Transcript 2008_08_27-Thompson-Acute_Renal_Failure

ACUTE RENAL FAILURE
Carly Thompson
MD, CCFP
August 27, 2008
Objectives
Definitions
Epidemiology
Differential Diagnosis
Investigations: Labs, Urinalysis, Imaging
Treatment:
– Medications
– Renal Replacement Therapy
Case 1
Mrs. K. Bean 78 yo female
– PMHx: liver cirrhosis, ascites, hepatic
encephalopathy due to hepatitis C
– Family is concerned that she is not drinking,
not eating, and having recurrent diarrhea as
she is getting sleepier
– Labs:
Na 140
BUN 20
Cr 247
Case 1
Is she in renal failure?
Definitions: Acute Renal Failure
The deterioration of renal function over
hours or days resulting in accumulation of
toxic wastes and the loss of internal
homeostasis
Indirect Measures:
– 50% increase in serum Cr
– 50% decrease in creatinine clearance / GFR
– Highly variable across different studies
Definitions:
Types of Acute Renal Failure
Non-oliguric
– Better prognosis
Oliguria:
– <1mL/kg/hr in infants
– <0.5mL/kg/hr in children
– <400mL / day in adults
<0.3mL/kg/hr OR 17mL / hour in 60kg x 24 hours
Anuria
– <100mL / day in adults
Definitions: Acute Kidney Injury
RIFLE Criteria
Mortality
Risk
2.4
4.15
6.37
Definitions: AKIN Criteria
Acute Kidney Injury Network
Stage
Serum Cr Criteria
Urine Output Criteria
1
Serum Cr increase ≥ 26.4 mmol/L
or increase ≥ 150 to 200% from
baseline
<0.5 mL/kg/hr x >6 hrs
2
Serum Cr increase ≥ 200 to 300%
from baseline
<0.5 mL/kg/hr x > 12 hrs
3
Serum Cr increase > 300% from
baseline (or serum Cr ≥ 354
mmol/L with an acute increase of
44 micromol/L)
<0.3 mL/kg/hr x 24 hrs or
anuria x 12 hrs
Quick Epidemiology Slide
Community-acquired ARF:
– Only diagnosed in 1% of hospital admissions at presentation
– Most commonly due to volume depletion
– 90% may have reversible cause
Hospital-acquired ARF:
– Up to 4% of admissions, 20% of critical care admissions
– Multifactorial: elderly, nephrotoxic medications, often in ICU
Mortality:
–
–
–
–
50% - minimal change since dialysis was invented!
25% in children, but 45% if intrinsic renal failure
75% for hospital acquired mortality
7% community-acquired prerenal ARF
Causes of Death:
– Sepsis, cardiac and pulmonary failure
Case 1 Follow-Up
Baseline Cr 165 -> Now 247
– 82 mmol/L increase, 150% increase
GFR 28 -> Now 21
– 25% decrease
Urine Output: Foley inserted
Diagnosis: AKIN Criteria - Stage 1 Acute Kidney
Injury
Plan: Admitted for rehydration, monitoring, and
placement issues.
Case 2
Mr. Pastie 68 yo man
Hx – unwell x 5 days, vomiting, diarrhea,
lightheaded, presents confused
PMHx – Htn, CHF
Meds – B-blocker, lasix
Case 2
What do you think is going on?
What would you look for on physical exam?
Prerenal Failure
History
– Clues to dehydration
Physical Exam
– Volume status exam
Differential Diagnosis of Prerenal
Failure
Volume Loss
- Hemorrhagic Shock, Vomiting, Diarrhea
- Drugs: Diuretics
- Other: Primary hypoaldosteronism, Salt-losing nephropathy, Postobstructive
diuresis
Decreased Cardiac Output
- Myocardial infarction / ischemia
- Obstructive: Valvular heart disease, tamponade
- Cardiomyopathy
- Drugs: B-blockers
- High-output: thyrotoxicosis, thiamine deficiency, Paget disease, AV fistula
Renal Artery and Small Vessel Disease
- Drugs: Cyclosporine, tacrolimus
- Embolic disease (septic, cholesterol), Sickle Cell Disease
- Artery: Malignant hypertension, preeclampsia, vasculitis
- Other: Transplant rejection, Hypercalcemia, Hemolytic-uremic syndrome
Case 2
What investigations would you like to order?
Renal Failure Work-Up
Labs:
– CBC, lytes, BUN, Cr
Urinalysis: R+M
Chest x-ray: Volume status
ECG: Screen for hyper / hypokalemia
Insert foley: input / output
Renal Failure Work-Up
How helpful is the BUN and Cr?
