ACUTE KIDNEY INJURY - an update -

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ACUTE KIDNEY INJURY- an update -

• Dr Pooran Kumar Kohistani
• FCPS
  Nephrology
• Liaquat university of medical and health
  sciences, Jamshoro

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What are the major functions of kidneys ?
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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
• Electrolytes balance
• Volume regulation (Sodium balance)
• Water balance tonicity regulation
• 3. Production secretion of enzymes hormones
• 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

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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

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TUBULAR FUNCTIONBasic principlesAbsorption
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.

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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.

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MEASURE OF KIDNEY FUNCTION 2

• Timed collection of urine for creatinine
  clearance
• U x V ( urinary creatinine x
  volume )
• P 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

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MEASURE OF KIDNEY FUNCTION - 3

• 40 yrs old black man Cr 1.1mg/dl
  96ml/min/1.73m2
• 70 yrs old white woman Cr 1.1mg/dl 52
  ml/min/1.73m2
• MDRD modified
• 50 yrs old lady, weighing 40 kg, Cr 0.5 mg/dl
  85 ml/min
• 50 yrs old lady, weighing 40 kg, Cr 1 mg/dl
  42.5 ml/min
• Cockcroft-Gault equation
• 50 yrs old lady, weighing 40 kg, Cr 4.0 mg/dl
  10.6 ml/min
• 50 yrs old lady, weighing 40 kg, Cr 4.5 mg/dl
  9.44 ml/min
• Cockcroft-Gault equation

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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

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• 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

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The RIFLE Criteria - Critical Care Clin. 2005
21223-237 The International Acute Dialysis
Quality Initiative Group
GFR Urine output
?S. Creatinine x 1.5 lt 0.5 ml/kg/hour GFR ?
gt25 x 6 hours
Risk Injury Failure Loss
ESRD

?S. Creatinine x 2 lt 0.5 ml/kg/hour GFR ?
gt50 x 12 hours
S. Creatinine x 3 lt 0.3 ml/kg/hour x 24 h
GFR ? gt75 anuria x 12 hrs S.
Creatinine ?4 mg/dl acute ?0.5 mg/dl
Persistant ARF complete loss of kidney
function gt 4 weeks
End Stage Renal Disease gt 3 moths
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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
• lt 0.5 ml/kg BW/hour
• for gt 6 hours

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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 lt 0.5 ml/kg
  BW/hour
• ?S. Creatinine 1.5-2 fold from baseline for gt
  6 hours
• 2 ?S. Creatinine gt2-3 fold from baseline lt 0.5
  ml/kg BW/hour
• for gt 12 hours
• 3 Creatinine ?4 mg/dl with an acute ?0.5 lt 0.3
  ml/kg BW/hour
• ?S. Creatinine gt3 fold from baseline for gt 24
  hrs or anuria for 24 hrs.
• RRT irrespective of any of the above criteria is
  stage 3

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Etiology of acute kidney
injury
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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

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ACUTE RENAL FAILURE - etiology

• Postrenal
• 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

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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?

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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)

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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.

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CLINICAL EVALUATIONPhysical Examination 2

• Intravascular Volume Depletion
• History Thirst, dry mucosae, Oliguria
• Record Excessive fluid loss, I/O chart,
• Weight Record
• Physical ?skin turgor,dry mucosa, ? JVP
• Examination Postural hypotension,
• Orthostatic tachycardia.

• Volume Overload
• Ankle swelling
• Weight gain, PND,
• Orthopnea,
• Pitting edema, ? JVP,
• S3, Pulmonary
• crackles, pleural
• effusion

INTAKE/ OUTPUT CHART, WEIGHT RECORD
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CLINICAL EVALUATIONLaboratory Tests

• Urinalysis
• Significant proteinuria, glomerular disease.
• RBC and RBC cast suggest glomerular cause.
• Large number of WBC and WBC cast pyelonephritis,
  interstitial nephritis.
• Eoisinophils gt 1 of WBC, allergic interstitial
  nephritis, cholesterol embolism.
• Lack of RBC despite large Hb on dipstick,
  myoglobinuria, hemoglobinuria.

