Transcript AKI_Resident

Acute Kidney Injury
No Good. Just Bad and Ugly.
CM Yuan (with bits by KC Abbott)
3/2010
The Overall Approach To AKI
•
•
Determine if the patient actually has acute
kidney injury, i.e., establish sudden loss of
function.
Determine etiology:
–
–
–
•
Post-renal
Pre-renal
Intra-renal
Determine treatment and need for renal
replacement therapy
What is AKI?
“…Precipitous impairment of kidney function
without regard to etiology or mechanism.”
Rudnick, et al, Acute Renal Failure, 1988.
Therefore, acute kidney injury (or acute renal
failure) is a syndrome in which renal function is
declining rapidly (ie: not in a steady state), and
which can be the common manifestation of a wide
variety of local or systemic mechanisms/diseases.
Difficult to precisely define AKI “numerically”. Older
literature didn’t clearly define AKI, and different
studies used different definitions. Clinically it was a
“I know it when I see it.” kind of diagnosis.
Clinical Features of AKI
• Accompanied by urea retention (azotemia), failure
to clear other waste products, and dysregulation of
extracellular volume and electrolytes.
• Usually marked by a rise in serum creatinine
concentration or azotemia.
– In early stages the sCr may be low even though the
GFR is markedly reduced.
• Don’t believe the reported eGFR derived from serum
creatinine in a setting of AKI! The patient is NOT in
a steady state, so the assumptions behind the eGFR
calculation do not apply.
– e.g., sCr rised from 0.8 to 1.3 to 2.3 mg/dL. eGFR reported
as 40 ml/min/1.73m2, but rate of rise suggests GFR truly
<10-15!
Rises in serum creatinine and BUN don’t
necessarily mean AKI is present!
• Serum creatinine is determined by both input (muscle mass and
breakdown) and output (GFR and proximal tubular secretion).
– sCr may increase without a GFR decline when medications (eg,
cimetidine, trimethoprim) that inhibit the tubular Cr secretion are given.
– sCr may also increase when there is muscle injury, as in rhabdomyolysis,
over and above any decline in GFR.
• ACE/ARBs can increase sCr due to glomerular hemodynamic
effects, reducing GFR in the short term, but stabilizing it over
the long term. They are often d/c’d in AKI or before high-risk
procedures (surgery, contrast).
• A rise in the BUN level can occur without renal injury, such as
in GI or mucosal bleeding, steroid use, or protein loading.
So the Creatinine is elevated…
AKI vs. CKD
• Is it Acute?
– This is the first step in assessing the “acute”
loss of renal function!
• Findings that suggest acute presentation
of CKD or AKI complicating CKD:
– Documented chronic increase in serum
creatinine
– Small kidneys on renal imaging
– Findings c/w osteitis fibrosa cystica on x-ray
– Relatively asymptomatic at very high levels of
BUN and creatinine
RIFLE Criteria:
An attempt to standardize the diagnosis of
AKI for research purposes
• Risk: > 150-200% increase in s.creatinine; UO < 0.5
ml/kg/hr for > 6 hrs.
• Injury: > 200-300% increase in s. creatinine; UO < 0.5
ml/kg/hr for > 12 hrs.
• Failure: > 300% increase in s. creatinine or serum
creatinine ≥ 4 mg%; UO < 0.3 ml/kg/hr for ≥ 24 hrs or
anuria ≥ 12 hrs.
• Loss: Complete loss of renal function lasting > 4 weeks
(need for RRT)
• ESRD: End-stage renal disease > 3 mo
ADQI Workgroup; Critical Care. 2004
RIFLE: Validation
• RIFLE was an attempt to standardize the
definition of AKI, but it was originally conceived
by committee, and NOT based on evidence.
• Multiple studies have validated the RIFLE criteria
as predictive of increasing mortality with
increasing RIFLE class (Ricci, et al. KI. 2008. 73:
538.).
– Compared to non-AKI, there is a stepwise increase in
RR for death from Risk (RR=2.40) to Injury (RR=4.15)
to Failure (RR=6.37); p<0.0001 for all.
AKIN
Modifications to the RIFLE
• The Acute Kidney Injury Network (AKIN) modified the
RIFLE to include less severe AKI, and recommended
volume correction and work-up for obstruction.
