**Acute Kidney Injury**

Acute Kidney Injury

Acute kidney injury (AKI) is a sudden decrease in kidney function, often reversible within a few hours to days.

Acute kidney injury (AKI) is a syndrome with varying severity over different stages, characterized by acute decline in glomerular filtration rate (GFR) (increased blood urea nitrogen, serum creatinine) within hours to days.

Definition: AKI is a syndrome characterized by:

• Rapid decline in GFR, hours to days

• Retention of nitrogenous waste products such as urea, creatinine

• Progression through different stages in terms of time, severity, onset, progression, and recovery

• Recovery depends on the cause, pre-existing kidney disease, and treatment

Non-oliguric form: Urine volume > 500ml/24h, rapid decline in GFR.

Causes of non-oliguric AKI:

• Antibiotics

• Contrast media

• Acute interstitial nephritis

• Acute glomerulonephritis

• Rhabdomyolysis

• Obstructive kidney disease

Markers used in AKI:

• Serum creatinine

• Urea, BUN

• Cystatin C

• Biomarkers in acute kidney injury

Serum creatinine:

• Filtered through the glomerulus

• Secreted in the renal tubules

• Not reabsorbed

Factors affecting creatinine without affecting kidney function:

• Increased creatinine due to inhibition of secretion:

• Trimethoprime

• Cimetidine

• Increased creatinine due to measurement effects:

• Ascorbic acid

• Cephalosporins

• Other factors:

• Age, gender, nutrition, volume of distribution

• Race

• Nutrition

• Amputation

BUN:

• Increased reabsorption with dehydration

• Increased BUN without affecting kidney function:

• Increased catabolism

• High protein intake

• Gastrointestinal bleeding

• High doses of corticosteroids

• Low BUN found in:

• Low protein diet, malnutrition, severe liver disease

Cystatin C:

• A protein produced by nucleated cells

• Freely filtered in the glomerulus

• Completely reabsorbed in the proximal tubules

• Not secreted

Advantages of Cystatin C over Creatinine:

• Related to muscle mass

• More variable than creatinine in AKI

Biomarkers of AKI:

• Urinary Interleukin 18 (IL18)

• NGAL

• Kim-1

Characteristics of AKI biomarkers:

• Secreted into blood and urine when acute kidney injury occurs (similar to troponin after myocardial infarction)

• Higher sensitivity and specificity than urea and creatinine

Diagnosis of AKI according to KDIGO 2012:

• When at least one of the following criteria is present:

• Increased Cr ? 0.3mg/dl within 48h

• Increased Cr ? 1.5 times baseline within 7 days

• Urine volume < 0.5ml/kg/h for 6h

RIFLE criteria in diagnosing AKI:

• Risk:

• Crea increased 1.5 times or GFR decreased > 20%

• UO: < 0.5ml/kg/h for 6h

• Injury:

• Creatinine increased 2 times

• GFR decreased > 50%

• UO: 0.5ml/kg/h for 12h

• Failure:

• Creatinine increased 3 times

• GFR decreased 75%

• UO: < 3ml/kg/h for 24h or anuria for 12h

• LOSS:

• Complete loss of kidney function for 4 weeks

• End stage:

• End-stage kidney disease

AKI in the community:

• Accounts for 1%

• Often accompanied by chronic kidney disease

• Pre-renal 70%

• Post-renal 17%

AKI acquired in hospital:

• According to RIFLE, 20% of hospitalized patients have AKI

• Causes: Anemia, hypovolemia, medications, contrast media.

Pre-renal injury is common in outpatient settings.

Tubular necrosis is common in the ICU.

AKI is a risk factor:

• Independent of mortality in hospital, and correlated with length of stay.

Differentiating between acute and chronic kidney failure:

• History: urea creatinine level, ultrasound shows kidney atrophy, loss of cortical medullary border

• Normocytic, normochromic anemia not explained by other diseases with GFR < 30

• Hypocalcemia

Causes of acute kidney injury:

• Pre-renal 50-60%

• Renal 35-40%

• Post-renal < 5%

Pre-renal acute kidney injury is also known as: Pre-renal azotemia.

Pre-renal acute kidney failure includes:

• True intravascular volume depletion

• Effective intravascular volume depletion

• Hemodynamic changes in the kidneys

True intravascular volume depletion includes:

• Hemorrhage

• Fluid loss through the gastrointestinal tract, through the kidneys (diuretics, osmotic diuretics, …)

• Fluid loss into the third space: burns, pancreatitis, decreased albumin, inflammatory response

• Loss through the skin: burns, sweating, hyperthermia

• Decreased intake: poor diet

Effective intravascular volume depletion includes:

• Decreased cardiac output: congestive heart failure, cardiogenic shock, acute cardiac tamponade, severe pulmonary embolism

• Peripheral vasodilation: Sepsis, anaphylactic shock, antihypertensive drugs, anesthesia

Hemodynamic changes in the kidneys include:

• Constriction of afferent arterioles

• Dilation of efferent arterioles

Groups of drugs that cause constriction of afferent arterioles:

• NSAID anti-inflammatory drugs

• Cyclosporine, Tacrolimus

• Hypercalcemia

Drugs that dilate efferent arterioles:

• ACE inhibitors

• Angiotensin receptor blockers

Response of the glomerulus and body when there is a decrease in circulatory volume:

• Sympathetic stimulation

• RAA stimulation

• Increased ADH release

• Release of vasoconstrictors of internal organs

• Autoregulation mechanism in the kidneys

Autoregulation mechanism in the kidneys:

• When BP drops to 70-80, there will be dilation of afferent arterioles and constriction of efferent arterioles to maintain GFR.