Importance of BUN and Cr
Creatinine
A patient with a low baseline Cr can lose more than ½ of
functioning nephrons before developing and elevated Cr
Breakdown product of skeletal muscle protein creatine
Linked to muscle mass, thus women and elderly have lower
GFR for any Cr level
Glomerulonephritis causes increased tubular secretion of
Cr independent of GFR
Trimethoprim, cimetidine, salicylates cause decreased
secretion
BUN
Decreased in patients with malnutrition and hepatic
synthetic dysfunction
Increased in setting of a protein load, GI hemorrhage,
trauma
Does the ratio of BUN/Cr help determine if
the patient is dry?
BUN:Cr Ratio
Quick Physiology Lesson:
Both Cr and BUN are passively filtered at the
glomerulus
Cr remains in the tubule
BUN is permeable and passively reabsorbed
with sodium
Therefore . . . In the setting of Na retention, urea
clearance can be as low as 30% of GFR in a
patient with normal concentrating ability
BUN:Cr >20 can suggest hypovolemia
Any other tests that can show prerenal
failure?
Fractional Excretion of Na
Fractional excretion of sodium
FeNa = Urine Na
÷
Urine Cr
Plasma Na
Plasma Cr
In normal kidneys under prerenal stress <1%
1-2% either ATN or prerenal failure
>2% ATN due to loss of concentrating ability
– Benefits: Most accurate test
– Limitations: Intrinsic renal failure when tubular
concentrating capacity is retained (i.e.
glomerulonephritis), the Fe Na may be depressed
Urine Sodium
Less accurate measurement of prerenal
failure
Urine Na concentration affected by the
rate of water reabsorption -> a patient may
have a relatively high urine sodium
concentration (20 - 40 meq/L or more) but
may be in prerenal failure
Urine Na < 20 meq/L
Urine Osmolality
Cause
Pre-renal
Renal
– Tubular injury
– Acute Interstitial Nephritis
– Acute Glomerulonephritis
Post-renal
Osmolality
> 500
<350
<350
>500
<350
Case 2 Summary
Pre-Renal Failure
BUN:Cr >20
FeNa <1%
Urine osmolality >500
Urinalysis: May have hyaline casts
– Secreted from tubular epithelial cells
Treatment
Rehydration!
Case 3
Mrs. Buckley
36 yo female
Nausea, vomiting, SOB x 1 week
Sore throat 3 weeks ago
Cr 300
What do you think is going on?
What would you like to order?
Case 3
Cr 300
BUN 20
BUN:Cr <20
Osmolality >500
Urine R+M – proteinuria and casts
Urine lytes – Na 20, Fe Na <1%
Renal U/S - normal
What kind of cast is this?
Intrinsic Renal Failure
Tubular Disease
Glomerular Disease
Interstitial Disease
Vascular Disease
Glomerulonephritis
Post-infectious (strep)
IgA nephropathy
SLE, PAN, Hep C, HIV, Wegener’s,
Goodpasture’s
HSP
HUS/TTP
Rapidly progressive glomerulonephritis RPGN
Membranoproliferative glomerulonephritis
Drugs
Tumors (leukemia, lymphoma)
Work-Up
ASO Titer
Renal biopsy
ASA / ANCA / serologies
Anti-GBM antibodies
Medication Hx
CT Scan
Renal Biopsy
Should be considered in all causes of acute
intrinsic renal failure
– Significantly changed dx and tx in 40% of cases
should be considered in all causes of intrinsic ARF:
significantly changed the dx and tx in 40% of cases
Complications:
– Common: Hematuria
– Serious: Blood transfusions, nephrectomy, puncture
of other organs, perinephric hematomas – 2%
– Mortality: 0.1%
Post-Strep Glomerulonephritis
6-14 days after pharyngitis with Group A
Strep or after skin infection
Hypertension, edema, pulmonary
congestion common presentation
Urinalysis: RBC, RBC casts
Prognosis:
– 5% progress to RPGN
– 70% recover
Antibiotics may be considered for contacts
Case 3 Summary
Intrinsic Renal Failure: Glomerulonephritis
BUN:Cr <20
FeNa <1%
Urine osmolality >500
Urinalysis: RBC, RBC casts, protein
Case 3 Continued
You insert a foley for Mrs. Buckley. Finish your
shift and go home for the night.
Your friend is on internal medicine call that night,
and calls you to debate whether he should start
a diuretic for Mrs. Buckley whose urine output
has dropped to <0.5mL/kg/hr for the past 6
hours.
What should you tell your friend?
Diuretic Use in Renal Failure
Rationale: Pts with non-oliguric ARF have improved
mortality and renal function recovery rates, therefore
using a diuretic to “convert” oliguric to nonoliguric ARF
may be beneficial.