• This is the group that recommended Acute Kidney Injury
(AKI) replace the term ARF.
• One problem with AKIN and RIFLE is that the underlying
assumption is that AKI is ATN. Some AKI is NOT ATN,
and a diagnostic work-up always should be done.
• Renal Failure (RIFLE) or Stage 3 (AKIN) is not an
indication for dialysis. It is a definition, NOT a decision
threshold!
• RIFLE and AKIN are epidemiologic and research tools (to
define inclusion and endpoint criteria for clinical studies).
Their clinical utility (except for prognosis, perhaps) is not
clear.
AKIN Criteria
Modification to RIFLE (Mehta, et al. Crit Care. 2007)
• Stage 1: Abrupt (within 48 hrs) increase in serum creatinine ≥
0.3 mg/dL or increase to ≥ 150 to 200% from baseline or UO <
0.5 ml/kg/hr > 6 hrs.
• Stage 2: Increase in serum creatinine to > 200 to 300% from
baseline or UO < 0.5 ml/kg/hr > 12 hrs.
• Stage 3: RRT or increase in serum creatinine > 300% from
baseline (or serum creatinine ≥ 4.0 mg/dL with an acute increase
of at least 0.5 mg/dL or UO < 0.3 ml/kg/hr for 24 hrs or anuria
for 12 hours.
Should only be used after volume status is optimized, and
obstruction should be ruled-out if oliguria/anuria is the only
diagnostic criteria. (Editorial comment: We’re only supposed to
look for obstruction if there is oliguria alone? Lots of urinary
obstruction presents with increased serum creatinine alone and
polyuria!)
AKI: Acute Tubular Necrosis
• ATN (acute tubular necrosis) first described by Bywaters
and Beal (BMJ, 1941) in patients who sustained crush
injury during the London Blitz. Death was due to
hypotension and hyperkalemia (the sine wave EKGs were
included in the paper!). Autopsy showed necrosis of the
renal tubular epithelial cells.
• Most AKI in the ICU-setting is due to ATN (acute tubular
necrosis).
– Most patients with ATN will recover renal function
spontaneously, IF they survive the period of renal
failure, usually 7-21 days (unreferenced nephrology
lore).
– This is usually heralded by an increase in UO, which
was well-described in the days before RRT was
available.
AKI: The course of ATN
• Teschan (Ann Intern Med, 1960) describes the course of
ATN:
– Defined as acute decline in UO ≤ 400 ml/24 hr with
compensated volume status, and no obstruction of renal
vasculature or lower urinary tract.
– Oliguric phase: Continues until UO ≥ 1000 ml/24 hr
(called “the day of diuresis).
– Early diuretic phase: Begins on day of diuresis, and
continues until BUN reaches peak.
– Late diuretic phase: Begins on day of BUN peak, and
continues until BUN < 30mg%.
– Recovery phase.
• “High output renal failure” exists when UO > 400 ml/24
hours.
Renal Tubular epithelial cells (RTE)’s are actually the sine qua non of ATN, shown
above; A is a squamous epi, and B is an RTE: rounder, smaller and more symmetrical.
Granular casts can be seen in hyperbilirubinemia without ATN
AKI--Prognosis
• Despite 60 years of RRT, hospital-acquired AKI
remains associated with about 40-60% mortality.
• Study Group on Acute Renal Failure--BAMC
(1957). Retrospective series of 1044 ARF
patients. 49% mortality despite availability of HD
for acute indications.
– 66% mortality for post-traumatic ARF.
– 30-32% mortality for obstetric- or nephrotoxinassociated ARF.
Clinical prognosis of AKI patients who
require RRT is poor!
• VA/NIH Acute Renal Failure Trial Network Study (NEJM,
2008) of subjects with AKI requiring RRT, 6 month
overall mortality 52%.
– Only 17% overall had recovery of renal function by
Day 28.
• Delannoy, et al (Int Care Med, 2009): prospective,
observational, multi-center study of 205 adult patients
undergoing RRT in ICU. 6 month mortality 62%.
– 12% of survivors on RRT.
• Lin, et al (Am J Surg, 2009): prospective, observational,
multi-center study of 342 patients s/p post-op AKI
requiring RRT (2002-2006). 90 day mortality 60%.
