Transcript Acute Renal Failure - Liaquat University of Medical & Health Sciences

ACUTE KIDNEY INJURY
- an update -
Dr Pooran Kumar Kohistani
FCPS Nephrology
Liaquat university of medical and health
sciences, Jamshoro
What are the major functions of kidneys
Functions of Kidney
1. Excretion of metabolic end products & foreign substances
like,urea,creatinine,toxins and drugs. (Function of
glomerulus)
2. Maintenance of body composition:
o
o
o
Electrolytes balance
Volume regulation (Sodium balance)
Water balance & tonicity regulation
3. Production & secretion of enzymes & hormones:
o
o
o
Renin –– an enzyme from JGC
Erythropoiten — glycoprotein hormone secreted by
cortical
interstitial cells.
1,25 dihydroxyvitamin D3 (active form) by
prox.tubular cells, responsible for calcium &
phosphate balance
Glomerular Filtration rate

Both kidneys receive ~= 20% of the
cardiac
output (~= 1200 ml / min)

On average Glomerular Filtration rate is
~= 125 ml / min.

Filtration rate is relatively constant – auto
regulation

Final urine output is ~= 1 ml / min.

So ~99% fluid of the filtrate is missing.
And also other solutes are missing too.
(So, Where this filtrate of blood is ???)
Reabsorption
TUBULAR FUNCTION:
Basic principles
Absorption & secretion in the Renal Tubules
•
The glomerular filtrate undergoes a series of
modifications before becoming the final urine.
These changes are:
1.
Absorption, the movement of solutes & water
from tubular lumen to blood e.g.
Na+,Cl¯,H2O,HCO3¯, glucose, amino acids,
proteins, phosphates, Ca2+, Mg2+, urea, uric
acid and other
2.
Secretion, the movement of solutes from the
blood or cell interior to tubular lumen e.g.
H+,NH4+,K+ and a number of organic acids and
bases.
MEASURE OF KIDNEY FUNCTION - 1
NKF CKD Guidelines
‘clinicians should not use serum creatinine concentration as
the sole means to assess the level of kidney function’
S. Creatinine reflects muscle mass –
Different kits may give a different result - up to 0.3 mg/dl
Estimate creatinine clearance via equations that take into
account variables as age, sex, race, body size.
MEASURE OF KIDNEY FUNCTION – 2
Timed collection of urine for creatinine clearance
UxV
P
( urinary creatinine x volume )
plasma creatinine
Cockcroft-Gault equation
140 - age x weight / 72 x s. creatinine
[ x .85 for females ]
MDRD modified
186 x [Cr.] -1.154 x [age] -0.203 x [0.742 for females] x
[1.210 for blacks]
MEASURE OF KIDNEY FUNCTION - 3
40 yrs old black man Cr 1.1mg/dl
70 yrs old white woman Cr 1.1mg/dl
96ml/min/1.73m2
52 ml/min/1.73m2
MDRD modified
50 yrs old lady, weighing 40 kg, Cr 0.5 mg/dl
50 yrs old lady, weighing 40 kg, Cr 1 mg/dl
85 ml/min
42.5 ml/min
Cockcroft-Gault equation
50 yrs old lady, weighing 40 kg, Cr 4.0 mg/dl
50 yrs old lady, weighing 40 kg, Cr 4.5 mg/dl
10.6 ml/min
9.44 ml/min
Cockcroft-Gault equation
ACUTE kidney Injury Definition
• Traditionally defined as the abrupt decrease of
renal function sufficient to result in retention of
nitrogenous waste products, as well as loss of
regulation of extracellular volume and electrolytes
Reduction in GFR that is often reversible.
there has been no agreement on how much
serum creatinine has to increase and over
what period of time for it to constitute AKI
Proposed definition for AKI:
•0.5 mg/dl within 48 hours
•50 % increase to at least 2 mg/dl.
•Urine out put (oliguria).
•Urea level
The RIFLE Criteria - Critical Care Clin. 2005; 21:223-237
The International Acute Dialysis Quality Initiative Group
GFR
Urine output
S. Creatinine x 1.5
GFR  >25%
Risk
S. Creatinine x 2
GFR  >50%
Injury
Failure
S. Creatinine x 3
GFR  >75%
S. Creatinine 4 mg/dl
acute 0.5 mg/dl
Loss
ESRD
< 0.5 ml/kg/hour
x 6 hours
< 0.5 ml/kg/hour
x 12 hours
< 0.3 ml/kg/hour x 24 h
anuria x 12 hrs
Persistant ARF = complete loss
of kidney function > 4 weeks
End Stage Renal Disease > 3 moths
Acute Kidney Injury Network: Report of an Initiative to
Improve Outcomes in Acute Kidney Injury.
Critical care 2007: 11 R 31
18 Nephrology Societies,
7 Critical Care Societies
Acute Kidney Injury (AKI) to reflect entire spectrum
Diagnostic Criteria:
Abrupt (within 48 h) reduction in kidney function
Absolute S. Creatinine  0.3 mg/dl
Percentage S. Creatinine  50% (1.5 fold)
Reduction in urine output
< 0.5 ml/kg BW/hour
for > 6 hours
Acute Kidney Injury Network: Report of an Initiative to
Improve Outcomes in Acute Kidney Injury.
Critical Care 2007: 11 R 31
Classification/ Staging system for Acute Kidney Injury
1
S. Creatinine  0.3 mg/dl or
S. Creatinine 1.5-2 fold from baseline
2
S. Creatinine >2-3 fold from baseline
3
< 0.5 ml/kg BW/hour
for > 6 hours
< 0.5 ml/kg BW/hour
for > 12 hours
Creatinine 4 mg/dl with an acute 0.5 < 0.3 ml/kg BW/hour
S. Creatinine >3 fold from baseline
for > 24 hrs or anuria
for 24 hrs.
RRT irrespective of any of the above criteria is stage 3
Etiology of acute kidney injury
ACUTE RENAL FAILURE - etiology
Pre Renal Failure
 Volume depletion



