Acute kidney injury (AKI)
DEFINITION OF ACUTE KIDNEY INJURY
Acute kidney injury (AKI) is characterized by impairment of kidney filtration and excretory function over days to weeks, resulting in the retention of nitrogenous and other waste products normally cleared by the kidneys. In short, impairment of kidney to eliminate waste products.
Symptoms:
Not enough urine / urinary obstruction, Swelling in legs, ankles or feet ,Respiratory abnormalities, Confusion, Nausea, chest pain
Acute kidney injury (AKI) exhibits a wide variety of aetiologies and pathophysiologic processes leading to decreased kidney function
ETIOLOGY AND PATHOPHYSIOLOGY OF ACUTE KIDNEY INJURY
The main causes of acute kidney injury (AKI) can be divided into three categories :
1.Prerenal azotemia.
2.Intrinsic renal parenchymal disease.
3.Postrenal obstruction
PRERENAL AZOTEMIA:
AZO: Nitrogen,-EMIA: Blood.
It is the most common form of Acute Kidney Injury (AKI) resulting from any condition that reduces blood flow to the kidney, such as hypovolemia(Decreased blood volume), decreased cardiac output, and medications interfering with the renal autoregulatory response( NSAIDS, ACE Inhibitors).
Prolonged periods of prerenal azotemia may lead to acute tubular necrosis (ATN), prerenal azotemia is reversed once parenchymal blood flow and
intraglomerular hemodynamics are restored.
Mild degrees of hypovolemia and reductions in cardiac output brings out compensatory renal physiologic changes such as renal vasoconstriction and salt and water reabsorption to maintain blood pressure and increase intravascular volume to withstand perfusion to the cerebral and coronary vessels.
Drugs can affect the renal regulatory mechanism to maintain GFR. Nonsteroidal anti-inflammatory agents inhibit renal prostaglandin production, thereby limiting renal afferent vasodilation.
Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) limit renal efferent vasoconstriction.
The combined use of NSAIDs with ACEi or ARBs poses a particularly high risk for developing prerenal azotemia.
This condition results in elevations of BUN and creatinine levels
BUN/creatinine ratio above 20, FeNa<1%, hyaline casts in urine sediment, urine specific gravity >1.018, urine osmolality >500 mOsm/kg
INTRINSIC Acute Kidney Injury (AKI)
Causes: sepsis, ischemia, and nephrotoxins(endogenous and exogenous)
SEPSIS-ASSOCIATED AKI(Acute Kidney Injury):
ISCHEMIA-ASSOCIATED AKI(Acute Kidney Injury):
The outer medulla is vulnerable to ischemic damage because of the structure of the blood vessels that supply oxygen and nutrients to the tubules.
In the outer medulla enhanced leukocyte-endothelial interactions in the small vessels lead to inflammation and reduced local blood flow to the metabolically very active segment of the proximal tubule, which depends on oxidative metabolism for survival.
Mitochondrial dysfunction due to ischemia and release of reactive oxygen species also plays a role in the renal tubular injury.
Acute Kidney Injury (AKI) more commonly develops when ischemia occurs in the context of limited renal reserve (e.g., CKD or older age) or coexisting conditions such as sepsis, vasoactive or nephrotoxic drugs, rhabdomyolysis, systemic inflammatory states associated with burns and pancreatitis.
NEPHROTOXIN-ASSOCIATED AKI(Acute Kidney Injury:
The kidney is highly susceptible to nephrotoxic agents due to extremely high blood perfusion and concentration of circulating substances along the nephron where water is reabsorbed; this results in high-intensity exposure of toxins to tubular, interstitial, and endothelial cells.
The nephrotoxic injury occurs in response to many pharmacologic compounds with diverse structures, endogenous substances, and environmental exposures.
All parts of the Kidney are vulnerable to toxic injury, including the tubules, interstitium, vasculature, and collecting system. Other risk factors for nephrotoxicity include older age, CKD, and prerenal azotemia.
Hypoalbuminemia can increase the risk of nephrotoxin-associated AKI(Acute Kidney Injury) due to increased free circulating drug concentrations.
Several antimicrobial agents are commonly associated with AKI(Acute Kidney Injury). Vancomycin is associated with AKI, particularly when trough levels are high and when used in combination with other nephrotoxic antibiotics.
Aminoglycosides and amphotericin B both cause tubular necrosis. Nonoliguric Acute Kidney Injury (i.e., with a urine volume >400 mL/day) accompanies 10–30% of courses of aminoglycoside antibiotics, even when plasma levels are in the therapeutic range.
Aminoglycosides are filtered across the glomerulus and then accumulate within the renal cortex, where concentrations can greatly exceed those of the plasma.
Amphotericin B can cause renal vasoconstriction from an increase in tubuloglomerular feedback, as well as direct tubular toxicity, mediated by reactive oxygen species.
Nephrotoxicity from amphotericin B is dependent on dose and duration.
AmpB drug binds to the tubular membrane cholesterol and introduces pores.
Clinical features of amphotericin B nephrotoxicity : polyuria, hypomagnesemia, hypocalcemia, and nongap metabolic acidosis.
Acyclovir can precipitate in tubules and cause AKI by tubular obstruction, particularly when given as an intravenous bolus at high doses (500 mg/m2 ) or in the setting of hypovolemia.
Foscarnet, pentamidine, tenofovir, cidofovir are also frequently associated with AKI due to tubular toxicity.
AKI(Acute Kidney Injury) secondary to acute interstitial nephritis can occur as a consequence of exposure to many antibiotics, including penicillins, cephalosporins, quinolones, sulfonamides, and rifampin.
POSTRENAL AKI (Acute Kidney Injury):
Postrenal AKI (Acute Kidney Injury) occurs when the normally unidirectional flow of urine is acutely blocked either partially or totally => increased retrograde hydrostatic pressure and interference with glomerular filtration.
Obstruction to urinary flow can be caused by functional or structural derangements anywhere from the renal pelvis to the tip of the urethra.
Postrenal AKI (Acute Kidney Injury) can be due to prostate disease (benign prostatic hypertrophy or prostate cancer), neurogenic bladder, or therapy with anticholinergic drugs. Obstructed Foley catheters can cause postrenal AKI
Other causes of lower tract obstruction are blood clots, calculi, urethral strictures.
Ureteric obstruction can occur due to intraluminal obstruction (e.g., calculi, blood clots, sloughed renal papillae), infiltration of the ureteric wall (e.g., neoplasia), or external compression (e.g., retroperitoneal fibrosis, neoplasia, abscess, or inadvertent surgical damage).
The pathology of postrenal AKI involves hemodynamic alterations triggered by an abrupt increase in intratubular pressures.
An initial period of excess blood flow from afferent arteriolar dilation is followed by intrarenal vasoconstriction from the generation of angiotensin II, thromboxane A2, and vasopressin, and a reduction in NO production.
Secondary reductions in glomerular function are mainly due to under perfusion of glomeruli and, possibly, changes in the glomerular ultrafiltration coefficient.