Acute Kidney Injury (AKI)

Hasnein Mohamedali

Supervisor: Dr Ernest Mrema

Outline• Definition• Classification systems• Pathophysiology• Etiology• Epidemiology• Clinical Presentation• Investigations• Management• Complications• Prognosis

Definition• Acute kidney injury (AKI) is defined as an abrupt or

rapid decline in renal function as measured by serum urea and creatinine leading to a failure to maintain fluid, electrolyte and acid – base hemostasis.

• The KDIGO guidelines suggest the following criteria for diagnosing AKI:

• Rise in creatinine >26 µmol/L in 48 hours• Rise in creatinine >1.5 from baseline (best figure in

3/12)• Urine output <0.5ml/kg/h for >6 consecutive hours

Categories• AKI may be classified into 3 general categories, as

follows:• Prerenal - As an adaptive response to severe

volume depletion and hypotension, with structurally intact nephrons

• Intrinsic - In response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage

• Postrenal - From obstruction to the passage of urine

The RIFLE Classification system

• In 2004, the Acute Dialysis Quality Initiative work group set forth a definition and classification system for acute renal failure, described by the acronym RIFLE (Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease)

Acute Kidney Injury Network classification system

• The Acute Kidney Injury Network (AKIN) has developed specific criteria for the diagnosis of AKI. The AKIN defines AKI as abrupt (within 48 hours) reduction of kidney function, manifested by any 1 of the following :

• An absolute increase in serum creatinine of 0.3 mg/dL or greater (≥26.4 µmol/L)

• A percentage increase in serum creatinine of 50% or greater (1.5-fold from baseline)

• A reduction in urine output, defined as less than 0.5 mL/kg/h for more than 6 hours

Pathophysiology

• Regardless of the cause of AKI, reductions in Renal Blood Flow (RBF) represent a common pathologic pathway for decreasing glomerular filtration rate (GFR).

• The etiology of AKI consists of 3 main mechanisms: prerenal, intrinsic, and obstructive.

• In prerenal failure, GFR is depressed by compromised renal perfusion. Tubular and glomerular function remain normal.

• Intrinsic renal failure includes diseases of the kidney itself. Ischemic renal injury is the most common cause of intrinsic renal failure.

• Obstruction of the urinary tract initially causes an increase in tubular pressure, which decreases the filtration driving force.

Etiology

• Prerenal AKI: most common form and can be due to:

1. Volume loss – GI, renal, cutaneous or hemorrhage

2. Decreased renal perfusion for e.g. in patients with heart failure or shock

3. Medications inducing AKI in volume depleted states including ACEI and ARBs, amphotericin B, aminoglycosides and radio contrast agents.

4. Arteriolar vasoconstriction e.g. hepatorenal syndrome

Intrinsic AKI

• Structural injury in the kidney is the hallmark of intrinsic AKI; the most common form is ATN, either ischemic or cytotoxic

• Vascular causes e.g. thrombosis, emboli, vasculitis, microangiopathies

• Glomerular causes e.g. anti-GBM disease, ANCA – associated glomerulonephritis

• Tubular causes – cytotoxic or ischemic• Drugs, infections and systemic causes

Postrenal AKI

• Mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters, bladder, or urethra.

• Causes of obstruction include the following: Stone disease, stricture,intraluminal, extraluminal, or intramural tumors, thrombosis or compressive hematoma, fibrosis.

Epidemiology• In the United States, approximately 1% of patients

admitted to hospitals have AKI at the time of admission.

• The estimated incidence rate of AKI during hospitalization is 2-5%.

• AKI develops within 30 days postoperatively in approximately 1% of general surgery cases and arises in up to 67% of intensive care unit (ICU) patients.

• Approximately 95% of consultations with nephrologists are related to AKI.

History and Clinical presentation

• Hx of etiologic factors• Co – morbid conditions which have high risk of

developing AKI• Urine output history – Oliguria or abrupt

anuria or gradually diminishing urine output.

