Transcript Acute Renal failure

Acute Renal failure
(Acute Kidney Injury)
DR. BHUMIKA SAMBYAL
To function properly
kidneys require:
• Normal renal blood flow
• Functioning glomeruli and
tubules
• Clear urinary outflow tract
– for drainage and elimination of formed
urine from the body.
Renal Autoregulation
Autoregulation is the maintenance of a
near normal intrarenal hemodynamic
environment (RBF, RPF, FF and GFR)
despite large changes in the systemic
blood pressure
Renal autoregulation
• RBF - blood perfusing the kidneys each
minute (1200 ml/min)
• Renal Plasma Flow (RPF) - plasma
flowing to kidneys each minute (670
ml/min or 55-60% of RBF)
• GFR - amount of plasma filtered each
minute by the glomeruli. (Normal GFR -125
ml /min for men and 100 ml/min for women)
• Filtration Fraction (FF) - the ratio of
GFR to RPF (Normal - .18 - .22)
Renal blood flow (RBF)
• Major sites of renal vascular resistance
-Glomerular afferent (Raff ) and efferent
(Reff) arterioles
• Changes in Raff and Reff affect RBF.
Intrarenal autoregulation
Vasoconstrictors
– Renin
– Angiotensin II
– Endothelin
– ADH
Vasodilators
–
–
–
–
PGs
Kinins
NO
ANP
RBF
GFR
Figure : RBF / GFR is maintained by a balance between vasodilators and
vasoconstrictors of Afferent and Efferent arterioles
Intrarenal Mechanisms for Autoregulation
Afferent
Arteriole
RBF
Efferent
Arteriole
PGC
Reff / Raff ratio =N
Glomerulus
Tubule
GFR.
N Engl J Med 357;8 August 23, 2007
Figure - shows normal conditions normal renal perfusion
pressure and a normal GFR.
Intrarenal Mechanisms for Autoregulation under
MAP
decreased Perfusion Pressure
RBF
Afferent
Arteriole
PGC
Efferent
Arteriole
Ang II
PGE
Reff / Raff ratio =
GFR.
N Engl J Med 357;8 August 23, 2007
Figure: shows reduced perfusion pressure within the autoregulatory range.
Normal glomerular capillary pressure is maintained by afferent
vasodilatation and efferent vasoconstriction.
Renal autoregulation failure
• Renal autoregulation breaks down as
MAP falls below 80 mm Hg,
• Further adjustments in intra-renal
hemodynamics are unable to maintain
RBF and GFR
• Hallmark of ARF
After age 30, RBF/ GFR decreases progressively with age; at 80 years it is
nearly half of that at 20 years
Acute renal failure (ARF) or acute
kidney injury (AKI)
• Deterioration of renal function over a period of hours to
days, resulting in
• the failure of the kidney to excrete nitrogenous waste
products and
• to maintain fluid and electrolyte homeostasis
• ARF Rapid deterioration of renal function
–
–
–
–
(increase of creatinine of >0.5 mg/dl in <72hrs.)
“azotemia” (accumulation of nitrogenous wastes)
elevated BUN and Creatinine levels
decreased urine output (usually but not always)
• Oliguria: <400 ml urine output in 24 hours
• Anuria: <100 ml urine output in 24 hours
The ARF Paradigm
1. Pre-renal
2. Intrinsic Renal
3. Post-renal
RIFLE CLASSIFICATION
CATEG
ORY
RISK
GFR&S.CREATININE CRITERIA
URINE OUTPUT
GFR decrease >25% or
creatinine up 1.5 times baseline
<0.5 ml/kg/hr for 6 hrs
INJURY
GFR decrease>50% or
Creatinine up 2 times baseline
<0.5 ml/kg/hr for 12 hrs
FAILURE
GFR decrease>75% or
Creatinine up 3 times baseline or
Creatinine>4 mg/dl or
Acute rise0.5 mg/dl
<0.3 ml/kg/hr for 24 hrs
Or anuria for 12 hrs
END
STAGE
End stage kidney disease(>3 months)
1. Pre-renal
Pre-renal ARF
2. Intrinsic Renal
3. Post-renal
Volume Depletion
Renal losses: diuretics,
osmotic diuresis, etc
Extra-renal losses:
vomiting, diarrhea,
skin
 Renal Perfusion
 Arterial Volume
Cardiogenic (CHF,
ACS, arrhythmias,
shock)
Septic shock
Hepatorenal syndrome
Adrenal insufficiency
Renal Vasoconstricn
Radiocontrast
Prostaglandin inhibition
Calcinurin inhibitors
ACE inhibitors
Amphotericin B
When autoregulatory mechanisms are maximized, any small
renal insult will subsequently precipitate acute renal failure.
