Acute Kidney Injury – Acute Renal Failure

Definition of Acute Kidney Injury

Acute kidney injury is a rapid deterioration of renal function with accumulation of uremic substances in the
blood. Synonym: acute renal failure (ARF).

Oliguria is defined as a urine output that is less than 1 ml/kg/h in infants, less than 0.5 ml/kg/h in children, and
less than 500 ml/day in adults.

Anuria is defined as a urine output that is less than 100 ml urine production in 24h.

Etiology of Acute Kidney Injury

Prerenal Kidney Failure

The failure of renal function is due to deteriorating working conditions of the kidney. The most common reason
is a reduced renal blood flow. Per definition, there is no primary renal disease or postrenal failure (no disorders
of urine transport).

Intravascular volume depletion:

Trauma, burns, bleeding, allergic shock, sepsis, pancreatitis, dehydration.

Decreased cardiac output:

Acute heart diseases such as myocardial ischemia, pulmonary embolism or decreased cardiac output due to
mechanical ventilation.

Decreased renal blood flow:

Medication with ACE inhibitors or NSAID, anesthesia, hepatorenal syndrome, hyperviscosity syndrome in
multiple myeloma or polycythemia.

Renal Kidney Failure

The failure of renal function is due to renal diseases.

Renal vessel diseases:

• renal artery stenosis

• renal artery embolism
• renal artery aneurysm
• renal vein thrombosis

Microvascular diseases:

• rapid-progressive glomerulonephritis
• Goodpasture's syndrome
• postinfectious glomerulonephritis
• polyarteritis nodosa
• Wegener's granulomatosis
• systemic lupus erythemathodes
• Henoch-Schonlein purpura
• essential cryoglobulinemia
 • hemolytic-uremic syndrome
• thrombotic thrombocytopenic purpura
• disseminated intravascular coagulation (DIC)

Tubulointerstitial diseases:

• allergic interstitial nephritis caused by drugs (beta-lactams, NSAID, thiazides, ACE inhibitors,
allopurinol, cimetidine).
• serious bacterial infections such as pyelonephritis or viral diseases such as CMV
• leukemic infiltration
• idiopathic

Acute tubular necrosis:

Acute necrosis of tubular cells is caused by ischemia or toxic substances. The damage to the kidney function is
aggravated by dead tubular cells, which occlude the renal tubules. After repair of the tubular cells, the renal
function can recover.

Toxic substances produced the tubular damage either by ischemia (e.g. vasoconstriction by contrast agents) or
cell damage (e.g. cisplatin). Further common toxic substances for acute tubular necrosis are aminoglycosides,
antibiotics, antifungals, chemotherapy, chemicals (heavy metals, solvents, insecticides), drugs (heroin,
amphetamines), or D-penicillamine. Endogenous toxins are free hemoglobin (hemolysis) or myoglobin
(rhabdomyolysis).

Postrenal Kidney Failure

Postrenal kidney failure is the deterioration of renal function due to inadequate drainage of urine. This is the
least common cause of acute renal failure, since one kidney is sufficient for the detoxification function and
causes of postrenal kidney failure have to affect both kidneys.

• bilateral diseases of the ureters:

o malignant obstruction
o Ormond's disease (retroperitoneal fibrosis)
o ureteral stones
o bleeding disorders
• urinary retention:
o benign prostatic hyperplasia (BPH)
o prostate cancer
o neurogenic bladder disorders
o urethral stricture
o posterior urethral valves
o phimosis

Pathophysiology of Acute Kidney Injury

Excess of Extracellular Fluid Volume

Acute kidney injury causes a reduced salt and water excretion. This leads to weight gain, shortness of breath
and pulmonary edema.

Hyperkalemia

Potassium increases 0.5 mmol/l/day during anuria. Hyperkalemia is particularly serious with additional cell
disintegration (tumor lysis, hemolysis, rhabdomyolysis).
Metabolic Acidosis

Metabolic acidosis is caused by the lack of elimination of acids from the protein metabolism, which cannot be
eliminated by respiration. Metabolic acidosis is pronounced in acute kidney injury due to diabetic ketoacidosis,
lactic acidosis, liver disease and tissue ischemia.

Hyperphosphatemia and Hypocalcemia

Hyperphosphatemia and hypocalcemia develops due to secondary hyperparathyroidism.