– Independent predictors of mortality: older age, sepsis,
higher SOFA score, CPR, TPN, need for CRRT.
Think About the Anatomy!
The Black Box Approach to AKI
Renal a.
Heart
Aorta
Kidney--glomeruli,
tubules, interstitium,
intra-renal vessels
Kidney
Ureter
Bladder
Urethra
Prostate (in some people...)
AKI: The Initial Differential
• Pre-renal: due to decreased renal blood flow
– Occurs when renal perfusion is decreased, without
associated tissue injury
– Most common cause of AKI in outpatients (50-70%)
– 30-40% of hospital-acquired AKI
– Function rapidly improves after perfusion is restored
• Post-renal: due to obstruction of urine flow
– Results from obstruction of urine flow at any site along
the tubule/collecting system
– Least common type of AKI, 2 - 10%
– Reversible if obstruction is relieved in a timely manner
AKI: The Initial Differential (cont.)
• Intra-renal: AKI due to an intrinsic,
parenchymal renal insult
– Wide differential includes ATN, but not
exclusively ATN
– 30-50% of all AKI
– 60-70 % of inpatient AKI
– Up to 80% of AKI in ICU
• Combinations of the above
Pre-Renal Causes of AKI
• Cardiac/CHF: Decrease in CO with resultant arterial
under-filling--total body volume often expanded
• Volume depletion
Environmental, intake deficit, and fever
GI (vomiting, diarrhea)
Renal (especially over-diuresis)
• Third Spacing/Peripheral Vasodilation/Hypotension
Hypoalbuminemic states (cirrhosis, nephrosis)
Sepsis, burns, crush injuries
Anti-hypertensive drugs
• Vascular Disasters: Aortic/Renal artery disruption
Using the FENa
FENa = (UNa x Pcreat)/(Ucreat x PNa) x 100,
where UNa = urine Na (meq/L); PNa = plasma Na (meq/L); Ucreat =
urine creatinine (mg%); and Pcreat = plasma creatinine (mg%).
In Nonoliguric States
• FENa < 1% in pre-renal azotemia
• FENa > 3% in oliguric ATN
Miller, et al, Ann Intern Med, 89:47, 1978
Exceptions may be seen in acute GN, early obstruction,
diuretic use, pre-renal states associated with metabolic
alkalosis, with NSAIDs, early in rhabdo, iv contrast ATN.
Using FEUrea
• In those who are receiving diuretics, a fractional
excretion of urea (FEUrea) can be obtained since
urea transport is not affected by diuretics.
– With loop or thiazide diuretic use, urine Na
excretion is increased distally due to inhibition of Na
reabsorption.
FEUrena = (Uurea x Pcreat)/(Ucreat x Purea) x
100, where Uurea = urine urea (mg/dL); Purea = plasma
urea (mg/dl); Ucreat = urine creatinine (mg%); and Pcreat =
plasma creatinine (mg%).
– FEUrea < 35% is suggestive of a prerenal state.
Post-renal Causes of ARF
• Need to Think Anatomically!
-Renal Pelvis and Ureter
Blood clot, stone/crystals, sloughed papilla, fungus
ball, malignancy, retroperitoneal fibrosis.
Iatrogenic obstruction (esp. in patients known
to be obstructed, or post retroperitoneal surgery)
-Bladder
Prostate, stone, blood clots, malignancy, neuropathic
(drugs, neurologic damage, systemic disease)
-Urethra
Strictures, iatrogenic (the obstructed Foley)
Intra-renal Causes of ARF
• Glomerulonephritis
Post-infectious, SLE, MPGN, RPGN, HSP
With a “nephritic sediment”, it is useful to send
C3/C4, which are depressed in acute nephritis (which has a
very limited differential: post-strep GN, SLE, MPGN
(including HepC), cryoglobulinemia, endocarditis
• Systemic/Intra-renalVasculitis
HUS, Wegener’s, Hypersensitivity angiitis,
Scleroderma, PAN/microscopic PAN
• Interstitial Nephritis
Drugs, infection, infiltrative (tumor/sarcoid)
• Acute Tubular Necrosis
A diagnosis of exclusion! Multiple etiologies and (as
yet) imperfectly understood pathophysiology!
