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Acute Kidney Injury and Chronic Kidney Disease: Classifications and Interventions for Children and Adults Teresa V

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Acute Kidney Injury and Chronic Kidney Disease: Classifications and Interventions for Children and Adults Teresa V Acute Kidney Injury and Chronic Kidney Disease: Classifications and Interventions for Children and Adults Teresa V. Lewis, PharmD, BCPS Assistant Professor of Pharmacy Practice University of Oklahoma College of Pharmacy Adjunct Assistant Professor of Pediatrics University of Oklahoma College of Medicine 1 Disclosures • Teresa V. Lewis, Pharm.D., BCPS • Nothing to disclose Objectives 1. When given specific patient details, identify those with increased Identify which adult or pediatric patients are at risk for development of acute kidney injury (AKI) and recommend appropriate preventive interventions. 2. Design an evidence-based plan to manage AKI for a given patient. 3. Compare and contrast the RIFLE, pRIFLE, and Kidney Disease Improving Global Outcomes (KDIGO) classification systems for AKI. 4. List risk factors for development of chronic kidney disease (CKD). 5. Compare and contrast the Kidney Disease Outcomes Quality Initiative (KDOQI) staging of CKD with the Kidney Disease Improving Global Outcomes (KDIGO) CKD staging criteria. 6. Design an evidence-based plan to prevent progression of CKD for a given patient. 3 Kidney Development and Maturation • Nephrogenesis • Begins around 9 weeks of gestation • Complete by 36 weeks of gestation • Immature renal function at birth • Lower renal blood flow • Immature glomeruli • Immature renal tubule function • Kidney function will be similar to adult values by age 2 years 4 Presentation Outline • Diagnostic Workup • Acute Kidney Injury • Drug Induced Nephrotoxicity • Chronic Kidney Disease 5 DIAGNOSTIC WORK-UP Blood Urea Nitrogen (BUN) • Normal: 8-20 mg/dL • Amino-acids metabolized to ammonia and converted in liver to urea • Urea is filtered and reabsorbed in proximal tubule (dependent on water reabsorption) • Normal BUN:Serum creatinine (Scr) ratio is 10-15:1 • Elevated BUN:Scr ratio suggests true or effective volume depletion 7 Serum Creatinine (Scr) • Freely filtered • Actively secreted • Scr lags behind glomerular filtration rate (GFR) by 1-2 days due to: 1. Slow accumulation 2. Increased tubular secretion 3. Increased extra-renal clearance 8 Glomerular Filtration Rate (GFR) • Amount of blood that passes through the glomeruli each minute • Best indicator of kidney function • Expressed as mL/minute/1.73 m2 9 Normal GFR Values By Age 160 ) 2 140 120 100 80 60 40 20 GFR (mL/min/1.73 m 0 10 Urinalysis Component Normal Comments Value • ĹpH suggest presence of bacteria pH 4.5-7.8 • ĹpH may be due to renal tubular dysfunction • Glucosuria when blood glucose > 180 mg/dL Glucose 0 • Fanconi syndrome: glucosuria with normal serum glucose Ketones 0 • Present in diabetic ketoacidosis, fasting, or starvation 11 Urinalysis Component Normal Comments Value • Present due to conversion from urinary nitrate by bacteria in the urine Nitrite Negative • Indication of urinary tract infection • Negative value does not rule out infection in children • Released by lysed granulocytes in urine Leukocyte • Normal: up to 3 per high-power field Negative esterase • Possible urinary tract infection or inflammation: > 3 per high-power field • Hemoglobin or myoglobin due to hematuria, Heme Negative hemolysis, or rhabdomyolysis 12 Urinalysis Component Normal Comments Value microalbuminuria: 30-300 mg/day Protein < 30 mg/day (Albumin) macroalbuminuria: >300 mg/day 1.003 to Most useful to evaluate sodium disorders or Specific gravity 1.030 volume status 13 Urine Dipstick Interpretations Result Protein amount Negative Less than 10 mg/dL Trace 10-20 mg/dL 1+ 30 mg/dL 2+ 100 mg/dL 3+ 300 mg/dL 4+ Greater than 1000 mg/dL 14 Urine Sodium (UNa) • Measures the ability of the kidney to concentrate urine • When volume depleted, the kidney will retain sodium so UNa will be low (5 -10 mEq/L) • When kidney cannot concentrate urine, UNa will be elevated > 30 mEq/L 15 Fractional excretion of sodium (FeNa) • Measures the ability of the kidney to concentrate urine • Reflects acute changes + + •FeNa % = [(Urine Na x Scr)/(Serum Na x Ucr)]x100 •FeNa ~1% = normal kidney function •FeNa < 1% = volume depletion •FeNa > 2% = renal damage or drug interaction •FeNa >4% suggests post-renal azotemia Fe may not be not reliable following recent diuretic therapy Na 16 Urine Osmolality • Measures the ability of the kidney to concentrate urine • Represents the number of osmotically active particles in the urine • Normal range • 50-1200 mOsm/kg • Depends on hydration status • > 500 mOsm/kg = highly concentrated urine 17 Acute Kidney Injury Kidneys Are Vulnerable To Injury Due To: • Large vascular surface area • High energy requirements of tubular cells (e.g. loop of