ACUTE RENAL

FAILURE
INTRODUCTION:

• Acute kidney injury (AKI) is a condition characterized by a sudden decline in

kidney function, typically indicated by changes in lab values such as serum
creatinine (Sr), blood urea nitrogen (BUN), and urine output.
• Acute renal failure, or acute kidney failure (AKF), occurs when the kidneys
quickly lose their ability to filter waste from the blood. This leads to the
accumulation of waste products and imbalances in fluid and electrolytes , which
develops rapidly, often over a span of hours or days.
• Acute kidney injury is frequently seen in hospitalized patients, especially those
who are critically ill and require intensive care. It impacts around 3-7% of hospital
admissions and about 25-30% of patients in the intensive care unit.
ETIOLOGY:

Acute renal failure can occur in the following situations:

Impaired Blood Flow to the Kidneys:
Conditions that reduce blood flow to the kidneys and potentially cause kidney
failure include:
1. Blood or fluid loss
2. Medications for high blood pressure
3. Heart attack or heart disease
4. Infection
5. Liver failure
6. Use of drugs like aspirin, ibuprofen, and naproxen
7. Severe allergic reactions (anaphylaxis)
8. Severe burns
9. Extreme dehydration
Damage to the Kidneys:
Certain diseases, conditions, and substances can harm the kidneys and lead to acute
renal failure. These include:
• Blood clots in the veins and arteries near the kidneys
• Cholesterol deposits blocking blood flow in the kidneys
• Glomerulonephritis (inflammation of kidney filters)
• Hemolytic uremic syndrome (premature destruction of red blood cells)
• Lupus (immune system disorder causing glomerulonephritis)
• Medications like certain chemotherapy drugs, antibiotics, contrast dyes, and
zoledronic acid (used for osteoporosis and high calcium levels)
• Scleroderma (rare diseases affecting skin and connective tissues)
• Thrombotic thrombocytopenic purpura (TTP), a rare blood disorder
• Toxins such as alcohol, heavy metals, and cocaine
• Vasculitis (inflammation of blood vessels)
Urinary Blockage:
Conditions that block urine flow from the kidneys and can lead to acute renal failure
include:
• Bladder cancer
• Blood clots in the urinary tract
• Cervical or colon cancer
• Enlarged prostate
• Kidney stones
• Nerve damage affecting bladder control
• Prostate cancer
RISK FACTORS:

Acute renal failure typically occurs alongside other medical conditions or events.
Factors that can increase the risk of acute renal failure include:
• Being hospitalized, particularly for a severe condition requiring intensive care
• Older age
• Blockages in the blood vessels of the arms or legs (peripheral artery disease)
• Diabetes
• High blood pressure
• Heart failure
• Kidney diseases
• Liver diseases
PATHOPHYSIOLOGY:

ARF is classified into three major types based on the underlying cause:
1. Prerenal AKI – Due to reduced renal perfusion (before the kidneys).

2. Intrinsic AKI – Due to direct kidney parenchymal damage.

3. Postrenal AKI – Due to obstruction of urine outflow (after the kidneys).

• Each type follows a different pathophysiological mechanism leading to impaired
renal function.
Prerenal AKI (Due to Reduced Renal Perfusion)
Prerenal AKI is caused by decreased renal blood flow without intrinsic kidney damage. It is
the most common form of AKI and is potentially reversible if the underlying cause is
corrected promptly.
• Decreased renal perfusion (due to hypovolemia, heart failure, or shock) leading to a Drop in
GFR

• Compensatory mechanisms are activated:

o The Renin-Angiotensin-Aldosterone System (RAAS) is activated → Angiotensin II
causes vasoconstriction to maintain glomerular pressure.
o Antidiuretic Hormone (ADH) is released → Increases water reabsorption to maintain
blood pressure.
o Sympathetic nervous system is activated → Causes systemic vasoconstriction to
improve perfusion.
• If the perfusion deficit persists, it leads to prolonged ischemia causes tubular epithelial
cell injury, leading to acute tubular necrosis (ATN), which progresses to intrinsic AKI.
• Common Causes of Prerenal AKI:
∙ Hypovolemia (dehydration, severe vomiting/diarrhea, hemorrhage, burns)

∙ Low cardiac output (heart failure, myocardial infarction, cardiogenic shock)

∙ Sepsis (systemic vasodilation leads to hypotension and hypoperfusion)