PRE-RENAL (Hemodynamic) AKI
Hypovolaemia
Hypotension
Haemorrhage
Volume depletion
( vomiting,
diarrhoea,
inappropriate
diuresis, burns)
Cardiogenicshock
Distributive shock
(sepsis,
anaphylaxis)
Generalized or localized
reduction in RBF
Oedema
states
Cardiac failure
Hepatic cirrhosis
Nephrotic syndrome
Renal
Hypoperfusion
NSAIDs
ACEI / ARBs
AAA
RAS /occlusion
Hepatorenal
syndrome
Reduced GFR
PRERENAL AKI
Renal / Intrinsic AKI
Glomerular
Ac.GN
Tubular
Interstitial
ATN
Ac. Interstitial
nephritis
Ischemia (50%)
–post-infectious,
Toxins (30%)
– SLE,
–ANCA associated,
85%
–anti-GBM disease
–Henoch-Schönlein
purpura
–Cryoglobulinaemia,
–Thrombotic
microangiopathy
•TTP
•HUS
5%
Drug induced NSAIDs,
antibiotics
Infiltrative lymphoma
Granulomatoussarcoidosis,
tuberculosis
Infection related post-infective,
pyelonephritis
Vascular
Vascular
occlusions
- Renal artery
occlusion
- Renal vein
thrombosis
- Cholesterol
emboli
< 2%
8 -12%
N Engl J Med 1996;334 (22):1448-60
Post-renal Urinary outflow tract obstruction
Intrinsic
Intra-luminal
Intra-mural
•Stone,
•Blood clots,
•Papillary
necrosis
•Urethral stricture,
•BPH,
•Carcinoma prostate,
• Bladder tumour,
• Radiation fibrosis
Extrinsic
•Pelvic
malignancies
•Prolapsed
uterus
•Retroperitonea
l fibrosis
Principal POST-RENAL causes of AKI
ACUTE RENAL FAILURE
Acute renal failure (ARF) has four welldefined stages/phases: onset, oliguric or
anuric, diuretic, and convalescent.
Treatment depends on stage and severity of
renal compromise.
Phases of ARF:
• Onset – initial phase of insult or injury
• Oliguric – less than 400cc/24 hr
- for older (600 – 700 cc/24 hr)
- lasts 8-14 days or 1-2 weeks
-↓K+, ↑Na, ↑Mg
• Diuretic – Lasts 10 days
- diuresis of 3-5L/day
- ↑BUN & Creatinine level
- dangers: hyponatremia,
hypotension, shock
• Recovery – lasts from 6-12 months
- avoid nephrotoxic drugs
Relationship between GFR and serum
creatinine in ARF
• S.Cr. poor marker of renal function.
• Poor correlation between S.Cr. and level of
GFR related to muscle mass.
S.Cr. of 1.0 does not represent the same level of GFR in a
cachectic 70-year-old as in a highly muscular 25-year-old.
How do we
diagnose it?
History & Physical Will Guide DDx
Primer on Kidney Diseases 3rd Ed. pg 248.
