Acute Kidney Injury PDF

# Acute Kidney Injury ## Introduction - The image shows a diagram of the human kidneys and blood circulation. - It has the title "Acute Kidney Injury" and includes the names and titles of the creators. - It is presented by Dr. Sherihan Ahmed Sayed, Lecturer of Clinical Pharmacy. ## Functions of...

# Acute Kidney Injury ## Introduction - The image shows a diagram of the human kidneys and blood circulation. - It has the title "Acute Kidney Injury" and includes the names and titles of the creators. - It is presented by Dr. Sherihan Ahmed Sayed, Lecturer of Clinical Pharmacy. ## Functions of the Kidney 1. **Execratory function:** - Metabolites - Drugs - Toxins 2. **Homeostatic function:** - Maintenance of water balance - Maintenance of electrolyte balance - Maintenance of acid-base balance 3. **Endocrine (hormonal) secretory function:** - Renin by the juxtaglomerular cells (JG) - Erythropoietin hormone by endothelial cells of peritubular capillaries of renal cortex - Prostaglandins 4. **Endocrine (hormonal) metabolic function:** - The kidney converts vitamin D3 → active 1,25-dihydroxycholecalciferol by alpha-one hydroxylase enzyme in cells of PCT under effect of PTH. ## Anatomy of the Kidney - The image depicts a diagram of the human kidneys, showing both an external view and a cross-section of the left kidney. - It highlights the following elements: - Adrenal Gland - Right Kidney - Inferior Vena Cava - Descending Aorta - Left Kidney (in cross-section) - Diaphragm - Ureters - Bladder - Renal Arteries (red) - Renal Veins (blue) - Pelvis of Kidney ## Physiology of the Kidney The image shows a diagram of a nephron, the basic functional unit of the kidney. It highlights three key processes: ### Glomerular Filtration - Water, salts, nutrient molecules, and waste molecules move from the glomerulus to the inside of the glomerular capsule. - These small molecules are called the glomerular filtrate. - The process occurs in the following sequence: - Glomerulus - Afferent arteriole - Renal artery - Glomerular capsule - Efferent arteriole - Proximal convoluted tubule (PCT) - Loop of the nephron - Renal vein ### Tubular Reabsorption - Nutrient and salt molecules are actively reabsorbed from the proximal convoluted tubule into the peritubular capillary network. - Water flows passively. ### Tubular Secretion - Certain molecules are actively secreted from the peritubular capillary network into the distal convoluted tubule. - The process occurs in the following sequence: - Distal convoluted tubule (DCT) - Collecing duct - Peritubular capillary network - Reabsorption of sodium from the DCT and water from the collecting duct are under hormonal control. ## Definition of Acute Renal Failure (ARF) Acute renal failure (ARF) is an abrupt and usually reversible decline in the glomerular filtration rate (GFR). Many patients become oliguric (low urine output). - This results in an elevation of nitrogenous waste products that are normally excreted by the kidney, urea and creatinine (azotemia), and the inability to maintain and regulate fluid, electrolyte, and acid-base balance. - In patients with pre-existing chronic kidney disease (CKD), a rapid decline in renal function is termed acute on chronic. ## Types of AKI The table below shows the types, mechanisms, and causes of AKI: | Types of AKI | Mechanism | Causes | |---|---|---| | **Prerenal** | Reduced blood flow to the kidneys | - Hypovolemic states (hemorrhage, GI loss, renal loss, severe burns, sepsis) - Systolic heart failure - Hypoalbuminemia - Medications (NSAIDs, ACE-inhibitors, ARBs, Cyclosporine, & iodinated contrast) | | **Intrarenal** | Damage to kidney tubules, glomerulus, or interstitium | - Acute tubular necrosis - Nephrotoxins (aminoglycosides, methotrexate, lead, ethylene