AKI: Acute Kidney Injury 2024 PDF

# AKI: Acute Kidney Injury ## Dr Hussein Mahdi Ahmed Consultant Physician & Nephrologist ## Introduction * Acute kidney injury (AKI) is rapid and usually reversible decline in renal function as evident by rapid decline in GFR over a period of hours to days. * It may occur in patients with previou...

# AKI: Acute Kidney Injury ## Dr Hussein Mahdi Ahmed Consultant Physician & Nephrologist ## Introduction * Acute kidney injury (AKI) is rapid and usually reversible decline in renal function as evident by rapid decline in GFR over a period of hours to days. * It may occur in patients with previously normal renal function or patients with chronic kidney disease. ## Definition Acute kidney injury (AKI) is a clinical syndrome defined by either an abrupt increase in serum creatinine concentration by ≥0.3 mg/dL within 48 hours, a ≥1.5-fold increase in serum creatinine over the prior 7 days, or urine output <0.5 mL/kg/h for 6 hours. Endorsed by KDIGO: only one criterion needs to be present to fulfill the definition. It highlights the increased mortality resulting from even small increases in creatinine. ## Limitations of Sr. Creatinine * **Levels affected by:** 1. Extracellular volume depletion 2. Decreased kidney blood flow 3. Age 4. Sex 5. Body mass 6. Nutritional status * **It is not specific for AKI and requires differentiation from other pre-renal or extra-renal causes.** * **It is not specific for renal tubular lesions.** * **Reflect the loss of glomerular filtration function, accompanying the development of AKI.** * **It is a poor marker of kidney dysfunction as changes in its concentrations are neither sensitive nor specific in response to slight GFR alterations and detected later than the actual GFR changes** ## Definitions of Terminology * **Azotemia:** The accumulation of nitrogenous wastes (high BUN). * **Uremia:** Clinical manifestation (symptomatic renal failure). * **Oliguria:** UOP < 400 mL/24 hours * **Anuria:** UOP < 100 mL/24 hours. ## AKI Prevalence * Incidence of Dialysis-dependent AKI: 7200 per million population annually. * 5 - 10% of general hospital admissions. * 20 - 25% of patients with sepsis and ≈ 50% with septic shock. * 50% of all ITU admissions (where it acts as an independent risk factors for mortality of 20 - 60%, depending on AKI stage). * KDIGO estimated a worldwide AKI prevalence of 72,100 per million population, the majority of which are community-acquired. * The burden of AKI may be highest in developing countries. * Individuals with CKD are at increased risk of AKI (and AKI is a risk factor for progression of CKD). ## Kidney Function To function properly, kidneys require: * Normal renal blood flow – **Prerenal**. * Functioning glomeruli, tubules, and interstitium – **Intrinsic/Renal**. * Clear urinary outflow track – **Postrenal**. ## Acute or Chronic? Distinguishing between AKI and chronic renal impairment is important as: * The approach to these patients differs greatly. * This may save a great deal of unnecessary investigation. ## Definition & Staging of AKI | Stage | Cr Criteria | UO Criteria | | :------- |:----------------------------------------------------------------------------------|:--------------------------------------------------------------------------| | **1** | Increase in Cr by ≥26.5 µmol/l within 48hrs OR <br> 50-99% increase in Cr from baseline (baseline is known or presumed to have occurred within prior 7 days) | < 0.5 ml/kg/h for 6-12 h | | **2** | 100 - 199% rise in Cr | < 0.5 ml/kg/h for ≥ 12 h | | **3** | ≥200% rise in Cr OR <br> Cr rising ≥ 354 OR <br> Initiation of RRT <br> In pts younger than 18, decrease in eGFR to < 35 ml/min/1.73 m² | < 0.3 ml/kg/h for ≥ 24h OR <br> Anuria for ≥ 12h | ## Risk Factors of AKI * eGFR <60 ml/min/1.73m² or history of AKI * Diabetes * Heart failure, liver disease * Neurological or cognitive impairment * Use of nephrotoxic drugs * Use of iodinated contrast agents within the past week * Symptoms or history of urological