ACUTE KIDNEY INJURY

(AKI)

Abdulsalam Halboup

M.Pharma (Clinical)

ACUTE KIDNEY INJURY

Acute kidney injury (AKI) is abrupt reduction in kidney

functions as evidence by changed in laboratory values; serum

creatinine, blood urea nitrogen(BUN)and urine output.

Acute kidney injury (AKI) is diagnosed if one of the

following criteria is met :

increase in serum creatinine (SCr) of at least 0.3 mg/dL

within 48 hours,

a 50% increase in baseline SCr within 7 days, or

a urine output of less than 0.5 mL/kg/hour for at least 6

hours.

EPIDEMIOLOGY AND ETIOLOGY

Between 5% and 7% of all hospitalized patients develop

AKI.

A greater prevalence of AKI is found in critically ill

patients ( ICU-Acquired AKI).

Despite improvements in the medical care of individuals

with AKI, mortality generally exceeds 50%.

EPIDEMIOLOGY

CLASSIFICATION OF AKI

Criteria used for AKI classification

RIFLE: Risk, Injury, Failure, Loss of Kidney

Function and End Stage Renal Disease).

AKIN: Acute Kidney Injury Network

KDIGO: Kidney Disease Improving Global

Outcome

AKI CLASSIFICATION SYSTEMS

PATHOPHYSIOLOGY

There are typically three categories of AKI:

1-prerenal AKI

2- intrinsic AKI

3- Postrenal AKI

PRERENAL AKI

Prerenal AKI: is characterized by reduced blood delivery to the kidney.

A common causes are:

Volume depletion hemorrhage

dehydration

GI fluid losses.

Decrease effective circulatory blood volume Decrease cardiac output (CHF, MI, hypotension

Pulmonary hypertension

Liver failure

Sepsis

Functional ACEIs, NSAIDs, ARBs, Cyclosporine and tacrolimus

Prompt correction of volume depletion can restore kidney function to normal because no structural damage to the kidney has occurred.

INTRINSIC AKI

Damage is within the kidney (structure of the nephron,);

Vascular damage (renal thrombosis)

Glomerular damage (nephrotic/nephritic glomerulonephritis

Acute tubular necrosis(ATN)(it accounts for 50% of all cases of AKI)

Ischemia (hypotension, sepsis

Endogenous toxins(uric acid ,hemoglobin

Exogenous toxin

Aminoglycosides

contrast induced nephropathy (CIN)

amphotericin B

Acute interstitial nephritis NSAIDs

infections

Prerenal AKI can progress to intrinsic AKI if the underlying condition is not promptly corrected

POSTRENAL AKI

Postrenal AKI is due to obstruction of urinary

outflow

Bladder outlet obstruction

Benign prostatic hypertrophy

Prostate cancer

Anticholinergic drug

Ureteral obstruction Malignancy

Pelvic / renal obstruction

Postrenal AKI accounts for less than 10% of cases of

AKI

Rapid resolution of Postrenal AKI without structural

damage restore kidney function

By monitoring Scr on a routine basis, it can be

estimated whether kidney function is improving or

worsening.

Kidney function can also be evaluated based on urine

output. Oliguria and anuria

Oliguria is defined as urine outputs of less than 400 ml

over 24 hours

anuria is defined as urine output of less than 50 mL over

24 hours.

CLINICAL PRESENTATION AND DIAGNOSIS OF AKI

Peripheral edema

Weight gain

Nausea/vomiting/diarrhea/anorexia

Mental status changes

Fatigue

Shortness of breath

Pruritus

LABORATORY TESTS

Elevated Scr (normal range approximately 0.6-1.2

mg/dL [53 to 106 μmol/L])

Elevated BUN concentration (normal range

approximately 8 to 25 mg/dL [2.9-8.9 mmol/L])

Decreased CrCl (normal 90–120 mL/min)

BUN: creatinine ratio

greater than 20:1 in Prerenal AKI

Less than 20:1 in intrinsic or Postrenal AKI

Hyperkalemia

Metabolic acidosis

PREVENTION APPROACHES

Non-pharmacology for prevention

Hydration to prevent contrast induced nephrotoxicity

KDIGO guideline recommend using normal saline or

sodium bicarbonate infusion

Normal saline regimen: 1ml/kg/h for 12hours before

and after procedure.

