesterol emboli – suspect if recent
trauma or angio in elderly patient
• TTP/HUS
• Antiphospholipid syndrome
• Renal vein thrombosis – suspect if
nephrotic levels of proteinuria
Acute tubular necrosis
• Ischemic – prolonged pre-renal azotemia,
hypotension, hypovolemic shock, cardiac
arrest, cardiopulmonary bypass
• Nephrotoxic – drug-induced (radiocontrast
agents, aminoglycosides, amphotericin B,
cis-platinum, acetaminophen). Pigment
nephropathy (hemoglobin, myoglobin)
• Sepsis
AKI causes
PRE RENAL - volume depletion, CHF, hepatorenal syndrome,
abdominal compartment syndrome, drugs (ACEI, NSAIDs)
POST RENAL
RENAL
acute tubular necrosis (ATN)
nephrotoxic (eg, contrast, aminoglycosides, rhabdomyolysis),
ischemic
sepsis
Interstitial - pyelonephritis, acute interstitial nephritis, myeloma,
hypercalcemia, hyperuricemia, tumor lysis syndrome, intratubular
obstuction - uric acid, myeloma
Glomerular - primary GN vs. secondary to a systemic disease
Vascular - renal emboli, cholesterol emboli, vasculitis,
anti-phospholipid syndrome, renal vein thrombosis
Prediction of AKI after renal insult
• Coronary intervention - risk factors: hypotension, IABP,
CHF, age>75, anemia, diabetes, contrast volume, and
serum creatinine. If patient has a very low score
likelihood of CIN -7.5% versus 57%
• Open heart surgery – risk factors: female, CHF, LVEF,
preop IABP, COPD, IDDM, prior surgery, emergency
surgery, prior creatinine elevation, valve surgery.
Variation in need for dialysis 0.4-21 %
• AKI after non cardiac surgery – risk factors: age>59,
BMI>32, emergency surgery, high risk surgery, PVD,
liver disease, COPD. Variation in risk of AKI 0.3 – 4.3
Prerenal
Prolonged
hypoperfusion
ATN
Acute kidney injury
• PRERENAL - volume depletion, CHF, hepatorenal syndrome,
abdominal compartment syndrome, drugs (ACEI, NSAIDs)
• POST RENAL
• RENAL
acute tubular necrosis (ATN)
nephrotoxic (especially contrast, aminoglycosides, rhabdomyolysis),
ischemic
sepsis
• interstitial - pyelonephritis, acute interstitial nephritis, myeloma,
hypercalcemia, hyperuricemia, tumor lysis syndrome, intratubular
obstuction - uric acid, myeloma
• glomerular - primary GN vs. secondary to a systemic disease
• vascular - renal emboli, cholesterol emboli, vasculitis,
anti-phospholipid syndrome, renal vein thrombosis
Treatment of hepato-renal
syndrome
• Management of underlying cause
• Stop diuretics
• Low salt diet and free water restriction if
hyponatremia
• Midodrine + Octreotide + Albumin
• Terlipressin + Albumin
• RRT
• TIPS
Shortcomings
• The assignement of corresponding changes in serum
creat and changes in urine output to the same strata is
not based on evidence. The criteria that results in the
least favorable rifle strata to be used.
• The patient would progress from "risk" on day one to
"injury" on day two and "failure" on day three, even
though the actual GFR has been <10 mL/min over the
entire period.
• It is impossible to calculate the change in serum
creatinine in patients who present with ARF but without a
baseline measurement of the serum creat. The authors
of the RIFLE criteria suggest back-calculating an
estimated baseline creat using the four-variable MDRD
equation, assuming a baseline GFR of 75 mL/min per
Nephrotoxic ATN
Exogenous
• RCN
• Aminoglycosides
• Others meds
Endogenous
• Heme pigment (rhabdo, or massive
intavascular hemolysis)
Pre renal disease
• Predisposing factors:
• Advanced cardiac failure with low mean arterial
pressure
• Volume depletion due to diuretic therapy
• The presence of renal vascular disease
• The concomitant use agents with
vasoconstrictor effects (NSAIDs,
cyclooxygenase-2 inhibitors, cyclosporine, and
tacrolimus)
• CKD: The risk of ARF is higher in patients with
chronic kidney disease of any cause than in
patients with normal renal function
Ischemic ATN
Medical
Surgical
Cardiogenic shock
Cardiac
Sepsis
Vascular
Burns
Severe volume
depletion
Type I HRS
• Doubling of the serum creatinine concentration
to a level of >2.5 mg/dl, or a reduction of the
creatinine clearance by 50% or more to a value
of <20 ml/min, over a duration of <2 wk
• Develops in hospitalized patients
• In 2/3 an inciting events is identified
Type II HRS
• Moderate and stable reduction in GFR
• Insidious onset and slow progression of renal
insufficiency in the setting of refractory ascites
• Better prognosis
Short-term Outcomes
• The outcome of ATN is highly dependent
on the severity of comorbid conditions.
• Uncomplicated ATN is associated with
mortality rates of 7 to 23%
• Mortality of ATN in postoperative or
critically ill patients with multisystem organ
failure is high as 50 to 80%.
• Mortality rates increases with the number
of failed organ systems
Testing in acute renal failure to try
to narrow down cause
•
•
•
•
•
•
•
•
•
•
•
Urinalysis – RBC or WBC casts
Urine Na+ or fractional Na+ excretion
Urine eosinophils
Urine protein/creatinine ratio
BUN/creatinine ratio
Serum LDH, uric acid, anion gap, BNP,CPK
Bladder scanner
Foley change or irrigate
Renal US
Abdominal CT
Renal Scan
RR= 2.4
RR= 4.15
RR=6.37
Intravascular volume
depletion
Altered intrarenal
hemodynamics
Etiologies of
Prerenal ARF
Decreased effective
arterial blood volume
Abdominal compartment
syndrome
hepatorenal syndrome
• type 1 - doubling of serum creatinine to a
level > 2.5 mg/dl or a reduction in
creatinine clearance by 50% or more or to
a value < 20 % over 2 weeks
• tye 2 - moderate and stable reduction in
ranal function