∙ Renal artery stenosis (narrowing of the renal artery reduces blood flow)
• If the underlying cause is not corrected, prolonged hypoperfusion leads to ischemic
damage of tubular cells, progressing to intrinsic AKI.
Intrinsic AKI (Due to Direct Kidney Damage)
Intrinsic AKI occurs when there is direct injury to the renal parenchyma, affecting
glomeruli, tubules, interstitium, or blood vessels. The most common cause is acute tubular
necrosis (ATN), which results from prolonged ischemia or nephrotoxic exposure.
• Acute Tubular Necrosis (ATN) – Most Common Cause
1. Ischemic or nephrotoxic injury → Tubular epithelial cells die and slough off → Obstruction of tubules

2. Back-leak of filtrate due to damaged tubules → Decreased GFR

3. Inflammatory response worsens injury → Loss of tubular function → Oliguria (low urine output)

• Acute Interstitial Nephritis (AIN) – Immune-mediated reaction

∙ Caused by drugs (NSAIDs, antibiotics), infections, or autoimmune diseases

∙ Inflammation of renal interstitium → Edema → Tubular dysfunction → Decreased GFR

• Acute Glomerulonephritis (GN) – Inflammatory damage to glomeruli
 Immune complex deposition (as seen in post-streptococcal GN, lupus nephritis) → Complement
activation → Glomerular inflammation and damage
 Leads to proteinuria, hematuria, and reduced GFR

• Common Causes of Intrinsic AKI:

 Acute Tubular Necrosis (ATN) – Ischemia, nephrotoxins (aminoglycosides, contrast
agents, NSAIDs)
 Acute Interstitial Nephritis (AIN) – Drug-induced hypersensitivity reaction, infections

 Acute Glomerulonephritis (GN) – Autoimmune diseases (lupus nephritis, Goodpasture

syndrome)
• If the damage is severe, intrinsic AKI may lead to permanent loss of nephron function,
progressing to chronic kidney disease (CKD).
Postrenal AKI (Due to Urinary Tract Obstruction)
Postrenal AKI occurs when urine outflow is obstructed, leading to increased pressure in the renal
tubules, which reduces the GFR and leads to renal dysfunction.
1. Obstruction of urinary tract → Urine accumulates → Increased hydrostatic pressure in Bowman's capsule

2. This pressure opposes glomerular filtration → Reduced GFR

3. If prolonged, tubular atrophy and interstitial fibrosis occur, leading to permanent kidney damage

• Common Causes of Postrenal AKI:

∙ Ureteral obstruction (kidney stones, strictures, tumors)

∙ Bladder outlet obstruction (benign prostatic hyperplasia - BPH, bladder cancer)

∙ Neurogenic bladder (spinal cord injury, multiple sclerosis)

• Postrenal AKI is usually reversible if the obstruction is promptly relieved, but prolonged obstruction can lead
to hydronephrosis and permanent kidney damage.
CLINICAL MANIFESTATIONS:

The signs and symptoms of acute renal failure may include:

• Reduced urine output, although in some cases, urine output may remain normal
• Fluid retention, leading to swelling in the legs, ankles, or feet
• Drowsiness
• Shortness of breath
• Fatigue
• Confusion
• Nausea
• Seizures or coma in severe instances
• Chest pain or pressure
In some cases, acute renal failure may not present noticeable signs or symptoms and is only
detected through tests.
COMPLICATIONS:
Potential complications of acute renal failure include:
• Fluid buildup: Acute renal failure can cause fluid to accumulate in the chest,
leading to shortness of breath.
• Chest pain: Inflammation of the lining around the heart may result in chest pain.
• Muscle weakness: An imbalance in the body’s fluids and electrolytes can lead to
muscle weakness, with elevated potassium levels being especially dangerous.
• Permanent kidney damage: In some cases, acute renal failure can cause lasting
kidney damage, resulting in end-stage renal disease.
• Death: If untreated, acute renal failure can lead to complete kidney failure and,
ultimately, death. The risk of death is higher in individuals with pre-existing
kidney issues.
DIAGNOSIS:

• Urine output measurements: The volume of urine produced each day can help
identify the underlying cause of kidney failure.
• Urine tests: Analyzing a urine sample can uncover abnormalities that indicate
kidney failure.
• Blood tests: A blood sample may show rapidly increasing levels of urea and
creatinine.
• Imaging tests: Imaging techniques like ultrasound and CT scans may be used to
detect any abnormalities in the kidneys.
• Biopsy: In some cases, a kidney biopsy may be recommended to collect a small
tissue sample from the kidneys for laboratory analysis.
TREATMENT:

Treatment goals:
• The short-term objectives are to minimize kidney damage, prevent complications
outside the kidneys, and promote the recovery of kidney function.
• The ultimate goal is to restore renal function to its pre-AKI baseline.
• At present, there is no specific cure for AKI. Supportive care remains the primary
approach to managing AKI, regardless of its cause.
 NON-PHARMACOLOGICAL TREATMENT:
• The goals of supportive care include maintaining adequate cardiac output and blood
pressure to ensure proper tissue perfusion while restoring kidney function to its pre-AKI
level.
• Medications that reduce renal blood flow should be discontinued, and appropriate
management of fluids and electrolytes should be initiated. It is also important to avoid
nephrotoxic substances.
• In severe AKI, renal replacement therapy (RRT), such as hemodialysis or peritoneal
dialysis, is used to maintain fluid and electrolyte balance while eliminating waste
products. Both intermittent and continuous dialysis methods have their own advantages
and disadvantages.
• Intermittent hemodialysis (IHD) is the most commonly used form of RRT, offering the
advantages of widespread availability and short treatment duration (3-4 hours).
• Several continuous RRT (CRRT) variations have been developed, including continuous
hemofiltration, continuous hemodialysis, or a combination. CRRT removes solutes
gradually, which makes it more tolerable for critically ill patients.
PHARMACOLOGICAL THERAPY:
• Mannitol 20% is usually administered at a dose of 12.5 to 25 g IV over 3 to 5
minutes. However, its disadvantages include the need for IV administration, the
risk of hyperosmolality, and the requirement for monitoring urine output and
serum electrolytes and osmolality, as mannitol can contribute to AKI.
• Loop diuretics are effective in reducing fluid overload but may exacerbate AKI.
Continuous loop diuretic infusions seem to overcome diuretic resistance and have
fewer side effects compared to intermittent boluses. An initial IV loading dose
(equivalent to 40-80 mg of furosemide) should be given before starting a
continuous infusion (equivalent to 10-20 mg/h of furosemide).
• Using drugs from different pharmacological classes, such as diuretics acting on
the distal convoluted tubule (thiazides) or the collecting duct (amiloride,
triamterene, and spironolactone), may be more effective when combined with loop
diuretics. Metolazone is commonly used because, unlike other thiazides, it is
effective at inducing diuresis even when the GFR is less than 20 ml/min.
Metolazone

•Dose: 2.5 to 5 mg daily for acute renal failure; can be increased to 10 mg/day.
Adjust dose in renal impairment.
•MOA: Thiazide-like diuretic; inhibits sodium-chloride symporter in the distal
convoluted tubule, increasing sodium, chloride, and water excretion.
•ADR: Electrolyte imbalances (hypokalemia, hyponatremia), dehydration,
hypotension, hyperglycemia, gout, renal dysfunction, rash, fatigue, and dizziness.
ELECTROLYTE MANAGEMENT AND NUTRITION
INTERVENTIONS:

• Serum electrolytes should be checked daily, as hyperkalemia is the most common

and serious electrolyte imbalance in AKI. Hypernatremia and fluid retention are
also frequent, requiring careful calculation of daily sodium intake.
• Phosphorus and magnesium levels should be monitored, particularly in patients
with significant tissue damage due to the release of increased amounts of
phosphorus, as neither is effectively cleared by dialysis.
• Nutritional management for critically ill patients with AKI is challenging due to
various metabolic disruptions. Nutritional needs are influenced by stress,
inflammation, and injury, which contribute to hypermetabolic and hypercatabolic
conditions.
DRUG-DOSING CONSIDERATIONS:

• Optimizing drug therapy in AKI is challenging due to several factors, including

residual drug clearance, fluid buildup, and the use of renal replacement therapies
(RRTs).
• Patients with AKI may have higher residual non-renal clearance compared to
those with CKD, even with similar creatinine clearances. This makes it more
difficult to personalize drug therapy, especially when RRTs are involved.
• The type of CRRT used also affects the rate at which drugs are removed, further
complicating individualized drug therapy. Factors such as ultra-filtration rates,
blood flow, and dialysate flow all influence drug clearance during CRRT.
PREVENTION:

• Acute renal failure is often challenging to predict or prevent, but the risk may be
reduced by taking steps to protect the kidneys.
• Annual physical exams, including blood tests and urinalysis, can help monitor
kidney and urinary tract health.
• It's important to stay hydrated to support proper kidney function and avoid
substances or medications that could harm kidney tissues.
• Patients with conditions like diabetes or high blood pressure, which increase the
risk of acute kidney failure, should follow management guidelines for these
conditions.
• People at higher risk for chronic renal failure may require more frequent tests to
assess kidney function and detect other issues related to declining kidney health.