glycol, radiocontrast dye) - Rhabdomyelisis - Glomerular disease - Acute interstitial nephritis | | **Postrenal** | Obstructed urine flow | - Kidney stones - Benign prostatic hyperplasia - Prostatic cancer - Intra-abdominal tumors | ## Pre-renal Failure - The most common cause of AKI ### Causes of Pre-renal Failure 1. **Intravascular volume depletion:** - Hemorrhage (post-partum, trauma, and surgical) - Dehydration (gastrointestinal losses; vomiting, diarrhea, aggressive diuretic administration) 2. **Decreased cardiac output:** 3. **Renovacular obstruction:** - Bilateral renal artery stenosis - Renal artery or vein thrombosis (embolism, atherosclerosis) 4. **Aggravation of renal hypoperfusion by interference with renal autoregulations:** (Functional AKI) - With a mild to moderate decrease in renal blood flow, intraglomerular pressure is maintained by: - Dilation of afferent arterioles (arteries supplying blood to the glomerulus) - Constriction of efferent arterioles (arteries removing blood from the glomerulus), and Redistribution of renal blood flow to the oxygen-sensitive renal medulla. - **Functional ARF occurs when these adaptive mechanisms are compromised by drugs:** - NSAIDs (Prostaglandin synthesis inhibitors) impair prostaglandin-mediated dilation of afferent arterioles. - ACE inhibitors and angiotensin receptor blockers (ARBs) inhibit angiotensin II-mediated efferent arteriole vasoconstriction. - Angiotensin converting enzyme inhibition (ACEI) contraindicated in patients with renal artery stenosis. - Cyclosporine and tacrolimus, especially in high doses, are potent renal vasoconstrictors. - All of these agents can reduce intraglomerular pressure, with a resultant decrease in GFR. ### Pre-renal ARF Symptoms - **Symptoms:** Thirst, hypotension, Tachycardia and Oliguria. - **Physical examination:** Postural hypotension and decrease skin elasticity. ### Pre-renal ARF Mechanism The image shows a diagram of two nephrons. The top nephron represents the state of "Hypoperfusion", while the bottom depicts a nephron treated with "ACE inhibitor" | | **Hypoperfusion** | **ACE Inhibitor Treated** | |---|---|---| | **Afferent Arteriole** | Decreased flow | Decreased or normal flow | | **Efferent Arteriole** | Constricted | Dilated | ### Combination of Hypotension and Hypovolemia - **Combination of hypotension and hypovolemia resulting in diminished renal perfusion is the most common cause of acute renal failure in hospitalized patients.** - **When renal hypoperfusion (due to hypotension and/or hypvolemia) is not severe enough to cause renal tubular damage, it will manifest as pre-renal failure in the form of oliguria and a rise in serum creatinine and blood urea.** - **As no structural renal damage, early diagnosis and correction of renal hypoperfusion result in immediate diuresis and rapid drop in serum creatinine and blood urea levels.** - **If hypoperfusion is severe, renal compensatory mechanisms will fail as an acute tubular necrosis occurs. In this new situation, correction of hypoperfusion will not be followed by diuresis or drop in serum creatinine.** - **Few days or weeks (mean 2-3 weeks) are needed for tubular regeneration and recovery of kidney function to occur.