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ACUTE RENAL FAILURE Carly Thompson MD, CCFP August 27, 2008 Objectives Definitions Epidemiology Differential Diagnosis Investigations: Labs, Urinalysis, Imaging Treatment: – Medications – Renal Replacement Therapy Case 1 Mrs. K. Bean 78 yo female – PMHx: liver cirrhosis, ascites, hepatic encephalopathy due to hepatitis C – Family is concerned that she is not drinking, not eating, and having recurrent diarrhea as she is getting sleepier – Labs: Na 140 BUN 20 Cr 247 Case 1 Is she in renal failure? Definitions: Acute Renal Failure The deterioration of renal function over hours or days resulting in accumulation of toxic wastes and the loss of internal homeostasis Indirect Measures: – 50% increase in serum Cr – 50% decrease in creatinine clearance / GFR – Highly variable across different studies Definitions: Types of Acute Renal Failure Non-oliguric – Better prognosis Oliguria: – <1mL/kg/hr in infants – <0.5mL/kg/hr in children – <400mL / day in adults <0.3mL/kg/hr OR 17mL / hour in 60kg x 24 hours Anuria – <100mL / day in adults Definitions: Acute Kidney Injury RIFLE Criteria Mortality Risk 2.4 4.15 6.37 Definitions: AKIN Criteria Acute Kidney Injury Network Stage Serum Cr Criteria Urine Output Criteria 1 Serum Cr increase ≥ 26.4 mmol/L or increase ≥ 150 to 200% from baseline <0.5 mL/kg/hr x >6 hrs 2 Serum Cr increase ≥ 200 to 300% from baseline <0.5 mL/kg/hr x > 12 hrs 3 Serum Cr increase > 300% from baseline (or serum Cr ≥ 354 mmol/L with an acute increase of 44 micromol/L) <0.3 mL/kg/hr x 24 hrs or anuria x 12 hrs Quick Epidemiology Slide Community-acquired ARF: – Only diagnosed in 1% of hospital admissions at presentation – Most commonly due to volume depletion – 90% may have reversible cause Hospital-acquired ARF: – Up to 4% of admissions, 20% of critical care admissions – Multifactorial: elderly, nephrotoxic medications, often in ICU Mortality: – – – – 50% - minimal change since dialysis was invented! 25% in children, but 45% if intrinsic renal failure 75% for hospital acquired mortality 7% community-acquired prerenal ARF Causes of Death: – Sepsis, cardiac and pulmonary failure Case 1 Follow-Up Baseline Cr 165 -> Now 247 – 82 mmol/L increase, 150% increase GFR 28 -> Now 21 – 25% decrease Urine Output: Foley inserted Diagnosis: AKIN Criteria - Stage 1 Acute Kidney Injury Plan: Admitted for rehydration, monitoring, and placement issues. Case 2 Mr. Pastie 68 yo man Hx – unwell x 5 days, vomiting, diarrhea, lightheaded, presents confused PMHx – Htn, CHF Meds – B-blocker, lasix Case 2 What do you think is going on? What would you look for on physical exam? Prerenal Failure History – Clues to dehydration Physical Exam – Volume status exam Differential Diagnosis of Prerenal Failure Volume Loss - Hemorrhagic Shock, Vomiting, Diarrhea - Drugs: Diuretics - Other: Primary hypoaldosteronism, Salt-losing nephropathy, Postobstructive diuresis Decreased Cardiac Output - Myocardial infarction / ischemia - Obstructive: Valvular heart disease, tamponade - Cardiomyopathy - Drugs: B-blockers - High-output: thyrotoxicosis, thiamine deficiency, Paget disease, AV fistula Renal Artery and Small Vessel Disease - Drugs: Cyclosporine, tacrolimus - Embolic disease (septic, cholesterol), Sickle Cell Disease - Artery: Malignant hypertension, preeclampsia, vasculitis - Other: Transplant rejection, Hypercalcemia, Hemolytic-uremic syndrome Case 2 What investigations would you like to order? Renal Failure Work-Up Labs: – CBC, lytes, BUN, Cr Urinalysis: R+M Chest x-ray: Volume status ECG: Screen for hyper / hypokalemia Insert foley: input / output Renal Failure Work-Up How helpful is the BUN and Cr? Importance of BUN and Cr Creatinine A patient with a low baseline Cr can lose more than ½ of functioning nephrons before developing and elevated Cr