Getting There….
The Diagnostic Approach to AKI
• History and Physical Examination
“A careful history and physical examination almost always
uncovers the most likely causes of ARF…”
Rudnick, et al, Acute Renal Failure, (ed, Brenner & Lazarus) 1988
• Some Often Overlooked Parts of the History & Physical
-Assessment of Volume Status: especially orthostatic
pulse and BP, weight, edema
-Historic or physical signs suggesting obstruction: sx of
prostatism, history of a single kidney, pelvic exam
-Medications: prescribed and OTC (esp. alternative tx)
Getting There….
The Diagnostic Approach to AKI
• The Flow Sheet Approach in complicated AKI
• Non-invasive Tests
-Urine Volume: anuria vs. oliguria vs. non-oliguria
Anuria (100 cc/day or less) suggests strong
possibility of urinary obstruction or vascular disaster.
-BUN and Creatinine: ratio, rate of rise, U/P ratio
-Fractional Excretion of Na (FENa) or Urea (FEUrea)
-Urinalysis: may yield important diagnostic information
in 70-80% of patients (Levinsky, et al, 1976).
Getting There….
The Diagnostic Approach to ARF
• Radiologic Studies
-Renal Ultrasound and Doppler Flow Studies
-Radioisotope studies (to establish renal arterial flow)
-Renal arteriogram and venogram*
• Other Invasive Tests
-Central hemodynamic monitoring
-Fluid challenge (only if you have reasonable evidence of
volume depletion)
-Renal Biopsy
Radiologic Rules to Live By….
• Don’t use iv contrast dye unless you have a very
good reason.
– To rule out cortical necrosis, renal arterial/aortic
interruption, polyarteritis nodosa, or renal vein
thrombosis.
• NEVER use gadolinium.
• The radiologist is your friend. Call and ask about
the best way to get the job done.
• Doppler US, radionuclide scanning, and CT and
MR without contrast can sometimes be adequate.
The AKI Game
Directions:
1. Read each case and answer the question.
2. Scoring will be done on the following scale.
3. You can score between 50 and -50 points.
40 to 50 points: Speak with me about a
nephrology fellowship.
-40 to -50 points: Hire a lawyer.
All others: We all need to read more...
Case 1
24 y/o male presents with a 10 day history of myalgia,
fatigue, anorexia, dark urine, decreased urine output,
and lower extremity edema.
PMH: + treatment with topical antibiotics for impetigo 4
weeks prior to admission.
MEDS: None.
PE: BP 172/106, P92
+ bilateral lower extremity edema
+ 1 cm diameter crusted lesion with surrounding
erythema on right upper arm, with tender right axillary
adenopathy.
Case 1 (continued)
LABS: BUN 94 mg%; creatinine 9.3 mg%
CXR: wnl.
UA: sp. gravity 1.010, pH 6.0, 2+ blood, 3+ protein. 1520 rbc/hpf, + 1-2 granular cast/lpf.
Mrs. Kiandoli calls you from
the lab to have you look at this
UA sediment finding
Case 1--The Question
1. What test would you get next to evaluate
this patient?
a) Renal ultrasound for renal size
b) Renal arteriogram to r/o PAN
c) ANCA panel/anti-GBM
d) C3/C4 and ASO titer
Case 1--The Answer Is...
d) C3/C4 and ASO titer (+10 points)
This is post-streptococcal glomerulonephritis with
ARF. Culture of skin lesion was + for group A
beta hemolytic strep. C3 was depressed (29),
ASO titer was v. elevated. Renal biopsy c/w
clinical diagnosis.
Case 1--Scores for the Other
Answers...
a) Renal US: 12 cm bilaterally, wnl (0 points)
b) A-gram to r/o PAN: Nl renal a-gram, patient sustains
femoral arterial tear requiring surgical repair. (-10 points)
c) ANCA and anti-GBM titre: Both return 2 weeks later,
negative. (-2 points)
The point of this case is to recognize that this is an “acute
nephritis”, and that the proper work-up is to consider that
differential for that syndrome. The combination of
impetigo and a delayed development of AKI (without other
systemic symptoms) suggests post-strep GN. The
treatment was antibiotic therapy and RRT. The patient
recovered.