Sodium bicarbonate regimen: 3ml/kg/hours for one

hour before procedure and 1ml/kg/hours for 6 hours

postcontrast.

PHARMACOLOGICAL THERAPY

For prevention of CIN

Ascorbic acid:3g orally pre and 2mg orally for two

doses postprocedure and N-acetylcysteine(600-1200mg

orally every 12 hours for 2-3 days, the first two doses

precontrast

Current KDIGO guideline suggest moderate control of

blood glucose to level of 110-149 mg/dl with insulin

prevent ICU-Acquired AKI

TREATMENT OF ACUTE KIDNEY INJURY

Goal of treatment:

Minimize the degree of kidney insult

Reduce extrarenal complication

Restoration of renal function to pre AKI is the

ultimate goal

TREATMENT APPROACHES

Currently, there is no definitive therapy for

AKI, supportive care is the mainstay of

management regardless of etiology.

SUPPORTIVE CARE IN AKI

Supportive care includes :

Adequate nutrition,

correction of electrolyte and acid-base abnormalities

(particularly hyperkalemia and metabolic acidosis)

Fluid management,

Correction of any hematologic abnormalities

Medical management of infections, cardiovascular and

GI conditions, and respiratory failure

all drugs should be reviewed, and dosage adjustments

made based on an estimate of the patient’s GFR.

NON-PHARMACOLOGICAL THERAPY

Maintenance of adequate cardiac output and blood pressure to optimize tissue perfusion

Discontinue medication associated with diminished renal blood flow

Initiate appropriate fluid and electrolyte

Renal replacement therapy RRT in sever AKI Hemodialysis

Peritoneal dialysis

Absolute indications for dialysis usually include: BUN greater than 100 mg/dL (35.7 mmol/L)

Potassium greater than 6 mEq/L (6 mmol/L)

Magnesium greater than 9.7 mg/dL (4.0 mmol/L)

Metabolic acidosis with a pH less than 7.15

Diuretic-resistant fluid overload.

RENAL REPLACEMENT THERAPY

PHARMACOLOGIC THERAPY

Loop diuretics : are effective to reduce fluid

overload.

it can worsen AKI.

Thiazide diuretics, when used as single agents, are

generally not effective for fluid removal.

Mannitol is also not recommended for treating volume

overload associated with AK.

Potassium sparing diuretics are not recommended.

low dose dopamine LDD is not indicated in treating the

AKI.

Equipotent dose of loop diuretics (Furosemide,

bumetanide, torsemide and ethacrinic acid ) all have

similar efficacy

Ethacrynic acid is reserved for sulfa-allergic patient

Continues infusion of loop diuretic overcome

diuretic resistance

associated with less adverse effect than intermittent bolus

Dose:

Initial iv loading dose equivalent to (40-60mg

furosemide )

Continuous infusion equivalent to 10-20mg/h

STRATEGY TO OVERCOME DIURETIC

RESISTANCE

Administration of agents from different

pharmacological classes, they act synergistically

Thiazide (works on: distal convoluted tubule)

loop diuretics (works on: ascending loop of Henle)

ELECTROLYTE MANAGEMENT

Serum electrolyte should be monitored

daily.

Hyperkalemia is the most common and serious

electrolyte abnormality in AKI

Hypernatremia and fluid retention commonly

occur …require daily calculation of sodium intake

Phosphorus and magnesium should be

monitored

PREVENTION OF ACUTE RENAL

FAILURE

Avoidance

The best preventive measure for AKI, especially in individuals at

high risk, is to avoid medications that are known to precipitate AKI.

Nephrotoxicity is a significant side effect of

aminoglycosides,

ACE inhibitors, angiotensin receptor

antagonists(ARBs),(what are the risk factors?)

Amphotericin B

NSAIDs

Cyclosporine, tacrolimus,

Radiographic contrast agents GFR less than 60 mL/min

, diabetes, dehydration, age more than 65 years,

How to reduce CI-AK?