Breakdown product of skeletal muscle protein creatine Linked to muscle mass, thus women and elderly have lower GFR for any Cr level Glomerulonephritis causes increased tubular secretion of Cr independent of GFR Trimethoprim, cimetidine, salicylates cause decreased secretion BUN Decreased in patients with malnutrition and hepatic synthetic dysfunction Increased in setting of a protein load, GI hemorrhage, trauma Does the ratio of BUN/Cr help determine if the patient is dry? BUN:Cr Ratio Quick Physiology Lesson: Both Cr and BUN are passively filtered at the glomerulus Cr remains in the tubule BUN is permeable and passively reabsorbed with sodium Therefore . . . In the setting of Na retention, urea clearance can be as low as 30% of GFR in a patient with normal concentrating ability BUN:Cr >20 can suggest hypovolemia Any other tests that can show prerenal failure? Fractional Excretion of Na Fractional excretion of sodium FeNa = Urine Na ÷ Urine Cr Plasma Na Plasma Cr In normal kidneys under prerenal stress <1% 1-2% either ATN or prerenal failure >2% ATN due to loss of concentrating ability – Benefits: Most accurate test – Limitations: Intrinsic renal failure when tubular concentrating capacity is retained (i.e. glomerulonephritis), the Fe Na may be depressed Urine Sodium Less accurate measurement of prerenal failure Urine Na concentration affected by the rate of water reabsorption -> a patient may have a relatively high urine sodium concentration (20 - 40 meq/L or more) but may be in prerenal failure Urine Na < 20 meq/L Urine Osmolality Cause Pre-renal Renal – Tubular injury – Acute Interstitial Nephritis – Acute Glomerulonephritis Post-renal Osmolality > 500 <350 <350 >500 <350 Case 2 Summary Pre-Renal Failure BUN:Cr >20 FeNa <1% Urine osmolality >500 Urinalysis: May have hyaline casts – Secreted from tubular epithelial cells Treatment Rehydration! Case 3 Mrs. Buckley 36 yo female Nausea, vomiting, SOB x 1 week Sore throat 3 weeks ago Cr 300 What do you think is going on? What would you like to order? Case 3 Cr 300 BUN 20 BUN:Cr <20 Osmolality >500 Urine R+M – proteinuria and casts Urine lytes – Na 20, Fe Na <1% Renal U/S - normal What kind of cast is this? Intrinsic Renal Failure Tubular Disease Glomerular Disease Interstitial Disease Vascular Disease Glomerulonephritis Post-infectious (strep) IgA nephropathy SLE, PAN, Hep C, HIV, Wegener’s, Goodpasture’s HSP HUS/TTP Rapidly progressive glomerulonephritis RPGN Membranoproliferative glomerulonephritis Drugs Tumors (leukemia, lymphoma) Work-Up ASO Titer Renal biopsy ASA / ANCA / serologies Anti-GBM antibodies Medication Hx CT Scan Renal Biopsy Should be considered in all causes of acute intrinsic renal failure – Significantly changed dx and tx in 40% of cases should be considered in all causes of intrinsic ARF: significantly changed the dx and tx in 40% of cases Complications: – Common: Hematuria – Serious: Blood transfusions, nephrectomy, puncture of other organs, perinephric hematomas – 2% – Mortality: 0.1% Post-Strep Glomerulonephritis 6-14 days after pharyngitis with Group A Strep or after skin infection Hypertension, edema, pulmonary congestion common presentation Urinalysis: RBC, RBC casts Prognosis: – 5% progress to RPGN – 70% recover Antibiotics may be considered for contacts Case 3 Summary Intrinsic Renal Failure: Glomerulonephritis BUN:Cr <20 FeNa <1% Urine osmolality >500 Urinalysis: RBC, RBC casts, protein Case 3 Continued You insert a foley for Mrs. Buckley. Finish your shift and go home for the night. Your friend is on internal medicine call that night, and calls you to debate whether he should start a diuretic for Mrs. Buckley whose urine output has dropped to <0.5mL/kg/hr for the past 6 hours. What should you tell your friend? Diuretic Use in Renal Failure Rationale: Pts with non-oliguric ARF have improved mortality and renal function recovery rates, therefore using a diuretic to “convert” oliguric to nonoliguric ARF may be beneficial. Evidence: RCTs have failed to show a benefit in administering diuretics to patients with ARF. – Shilliday IR, Quinn KJ, Allison ME. Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized study. Nephrol Dial Transplant 1997 Dec;12(12):2592-6 – No change in recovery, hemodialysis, or death Bottom-Line: Diuretics are only useful in the management of volume-overloaded patients. What about “renal dose” dopamine? Low-dose “renal” dose dopamine (1-5ug/kg/min) was used for many years to treat ARF Rationale: Increases urine output Evidence: No evidence that it improves renal recovery or mortality Side effects: Pro-arrhythmic, and may cause increased medullary O2 consumption without increased O2 delivery Bottom Line: Say NO to “renal dose” dopamine! Case 4 Mr. Dye 50 year old male CC: Not peeing HPI: 4 days of minimal urine output – Cardiac catheterization 1 week ago PMHx: 15 years of DM II, lisinopril, insulin O/E: BP 190/110 – JVP 9cm – Bibasilar crackles – Edema Labs: – BUN: 20 – Cr: 450 (Baseline = 150) What is going on? Intrinsic Renal Failure Tubular Disease Ischemic acute tubular necrosis Nephrotoxins Heme pigments: rhabdomyolysis, massive hemolysis Interstitial Disease Acute interstitial nephritis (drug reaction) Infiltrative disease Autoimmune disease: SLE Infectious: Legionnaire, hanta virus Vascular Disease Malignant hypertension Scleroderma TTP, HUS, PAN Renal Vein Thrombosis Glomerular Disease Nephrotoxins Drugs that alter blood flow NSAIDs, ACEI, cyclosporine, tacrolimus, contrast, amphotericin B, interleukin2 Drugs that are toxic to tubules Aminoglycosides, contrast, cisplatin, cyclosporine, tacrolimus, amphotericin B, methotrexate, solvents, heavy metals, IVIG Heme-Pigment-Induced toxicity Cocaine, EtOH, lovastatin Drugs that precipitate and cause tubular obstruction Acyclovir, sulfonamides, ethylene glycol, chemo drugs, methotrexate Allergic interstitial nephritis Penicillins, cephalosporins, sulfonamides, rifampin, cipro, NSAIDs, TZDs, furosemide, cimetidine, phenytoin, allopurinol Hemolytic-Uremic Syndrome Cyclosporine, tacrolimus, cocaine, quinine, conjugated estrogens What puts Mr. Dye at risk for renal failure? (i.e. What are the risk factors for contrastinduced renal failure?) Contrast-Induced Renal Failure Course: – Increasing Cr for 3-5 days, then resolution Risk Factors: – – – – – – – Chronic renal insufficiency DM (Approximately 40% risk!) Age Hypovolemia Hypoalbuminemia Myeloma Type and Dose of Contrast How can you prevent contrast-induced renal failure? Prevention Alternative studies – MRI, ultrasound Low-dose contrast, avoid repetitive studies (<72 hours), low or iso-osmolal nonionic contrast Avoid hypovolemia – IV NS or NaHCO3 Avoid NSAIDs N-Acetylcysteine – Minimizes vasoconstriction and free radicals? – Much heterogeneity in trials, largest meta-analysis showed RR 0.62 (.44 - .88) – NAC 600 - 1200mg po bid day before and of procedure – IV NAC for emergent scans? Risk of anaphylaxis, unclear data. What if Mr. Dye had just been started on his ACE inhibitor? What condition would you be concerned about? ACE Inhibitors Dilate postglomerular capillaries -> increase renal blood flow and decrease GFR -> natural increase in serum Cr 1020% ARF after ACEI initiation -> bilateral renal artery stenosis ARBs may also cause ARF Check Cr, lytes 2 weeks after starting ACE NSAIDs / COX Inhibitors Risk Factors for Renal Failure: – Age – Chronic Renal Failure – CHF – DM – Hypovolemia – Diuretics – ACEI Aminoglycosides Trough concentration is relevant Once daily dosing can reduce toxicity Heme-Pigment Induced Acute Renal Failure History: Crush injuries Exam: Pigmented granular casts, heme pigment in urine Pathophysiology: Deposited in and