Pre renal failure

• Symptoms related to hypovolemia – thirst, dizziness, decreased urine output, orthostasis

Intrinsic renal failure

• Can be divided into glomerular and tubular etiologies.

• Nephritic syndrome suggest glomerular etiology

• Query about prior throat or skin infections• ATN should be suspected in pts presenting

after a period of hypotension• Hx of exposure to nephrotoxins

Postrenal failure

• Usually older men with symptoms of urgency, frequency and hesitancy.

• Previous hx of pelvic surgery or malignancy• Flank pain and hematuria which could be due

to renal calculi• Use of acyclovir, methotrexate, triamterene,

indinavir, or sulfonamides implies the possibility that crystals of these medications have caused tubular obstruction.

Physical examination

• The most important part of the physical examination is the assessment of cardiovascular and volume status.

• Pulse rate and blood pressure recordings measured in the supine and the standing position

• Careful examination of the heart and lungs, skin turgor, and mucous membranes

• Assessment for peripheral edema

• Obtaining a thorough physical examination is extremely important when collecting evidence about the etiology of AKI. Clues may be found in any of the following:

• Skin e.g. butterfly rash, purpura• Eyes eg. Hypertensive or diabetic changes• Cardiovascular system (signs of heart failure)• Abdomen (costoverterbral angle tenderness)

Investigations

• Renal function tests• Normal ranges; Urea: 2.5 – 6.7 mmol/L

Creatinine: 70 – 150 µmol/L

eGFR: 90 – 120 ml/min/1.73m2

• The ratio of BUN to creatinine is an important finding. The ratio can exceed 20:1 in conditions in which enhanced reabsorption of urea is favored (eg, in volume contraction); this suggests prerenal AKI.

Urinalysis

• Granular, muddy brown casts• Sloughing of cells• Presence of RBCs – Eumorphic vs Dysmorphic• Presence of WBCs

CBC and peripheral smear

• To define the etiology e.g. the peripheral smear may show schistocytes in conditions such as hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP)

Ultrasonography

• For evaluating existing renal disease and obstruction of the urinary collecting system.

• Use of IVCD in evaluating the volume status of the body (normal 15 – 25 mm)

Renal Biopsy

• Useful in identifying intrarenal causes of AKI• Can be justified if the results may change

management (eg, initiation of immunosuppressive medications)

• may also be indicated when renal function does not return for a prolonged period

Management:• Maintenance of volume homeostasis and correction of

biochemical abnormalities remain the primary goals of treatment and may include the following measures:

Correction of fluid overload with furosemide (rule out obstructive causes first!!)

Correction of severe acidosis with bicarbonate administration, which can be important as a bridge to dialysis

Correction of hyperkalemiaCorrection of hematologic abnormalities (eg, anemia,

uremic platelet dysfunction) with measures such as transfusions.

Dialysis

• The indications for dialysis (AEIOU) includes:• Volume expansion that cannot be managed

with diuretics• Hyperkalemia refractory to medical therapy

(K > 7mmol/L)• Severe metabolic acidosis (pH < 7.2) • Drug overdose – BLAST • Uremia

Dietary Modification

• Restriction of salt and fluid • Because potassium and phosphorus are not

excreted optimally in patients with AKI, blood levels of these electrolytes tend to be high. Restriction of these elements in the diet may be necessary.

Complications• Cardiovascular complications – Fluid overload

leading to HF, cardiac arrest secondary to hyperkalemia

• GI complications - Nausea, vomiting, and anorexia are frequent complications of AKI and represent one of the cardinal signs of uremia.

• Neurologic complications - Neurologic sequelae include lethargy, somnolence, reversal of the sleep-wake cycle, and cognitive or memory deficits

Prognosis

• Age• Cause of renal failure e.g. burns (80%) and, • The presence or absence of preexisting kidney

disease (estimated GFR [eGFR] < 60 mL/min), • The duration of renal dysfunction prior to

therapeutic intervention.• Hypotension and the need for inotropic

support during renal replacement therapy are significant poor predictors for patient survival