[04.02] CMD - Acute Kidney Injury V2.pdf

Impairment of kidney filtration and excretory function occurring within 7 days

Definition of Acute Kidney Injury (AKI)

Retention of nitrogenous and other waste products normally cleared by the kidneys

Primary biochemical consequence of AKI

Clinical diagnosis

Is Acute Kidney Injury (AKI) classified as a structural diagnosis or a clinical diagnosis?

A patient can have AKI with or without actual structural injury to the kidney parenchyma

Why is the term 'AKI' considered a clinical misnomer?

Elimination of toxins and natural physiological by-products

Normal physiological purpose of urination

Delay in waste and toxin clearance leading to systemic complications

Consequence of impaired renal function on metabolic waste products

Incidence of stroke

Which major acute medical condition has a lower incidence in admitted hospital patients than AKI?

Spectrum of kidney impairment syndromes

Broad classification of functional renal disorders that includes AKI, AKD, and CKD

≤7 days

Duration criterion defining Acute Kidney Injury (AKI)

7 days but <3 months

Duration criterion defining Acute Kidney Disease (AKD)

3 months

Duration criterion defining Chronic Kidney Disease (CKD)

Stable GFR ≥60 mL/min/1.73 m², stable serum creatinine, no oliguria for ≥6 hours, and no structural markers

Definition of Normal Kidney Function / NKD

Increase in serum creatinine by ≥0.3 mg/dL (26.5 μmol/L) within 48 hours

Serum creatinine increase criterion within 48 hours for AKI diagnosis

Increase in serum creatinine >1.5 times baseline known or presumed within the past 7 days

Serum creatinine increase criterion within 7 days for AKI diagnosis

Urine volume <0.5 mL/kg/h for 6 hours

Urine output criterion for AKI diagnosis

Urine output

Definition of oliguria in the diagnostic criteria of AKI

Not required

Is structural kidney damage required to diagnose AKI?

Required

Is structural kidney damage required to diagnose AKD and CKD?

Proteinuria and structural abnormalities visible on imaging

Two diagnostic manifestations of structural kidney damage

Small or shrunken kidneys

Characteristic renal ultrasound finding in Chronic Kidney Disease

Serum creatinine level and urine output

Two clinical parameters used to stage the severity of AKI

Choose the stage corresponding to the more severe criterion

Rule applied when serum creatinine and urine output indicate different AKI stages

Urine output

Which diagnostic parameter allows faster clinical detection of AKI: serum creatinine or urine output?

Urine output provides immediate feedback, whereas serum creatinine lab testing involves processing delays

Why does urine output diagnose AKI faster than serum creatinine?

Serum creatinine 1.5–1.9 times baseline OR increase by ≥0.3 mg/dL (≥26.5 μmol/L)

Serum creatinine criteria for Stage 1 AKI

Urine output <0.5 mL/kg/h for 6–12 hours

KDIGO and Harrison's urine output criteria for Stage 1 AKI

Urine output <0.5 mL/kg/h for 6–8 hours

Lecture note urine output criteria for Stage 1 AKI

Serum creatinine 2.0–2.9 times baseline

Serum creatinine criteria for Stage 2 AKI

Urine output <0.5 mL/kg/h for ≥12 hours

Urine output criteria for Stage 2 AKI

Serum creatinine 3.0 times baseline, SCr ≥4.0 mg/dL (≥353.6 μmol/L), initiation of RRT, or eGFR <35 mL/min/1.73m² in patients <18 years

Serum creatinine and clinical criteria for Stage 3 AKI

Urine output <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours

Urine output criteria for Stage 3 AKI

Urine output

Alternative urine output interpretation for Stage 3 AKI

Complicates hospital admissions and increases morbidity and mortality

Short-term clinical impact of AKI during hospitalization

Development or worsening of CKD and increased risk of future cardiovascular diseases

Long-term health risks in patients who recover from an episode of AKI

Cardiovascular complications

Most common actual cause of death in patients with chronic kidney disease secondary to AKI