** ## Acute Intrinsic Renal Failure - Caused by diseases that can affect the integrity of the tubules, glomerulus, interstitium, or blood vessels. Changes in kidney structure can be seen on microscopy. ### Classifications of Acute Intrinsic Renal Failure 1. **Acute tubular necrosis (ATN) (the most common)** 2. **Renal vascular damage** 3. **Inflammation in kidney** - a) Tubulointerstitial nephritis - b) Glomerulonephritis ## Acute Tubular Necrosis (ATN) - In > 80% of intrinsic RF cases - Acute tubular necrosis can be induced by renal hypoperfusion (ischemia) or exposure to nephrotoxins (exogenous or endogenous toxins) and by a combination of both. ### Causes of Ischemic ATN: (Longstanding renal hypoperfusion ) 1. **Intravascular volume depletion** 2. **Low effective circulating volume** 3. **Renovacular obstruction** 4. **Aggravation of renal hypoperfusion by interference with renal autoregulations** ### Causes of Toxic ATN: (A) **Exogenous nephrotoxins include:** - Aminoglycosides - Cisplatin - Quinolone - Methotrexate - N.B: Medullary ischemia may result from contrast media–induced renal vasoconstriction. The high ionic load of contrast media may produce ischemia, particularly in patients with diabetes. (B) **Endogenous nephrotoxins include:** - **Pigments:** - Myoglobin (Rhabdomyolysis) - Hemoglobin (hemolysis) - **Crystals:** - Uric acid - Calcium oxalate ## Renal Vascular Damage - Occlusion of either renal arterioles or venous supply - **E.g : emboli, thrombocytopenic purpura (blood clots in kidney vessels due to blood transfusion or severe hypertension) or use of ACEI with renal artery stenosis** - **Haemloytic uramic syndrome : in infant or children associated with E.coli which release toxins causing damage to blood vessels and causing hemolysis to RBCs** ## Inflammation in Kidney ### a) Tubulointerstitial nephritis: - Inflammation affecting those cells lying between nephrons - Drug induced (quinolones, penicillin, sulfadrugs) ### b) Glomerulonephritis: - Glomerulonephritis is often (but not always) inflammatory in nature and can be primary or secondary to another systemic illness - (e.g. Systemic lupus erythematosus and streptococcal infection). - Drug may cause: phenytoin and penicillamine ## Post-renal Acute Renal Failure - Post-renal ARF (10% of cases) is due to obstruction of urinary outflow. - Causes include benign prostatic hypertrophy (BPH), pelvic tumors, and precipitation of renal calculi. - Rapid resolution of post-renal ARF without structural damage to the kidney can occur if the underlying obstruction is corrected. - **Note that:** - both kidneys must be obstructed for creatinine to rise. - Post-renal obstruction, if untreated, can lead to ATN. - **Symptoms: hypertension, edema, hematuria, distended bladder, difficult urination** ## Risk Factors Associated with ARF 1. **Preexisting CKD (GFR < 60 mL/min per 1.73m2 for > 3 months)** 2. **Diabetes mellitus** 3. **Volume depletion:** Vomiting, diarrhea, poor fluid intake, fever, diuretic use, effective volume depletion (e.g., CHF, liver disease with ascites). 4. **Use of nephrotoxic agents/medications:** - a. Intravenous radiographic contrast media - b. Aminoglycosides and amphotericin - c. NSAIDs and COX-2 inhibitors - d. ACEIs and ARBs - e. Cyclosporine and tacrolimus 5. **Obstruction of the urinary tract** ## Clinical Features of ARF 1. **Usually, the patient gives history of the etiologic cause such as trauma, shock, hemolysis, drug intake, infection, or stone disease.** 2. **Patient may notice a change in urine volume and character, oliguria is common, but in 10-50% of cases urine volume will be normal or even higher (as in toxic ATN) this is called polyuric ATN. Absolute anuria is highly suggestive of obstructive ARF (post-renal) or very severe form of ATN (cortical necrosis).** 3. **Manifestation of salt and water retention (edema, puffiness, hypertension and even heart failure).** 4. **By time, manifestations of uremia, acidotic breathing, dyspnea, nausea, vomiting, headache, muscle twitches and even encephalopathy and coma in severe cases.** 5. **Colicky abdominal pain radiating from flank to groin (post-renal AKI)** **In some cases, AKI causes no symptoms and is only found through other tests done.