obstruction * Sepsis * Age 65 years or over ## Classification of AKI A diagram shows AKI at the top with three branches: Pre-renal, Intrinsic, and Post-renal. Under the Intrinsic branch are four more categories: * Acute GN (Glomerulonephritis) * ATN (Acute Tubular Necrosis) * AIN (Acute Interstitial Nephritis) * Acute Tubular Obstruction * Acute TMA (Thrombotic Microangiopathy) ## Causes of AKI in Hospital Setting A pie chart shows the causes of AKI. The chart is divided into the following sections: * Pre-renal (largest slice) * Acute-on-chronic renal failure * Acute tubular necrosis (largest slice) * Acute interstitial nephritis * Obstruction * RPGN (smallest slice) * Vascular (smallest slice) ## I- Prerenal: (correctable, i.e., normal kidney with ↓perfusion) Prerenal AKI is characterized by a decrease in glomerular filtration rate (GFR) in response to impaired renal perfusion with intact renal parenchyma. However, intact tubular function with high urine osmolality and low urine sodium concentrations should not necessarily be interpreted as prerenal AKI, as many intrinsic etiologies, such as glomerulonephritis or AKI due to sepsis, may initially have intact tubular function. ### Causes of Prerenal AKI: The causes of prerenal AKI are listed in a table: | Causes | |--------| | **Decreased effective circulatory volume (Hypovolemia)** | | 1. Hemorrhage: Traumatic, surgical, postpartum, gastrointestinal GI) | | 2. GI fluid loss: Vomiting, diarrhea, surgical drainage. | | 3. Kidney loss: Diuretic therapy, osmotic diuresis in diabetes, and adrenal insufficiency. | | 4. Vasodilatory loss of the extravascular compartments: Sepsis syndromes, acute pancreatitis, peritonitis severe trauma, burns, and severe hypoalbuminemia. | | **Reduced COP** | | 1. Diseases of the myocardium, valves, and pericardium; | | 2. arrhythmias; | | 3. massive pulmonary embolism; | | 4. positive-pressure mechanical ventilation | ## Pathogensis of Prerenal Failure A graphic diagram shows the pathogeneses of prerenal failure in three boxes: * **Box 1:** The kidneys receive about 25% of the cardiac output at rest. * **Box 2:** If cardiac output is reduced or there is hypovolemia, regional vasoconstriction occurs limiting the blood flow to organs other than the heart and brain. * **Box 3:** Initially the blood flow is diminished to the skin then GIT and muscles. A second graphic diagram shows the pathogeneses of prerenal failure in two boxes: * **Box 1:** Usually, the kidney can maintain GFR close to normal despite wide variations in renal perfusion (autoreguation through VC of efferent). * **Box 2:** Further decrease of COP or intravascular volume leads to further depression of renal perfusion with drop of glomerular filtration due to selective cortical vasoconstriction → oliguria. ## Pathophysiology of Ischemic Acute Renal Failure A diagram shows the pathophysiology of ischemic acute renal failure. The diagram shows two sections, **Microvascular** and **Tubular**. **Microvascular** includes three types of microvascular response: * Vasoconstriction in response to: endothelin, adesonine, angiotensin II, thromboxane A2, leukotrienes, sympathetic nerve activity. * Vasodilation in response to: nitric oxide, PGE2, acetylcholine, bradykinin. * Endothelial and vascular smooth muscle cell structural damage. **Tubular** includes six types of tubular response: * Cytoskeletal breakdown * Loss of polarity * Apoptosis and necrosis * Inflammatory and vasoactive mediators * Desquamation of viable and necrotic cells. * Tubular obstruction ## There are 4 phases that can be distinguished in the natural history of AKI 1. **Initiation Phase:** This phase presents with normal urine output as it commences from the initial impact of the insult (cause) until the point of actual kidney damage. The duration of this phase is usually several hours and caries depending on the causative factor. 