Henle) • High renal blood flow requirements: ~20-25% of resting cardiac output • Intrarenal drug metabolism can lead to toxicity if metabolism results in a nephrotoxic metabolite or prolonged exposure • Proximal tubule uptake of toxins 19 Epidemiology • AKI is common in hospitalized patients (incidence: 13-18%) • Main causes of AKI in hospitalized patients • Pre-renal azotemia • Intrinsic azotemia (a.k.a renal azotemia) due to acute tubular necrosis (ATN) is associated with a high incidence of AKI in critical care patients • Drug-induced nephrotoxicity 20 Morbidity • ~90% will recover and live independently, but half will have subclinical effects • Some will have chronic kidney disease (CKD) or require long- term dialysis • AKI is associated with an increased risk for developing CKD 21 Mortality • AKI is an independent risk factor for mortality • Mortality: ~15-80% depending on the cause, severity of AKI and clinical setting • 10% mortality with uncomplicated AKI • > 50% mortality rate in patients with AKI and multi-organ failure • Up to 80% mortality rate in patients who require renal replacement therapy 22 General Recommendations 1. Assess risk for AKI 2. Prevent AKI 3. Detect AKI 4. Identify cause of AKI 5. General management of AKI 23 AKI Risk Factors • Neonates have higher rates of AKI (especially premature babies) • Age older than 65 years • History of AKI • Chronic kidney disease (CKD) • Hypovolemia (true or effective volume depletion) • Obstruction of urine flow (e.g. BPH, kidney stones, anatomical abnormalities such as posterior urethral valves, etc) • Exposure to nephrotoxic medications • Use of iodinated contrast within the past week • Presence of Comorbidities 24 Comorbidities (Other Disease States) • Diabetes • Heart failure • Hypertension or hypotension • Liver disease • Malignancy • Organ failure • Sepsis 25 Question: Which of the following increases a patient’s risk for developing AKI? A. AKI 12 years ago B. Premature neonate C. Congestive heart failure D. Dehydration 26 General Recommendations 1. Assess risk for AKI 2. Prevent AKI 3. Detect AKI 4. Identify cause of AKI 5. General management of AKI 27 PREVENT AKI • Identify patients at risk for AKI and correct factors when possible • Use a tracking system to permit early recognition of patients who are at risk for AKI • Increase frequency of monitoring 28 Risk Minimization Strategies • Assess baseline renal function (Clcr, GFR, historical SCr) • Adjust doses for renal function (use Cockcroft-Gault for adults, Schwartz or Bedside Schwartz for children) • Discontinue or avoid concomitant nephrotoxins • Use alternative agents where possible • Limit dose and duration of nephrotoxic medications • Take appropriate measures prior to nephrotoxic procedures • Supportive measures 29 General Recommendations 1. Assess risk for AKI 2. Prevent AKI 3. Detect AKI 4. Identify cause of AKI 5. General management of AKI 30 Detect AKI • Standardized definition for diagnosis and classification • AKI classification and staging helps predict patient outcomes • Detection is mostly based on monitoring serum creatinine + urine output • The different staging systems are generally similar with some differences in Scr and urine output criteria 31 AKI Classification Systems 1. RIFLE 2. pRIFLE 3. KDIGO 32 RIFLE Glomerular Filtration Rate (GFR) Urine Output (UO) Criteria Criteria Scr Ĺ x 1.5 Or Risk < 0.5 mL/kg/hr > 6 h GFR decreased > 25% from baseline Scr Ĺ x 2 Or Injury < 0.5 mL/kg/hr > 12 h GFR decreased > 50% from baseline Scr Ĺ x 3 Or GFR decreased > 75% Or < 0.3 mL/kg/hr for 24 h Or Failure Acute on chronic kidney injury: Scr > 4 mg/dL Anuria for 12 h & Scr acutely Ĺ by 0.5 mg/dL or higher 33 RIFLE Criteria Persistent acute renal failure (ARF): complete loss of kidney function Loss requiring dialysis > 4 weeks End Stage Renal Disease: complete loss of kidney function requiring ESRD dialysis > 3 months 34 Considerations With Urine Output As A Marker of AKI In Adults • Weight and urine output is a non-linear relationship so overweight/obese patients may be misclassified as having AKI if using a weight based urine output criterion • Urine output criterion will not be reliable if patients are receiving diuretic therapy 35 Pediatric RIFLE (pRIFLE) Glomerular Filtration Rate Urine Output (UO) Criteria (GFR) Criteria Risk GFR decreased > 25% UO < 0.5 mL/kg/hr x 8 h Injury GFR decreased > 50% UO < 0.5 mL/kg/hr x 16 h Failure GFR decreased > 75% Or UO < 0.3 mL/kg/hr x 24 h Or GFR < 35mL/min/1.73m2 Anuria x 12 h 36 pRIFLE Criteria Loss Persistent ARF: complete loss of kidney function requiring dialysis > 4 weeks ESKD End Stage Kidney Disease: complete loss of kidney function requiring dialysis > 3 months 37 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline For AKI • Increase in Scr by > 0.3 mg/dL within 48 hours; Or • Increase in Scr to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days;
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