Anemia - Acute kidney injury leads to a decreased renal erythropoietin secretion, hemodilution and decreased
survival of erythrocytes. The risk of bleeding is increased due to dysfunction of thrombocytes.

Signs and Symptoms of Acute Kidney Injury

Uremia resulting from acute renal failure causes non-specific complaints. The underlying disease for the acute
kidney injury is crucial for most of the symptoms.

Symptoms of Prerenal Kidney Failure

• thirst, decreased skin turgor

• oliguria or anuria
• hypotension, tachycardia
• signs and symptoms of underlying diseases such as trauma, cardiac diseases or dehydration

Symptoms of Renal Kidney Failure

Usually, a risk situation for renal ischemia or toxic renal damage is observable.

Symptoms of Postrenal Kidney Failure Flank pain, abdominal pain or neurological symptoms are
suspicious for a postrenal kidney failure.

Symptoms due to Complications of Acute Kidney Injury

• dyspnea (pulmonary edema)

• arrhythmia (hyperkalemia)
• gastrointestinal bleeding
• hypotension and shock (infections, metabolic acidosis)
• coma and death (metabolic acidosis, hyperkalemia, uremia)
• polyuria and electrolyte imbalance after recovery of renal function
• The kidney normally receives 20% to 25% of cardiac output or approximately 1200 mL/min of blood
flow.12 This flow is normally protected by autoregulation mechanisms, keeping flow and pressure
constant and maintaining oxygen delivery, which is necessary for the wide variety of highly metabolic
renal functions, underscoring the kidney's vulnerability to ischemic and toxic injury.12,13 The 3 major
determinants of renal blood flow are cardiac output, renal perfusion pressure, and glomerular
hemodynamic factors. Cardiac output is affected by volume status, inotropy, and sodium/water
retention. Renal perfusion pressure is influenced by mean arterial pressure, renal artery integrity, and
renal venous outflow.13 Afferent and efferent arterial vasoconstriction and vasodilatation of the
glomerulus ultimately determine glomerular filtration pressure and GFR. Glomerular autoregulation by
this means is functional only when systolic arterial pressure is 80 to 170 mm Hg.12 Renal blood flow
and urine formation are also regulated by the renin-angiotensin-aldosterone system, sympathetic
nervous system, and antidiuretic hormone from the hypothalamus. Renal endothelial-derived
prostaglandins (eg, PGE2) modulate the renal/glomerular vasoconstriction caused by increased
sympathetic tone and vasoactive drugs.12 Loss of these prostaglandins by administration of aspirin,
 nonsteroidal anti-inflammatory drugs, and other prostaglandin inhibitors can result in severe intrarenal
vasoconstriction, decreased GFR, and onset or worsening of AKI.2,14,15
• AKI and Sepsis
• Septic AKI accounts for approximately 50% of all AKIs in critically ill patients.3 The pathogenesis of AKI
in sepsis is not fully understood and is more complex than previously thought. It is known that AKI
develops early in sepsis; 64% of AKI occurs within 24 hours of septic onset.16 The lack of histologic
evidence limits progress in this area because a renal biopsy in a critically ill patient is prohibitive. Our
knowledge in this area is mostly based on animal models.16,17
• Several pathways of septic renal injury are currently recognized. Renal cell necrosis is caused by intra-
and extrarenal hypoperfusion. Apoptosis, or genetically induced cellular death, is caused primarily by
inflammatory mediators and ongoing ischemia. Tumor necrosis factor (TNF) [alpha]-1, in particular, has
been shown in animal models to upregulate renal apoptosis by binding with TNF receptor 1 on
glomerular cells and the TNF receptor 2 sites on renal tubular cells.16,17 Cytokines interleukin 1 and 6
also amplify inflammatory and proapoptotic pathways in the kidneys. Thromboxane and other
thrombogenic compounds cause platelet adhesion, capillary thrombosis, and ischemia.16,18,19
• The loss of tubular cell adhesion is the most recently recognized mechanism. In 2000, Schrier and
Wang20 demonstrated that of the renal tubular cells found in urine after acute tubular necrosis, 40%
were metabolically functional. Nitric oxide, which is released systemically in sepsis, has been implicated
as a possible cause of loss of tubular cell adhesion to the tubular basement membrane. Kidney injury
molecule-1 is a transmembrane protein that is released in proximal tubular damage and loss of cell
adhesion. Loss of tubular cellular adhesion results in tubular desquamation, plugging, and
backpressure.21
• The initial theories of septic injury were based on systemic and intrarenal hypoperfusion, decreasing
GFR, ischemia, and cellular necrosis. Recent studies, however, show that the kidney experiences the
initial hyperperfusion that occurs systemically in sepsis, but renal injury and apoptosis are significant
during this period.16,17 Brenner et al18 placed thermodilution renal blood flow catheters in 8 intensive
care unit patients with septic AKI. The researchers demonstrated that septic AKI occurred despite
normal renal blood flow.18 Other studies have shown that induction of endotoxin can alter glomerular
blood flow and GFR despite normal perfusion pressures. This was initially thought to be due to
intrarenal hypoperfusion; however, data now support that this may be due to severe efferent arteriole
vasodilatation, resulting in decreased glomerular filtration pressure and GFR. Blood flow in the
glomerulus remains high, but the pressure falls because of low glomerular vascular resistance, which
might explain why the kidney, during hyperperfusion, experiences a decrease in GFR and urine
production.16,17Figure 1 is a flow diagram representing the processes described previously. Although
the truth is still evolving in this area, it has become clear that septic AKI is a distinct and different form
of this disease. As data become available, the focus in septic AKI may shift from prevention of
vasoconstriction and ischemia to prevention of apoptosis and cell exfoliation.16,21
http://www.nursingcenter.com/library/JournalArticle.asp?Article_ID=1081416