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CLINICAL EVALUATIONLaboratory Tests

• Urine Volume
• Oliguria lt 500ml/day, lt 20 ml/hour.
• Anuria lt 100 ml/day.
• Non-oliguric better prognosis
• Anuria
• RPGN,
• Acute cortical necrosis,
• Total renal arterial or venous occlusion,
• Complete urinary tract obstruction

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DIAGNOSTIC URINARY INDICES IN AKI

• Pre renal
• Urine Osmolality gt 500
• U- Na (meq/L) lt 20
• FENA lt 1

• Renal
• lt 350
• gt 40
• gt 2

FENA (U-Na x P-Cr/Pl-Na x U- Cr) Diuretic
therapy, glycosuria, CRF (FeNa lt 1 CIN, pigment
induced AKI, acute GN, some cases of acute
interstital nephritis and obstruction)
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CLINICAL EVALUATIONLaboratory 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.

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CLINICAL EVALUATION Ultrasonography

• Observation Clue to diagnosis
• Shrunken Kidneys Chronic intrinsic renal
  disease.
• Normal sizes
• Echogenic Acute GN, ATN
• Normal Echo Pre renal AKI, Ac. Renal artery
  obstruction
• Enlarged Malignant infiltration, Amyloid,
  Renal vein thrombosis,, HIV associated
• Pelviicalyceal dilatation Obstructive
  nephropathy

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STRATEGIES TO DECREASE AKI
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STRATEGIES TO DECREASE AKI

• Volume Expansion
• ? risk of AKI, radio contrast agents
• isotonic soda bicab_at_ 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
  gt 300 ml/hr.
• ??? ICU patients with multiple risk factors,
  third-space loss.
• Cardiac failure with ? renal perfusion,
  precipitate pulmonary edema.

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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

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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-a
  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

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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) 24 (CI 14-35)
• improvement in S creatinine 4 (CI 1-7)
• e Creatinine clearance 6 (CI 1-11)
• Ann. Int. Med 2005142510-524

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FRUESEMIDE to prevent or treat ARF Meta-analysis
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• 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 333420

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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.

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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

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Timing of Initiation Discontinuation of RRT in
AKI Unanswered Key Questions. Clin J Am Soc
Nephrol 3 876-880, 2008

• Indication Absolute/Relative
• Metabolic Abnormality
• BUN gt 76 R
• BUN gt 100 A
• K gt 6 R
• K gt 6 e ECG abnormality A
• Dysnatremia R
• Mg gt 8 R
• Mg gt8 e anuria, absent tendon jerks A

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Timing of Initiation Discontinuation of RRT in
AKI Unanswered Key Questions. Clin J Am Soc
Nephrol 3 876-880, 2008

• Indication - 2 Absolute/Relative
• Acidosis
• PH gt 7.15 R
• PH lt 7.15 A
• Lactic acidosis with metformin A
• Anuria / Oliguria
• RIFLE class R, I, F R
• Fluid Overload
• Diuretic Sensitive R
• Diuretic Resistant A

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Timing of Initiation Discontinuation of RRT in
AKI Unanswered Key Questions. Clin J Am Soc
Nephrol 3 876-880, 2008

• Indication - 2 Absolute/Relative
• Acidosis
• PH gt 7.15 R
• PH lt 7.15 A
• Lactic acidosis with metformin A
• Anuria / Oliguria
• RIFLE class R, I, F R
• Fluid Overload
• Diuretic Sensitive R
• Diuretic Resistant A

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Timing of Initiation Discontinuation of RRT in
AKI Unanswered Key Questions. Clin J Am Soc
Nephrol 3 876-880, 2008

• Research Questions
• 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?

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Delivery of RRT in AKI What are the key issues.
Clin J Am Soc Nephrol 3 876-880, 2008

• 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..

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Take home message

• AKI , most of the time reversible.
• Furosimide (lasix) no more recommended.
• Renal dose dopamine no more validated.

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• END