Evidence: RCTs have failed to show a benefit in
administering diuretics to patients with ARF.
– Shilliday IR, Quinn KJ, Allison ME.
Loop diuretics in the management of acute renal failure: a prospective,
double-blind, placebo-controlled, randomized study.
Nephrol Dial Transplant 1997 Dec;12(12):2592-6
– No change in recovery, hemodialysis, or death
Bottom-Line: Diuretics are only useful in the
management of volume-overloaded patients.
What about “renal dose”
dopamine?
Low-dose “renal” dose dopamine (1-5ug/kg/min)
was used for many years to treat ARF
Rationale: Increases urine output
Evidence: No evidence that it improves renal
recovery or mortality
Side effects: Pro-arrhythmic, and may cause
increased medullary O2 consumption without
increased O2 delivery
Bottom Line: Say NO to “renal dose” dopamine!
Case 4
Mr. Dye
50 year old male
CC: Not peeing
HPI: 4 days of minimal urine output
– Cardiac catheterization 1 week ago
PMHx: 15 years of DM II, lisinopril, insulin
O/E: BP 190/110
– JVP 9cm
– Bibasilar crackles
– Edema
Labs:
– BUN: 20
– Cr: 450 (Baseline = 150)
What is going on?
Intrinsic Renal Failure
Tubular Disease
Ischemic acute tubular necrosis
Nephrotoxins
Heme pigments: rhabdomyolysis, massive hemolysis
Interstitial Disease
Acute interstitial nephritis (drug reaction)
Infiltrative disease
Autoimmune disease: SLE
Infectious: Legionnaire, hanta virus
Vascular Disease
Malignant hypertension
Scleroderma
TTP, HUS, PAN
Renal Vein Thrombosis
Glomerular Disease
Nephrotoxins
Drugs that alter blood flow
NSAIDs, ACEI, cyclosporine, tacrolimus, contrast, amphotericin B, interleukin2
Drugs that are toxic to tubules
Aminoglycosides, contrast, cisplatin, cyclosporine, tacrolimus, amphotericin B,
methotrexate, solvents, heavy metals, IVIG
Heme-Pigment-Induced toxicity
Cocaine, EtOH, lovastatin
Drugs that precipitate and cause tubular obstruction
Acyclovir, sulfonamides, ethylene glycol, chemo drugs, methotrexate
Allergic interstitial nephritis
Penicillins, cephalosporins, sulfonamides, rifampin, cipro, NSAIDs, TZDs,
furosemide, cimetidine, phenytoin, allopurinol
Hemolytic-Uremic Syndrome
Cyclosporine, tacrolimus, cocaine, quinine, conjugated estrogens
What puts Mr. Dye at risk for renal failure?
(i.e. What are the risk factors for contrastinduced renal failure?)
Contrast-Induced Renal Failure
Course:
– Increasing Cr for 3-5 days, then resolution
Risk Factors:
–
–
–
–
–
–
–
Chronic renal insufficiency
DM (Approximately 40% risk!)
Age
Hypovolemia
Hypoalbuminemia
Myeloma
Type and Dose of Contrast
How can you prevent contrast-induced renal
failure?
Prevention
Alternative studies – MRI, ultrasound
Low-dose contrast, avoid repetitive studies (<72 hours),
low or iso-osmolal nonionic contrast
Avoid hypovolemia
– IV NS or NaHCO3
Avoid NSAIDs
N-Acetylcysteine
– Minimizes vasoconstriction and free radicals?
– Much heterogeneity in trials, largest meta-analysis showed RR
0.62 (.44 - .88)
– NAC 600 - 1200mg po bid day before and of procedure
– IV NAC for emergent scans? Risk of anaphylaxis, unclear data.
What if Mr. Dye had just been started on his
ACE inhibitor? What condition would you
be concerned about?