Hypotension
congestive cardiac failure
Hemodynamic causes
 (intrarenal vasoconstriction)







Radiocontrast
PGinhibitors(NSAIDs)
CNI inhibitors
ACE inhibitors, ARBs
Amphotericin
Hypercalcemia
Hepato renal syndrome
intrinsic / intra Renal
 Vascular
 Renal infarction,renal artery or
vein thrombosis
 Malignant hypertension
 Tubular
 Ischemia
 nephrotoxic
 Glomerular
 Acute GN
 Vasculitis
 Thrombotic microangiopathy
 Interstitium
 Drugs
 tumor infilteration
ACUTE RENAL FAILURE - etiology
Postrenal:
a) Intra renal (tubular):
precipitation of insoluble crystals (phosphates,
methotraxate, acyclovir,sulfonamides,uric acid), or
protein hemoglobin , myoglobin, paraprotein.
b) Obstruction of extra renal collecting system:
Prostate hypertophy
Neurogenic bladder
Intraureteral obstruction:( stones,tumor, clot, crystal ie uric
acid,acyclovir,indinavir )
Extra ureteral obstruction: tumor , retroperitoneal fibrosis
CLINICAL EVALUATION OF PATIENT
WITH AKI
•Is injury acute, Chronic or acute on Chronic?
•Is there hypovolemia/  effective arterial blood volume?
•Has there been a major vascular occlusion?
•Evidence of parenchymal renal disease other than ATN?
•Is there renal tract obstruction?
AKI vs. CHRONIC KIDNEY DISEASE
•History
•Serial record of serum creatinine (drug therapies/interventions)
•Laboratory tests.
•Normochromic, normocytic anemia
•Hyperphosphatemia.
•Hypocalcemia
•Ultrasound of kidneys.
•Normal – does not exclude CRF (DM, amyloid Polycystic)
•Bilateral small, echogenic – consistent with CRF. ( acute on
chronic)
CLINICAL EVALUATION – History
•DM, HTN, CCF
•Liver disease (pre renal, renal, hepato-renal)
•Health checks
•Urinary symptoms, recurrent UTI
•Systemic illness
•Recent surgery/ procedures
•Radiocontrasts.
•Arterial catheterization involving aorta, AF
•Drug history, NSAIDS, ACE, ARB, Herbal, Hakim,
Recreational
•Volume loss/ sequestration.
•Muscle pain weakness, rhabdomyolysis, muscle trauma drugs.
CLINICAL EVALUATION–Physical Examination 2
Intravascular Volume
Depletion
Volume Overload
History
Record
Thirst, dry mucosae, Oliguria
Excessive fluid loss, I/O chart,
Weight Record
Ankle swelling
Weight gain, PND,
Orthopnea,
Physical
Examination
skin turgor,dry mucosa,  JVP
Postural hypotension,
Orthostatic tachycardia.
Pitting edema, ↑ JVP,
S3, Pulmonary
crackles, pleural
effusion
INTAKE/ OUTPUT CHART, WEIGHT RECORD
CLINICAL EVALUATION–Laboratory Tests
•Urinalysis
–Significant proteinuria, glomerular disease.
–RBC and RBC cast suggest glomerular cause.
–Large number of WBC and WBC cast pyelonephritis,
interstitial nephritis.
–Eoisinophils > 1% of WBC, allergic interstitial nephritis,
cholesterol embolism.
–Lack of RBC despite large Hb on dipstick, myoglobinuria,
hemoglobinuria.
CLINICAL EVALUATION–Laboratory Tests
•Urine Volume
–Oliguria < 500ml/day, < 20 ml/hour.
–Anuria < 100 ml/day.
–Non-oliguric better prognosis
–Anuria:
RPGN,
Acute cortical necrosis,
Total renal arterial or venous occlusion,
Complete urinary tract obstruction