2. **Oliguria (urine output 100 - 400 mL/d) or Anuria (urine output < 100 mL/d):** This phase occurs when urine output is typically between 50 and 400 mL/d. It develops in~50% of patients and lasts an average of 10 to 14 days but can vary from 1 day to 8 weeks. 3. **Polyuria:** This phase begins with rapidly increasing urine output over several days after a period of oliguria or anuria. It occurs due to tabular dysfunction and is manifested by sodium wasting and polyuria. Serum creatinine and urea levels may not decrease for several days. The duration of polyuria is proportional to the duration of oliguria/anuria and may last up to several weeks. This phase of AKI is associated with considerable risk of dehydration and severe loss of electrolytes, particularly postassium and calcium. 4. **Recovery Phase:** During this phase, urine output gradually returns to normal and serum creatinine and urea begin to normalize. It may take up to several months for complete recovery or for a new baseline function to be established. ## Renal / Intrinsic AKI A table lists the causes of renal / intrinsic AKI: | Category | Cause | |---------------|------------------------------------------------------------------------------| | **Glomerular** | PSGN, SLE, ANCA associated, anti-GBM disease, HSP, cryoglobulinemia, TTP, HUS | | **Tubular** | Ischemia -50%, Toxins -30% | | **Interstitial** | Drug: NSAIDs, antibiotics <br> Infiltrative: lymphoma <br> Granulomatous- Sarcoidosis, Tb <br> Infection: APN | | **Vascular** | Vascular occlusions <br> - Renal artery occlusion <br> - Renal vein thrombosis <br> - Cholesterol emboli | ## Post-Renal Urinary Outflow Tract Obstruction A diagram shows two causes of post-renal urinary outflow tract obstruction: * **Intrinsic:** * Intra-luminal * Stone * Blood clots * Papillary necrosis * Intra-mural * Urethral stricture * BPH * Ca prostate * Bladder tumor * Radiation fibrosis * **Extrinsic:** * Pelvic malignancies * Prolapsed uterus * Retroperitoneal fibrosis ## Diagnostic Evaluation * **Careful history taking**, and **physical examination** often narrow the differential diagnosis for the cause of AKI. * **Prerenal azotemia** should be suspected in the setting of vomiting, diarrhea, glycosuria causing polyuria, and several medications including diuretics, NSAIDs, ACE inhibitors, and ARBs. * **Physical signs of orthostatic hypotension, tachycardia, reduced jugular venous pressure, decreased skin turgor, and dry mucous membranes** are often present in prerenal azotemia. * **A history of prostatic disease, nephrolithiasis, or pelvic or paraaortic malignancy** would suggest the possibility of postrenal AKI. ## AKI Outcomes A diagram shows the outcomes of AKI. * **Risk Factors:** * Age * Race or ethnic group * Genetic factors * Hypertension * Diabetes Mellitus * Metabolic Syndrome * **Disease Modifiers:** * Severity of acute kidney injury * Stage of chronic kidney disease * Number of episodes * Duration of acute kidney injury * Proteinuria * **Outcomes:** * Cardiovascular events * Kidney events * End-stage renal disease * Disability * Diminished quality of life * Death ## Initial 7 Steps of AKI Management Bundle * Confirm AKI. * Assess emergency: Pulmonary edema, Hyperkalemia, Acidosis. * Undertake ABCDE - full clinical examination. * Stop nephrotoxic drugs. * Urine dipstick test and confirm by RME. * Biochemistry - Check & repeat * Renal ultrasound and consider urinary catheter. * Urgent senior review. ## Management Principles * Identify the source of infection and treat aggressively keeping dose adjustment. * Minimise indwelling lines * Remove bladder catheter in anuric patients. * Identify and treat bleeding tendency: * PPI, H2 antagonist, avoid aspirin * Transfuse if required. ## Optimise Nutritional Support * Maintaining adequate nutrition enhances patient survival. * Maintain protein intake of about 1gm/Kg/Day. Protein intakes of > 1.2 g/kg/day can dramatically increase azotemia. ## RRT * Initiate dialysis before uraemic complications set in. * Early RRT improves mortality and recovery. * Specific types of therapy are available for critically ill patients.