ACUTE KIDNEY INJURY - an update - Dr Pooran Kumar Kohistani FCPS Nephrology Liaquat university of medical and health sciences, Jamshoro.

ACUTE KIDNEY INJURY- an update -

Dr Pooran Kumar Kohistani FCPS NephrologyLiaquat 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 Electrolytes balance o Volume regulation (Sodium balance)o Water balance & tonicity regulation

3. Production & secretion of enzymes & hormones:o Renin –– an enzyme from JGCo Erythropoiten — glycoprotein hormone secreted by

cortical interstitial cells.

o 1,25 dihydroxyvitamin D3 (active form) by prox.tubular cells, responsible for calcium & phosphate balance

Glomerular Filtration rateGlomerular 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 U x V ( urinary creatinine x volume ) P plasma creatinineCockcroft-Gault equation

140 - age x weight / 72 x s. creatinine [ x .85 for females ]

MDRD modified186 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 96ml/min/1.73m270 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/min50 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/min50 yrs old lady, weighing 40 kg, Cr 4.5 mg/dl 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 AKIProposed 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 < 0.5 ml/kg/hour GFR >25% x 6 hours

S. Creatinine x 2 < 0.5 ml/kg/hour GFR >50% x 12 hours

S. Creatinine x 3 < 0.3 ml/kg/hour x 24 h GFR >75% anuria x 12 hrs S. Creatinine 4 mg/dl acute 0.5 mg/dl

Persistant ARF = complete loss of kidney function > 4 weeks

End Stage Renal Disease > 3 moths

Risk

Injury

Failure

Loss

ESRD

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

functionAbsolute S. Creatinine 0.3 mg/dlPercentage 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 < 0.5 ml/kg BW/hour S. Creatinine 1.5-2 fold from baseline for > 6 hours

2 S. Creatinine >2-3 fold from baseline < 0.5 ml/kg BW/hour

for > 12 hours

3 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

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 swellingWeight gain, PND,Orthopnea,

Pitting edema, ↑ JVP,

S3, Pulmonarycrackles, pleuraleffusion

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

Pre renal

Urine Osmolality > 500U- Na (meq/L) < 20FENA* < 1%

Renal

< 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)

DIAGNOSTIC URINARY INDICES IN AKI

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 Chronic intrinsic renal disease.Normal sizes

Echogenic Acute GN, ATNNormal Echo Pre renal AKI, Ac.

Renal artery obstructionEnlarged Malignant infiltration, Amyloid, Renal vein thrombosis,, HIV associatedPelviicalyceal dilatation Obstructive nephropathy

STRATEGIES TO DECREASE AKI

STRATEGIES TO DECREASE AKIVolume Expansion

risk of AKI, radio contrast agentsisotonic 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 AKIThe 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 - 261 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 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 Absolute/RelativeMetabolic AbnormalityBUN > 76 RBUN > 100AK > 6RK > 6 ė ECG abnormalityADysnatremiaRMg > 8 RMg >8 ė anuria, absent tendon jerksA

Timing of Initiation & Discontinuation of

RRT in AKI: Unanswered Key Questions. Clin J Am Soc Nephrol 3: 876-880, 2008 Indication - 2 Absolute/RelativeAcidosisPH > 7.15 RPH < 7.15 ALactic acidosis with metformin

AAnuria / OliguriaRIFLE class R, I, FRFluid OverloadDiuretic SensitiveRDiuretic ResistantA

Timing of Initiation & Discontinuation of

RRT in AKI: Unanswered Key Questions. Clin J Am Soc Nephrol 3: 876-880, 2008 Indication - 2 Absolute/RelativeAcidosisPH > 7.15 RPH < 7.15 ALactic acidosis with metformin

AAnuria / OliguriaRIFLE class R, I, FRFluid OverloadDiuretic SensitiveRDiuretic ResistantA

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 RRTWhat 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 • 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