Acute Kidney Injury

Dr. Jayachandran N
Assistant Professor
Dept. Of Medicine
● Definition
● Pathophysiology
● Classification
● Causes
Definition
● sudden and often reversible loss of renal function
● develops over days or weeks
● often accompanied by a reduction in urine volume and increase in serum creatinine
● Clinical diagnosis
● Can occur without any structural damage to kidneys

● Acute kidney injury (AKI) is defined by the impairment of kidney filtration and
excretory function over days to weeks (generally known or expected to have occurred
within 7 days), resulting in the retention of nitrogenous and other waste products
normally cleared by the kidneys.
● 7% of hospitalized patients
● 20% of acutely ill
● Elderly more prone
Classification & pathophysiology
● Pre renal
○ Perfusion to kidney decreased
● Renal
○ When the primary insult affects the kidney itself
● Post renal
○ Obstruction to urine flow at any point from the tubule to urethra
Pre renal AKI
● most common form of AKI
● rise in SCr or BUN concentration
● inadequate renal plasma flow and intraglomerular hydrostatic pressure to support
normal glomerular filtration
● no parenchymal damage to the kidney
● rapidly reversible once parenchymal blood flow and intraglomerular
hemodynamics are restored
● If prolonged→ acute tubular necrosis
Causes
● hypovolemia
● decreased cardiac output
● medications that interfere with renal autoregulatory vascular responses
○ nonsteroidal anti-inflammatory drugs (NSAIDs)
○ inhibitors of angiotensin II
● Renal blood flow accounts for 20% of the cardiac output
● Decreased effective circulating volume or cardiac output → renal hypoxia→
RAASactivation→ vasoconstriction and salt and water reabsorption
● To maintain BP and increase intravascular volume
● To sustain perfusion to the cerebral and coronary vessels
Counter regulatory mechanisms
● Vasoconstriction of efferent arterioles mediated primarily by angiotensin II
● Vasodialatation of afferent arterioles
○ Myogenic reflex(prostaglandins, kallikrien,kinins, NO)
○ Tubulo glomerular feedback (NO)
● Failure of auto regulation
○ SBP < 80 mm Hg
○ CKD
○ Advanced age
○ Atherosclerosis
○ Long standing hypertension
○ NSAIDs
○ ACEI/ARBs
○ CLD
Intrinsic renal disease
● Glomerulus
● Tubules
● Interstitium
● Vascular
● Renal medulla- one of the most hypoxic regions in the body
● The outer medulla is particularly vulnerable to ischemic damage because of the
architecture 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 S3 segment of the proximal tubule, which depends on oxidative
metabolism for survival.
● Mitochondrial dysfunction due to ischemia and mitochondrial release of reactive
oxygen species also play a role in renal tubular injury.
Sepsis
● Generalized arterial vasodilation
○ cytokines→ upregulate the expression of inducible NO synthase in the vasculatue→ reduction in
GFR
○ Excessive efferent arteriole vasodilation, particularly early in the course of sepsis
● Renal vasoconstriction
○ sympathetic nervous system
○ RAAS
○ vasopressin or endothelin.
● Sepsis→ endothelial damage→increased microvascular leukocyte adhesion and
migration, thrombosis, permeability, increased interstitial pressure, reduction in
local flow to tubules, and activation of reactive oxygen species, all of which may
injure renal tubular cells.
Ischemia associated
● Any prerenal AKI if prolonged can lead to ischemic ATN
● Post operative
○ Hypotension
○ Extracorporeal circuit
○ Cholesterol emboli
● Burns & Acute Pancreatitis
○ Extensive fluid loss into extra vascular compartment
○ Dysregulated inflammation
○ Abdominal compartment syndrome
● Diseases of the vasculature
○ Microvascular - thrombotic micro angiopathy, scleroderma, atheroemboli
○ Large vessel- renal artery thrombus/dissection, renal vein thrombus/ compression
● Limited renal reserve (e.g., CKD or older age)
● Coexisting insults such as sepsis, vasoactive or nephrotoxic drugs,
rhabdomyolysis, or the systemic inflammatory states associated with burns and
pancreatitis.
● Persistent preglomerular vasoconstriction
○ activation of tubuloglomerular feedback from enhanced delivery of solute to the macula densa
following proximal tubule injury,
○ increased basal vascular tone and reactivity to vasoconstrictive agents
○ decreased vasodilator responsiveness.
● Backleak of filtrate across damaged and denuded tubular epithelium
● Mechanical obstruction of tubules from necrotic debris
Nephrotoxin associated AKI
● All structures of the kidney are vulnerable to toxic injury, including the tubules,
interstitium, vasculature, and collecting system.
● Risk factors
○ Older age
○ CKD
○ Prerenal azotemia.
○ Hypoalbuminemia may increase the risk of some forms of nephrotoxin-associated AKI due to
increased free circulating drug concentrations.
Nephrotoxin associated AKI
● Contrast induced
● Drugs
○ Antibiotics
○ Chemotherapeutics
○ NSAID
○ PPI
○ ACEI/ARB
● Toxin ingestion/envenomation
● Endogenous toxins
Post renal AKI
● Normally unidirectional flow of urine is acutely blocked either partially or
totally→ leading to increased retrograde hydrostatic pressure and interference
with glomerular filtration.
● Functional or structural derangements anywhere from the renal pelvis to the tip
of the urethra.
Thank you