Acute Renal Failure
Diagnosis
•
•
•
•
•
•
Blood urea nitrogen and serum creatinine
CBC, peripheral smear, and serology
Urinalysis
Urine electrolytes
U/S kidneys
Serology: ANA,ANCA, Anti DNA, HBV, HCV, Anti
GBM, cryoglobulin, CK, urinary Myoglobulin
Acute Renal Failure
Diagnosis
• Urinalysis
– Unremarkable in pre and post renal causes
– Differentiates ATN vs. AIN. vs. AGN
• Muddy brown casts in ATN
• WBC casts in AIN
• RBC casts in AGN
– Hansel stain for Eosinophils
Acute Renal Failure
Diagnosis
• Laboratory Evaluation:
– Scr, More reliable marker of GFR
• Falsely elevated with Septra, Cimetidine
• small change reflects large change in GFR
– BUN, generally follows Scr increase
• Elevation may be independent of GFR
– Steroids, Catabolic state, hypovolemia
– BUN/Cr helpful in classifying cause of ARF
• ratio> 20:1 suggests prerenal cause
The Value of Urinalysis
Urinalysis
Pre-renal
High specific gravity, normal or hyaline casts
Intrinsic renal
Glomerular
Proteinuria, hematuria, RBC casts
ATN
Low specific gravity, muddy brown casts, tubular epithelial cells
AIN
Mild proteinuria, hematuria, WBC, WBC casts, eosinophils
Post-renal
Normal or hematuria, WBC, occasional granular casts
Pre-renal vs. ATN
Favours
Pre-renal
Favours
ATN
> 20:1
<10-15:1
UNa
< 20
> 40
Uosm
> 500 mO/kg
~ isotonic
FENa
<1%
>2%
U specific gravity
> 1.018
< 1.010
Normal or hyaline
casts
Tubular cells & “muddy
brown” granular casts
Creatinine:Urea ratio
Urinalysis
Acute Tubular Necrosis
– Most common cause of intrinsic cause of ARF
– Often multifactorial
– Ischemic ATN:
• Hypotension, sepsis, prolonged pre-renal state
– Nephrotoxic ATN:
• Iodinated contrast
• Rhabdomyolysis
• Hemoglobinuria
• Cast nephropathy(myeloma &Tamm horsfall prteins)
• Antibiotics-Aminoglycosides,Amphotricin B,I/V acyclovir
• Other drugs-Cisplatin,ethylene glycol/methanol
• Tumor lysis syndrome
Acute Tubular Necrosis
• Diagnose by history,  FENa (>2%)
• sediment with coarse granular casts, RTE cells
• Treatment is supportive care.
– Maintenance of euvolemia (with judicious use of
diuretics, IVF, as necessary)
– Avoidance of hypotension
– Avoidance of nephrotoxic medications (including
NSAIDs and ACE-I) when possible
– Dialysis, if necessary
• 80% will recover, if initial insult can be reversed
Contrast nephropathy
• 12-24 hours post exposure, peaks in 3-5
days
• Non-oliguric, FE Na <1% !!
• RX/Prevention: 1/2 NS 1 cc/kg/hr 12 hours
pre/post
• Mucomyst 600 BID pre/post (4 doses)
• Risk Factors: CKD, Hypovolemia
,DM,CHF
Acute Glomerulonephritis
• Rare in the hospitalized patient
• Diagnose by history, hematuria, RBC casts,
proteinuria (usually non-nephrotic range),
low serum complement in post-infectious
GN), RPGN often associated with antiGBM or ANCA
• Usually will need to perform renal biopsy
Atheroembolic ARF
• Associated with emboli of fragments of
atherosclerotic plaque from aorta and other large
arteries
• Diagnose by history, physical findings (evidence
of other embolic phenomena--CVA, ischemic
digits, “blue toe” syndrome, etc), low serum C3
and C4, peripheral eosinophilia, eosinophiluria,
rarely WBC casts
• Commonly occur after intravascular procedures or
cannulation (cardiac cath, CABG, AAA repair,
etc.)
Acute Interstitial Nephritis
– Usually drug induced
• methicillin, rifampin, NSAIDS
– Develops 3-7 days after exposure
– Fever, Rash , and eosinophilia common
– U/A reveals WBC, WBC casts, + Hansel
stain
– Often resolves spontaneously
– Steroids may be beneficial ( if Scr>2.5
mg/dl)
How do we assess a patient with AKI?
• Is this acute or chronic renal failure?
– History and examination
– Previous Serum creatinine measurements
– Small kidneys on ultrasound (except for in Diabetes, PCKD, Urinary Tract
Obstruction)
Hilton et al, BMJ 2006;333;786-790
Distinguishing ARF from CRF
Helpful clues…
Previous creatinine values
Hb – anemia suggests chronic problem
Renal ultrasound – small, echogenic kidneys suggest a
chronic problem
X-rays – renal osteodystrophy suggests chronic problem
Renal biopsy
Exceptions to the “small kidneys = CRF” rule:
early DM, amyloid, HIV nephropathy, PCKD
RBCs
•Dysmorphic red blood cells suggest glomerular injury.
Granular cast
Red blood cell cast
Marker of glomerular injury
Pigmented granular (“muddy brown”) casts
Marker of acute tubular necrosis
May- Grünwald - Giemsa staining
Marker of acute interstitial nephritis.