ACE Inhibitors
Dilate postglomerular capillaries ->
increase renal blood flow and decrease
GFR -> natural increase in serum Cr 1020%
ARF after ACEI initiation -> bilateral renal
artery stenosis
ARBs may also cause ARF
Check Cr, lytes 2 weeks after starting ACE
NSAIDs / COX Inhibitors
Risk Factors for Renal Failure:
– Age
– Chronic Renal Failure
– CHF
– DM
– Hypovolemia
– Diuretics
– ACEI
Aminoglycosides
Trough concentration is relevant
Once daily dosing can reduce toxicity
Heme-Pigment Induced
Acute Renal Failure
History:
Crush injuries
Exam:
Pigmented granular casts, heme pigment in urine
Pathophysiology:
Deposited in and concentrated in tubules
Obstruction and direct toxicity depending on acidic urine
Treatment
Volume Replacement
– Normal saline 1-2L / hour
– Urine output 200 – 300 mL/hour
Forced Alkaline-Mannitol Diuresis
–
–
–
–
Urine pH >6.5
Once diuresis established 75mmol/L of NaHCO3
Caution re: hypercalcemia
Consider mannitol / diuretic if not effective diuresis
Case 4 Summary
Condition
Dipstick
Sediment
Urine
Osm
Fe of Na
(%)
Prerenal
Trace or no
proteinuria
Hyaline casts possible
>500
<1
Renal
- Tubular injury
(ischemic or
toxic)
- Acute Interstitial
Nephritis
- Mild to mod
proteinuria
- Pigmented granular
casts
<350
>1
- Mild to mod
- WBC, white cell
proteinuria;
casts, eosinophils
Hb, WBC
and eosinophil
casts; red cells
<350
>1
>500
<1
- Acute
- Mod to
- RBC and red cell
Glomerulonephritis
casts
severe
proteinuria;
Hb
Case 5
Mr. Peebody
69 yo male
CC: Unable to urinate for 24 hours
PMHx: BPH
Meds: Amitriptyline – started recently for
insomnia
O/E: Distended bladder, tender
suprapubic area
What is going on?
Post-Renal Failure in Adults
Urethra and Bladder Outlet
Infiltration: Cancer – prostate, bladder, cervix, colon
Blockage: Calculi, clot
Pressure: BPH
Narrowing: Stricture, phimosis
Innervation: Neurogenic bladder
Trauma
Ureter
Infiltration: Cancer, Retroperitoneal fibrosis, IBD
Blockage: Calculi, crystals, clot, ligation
Pressure: AAA, Pregnancy
Narrowing: Stricture
Reflux
Trauma
Intrarenal
Crystals: Uric acid, sulfonamide, acyclovir, indinavir
Protein casts: multiple myeloma, amyloidosis
What conditions might cause this in
children?
Post-Renal Failure in Children
Urethra and Bladder Outlet
Blockage: Urethral atresia, phimosis, meatal stenosis,
anterior and posterior urethral valves (males), calculus,
clot
Innervation: Neurogenic bladder
Ureter
Reflux
Blockage: ureterovesical junction obstruction,
ureterocele, clot
Anatomic: megaureter, retrocaval ureter
Pressure: retroperitoneal tumour
What orders would you like?
What would you get if you order urine lytes
for Fe Na and osmolality?
Post-Renal Failure
Insert foley (consider coude tip)
Bladder scan
Monitor urine output
Urine R+M
– May see Hb, protein, WBC
– Osmolality <350
Urine lytes
– Fe Na >1
What complication are you concerned
about?
Postobstructive Diuresis
Monitor urine output x 2 hours
>250mL / hour for >2 hours after
uncomplicated urethral obstruction ->
consider admission
May result in severe dehydration and
hyponatremia
End-Stage Renal Disease
Azotemia: Accumulation of nitrogenous
wastes
Uremia: Contamination of blood with
urine, the clinical syndrome resulting from
ESRD
Results of Uremia
Renal Bone Disease
– Loss of vitamin D3 -> decreased calcium
absorption -> secondary hyperparathyroidism
– Metastatic calcification
Hematologic
– Anemia -> Loss of erythropoietin
– Immunodeficiency
Can you name some of the outcomes of
uremia?
Results of Uremia
Neurologic
–
–
–
–
Uremic encephalopathy
Dialysis dementia
Subdural hematoma
Peripheral neuropathy
Cardiovascular
–
–
–
–
Coronary Artery Disease
Hypertension
CHF
Pericarditis
Gastrointestinal
–
–
–
–
Anorexia, nausea, vomiting, metallic taste
GI bleed
Diverticulosis, Diverticulitis
Ascites
When would you consider hemodialysis?
Indications for Hemodialysis
Volume overload
Hyperkalemia >6.5 or rising
Acid-base imbalance
Symptomatic uremia (pericarditis,
encephalopathy, bleeding dyscrasia, nausea,
vomiting, pruritis)
Uremia (BUN >100)
Dialyzable intoxications – methanol, ethylene
glycol, theophylline, ASA, lithium
Consider severe dysnatremia <115 or >165)
Consider dysthermia
Summary
Think pre-renal, renal, post-renal
Labs:
– Recognize the limitations of Cr
– Use BUN:Cr, urinalysis, urine lytes (Fe Na),
osmolality to your advantage!
Admit and monitor invasively (foley, etc)
Treat underlying condition, maintain hydration.
Consider hemodialysis and it’s complications.
Thank You!