** ## Diagnosis and Clinical Evaluation 1. **Full history including drug history** 2. **Physical examination:** - **A-Pre-renal:** Postural hypotension and decrease skin elasticity. - **B-Intrinsic:** Rash and vacuities lesions - **C-Post-renal:** Distended bladder on rectal or vaginal examination. 3. **Urine Examination:** Creatinine Clearance 4. **Blood examination:** Serum creatinine concentration 5. **Radiological study** ## Assessment of Renal Function - **The most common measure of overall kidney function is GFR. It is defined as the volume of plasma filtered across the glomerulus per unit time which correlates with the filtration, secretion, reabsorption, endocrine, and metabolic functions of the kidney.** - **In normal kidney function, GFR ranges from 90 to 120 mL/minute.** - **GFR is estimated by determining the renal clearance of creatinine that is filtered at the glomerulus and does not undergo significant tubular reabsorption.** - **Creatinine is an endogenous substance that is a normal by-product of muscle metabolism.** - **Blood Urea nitrogen is produced from the breakdown of food protein.** - **As kidney function decreases, the serum creatinine and BUN level increases.** ## Creatinine Clearance - **A creatinine clearance test compares the creatinine in a 24-hour sample of urine to the creatinine level in the blood, to show how many milliliters of blood the kidneys are filtering out each minute (ml/min)** - **Numerous equations have been developed to estimate creatinine clearance or GFR.** ### Estimating Creatinine Clearance (Cockroft- Gault Formula): (Used in chronic kidney disease Only for its stable Scr) Creatinine Clearance (ml/min)=(140 - age) x weight (kg) / 72 x Serum creatinine (mg/dl) * Multiply X 0.85 in a female patient * Normal creatinine clearance is 100-120 ml/min ## In AKI we are using **Jelliffe equation** for calculating CrCl * **Accounts for fluctuations in Scr overtime** ### Jelliffe Equation for Changing Renal Function | | **Males** | **Females** | |---|---|---| | **E** | IBW ([29.3-0.203 [age]]) | IBW ([25.1-0.175 [(age)]) | | **E** | E (1.035-0.0337 [SCr)) | E(1.035-0.0337 [SCr]) | | **Econ** | ESS (4 x IBW x [SCr₂- SCr]) / ΔΙ | ESS (4 x IBW x [SCr, - SCT)) / ΔΙ | | **CrCl (mL/min/1.73 m²)** | E/((14.4](SCr])) | E/([14.4][SCr]) | **where** - ESS = steady-state creatinine excretion - At = time in days between measurement of SCr, and SCr, - IBW = ideal body weight, kg - Econ = corrected steady-state creatinine excretion - SCr, = first serum creatinine concentration - SCr₂ = second serum creatinine concentration - E = creatinine excretion - CrCl, creatinine clearance. For conversion of mg/dL to µmol/L creatinine multiply by 88.4. ## The BUN/SCr ratio - **Normal value is 10:1 to 20: 1** - **ratio can differentiate prerenal causes from intrinsic and post-renal causes.** - **In prerenal conditions, the BUN:SCr ratio is greater than 20:1.** | | | | |---|---|---| | **BUN** | **< 15** | **> 20** | | **Cr** | - intra-renal - late post-renal | - pre-renal - early post-renal | - **N.B: Early post-renal AKI due to obstruction does not damage the kidney tubules but the urinary flow is slow allows more urea to be reabsorbed hence, increasing serum BUN level.** ## Evaluating Kidney Function - **Estimating creatinine clearance is only one part of evaluating and monitoring a patient's overall kidney function and other factors, such as symptoms, laboratory tests and diagnostic procedures.** - **Kidney function can also be evaluated based on urine output.** - **Anuria:** < 50 mL/24 hours (Worse outcomes) - **Oliguria:** 50–400 mL/24 hours - **Nonoliguria:** > 400 mL/24 hours (associated with better patient outcomes. Easier to manage because of fewer problems with volume overload). - **Patients with reduced urine output often have an increased mortality and may represent a more severe form of ARF.