Biochemistry
• Serial blood urea, creatinine, electrolytes,
Blood gas analysis, serum bicarbonate –
– Important metabolic consequences of ARF
include hyperkalaemia, metabolic acidosis,
hypocalcaemia, hyperphosphataemia
Biochem….
• Creatine kinase, myoglobinuria –
– Markedly elevated CK and myoglobinuria
suggests rhabdomyolysis
• Serum immunoglobulins, serum protein
electrophoresis, Bence Jones proteinuria –
– Immune paresis, monoclonal band on serum
protein electrophoresis, and Bence Jones
proteinuria suggest multiple myeloma
Haematology
• Full blood count, blood film:
– Eosinophilia may be present in acute interstitial nephritis,
cholesterol embolization, or vasculitis (CSS)
– Thrombocytopenia and red cell fragments suggest
thrombotic microangiopathy –TTP, HUS
Haem….
• Coagulation studies
– Disseminated intravascular coagulation
associated with sepsis
Immunology
• Antinuclear antibody (ANA) , Anti-double stranded
(ds) antibody – ANA positive in SLE and other autoimmune
disorders;DNA antibodies anti-ds DNA antibodies more
specific for SLE
• C3 & C4 complement concentrations– Low in SLE, acute post infectious glomerulonephritis,
Cryoglobulinemia
• ASO and anti-DNAse B titres
– High after streptococcal infection
Hilton et al, BMJ 2006;333;786-790
Immunology
• ANCA
• p-ANCA - Anti PR3 antibodies
• c-ANCA - Anti MPO antibodies
– Associated with systemic vasculitis - Wegener’s
granulomatosis; CSS, Microscopic polyangiitis.
• AntiGBM antibodies
– Present in Goodpasture’s disease
serology
• Hepatitis B and C, HIV serology–
– Important implications for infection control
within dialysis area
• Radiology
• Renal ultrasonography
– For renal size, symmetry, evidence of
obstruction
Management principles in ARF
• Identify and correct pre-renal and postrenal factors
• Optimise cardiac output and RBF• Review drugs:
– Stop ACEI, ARBs, NSAIDs
– Adjust doses / monitor drug concentrations
(where appropriate)
Avoid
• Aminoglycosides
– 33 % of nephrotoxicity “therapeutic levels”
• Amphotericin
– hydration,
– Liposomal formulation
• Radiocontrast media – Hydration
– N-acetyl cysteine
Management principles..
• Accurately monitor fluid balance and
daily body weight
• Identify and treat acute complications
– Hyperkalaemia,
– Acidosis,
– Pulmonary oedema
Optimise nutritional support
• Maintaining calories enhances patient
survival
• Maintaining protein intake MAY
enhance recovery & outcome
• protein intakes of > 1.2- 1.4 g/kg/ day
can dramatically increase urea
production WITHOUT evidence of
outcome benefit
Management principles…
• Identify and aggressively treat infection;
– Minimise indwelling lines
– Remove bladder catheter if anuric.
• Identify and treat bleeding tendency:
– Prophylaxis - proton pump inhibitor or H2
antagonist, avoid aspirin
– transfuse if required
• Initiate dialysis before uraemic
complications set in.
Radiocontrast induced
nephropathy (RCIN)
• Less than 1% in patients with normal
renal function
• Increases significantly with renal
insufficiency
• Dialysis - rarely needed
Prophylactic Strategies
• Use I.V. contrast only when necessary
• Hydration with normal saline (1-1.5 mL/Kg/ h)
6 -12 h before and after the procedure.
• Use Low/ iso osmolar (nonionic) contrast
media
• Minimize contrast volume
• N-acetylcysteine - 600-1200 mg BID for two
doses before and 2 doses after the procedure
Indications for Dialysis
HYPERKALEMIA not amenable to medical therapy
ACIDOSIS not amenable to medical therapy
UREMIA resulting in pericarditis, neuropathy or
encephalopathy
Critical VOLUME OVERLOAD not responsive to diuresis
(dialyzable drug intoxication)
Conclusions.
• ARF is common worldwide
• Occurs in all clinical & community
settings
• It carries a high morbidity and
mortality risks.
• Involves high cost of management.
Conclusions..
• ARF is often preventable.
• Rapid recognition of incipient ARF
and early treatment of established ARF
may prevent irreversible loss of
nephrons.
Conclusions..
• No drug treatment has been shown to limit
the progression of, or speed up recovery
from, ARF.
• Advice from a nephrologist should be
sought for all cases of ARF.
THANK YOU