Sepsis, major surgical procedures, critical illness (heart/liver failure), and nephrotoxic drug administration

Four primary hospital-acquired causes of AKI

Volume depletion/dehydration, heart failure, maintenance medication side effects, urinary tract obstruction, and malignancy

Five primary community-acquired causes of AKI

Benign prostatic hyperplasia (BPH) / enlarged prostate in elderly males and pregnancy

Two common causes of urinary tract obstruction leading to community-acquired AKI

Prerenal azotemia

Most common category and etiology of Acute Kidney Injury

Supply problem due to inadequate renal plasma flow / blood flow to the kidney

Core pathophysiological mechanism of prerenal azotemia

Rise in SCr or BUN due to inadequate renal plasma flow and intraglomerular hydrostatic pressure

Definition of prerenal azotemia

Hypovolemia, decreased cardiac output, decreased effective circulating volume, and impaired renal autoregulation

Four main etiologic categories of prerenal AKI

Congestive heart failure and liver failure

Two conditions causing decreased effective circulating arterial blood volume despite systemic fluid retention

NSAIDs, ACE inhibitors, ARBs, and Cyclosporine

Four major drug classes that impair renal hemodynamics and autoregulation

Naproxen, Celecoxib, and Arcoxia

Three over-the-counter or prescription NSAID examples associated with prerenal AKI

Enalapril and Captopril

Two ACE inhibitor examples that blunt renal efferent vasoconstriction

Immunosuppressant used in kidney transplant recipients and autoimmune diseases

Clinical indication for Cyclosporine

Rapidly reversible

Reversibility of prerenal azotemia upon prompt restoration of renal blood flow

Ischemic injury and acute tubular necrosis (intrinsic AKI)

Consequence of prolonged, untreated prerenal azotemia

How efficiently the kidneys filter blood passing through the glomerulus

Definition of Glomerular Filtration Rate (GFR)

Connected to the water faucet

Garden hose analogy component representing the afferent arteriole

Mouth or exit of the hose

Garden hose analogy component representing the efferent arteriole

Water leak coming out of the hose

Garden hose analogy component representing GFR

Decreases blood flow entering the glomerulus, causing GFR to drop

Effect of afferent arteriolar constriction on GFR

Increases blood flow entering the glomerulus, causing GFR to rise

Effect of afferent arteriolar vasodilation on GFR

Reduces intraglomerular hydrostatic pressure, causing GFR to drop

Effect of efferent arteriolar vasodilation on GFR

Increases intraglomerular hydrostatic pressure, causing GFR to rise

Effect of efferent arteriolar constriction on GFR

Afferent arteriolar vasodilation and efferent arteriolar vasoconstriction

Two glomerular arteriolar adjustments that increase GFR during low perfusion

Myogenic reflex and Tubuloglomerular feedback

Two innate intrarenal mechanisms responsible for autoregulation of blood flow and GFR

Myogenic reflex

First line of defense mechanism responding to acute changes in afferent perfusion pressure

Dilates the afferent arteriole to increase intraglomerular blood flow

Myogenic reflex response to decreased renal perfusion pressure

Constricts the afferent arteriole to protect the glomerular capillaries from elevated pressure

Myogenic reflex response to excessive renal perfusion pressure

Afferent arteriole only

Which arteriole is selectively modulated by the myogenic reflex?

Tubuloglomerular feedback

Mechanism mediated by the juxtaglomerular apparatus that senses solute delivery changes at the macula densa

Macula densa cells in the distal tubule and juxtaglomerular (JG) cells in afferent/efferent arterioles

Two cellular components comprising the juxtaglomerular apparatus

Decrease in sodium chloride (NaCl / salt) delivery

Specific chemical change detected by macula densa cells

Decreases afferent arteriolar resistance via vasodilation

Tubuloglomerular feedback action on the afferent arteriole when NaCl delivery drops

Increases efferent arteriolar resistance via vasoconstriction

Tubuloglomerular feedback action on the efferent arteriole when NaCl delivery drops

Renin-Angiotensin-Aldosterone System (RAAS) via increase in renin and Angiotensin II

Endocrine pathway mediating efferent arteriolar vasoconstriction in tubuloglomerular feedback

Both afferent and efferent arterioles

Which arterioles are modulated by tubuloglomerular feedback?