Kidney Injuries

The kidney is injured more often than any of the organs along the urinary tract. Blunt force due to motor
vehicle collisions, falls, or sports injuries is the usual cause of injury. Penetrating kidney injuries can
result from gunshot or stab wounds. Less commonly, injuries can occur during diagnostic tests, such as
a kidney biopsy, or during various treatments, such as those for kidney stones, including extracorporeal
shock wave lithotripsy. Most blunt kidney injuries are minor. However, some are serious. If serious blunt
or penetrating kidney injuries are not treated, complications, such as kidney failure, high blood
pressure, delayed bleeding, and infection may result.

Symptoms and Diagnosis

Symptoms of a blunt kidney injury may include pain in the upper abdomen or flank (the area between
the ribs and hip), bruising of the flank, blood in the urine, marks near a kidney made by a seat belt, or
pain resulting from fractures of the lower ribs. With severe kidney injuries, low blood pressure (shock)
and anemia may occur if the person loses a significant amount of blood.

Kidney Injuries: Minor to Severe

The severity of kidney injuries varies widely. When an injury is minor, the kidney may be
only bruised. When an injury is more severe, the kidney may be cut or torn (lacerated),
and urine and blood may leak into the surrounding tissue. If the kidney is torn from its
attachment to blood vessels, bleeding may be profuse, resulting in shock or death. Most
kidney injuries result in blood in the urine.

The history of events that led to the injury, the person's symptoms, and a physical examination help
doctors recognize kidney injuries. A sample of urine is taken and examined to see if blood is present.
Blood in the urine in a person with an injury to the trunk suggests that the injury involves the kidney.
The blood may be visible with the naked eye (gross hematuria) or visible only using a microscope
(microscopic hematuria). With penetrating injuries, the location of the wound (whether in the upper or
mid part of the abdomen, back, or flank) may help doctors determine if the kidney is involved.

Adults who have mild symptoms and blood in the urine that is visible only with a microscope probably
have a minor bruise that will heal on its own. Further tests are usually not needed. For children, and for
adults in whom doctors suspect a more serious injury, computed tomography (CT) with radiopaque dye
(contrast agent) is done. Occasionally, additional imaging tests may be needed to confirm the
diagnosis.

Treatment

For minor kidney injuries, careful control of fluid intake and bed rest are often the only treatment
needed, because these measures allow the kidney to heal itself. For more serious injuries, treatment
begins with steps to control blood loss and to prevent shock. Fluids and sometimes blood are given
intravenously to help keep blood pressure within a normal range and stimulate urine production. Only
the most serious injuries, such as when the kidney is torn from its attachments to blood vessels, require
surgical repair. Rarely, the injured kidney needs to be removed.
Most people recover from even serious kidney injuries, provided the injuries are diagnosed and treated
promptly. Kidney failure, when it develops, may require lifelong treatment. Other complications of
kidney injuries that require treatment include high blood pressure, delayed bleeding, and infection.