concentrated in tubules Obstruction and direct toxicity depending on acidic urine Treatment Volume Replacement – Normal saline 1-2L / hour – Urine output 200 – 300 mL/hour Forced Alkaline-Mannitol Diuresis – – – – Urine pH >6.5 Once diuresis established 75mmol/L of NaHCO3 Caution re: hypercalcemia Consider mannitol / diuretic if not effective diuresis Case 4 Summary Condition Dipstick Sediment Urine Osm Fe of Na (%) Prerenal Trace or no proteinuria Hyaline casts possible >500 <1 Renal - Tubular injury (ischemic or toxic) - Acute Interstitial Nephritis - Mild to mod proteinuria - Pigmented granular casts <350 >1 - Mild to mod - WBC, white cell proteinuria; casts, eosinophils Hb, WBC and eosinophil casts; red cells <350 >1 >500 <1 - Acute - Mod to - RBC and red cell Glomerulonephritis casts severe proteinuria; Hb Case 5 Mr. Peebody 69 yo male CC: Unable to urinate for 24 hours PMHx: BPH Meds: Amitriptyline – started recently for insomnia O/E: Distended bladder, tender suprapubic area What is going on? Post-Renal Failure in Adults Urethra and Bladder Outlet Infiltration: Cancer – prostate, bladder, cervix, colon Blockage: Calculi, clot Pressure: BPH Narrowing: Stricture, phimosis Innervation: Neurogenic bladder Trauma Ureter Infiltration: Cancer, Retroperitoneal fibrosis, IBD Blockage: Calculi, crystals, clot, ligation Pressure: AAA, Pregnancy Narrowing: Stricture Reflux Trauma Intrarenal Crystals: Uric acid, sulfonamide, acyclovir, indinavir Protein casts: multiple myeloma, amyloidosis What conditions might cause this in children? Post-Renal Failure in Children Urethra and Bladder Outlet Blockage: Urethral atresia, phimosis, meatal stenosis, anterior and posterior urethral valves (males), calculus, clot Innervation: Neurogenic bladder Ureter Reflux Blockage: ureterovesical junction obstruction, ureterocele, clot Anatomic: megaureter, retrocaval ureter Pressure: retroperitoneal tumour What orders would you like? What would you get if you order urine lytes for Fe Na and osmolality? Post-Renal Failure Insert foley (consider coude tip) Bladder scan Monitor urine output Urine R+M – May see Hb, protein, WBC – Osmolality <350 Urine lytes – Fe Na >1 What complication are you concerned about? Postobstructive Diuresis Monitor urine output x 2 hours >250mL / hour for >2 hours after uncomplicated urethral obstruction -> consider admission May result in severe dehydration and hyponatremia End-Stage Renal Disease Azotemia: Accumulation of nitrogenous wastes Uremia: Contamination of blood with urine, the clinical syndrome resulting from ESRD Results of Uremia Renal Bone Disease – Loss of vitamin D3 -> decreased calcium absorption -> secondary hyperparathyroidism – Metastatic calcification Hematologic – Anemia -> Loss of erythropoietin – Immunodeficiency Can you name some of the outcomes of uremia? Results of Uremia Neurologic – – – – Uremic encephalopathy Dialysis dementia Subdural hematoma Peripheral neuropathy Cardiovascular – – – – Coronary Artery Disease Hypertension CHF Pericarditis Gastrointestinal – – – – Anorexia, nausea, vomiting, metallic taste GI bleed Diverticulosis, Diverticulitis Ascites When would you consider hemodialysis? Indications for Hemodialysis Volume overload Hyperkalemia >6.5 or rising Acid-base imbalance Symptomatic uremia (pericarditis, encephalopathy, bleeding dyscrasia, nausea, vomiting, pruritis) Uremia (BUN >100) Dialyzable intoxications – methanol, ethylene glycol, theophylline, ASA, lithium Consider severe dysnatremia <115 or >165) Consider dysthermia Summary Think pre-renal, renal, post-renal Labs: – Recognize the limitations of Cr – Use BUN:Cr, urinalysis, urine lytes (Fe Na), osmolality to your advantage! Admit and monitor invasively (foley, etc) Treat underlying condition, maintain hydration. Consider hemodialysis and it’s complications. Thank You!