Case 2
85 y/o male with a recent history of retinal
toxoplasmosis presents with fatigue, malaise,
anorexia, decreased urine output, and dark urine.
PMH: + History of benign prostatic hypertrophy
+ History of hypertension x 35 years, with
presumed secondary CKD, baseline creatinine of 2
mg%
MEDS: Sulfadiazine 4 gm qid Cipro 500 mg bid
Septra DS 1 tab po BID Captopril 25 mg qid
Case 2 (continued)
PE: BP 122/70, P65, Tilt negative
CV: +S4, no murmur.
Abdomen benign. Prostate firm, large, with no
nodules.
No edema.
LABS: BUN 70 mg%, creatinine 7.3 mg%
UA: sp. gravity 1.011, pH 6.0, large blood, 100
mg% SSA,
TNTC WBC and rbc/hpf and crystals shown.
Case 2: Crystals seen on urine microscopy
…My! He’s on a lot of sulfa…
Case 2--The Question
1. What single test will best assist you in
determining the etiology of ARF?
a) Foley catheterization.
b) Urine eosinophils.
c) Renal ultrasound.
d) CO2 arteriogram to r/o bilateral renal
artery stenosis.
Case 2--The Answer Is...
c) Renal ultrasound (+ 10 points)
This demonstrated bilateral pelvocaliectasis with
numerous echogenic foci c/w sulfadiazine stones. The
crystal is a typical sulfa “wheat sheaf” crystal.
The patient required acute dialysis, bilateral
percutaneous nephrostomy and urinary tract lavage.
He recovered, but was left with Stage 4 CKD.
Case 2--Scores for the Other
Answers...
a) Foley catheter: placed successfully, UO 20 cc/hr
(+ 5 points)
b) Urine eosinophils: negative (0 points)
c) Renal a-gram: arteries with insignificant
narrowing--patient has atheroembolic event,
develops small bowel infarct, and dies. (-10
points)
The point of this case--the urinalysis is always
useful, and make sure to rule out obstruction!
Case 3
68 y/o male admitted to CCU with unstable angina.
Stabilized with iv TNG/heparin/B-blocker. Cardiac
catheterization and angioplasty within 48 hours of
admission. Developed a large hematoma after sheath
removal, and is at bedrest. Baseline s. creatinine--1.4
mg%. One day post procedure, creatinine was 1.9
mg%, and is 2.4 mg% today.
ROS: + urinary frequency, hesitancy (has difficulty
urinating supine, but has “managed”). + mild nausea
since cath. Foley placed at time of cath, removed with
no difficulty.
PMH: HTN x 20 years, AODM (diet controlled x 5
years), Chronic insomnia.
Case 3 (continued)
MEDS: Isordil 20 mg tid
Atenolol 50 mg qd
ASA 325 mg qd
Lisinopril 10 mg qd
Elavil 75 mg qhs
Phenergan 25 mg prn nausea
D5 1/2 NS at 100 cc/hr
PE: BP 135/86, P 56 regular, Tilt negative.
No skin changes c/w atheroemboli. CV: +S4. Lungs clear.
No peripheral edema. Abdomen soft, + BS, mild
suprapubic tenderness. Right groin hematoma resolving.
UA: Sp. gravity 1.010, pH 6.0, trace protein, occ. fine
granular/hyaline cast.
Case 3--The Question
1. What is the next step in evaluating this
patient?
a) Conservative management of iv contrast
induced ATN.
b) Foley catheter placement.
c) Renal ultrasound.
d) 24-hour urine for protein and creatinine.
Case 3--The Answer Is…
b) Foley catheter placement. (+10 points)
Acute/chronic bladder outlet obstruction/urinary
retention. Post-void residual--400 cc. Prostate
was enlarged. Contributing--Phenergan, Elavil, the
need to urinate supine, and ? urethral trauma from
previous Foley.
Case 3--Scores for the Other
Answers…
a) Conservative management: Renal function
deteriorates. Sudden hyperkalemia, arrythmia,
and death (-10 points).
c) Renal ultrasound--mild pelvocalyceal dilation and
a very enlarged bladder--Foley placed post (+ 5
points).
d) 24-hour urine: dropped in the lab--housekeeping
called (0 points).