Systolic blood pressure < 80 mmHg

Systolic blood pressure threshold below which renal autoregulation completely fails

Structural narrowing of intrarenal arterioles impairing afferent vasodilation

How atherosclerosis, longstanding hypertension, and advanced age impair renal autoregulation

Pre-existing nephron loss causes remaining nephrons to already max out afferent vasodilation

Why Chronic Kidney Disease blunts the renal autoregulatory response

Inhibition of renal prostaglandin production, preventing afferent arteriolar vasodilation

Mechanism of NSAID-induced renal autoregulatory failure

Vasodilation of the afferent arteriole to maintain glomerular blood flow

Normal hemodynamic role of renal prostaglandins in the glomerulus

Inhibition of RAAS, preventing efferent arteriolar vasoconstriction

Mechanism of ACEi/ARB-induced renal autoregulatory failure

Vasoconstriction of the efferent arteriole to maintain intraglomerular pressure

Normal hemodynamic role of Angiotensin II in the glomerulus

Direct parenchymal damage within kidney structures (glomerulus, tubules, interstitium, or blood vessels)

Core definition of intrinsic AKI

Glomerular, Tubular/Interstitium, and Vascular

Three structural anatomic categories of intrinsic AKI

Glomerulonephritis

Primary glomerular etiology causing intrinsic AKI

Ischemia, sepsis/infection, and nephrotoxins

Three major etiologies causing intrinsic damage to renal tubules and interstitium

Exogenous nephrotoxins

Toxic substances introduced into the body from external sources

Endogenous nephrotoxins

Toxic substances produced within the body itself, such as myoglobin or uric acid

Vasculitis, malignant hypertension, and TTP-HUS

Three vascular disorders leading to intrinsic AKI

Proton Pump Inhibitors (PPIs) such as omeprazole, pantoprazole, and esomeprazole

Drug class used for hyperacidity that is associated with allergic interstitial nephritis

Dysregulated host response to infection producing inflammatory cytokines

Core disease mechanism of sepsis causing renal injury

Endothelial damage, reactive oxygen species (ROS) activation, excessive renal vasoconstriction, and cytokine-mediated vasodilation

Four pathophysiological mechanisms involved in sepsis-associated AKI

Cytokine-mediated vasodilation systemically, but excessive renal vasoconstriction intrarenally

Vascular disparity between systemic and renal blood flow during sepsis

Direct tissue toxicity and tubular injury

Pathological effect of reactive oxygen species (ROS) in SA-AKI

20%

Percentage of total cardiac output received by the kidneys

Prolonged lack of blood flow and oxygen supply to renal tissues

Etiology of ischemic AKI

Muddy brown casts

Classic pathognomonic urinalysis/microscopy finding in ischemic AKI / ATN

Interplay of microvascular events (vasoconstriction, endothelial injury) and tubular events (necrosis, obstruction, backleak)

Pathophysiological interplay in ischemic acute renal failure

Cytoskeletal breakdown, mitochondrial injury, loss of polarity, apoptosis/necrosis, brush border desquamation, and intratubular debris obstruction

Tubular cellular changes during ischemic AKI

Post-operative / post-surgical setting

Most common clinical scenario for ischemia-associated AKI

Surgical blood loss and intra-operative hypotension

Two intraoperative factors contributing to post-surgical ischemic AKI

Cuboidal epithelial cells with brush borders

Normal histological structure of proximal convoluted tubule cells

Necrosis and desquamation/sloughing off of brush borders

Histological hallmark in proximal convoluted tubules during ischemic AKI

Kidneys filter all systemic blood and concentrate excreted toxins within tubular fluid

Why kidneys are uniquely susceptible to nephrotoxic injury

High-osmolar contrast media

Older CT scan contrast media class strongly associated with contrast-induced AKI