** - **Urine analysis:** - **Urine Na < 20mEq/L (prerenal AKI), > 40 mEq/L _(intrinsic AKI)** - **Brownish tubular epithelia casts (intrinsic AKI)** ## Comparing Laboratory Results The table below compares laboratory results from different types of AKI: | | **Prerenal and Functional** | **Intrinsic (ATN and AIN)** | **Postrenal** | |---|---|---|---| | **History and clinical presentation** | - Volume depletion - Renal artery stenosis - CHF - Hypercalcemia - NSAID, ACEI, and ARB use - Cyclosporine | - Long-standing renal hypoperfusion - Nephrotoxins (e.g., contrast or antibiotics) - Vasculitis - Glomerulonephritis | - Kidney stones - BPH - Cancers | | **Physical examination** | - Hypotension - Dehydration - Petechia if thrombotic - Ascites | - Rash, fever (with AIN) | - Distended bladder - Enlarged prostate | | **Serum BUN/SCr ratio** | Greater than 20:1 | 15:1 | 15:1 | | **Urine sodium** | Less than 20 mEq/L | Greater than 40 mEq/L | Greater than 40 mEq/L | | **FENa** | Less than 1% | Greater than 2% | Greater than 2% | | **Urine osmolality** | High urine osmolarity | Low urine osmolarity | Low urine osmolarity | | **Urine sediment** | Normal | Muddy brown granular casts; tubular epithelial casts | Variable; may be normal | ## The Acute Kidney Injury Network (AKIN) - **AKIN stands for Acute Kidney Injury Network.** - **Diagnostic criteria:** - **One of the following criteria is required within a 48-hour period to diagnose ARF : ** - **An absolute increase in SCr of more than 0.3 mg/dL** - **An increase in baseline SCr by 50% or greater** - **Urine output of < 0.5 mL/kg/hour for > 6 hours.** ## ARF Diagnostic Criteria - **The first AKI classification system was RIFLE, which stands for Risk, Injury, Failure, Loss, and End stage.** - **It categorizes patients into stages based on change in SCr or GFR from baseline,or decreased urine output.** - **After development of the RIFLE criteria, the Acute Kidney Injury Network (AKIN) modified the RIFLE definition and staging for AKI.** - **The AKIN staging system is based on changes in SCr (and not GFR) and uses three stages (stages 1 to 3); Stage 1 also includes an absolute increase in SCr of 0.3 mg/dL (27 µmol/L) or greater.** - **This highlights the association of even small increases in SCr concentration with morbidity and mortality, making early detection critical.** - **The second modification of RIFLE and AKIN criteria was recently published by the Kidney Disease: Improving Global Outcomes (KDIGO)** ## Stratification of AKI - **This table compares the RIFLE and AKIN classification systems for AKI.** | | **RIFLE Classification** | **Common Criteria** | **AKIN Criteria** | |---|---|---|---| | **Classification** | **SCr or GFR Criteria** | **Urine output** | **Stage** | **SCr or GFR Criteria** | | **R Risk of renal dysfunction** | - SCr increase to 1.5 times baseline or - GFR decrease by more than 25% | - Less than 0.5 mL/kg/hour for more than 6 hours| **1** | - SCr increase to more than 0.3 mg/dL or - 1.5-1.9 times baseline | | **I Injury to kidney** | - SCr increase to 2 times baseline or - GFR decrease by more than 50% | - Less than 0.5 mL/kg/hour for more than 12 hours | **2** | - SCr increase to 2-2.9 times baseline | | **F Failure of kidney function** | - SCr increase to 3 times baseline or - GFR decrease by more than 75% or - SCr greater than 4 mg/dL with acute rise greater than 0.5 mg/dL | - Less than 0.3 mL/kg/hour for more than 24 hours or - anuria × 12 hours | **3** | - SCr increase to 3 times baseline or more or - SCr greater than 4 mg/dL with an acute increase of more than 0.5 mg/dL; or on RRT | | **L Loss of kidney function** | - Complete loss of kidney function for more than 4 weeks | | | | **E End-stage kidney disease** | - Complete loss of kidney function for more than 3 months | | |