Always assess for obstruction. Always….
Case 4
65 y/o male with squamous cell ca of the piriform sinus.
7 days prior to admission, he received 100 mg/m2
cisPlatin, followed by 5 days 5-FU. 3 days prior to
admission he developed severe mucositis, fatigue,
weakness, and poor oral intake. Now presents with
above symptoms.
PMH: HTN x 20 years. 60 pack year smoker.
Baseline s. creatinine--1.1 mg%.
MEDS: Maxzide 1 po qd
Atenolol 100 mg qd
Case 4
PE: BP (standing) 98/54, P 72
BP (supine) 154/62, P 60
Weight 198 lbs (206 lbs at last follow-up).
Severe oral mucositis. Lungs clear. CV no gallop,
murmur, or rub. Abdomen soft, and non-tender.
Prostate mildly enlarged. No edema.
LABS : Na 136, K 3.7, Cl 97, HCO3 23
BUN/creat--60/3.6 mg%. WBC 2.6K, Plat 73K
UA: Sp gravity 1014, pH 5.0, 0-1 fine granular cast/lpf.
Case 4--The Question
1. What is the next step in this patient’s
evaluation?
a) Urine eos--? Maxzide-induced AIN.
b) Send urine for FENa to determine etiology
and guide therapy.
c) Volume replete with NS until tilt negative.
d) Foley placement to monitor urine output.
Case 4--The Answer Is...
c) Volume repletion until tilt negative (+10 points)
Although this may be ATN due to cisPlatin, he is
volume depleted, and must be resuscitated. Poor
po intake, diuretics, tubular damage due to
cisPlatin toxicity all may contribute. Creatinine
came down to 2.1 mg% with volume repletion
alone.
Case 4--Scores for the Other Answers...
a) Urine eos: negative (0 points).
b) FENa= 2%, not helpful. Nephrology staff abuses
you at morning report for not volume repleting
the patient promptly (-5 points).
c) Foley: UO 20 cc/hr. This immunocompromised
patient develops urinary sepsis and multi-organ
failure syndrome (-10 points).
This is an example of pre-renal AKI. Urine
eosinophils can be suggestive of AIN, but they
are not diagnostic of it. FENa > 1% will not be
helpful in a patient on diuretics. Foley catheters
are dangerous due to the infection risk, and
should only be used if indicated.
Case 5
21 y/o female s/p cadaveric kidney transplant 7 years ago
for ESRD due to renal dysplasia. Maintained on CyA
100 mg bid and Medrol 10 mg qod with creatinine of
2.4 mg%, 6 months ago. Returns after 4 month workstudy experience in Australia for medication refills
and follow-up labs.
LABS: BUN/creat--290/25.5 mg%, Na 131, K 5.0, Cl
97, HCO3 8, Ca 5.2, PO4 10.4. Hct 24%.
----------------------------------You call her at home, and ask that she come back
immediately for evaluation (with someone else
driving…)
Case 5 (continued)
She returns, reports fatigue “due to jet lag, “food
poisoning” 4 weeks ago with nausea and vomiting,
some mild nausea and episode of vomiting last week,
and a 2-day history of a lacy-red rash. Urine output is
“fine”. No medication missed. Repeat stat labs are
c/w previous.
PE: BP 100/54, P88, Wght 49 kg, + uremic fetor.
Pink macular/papular eruption over back, chest, and
arms, with excoriations. CV: RRR, no rub, no
murmur. No edema. Lungs clear. A&O x3, 3+
DTR’s, + asterixis.
UA: Sp gravity 1.010, 2+ protein, 10-20 wbc/hpf, nitrite
neg.
Case 5--The Question
1. What do you do next?
a) After a momentary personal decompensation,
you call a nephrologist.
b) Emergent renal ultrasound for size and to rule
out obstruction, followed by dialysis.
c) 1 gm of Solu-Medrol iv, followed by renal
biopsy to r/o acute rejection.
d) Admit to ICU, start renal dose dopamine,
fenoldopam, and a furosemide drip.