DIAGNOSTIC URINARY INDICES IN AKI
Urine Osmolality
U- Na (meq/L)
FENA*
Pre renal
Renal
> 500
< 20
< 1%
< 350
> 40
> 2%
FENA= (U-Na x P-Cr/Pl-Na x U- Cr)
Diuretic therapy, glycosuria, CRF
(FeNa < 1%: CIN, pigment induced AKI, acute GN, some cases of
acute interstital nephritis and obstruction)
CLINICAL EVALUATION–Laboratory Tests
Serum Creatinine
•in complete absence of GFR S. Creatinine es by 1-1.5
mg/day.
•When an abrupt and complete interruption in GFR is
followed by progressive recovery, S. creatinine will increase
with peak on day 3-5.
•After nephrotoxic insult, no. of days that serum creatinine
continues to increase has prognostic value.
CLINICAL EVALUATION– Ultrasonography
Observation
Clue to diagnosis
Shrunken Kidneys
Normal sizes
Echogenic
Normal Echo
Chronic intrinsic renal disease.
Enlarged
Pelviicalyceal dilatation
Acute GN, ATN
Pre renal AKI, Ac. Renal artery
obstruction
Malignant infiltration, Amyloid,
Renal vein thrombosis,, HIV
associated
Obstructive nephropathy
STRATEGIES TO DECREASE AKI
STRATEGIES TO DECREASE AKI
Volume Expansion
•  risk of AKI, radio contrast agents
isotonic soda bicab@ 3ml/kg BW x 6 hrs superior
•  risk of AKI, surgery of aorta, of obstructive jaundice, renal Tx
• early fluid resuscitation in critically ill é sepsis in ER.  mortality
&  risk of AKI
• Crush syndrome-myoglobin induced AKI hydration as early as
possible. 1-1.5 L first hr, 10 L/day. UO > 300 ml/hr.
• ??? ICU patients with multiple risk factors, third-space loss.
• Cardiac failure with  renal perfusion, precipitate pulmonary
edema.
Evaluation and Initial Management of Acute
Kidney Injury. Clin J Am Soc Nephrol 2008
Volume – responsive AKI
Volume – unresponsive AKI
Volume responsive of the kidney
Volume responsive patient
STRATEGIES TO DECREASE AKI
The main effect of protein C is to
• Reduce the production of thrombin, by inactivating factors Va
and VIII.
• Inhibits the influence of tissue factor on the clotting system
• Reduces the production of IL-1, IL-6, and TNF-α by monocytes,
and has profibrinolytic properties by inactivating PAI-1 (it
inactivates the inhibitor of the activator of the agent that converts
plasminogen into plasmin)
• There is now compelling evidence that the exogenous
administration of activated protein C to patients, in severe sepsis,
improves outcome.
• Drotrecogin alpha (Xigris) 24 mcg/hr 96 hrs
• Risk of increased bleeding
DOPAMINE (low dose) in ARF Meta-analysis - 2
61 trials 3359 patients identified.
Meta-analysis showed no effect of low dose dopamine on
Mortality
RR 0.96 (95% CI 0.78-1.19)
Need for RRT
RR 0.93 (95% CI 0.76-1.15)
Adverse events
RR 1.13 (95% CI 0.90-1.41)
Low dose dopamine
urine out-put by (on day 1)
improvement in S creatinine
e Creatinine clearance
24% (CI 14-35%)
4% (CI 1-7%)
6% (CI 1-11%)
Ann. Int. Med 2005;142:510-524
FRUESEMIDE to prevent or treat ARF: Meta-analysis 4
Frusemide is NOT associated with
any significant clinical benefits
in the prevention and treatment of
acute kidney injury in adults.
