Acute Kidney Injury and Laboratory Investigations I PDF

Acute Kidney Injury and Laboratory Investigations Part I Dr Taryn Pillay Department of Chemical Pathology University of Witwatersrand Charlotte Maxeke Johannesburg NHLS  Objectives By the end of these...

Acute Kidney Injury and Laboratory Investigations Part I Dr Taryn Pillay Department of Chemical Pathology University of Witwatersrand Charlotte Maxeke Johannesburg NHLS  Objectives By the end of these lectures you should be able to: Explain the 3 categories of AKI viz. prerenal, renal and postrenal Incorporate history taking , clinical presentation and investigations to differentiate Acute Kidney Injury Explain acute tubular necrosis (ATN) and the ischemic spectrum Discuss the KDIGO guidelines in the definition of AKI, and to determine severity Explain the role laboratory investigation plays in the diagnosis and management of the patient with AKI Discuss laboratory tests and their significance: urine microscopy and biochemistry Outline 1.Introduction 2.Acute vs Chronic Injury 3.Epidemiology 4.Clinical Presentation PreRENAL RENAL 5.Etiology and Pathophysiology POSTRENAL 6.Treatment 7.Prognosis/Disease Course  Introduction Acute kidney injury (AKI) is characterized by the sudden impairment of kidney function It results in the retention of nitrogenous and other waste products normally cleared by the kidneys This heterogeneous group of conditions share common diagnostic features: specifically, - Increase in the serum Urea concentration +/- - Increase in the serum Creatinine (SCr) - often associated with a Decrease in Urine Volume  AKI = Acute Kidney Injury Replaces the term Acute Renal Failure A Clinical Syndrome of Multiple Causes resulting in Rapid Reduction of Kidney function Results in failure to maintain: - Fluid - Electrolyte HOMEOSTASIS - Acid Base  Acute vs Chronic ACUTE KIDNEY INJURY CHRONIC KIDNEY INJURY  Progressive loss of kidney function over a long period Rapid Loss of Kidney Function (months to years) (hours to days)  Usually IRREVERSIBLE leading to established renal failure, requiring Renal Replacement Potentially REVERSIBLE Therapy  Epidemiology AKI complicates 5–7% of acute hospital admissions and up to 30% of ICU admissions It increases the risk for : - development or worsening of chronic kidney injury (CKI), and - is associated with a markedly increased risk of death  Clinical Presentation Highly variable AKI can range in severity from : - Asymptomatic  with transient changes in laboratory parameters of glomerular filtration rate (GFR), to - Severe  overwhelming and rapidly fatal derangements in volume regulation, electrolyte and acid-base composition of the plasma  Metabolic and Clinical Features of Acute Kidney Injury METABOLIC FEATURE CLINICAL FEATURE Retention of Nitrogenous Waste Nausea, Vomiting, Hiccoughs, Altered Consciousness, Products GIT Bleeding (Increased Urea and Creatinine) Retention of Water Peripheral and Pulmonary Oedema (Hyponatremia) Ascites Pleural Effusion Retention of K Typical ECG Changes (peaked T waves, flattened P (Hyperkalaemia) waves, QRS depression, widened QRS complex Muscle Weakness, Paralysis Cardiac Arrest Retention of Acid Kussmaul Breathing Metabolic Acidosis  Uraemia/Azotemia = an increase in the blood concentration of nitrogenous compounds  Etiology and Pathophysiology Can be divided into three categories:  Pre-Renal  Functional impairment due to decrease in renal blood flow to the kidney  ischaemia Intrinsic Renal  Intrinsic kidney damage: glomeruli / tubules / interstitium / vasculature/ Parenchymal Disease , Post-Renal  Obstruction to extra-renal collecting system at any level: renal pelvis/ureters/bladder /urethra  Pre-Renal Most common form of AKI Characterised by: - Circulatory Insufficiency  bleeding, fluid loss, hypotension - Renal Hypoperfusion  ↓ GFR - A lack of structural renal damage - Preservation of normal tubular function (Concentrating Ability and Na Reabsorption) - Rapid Reversibility **If the underlying cause is appropriately managed  Pre-Renal AKI: Causes The most common clinical conditions associated with prerenal AKI are: Hypovolemia:  Haemorrhage, GIT Fluid Loss, Diuresis, Burns Decreased Cardiac Output :  Cardiogenic Shock, Massive Pulmonary Embolus, Cardiac Tamponade Hypotension :  Sepsis Drugs :  Vasodilators, ACE inhibitors  Pre-Renal AKI: Pathophysiology Normal GFR is maintained by the relative resistance of the afferent and efferent renal arterioles Determines the glomerular plasma flow and the transcapillary hydraulic pressure gradient which drives glomerular ultrafiltration Mild degrees of Hypovolemia/Reductions in cardiac output elicit