Diagnosis of pre-renal acute kidney failure:

• Clinical presentation suggestive of dehydration, heart failure

• Laboratory tests:

• BUN/ serum creatinine > 20

• U Na < 20 meq/L

• FE Na < 1%

• Concentrated urine

• Specific gravity 1.018

• Osmolality > 500 mOsmol/ Kg H2O

• Clean urine sediment, no casts

Post-renal acute kidney failure due to:

• Bilateral obstruction of ureters or unilateral obstruction on a single kidney

• Obstruction of the urethra or bladder neck

Obstruction of 2 ureters or obstruction of one side on a single kidney includes:

• Within the ureter: stones, blood clots, pus, or renal papillae, edema after retrograde ureterography, transitional cell carcinoma

• Outside the ureter: Abdominal tumors, pelvis, retroperitoneal fibrosis, ureteral misplacement or trauma during abdominal surgery, pelvis

Obstruction of the urethra or bladder neck includes:

• Benign prostatic hyperplasia

• Bladder or prostatic cancer

• Neurogenic bladder, or use of anticholinergics causing urinary retention

• Urethral stricture

• Bladder stones

• Fungal infection

• Blood clots

Diagnosis of post-renal AKI includes:

• Clinical presentation

• Ultrasound: hydronephrosis, cause of obstruction

• Non-contrast CT scan

• Urinary MRI

Renal acute kidney failure includes:

• Blood vessels

• Glomerulus

• Interstitial tissue

• Renal tubules

Renal acute kidney failure due to blood vessels:

• Large and medium-sized blood vessels such as: Renal arteries: Embolism or thrombosis, renal artery clamping, bilateral renal artery embolism

• Polyarteritis nodosa

• Small blood vessels: Microangiopathic thrombosis, malignant hypertension, HELLP syndrome

• HUS/ TTP: increased blood urea nitrogen/ thrombotic thrombocytopenic purpura

• Athrombolisic dieases Atherosclerosis

• Scleroderma

Renal acute kidney failure due to glomerulus:

• Nephrotic syndrome

• Acute glomerulonephritis

• Rapidly progressive glomerulonephritis

Renal acute kidney failure due to interstitial tissue:

• Drug-induced interstitial nephritis

• Infection-related interstitial nephritis

Drug-induced interstitial nephritis includes:

• Antibiotics

• Diuretics

• NSAIDs

• Anticonvulsants

• Allopurinol

Antibiotics causing interstitial nephritis:

• Methicillin, cephalosporins, rifampicin, sulfonamides, erythromycin, ciprofloxacin

Diuretics causing interstitial nephritis:

• Furosemide, thiazide, chlorthalidone

Anticonvulsants causing interstitial nephritis:

• Phenytoin, carbamazepine

Infection-related interstitial nephritis includes:

• Bacteria: Streptococcus, Staphylococcus

• Viruses: CMV, EBV

• Tuberculosis

Renal acute kidney failure due to renal tubules:

• Renal tubular ischemia

• Toxic substances

Renal tubular ischemia causing acute kidney failure due to renal tubular injury:

• Shock

• Hemorrhage

• Trauma

• Septic shock

• Acute pancreatitis

• Hypotension

Toxic substances causing renal tubular injury:

• Exogenous toxins: Medications

• Endogenous toxins:

Exogenous toxins causing renal tubular injury:

• Myoglobin rhabdomyolysis

• Hemoglobin hemolysis

• Uric acid

Exogenous toxins causing tubular necrosis/ renal AKI:

• Aminoglycosides

• Amphotericin B

• Acyclovir

• Indinavir

• Pentamidine

• Foscarnet

• Contrast media

Cancer treatment drugs causing tubular necrosis:

• Cisplatin

Anesthetic drugs causing tubular necrosis:

• Enflurane

Drugs used in colonoscopy preparation causing tubular necrosis:

• Phospho soda

Mechanism of decreased glomerular filtration rate in acute tubular necrosis:

• Renal tubular injury: Fluid leakage into the interstitial space, compression of the renal tubules, obstruction of the lumen of the renal tubules

• Hemodynamic changes in the kidneys

• Inflammatory response in the kidneys

• Vasoconstriction in the kidneys

Clinical presentation of acute tubular necrosis:

• Onset

• Spread

• Maintenance

• Recovery

Onset phase:

• Hours, days

• Decreased glomerular filtration rate due to decreased renal blood flow

Spread phase:

• Prolonged ischemia causes cellular polarization, apoptosis, necrosis of renal tubular cells

• Cell shedding, sticking together, causing obstruction of the lumen, interstitial edema

Maintenance phase:

• Lasts 1-2 weeks

• Despite decreased renal blood flow, the injury continues to progress

• Prolonged oliguria, severe decrease in glomerular filtration rate

Recovery phase:

• Marked by increased urine volume

• Complications can still occur, decreased blood flow can lead to recurrent kidney failure, electrolyte disturbances

Treatment goals:

• Reduce multi-organ tubular injury by early intervention in the early stages

• Treatment and prevention of complications due to high uremic levels in the oliguric and anuric phases

• Timely adjustment to changes in progression in the polyuric phase until complete recovery

Treatment of pre-renal kidney failure due to dehydration:

• 0.9% NaCl

• Infuse 1000ml in 1h or 250ml/h

• Monitor urine output, jugular venous pressure, lung sounds, blood pressure

• If central venous pressure is measured, pulmonary artery occlusion pressure is blocked

Treatment of pre-renal acute kidney failure due to heart failure:

• Diuretics

• Preload reducing drugs

• Afterload

• Increased contractility

• Antiarrhythmic drugs

• Hemofiltration may be required

Treatment of pre-renal acute kidney failure due to cirrhosis:

• It is necessary to distinguish between dehydration or hepatorenal syndrome

• Diuretics

• Paracentesis, albumin supplementation

• Portocaval shunt

• Vasopressin analogs

Treatment of pre-renal acute kidney failure due to nephrotic syndrome:

• Diuretics

• Albumin supplementation if BP drops

• Treat underlying disease (corticosteroids, cytotoxic drugs)

Treatment of renal acute kidney failure due to interstitial nephritis:

• Remove the causative agent

• Antibiotics if infected

• Consider corticosteroids

Treatment of renal acute kidney failure due to acute tubular necrosis:

• Use diuretics cautiously, when enough fluid has been replenished and in the oliguric phase (80-500mg/24h)

• Low-dose dopamine is not beneficial

• Avoid nephrotoxic drugs and adjust drugs that are excreted by the kidneys

Treatment of post-renal acute kidney injury:

• Remove the cause of obstruction

• Such as urinary catheterization, JJ placement, ureteral externalization

Supportive treatment includes:

• Nutrition 30-35 kcal/kg/day

• Limit protein to 0.8g/kg/day

• Adjust medications according to glomerular filtration rate

• Renal replacement therapy

Indications for emergency renal replacement therapy:

• Manifestations of increasing uremic levels: tremor, pericardial friction rub, neurological manifestations, nausea, vomiting

• Oliguria or anuria

• Severe hyperkalemia not responsive to medical management

• Acute pulmonary edema not responsive to medical management

• Metabolic acidosis not responsive to medical management

• BUN > 100 mg/dl, Creatinine > 10 mg/dl

• Drug overdose: Removal through renal replacement therapy

Earlier dialysis should be indicated if there are severe underlying medical conditions:

• Drug overdose

• Severe burns

• Obstetrical complications

• Bee stings

• Multiple trauma

Factors that contribute to more severe hyperkalemia:

• Acidosis, insulin deficiency

• Potassium release from damaged tissue: severe trauma, rhabdomyolysis, hemolysis, tumor lysis syndrome

• Medications, potassium-containing preparations such as: IV fluids, potassium-sparing diuretics

• NSAIDs, beta blockers, ACE inhibitors, angiotensin II receptor blockers

Dangerous effects of hyperkalemia:

• Cardiac toxicity

• Tall T wave

• PR, QRS prolongation, delayed atrioventricular conduction, loss of P wave

• Finally ventricular fibrillation, asystole

Treatment of hyperkalemia:

• Stop sources of potassium: diet, medications, remove tissue, treat infection

• Calcium gluconate

• Insulin

• Alkalization of blood

• Beta 2 stimulation

• Actual removal of potassium such as diuretics, ion exchange resins, kayexalate, renal replacement therapy

Calcium gluconate has the effect of:

• Preventing cardiac toxicity

Dose of Calcium gluconate:

• 10% /5ml 2A diluted, slow IV

• Effect within minutes

• T1/2 30-60 minutes

Use of insulin in hypokalemia:

• 10 UI actrapid with every 25 grams of glucose

• Has the effect of moving potassium into cells

Alkalization aims to:

• Move potassium into cells

• Dose 150 mEq IV

Beta stimulation in hyperkalemia:

• Move potassium into cells

• Duration 2-4h

• Albuterol 0.5mg nebulized or 10mg inhaled

Actual removal of potassium from the body such as:

• Diuretics

• Ion exchange resin Kayexalate 1-2 packets 15g 2-3 times daily

• Renal replacement therapy

Note: This article is for general information about acute kidney injury only, and does not replace professional medical advice. Consult with a doctor for a proper diagnosis and treatment.