High doses may be associated with an
increased risk of ototoxicity.
BMJ 2006; 333:420
Timing of Initiation & Discontinuation of RRT in AKI:
Unanswered Key Questions.
Clin J Am Soc Nephrol 3: 876-880, 2008
Indication – clinical or biochemical conditidion that defines the
need for RRT in the presence of AKI
Absolute – each indication can represent a stand-alone condition
making RTT mandatory.
Relative – requires concomitant conditions without which RRT
can only be suggested or recommended but not considered
mandatory.
Timing of Initiation & Discontinuation of RRT in AKI:
Unanswered Key Questions.
Clin J Am Soc Nephrol 3: 876-880, 2008
Timing – time in which RRT is initiated in patients with AKI
Early/ Late
RIFLE/AKI staging system.
Severity score – no. and severity of comorbidities.
Trends – rate of biochemical changes.
Illness trajectory – pace of clinical evolution of the patient
Timing of Initiation & Discontinuation of RRT in AKI:
Unanswered Key Questions.
Clin J Am Soc Nephrol 3: 876-880, 2008
Indication
Metabolic Abnormality
BUN > 76
BUN > 100
K>6
K > 6 ė ECG abnormality
Dysnatremia
Mg > 8
Mg >8 ė anuria, absent tendon jerks
Absolute/Relative
R
A
R
A
R
R
A
Timing of Initiation & Discontinuation of RRT in AKI:
Unanswered Key Questions.
Indication - 2
Acidosis
PH > 7.15
PH < 7.15
Lactic acidosis with metformin
Anuria / Oliguria
RIFLE class R, I, F
Fluid Overload
Diuretic Sensitive
Diuretic Resistant
Clin J Am Soc Nephrol 3: 876-880, 2008
Absolute/Relative
R
A
A
R
R
A
Timing of Initiation & Discontinuation of RRT in AKI:
Unanswered Key Questions.
Indication - 2
Acidosis
PH > 7.15
PH < 7.15
Lactic acidosis with metformin
Anuria / Oliguria
RIFLE class R, I, F
Fluid Overload
Diuretic Sensitive
Diuretic Resistant
Clin J Am Soc Nephrol 3: 876-880, 2008
Absolute/Relative
R
A
A
R
R
A
Timing of Initiation & Discontinuation of RRT in AKI:
Unanswered Key Questions.
Clin J Am Soc Nephrol 3: 876-880, 2008
Research Questions
1
Timing of initiation of RRT
What are the indications of RRT in in AKI?
What factors determine timing of initiation of RRT?
Does the timing of initiation of RRT influence outcome in AKI?
2
Does the timing of discontinuation of RRT in AKI influence
renal recovery and out come?
Delivery of RRT in AKI: What are the key issues.
Clin J Am Soc Nephrol 3: 876-880, 2008
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•
•
•
•
Data on optimal dosage of RRT for AKI in IHD, Hybrid
techniques, and PD are limited.
An UF flow rate of 35 ml/kg /hr in CVVH and dialysate
clearance of 18 ± 5 ml/kg/hr – superior outcome compared
with 20-25 ml/kg/hr.
Current data do not suggest that any specific modality of
RRT in AKI is superior, PD may be inferior.
Benefit with less bioincompatible dialysis membrane in AKI
is uncertain.
Heparin is the most common anticoagulant, yet citrate may
offer certain advantages during CRRT..
Take home message
• AKI , most of the time reversible.
• Furosimide (lasix) no more recommended.
• Renal dose dopamine no more validated.
END