compensatory renal physiologic changes  renal vasoconstriction and salt and water reabsorption occur as homeostatic responses  Mediators of this response include: - Renin-Angiotensin-Aldosterone System - Norepinephrine, and - Vasopressin (also termed antidiuretic hormone) - Intrarenal prostaglandins (prostacyclin, prostaglandin E2), kallikrein, kinins, and nitric oxide(NO) There is a limit to counterregulatory mechanisms to maintain GFR in systemic hypotension Renal autoregulation usually fails once systolic BP < 80 mmHg. Several factors determine the robustness of this response and the risk for prerenal acute kidney injury 1. Atherosclerosis, Structural narrowing of intra-renal Long-standing Hypertension arterioles  impaired capacity for Older Age  renal afferent vasodilation 2. Drugs can affect the compensatory changes 2.1 NSAIDs inhibit renal prostaglandin production, limiting renal afferent vasodilation 2.2 Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) limit renal efferent vasoconstriction; Prerenal AKI involves no parenchymal damage to the kidney and is rapidly reversible once intraglomerular hemodynamics are restored It may however, co-exist with other forms of Intrinsic AKI Prolonged periods of Prerenal AKI may lead to ischemic injury  often termed Acute Tubular Necrosis (ATN)  Intrinsic/Renal AKI Causes The most common causes of Intrinsic AKI are: Renal Ischaemia  Tubular Injury  ATN , and Nephrotoxins  both endogenous and exogenous Sepsis, Severe Bleeding, Burns, Heart Failure Specific kidney diseases and systemic diseases that affect the kidney are also important Other causes of intrinsic AKI are less common and can be conceptualized anatomically according to the major site of renal parenchymal damage: glomeruli, tubulointerstitium, and vessels.  Intrinsic Renal AKI : Pathophysiology Prerenal azotemia and ischemia-associated AKI represent a continuum of the manifestations of renal hypoperfusion  CAUSES: INTRINSIC Glomerulonephritis Vascular Disease Severe Hypertension Ischaemia Nephrotoxins: Aminoglycosides, NSAID’s, X-Ray contrast media, Heavy Metals, Animal and Plant Toxins Hypercalcaemia Infiltrative Disorders: Sarcoidosis, Lymphoma, Leukaemia  2 COMMONEST CAUSES OF AKI (account for 65-75% patients with AKI) - Acute Tubular Necrosis (ATN) - 45% - Pre-Renal AKI  Ischaemic Spectrum Pre-renal AKI ATN Bilateral Cortical Necrosis Normal kidney Mainly Tubular No tubular damage damage Irreversible (progression to ATN Potentially is preventable) Reversible NB. Individual differences in susceptibility ATN (ISCHAEMIC CAUSES) ISCHAEMIA Loss if integrity of tight junctions with back leakage of glomerular filtrate Devarajan et al. J Am Soc Nephrol 17: 1503–1520, 2006  Post-Renal AKI Urine flow is acutely blocked (partially or totally)  increased retrograde hydrostatic pressure and interference with glomerular filtration If prolonged  leads to secondary renal tubular damage Obstruction to urinary flow may be caused by functional or structural derangements anywhere from the renal pelvis to the tip of the urethra Post-Renal: Causes  Post-Renal AKI: Pathophysiology Involves hemodynamic alterations triggered by an abrupt increase in intra- tubular pressures An initial period of afferent arteriolar dilation is followed by intrarenal vasoconstriction from the generation of angiotensin II, thromboxane A2, and vasopressin, and a reduction in NO production Reduced GFR is due to underperfusion of glomeruli and, possibly, changes in the glomerular ultrafiltration coefficient Treatment The management of individuals with and at risk for AKI varies according to the underlying cause Common Principles: Critical - Optimization of hemodynamics - Correction of fluid and electrolyte imbalances - Discontinuation of nephrotoxic medications, and - Dose adjustment of administered medications - Avoidance of Complications - Treat underlying Infections - Provision of Renal Replacement Therapy  Dialysis is indicated when medical management fails to control: - Volume overload, - Severe hyperkalemia, - Severe Acidosis, - Some toxic ingestions, and - when there are severe complications of uremia (asterixis, pericardial rub or effusion, encephalopathy, uremic bleeding)  Principle = semi-permeable membrane surrounded by a dialysate bath The timing of dialysis is still a matter of debate Prognosis/Disease Course AKI is associated with a significantly increased risk of in-hospital and long-term mortality (~50% with RRT), longer length of stay, and increased costs In **general Prerenal AKI carries a better prognosis than most cases of intrinsic AKI Prognosis varies from Complete Recovery to Progressive CKD(ESRD)