Case 5--The Answer Is...
a) Call a nephrologist (+ 10 points). (You know when you
are out of your depth….)
b) Emergent renal ultrasound, followed by dialysis (+10
points)
This is most c/w acute presentation of chronic renal failure.
eGFR was 25 ml/min/1.73 m2, 6 months ago. Patient is
remarkably tolerant of the degree of uremia. Renal
ultrasound shows an 8 cm kidney and no obstruction.
Asterixis is an acute indication for dialysis--(which
suggests uremic encephalopathy).
Case 5--The Answer Is...
c)
d)
Solumedrol followed by kidney biopsy: The patient
seizes during kidney biopsy. (-10 points)
Dopamine, etc: there is no change in renal function, and
she has a uremic seizure the following morning.
Miracles happen, but not this time… (-10 points)
Noteworthy that this patient began hemodialysis (2 hours,
concurrent dialysis flow, inefficient kidney, mannitol
treatment) that evening, and had a seizure secondary to
disequilibrium syndrome immediately post. She finally
had to be loaded with dilantin to prevent seizures as
dialysis was initiated.
Therapy of AKI/ATN
“An ounce of prevention is worth a
pound of cure.”
B. Franklin
“If you’re a rat, I can help you…”
C.M.Yuan
Therapy of AKI
• Specific to the Underlying Cause
• General Conservative Measures
-Volume restriction if oliguric
-Avoid further insults--nephrotoxins, volume depletion
-Adjust medication doses for estimated GFR (but not the
one you get off CHCS, unless creatinine has stabilized!)
-Diet: protein (1 gm/kg/d), potassium(1meq/Kg/d), low
phosphorus, 2 gm Na, if volume overload or HTN
-Remove indwelling urinary catheters if at all possible
-Phosphorus binders as required
-Avoid exogenous potassium and acid loads
Do Pharmacologic Therapies
Shorten Duration or Improve Prognosis in
AKI/ATN?
• Short answer: No.
• Loop Diuretics:
– (Conger. AJKD 1995) Critical review. “No significant
beneficial effects of diuretics for prophylaxis or
treatment in early or established ARF.”
– No evidence loop diuretics reduce need for dialysis,
improve renal recovery, or reduce mortality in AKI.
This has been demonstrated in at least one prospective
RCT subsequently (Cantarovich, et al. AJKD, 2004),
and confirmed by meta-analysis (Ho and Sheridan,
BMJ. 2006).
Do Pharmacologic Therapies
Shorten Duration or Improve Prognosis in
AKI/ATN?
• Anaritide:
– Lewis, et al. AJKD. 2000. Anaritide (ANP) did not improve
mortality or dialysis free survival in oliguric or non-oliguric
subjects with AKI.
• Dopamine:
– No benefit in terms of mortality, RRT requirement, or morbidity
(Friedrich, et al. Ann Int Med. 2005; Marik, et al. Am J Med.
1999).
• Fenoldopam:
– Landoni, et al. AJKD. 2007. Meta-analysis of conflicting trials
suggests that there may be benefit in terms of mortality and need
for RRT. Confirmation is required via adequately powered RCT.
Therapy of AKI
Acute Indications for Renal Replacement
Therapy
•
•
•
•
•
•
Hyperkalemia not controlled by medical management
Serious volume overload not responsive to diuretics
Serious acidosis not amenable to NaHCO3 replacement
Uremic pericarditis
Uremic encephalopathy
Other: Convention is to start at a BUN of 80-100 mg/dl;
but this is only a convention. It has not been shown to be
of benefit in terms of mortality.
RRT in AKI
• Is more better? Not if you are giving “adequate therapy”.
VA/NIH Acute Renal Failure Trial Network Study (NEJM,
2008) showed no difference in 60-day mortality between
intensive vs. standard iHD and CRRT.
• Biocompatible membranes? Appear superior to
cuprophan membranes in terms of recovery/survival from
ARF (Hakim, et al, NEJM, 1994; Himmelfarb,et al, JASN,
1998).
• Continuous vs. Intermittent Therapies? RCTs indicate
that CRRT is NOT superior to IHD in terms of mortality or
renal recovery (Mehta, et al, KI, 2001; Visonneau, et al,
Lancet, 2006; Lins, et al, NDT, 2009). Modality best
determined by individual patient requirements.
So…
“Avoid Nephrotoxins.”
J. D. Oliver, 3rd