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ACUTE RENAL FAILURE

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

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ACUTE RENAL FAILURE

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  1. ACUTE RENAL FAILURE Carly Thompson MD, CCFP August 27, 2008

  2. Objectives • Definitions • Epidemiology • Differential Diagnosis • Investigations: Labs, Urinalysis, Imaging • Treatment: • Medications • Renal Replacement Therapy

  3. 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

  4. Case 1 Is she in renal failure?

  5. 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

  6. 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

  7. Definitions: Acute Kidney Injury • RIFLE Criteria Mortality Risk 2.4 4.15 6.37

  8. Definitions: AKIN Criteria Acute Kidney Injury Network

  9. 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

  10. 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.

  11. Case 2 • Mr. Pastie 68 yo man • Hx – unwell x 5 days, vomiting, diarrhea, lightheaded, presents confused • PMHx – Htn, CHF • Meds – B-blocker, lasix

  12. Case 2 What do you think is going on? What would you look for on physical exam?

  13. Prerenal Failure • History • Clues to dehydration • Physical Exam • Volume status exam

  14. Differential Diagnosis of Prerenal Failure

  15. Case 2 What investigations would you like to order?

  16. 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

  17. Renal Failure Work-Up How helpful is the BUN and Cr?

  18. 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

  19. Does the ratio of BUN/Cr help determine if the patient is dry?

  20. 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

  21. Any other tests that can show prerenal failure?

  22. 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

  23. 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

  24. Urine Osmolality Cause Osmolality • Pre-renal > 500 • Renal • Tubular injury <350 • Acute Interstitial Nephritis <350 • Acute Glomerulonephritis >500 • Post-renal <350

  25. 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!

  26. Case 3 Mrs. Buckley • 36 yo female • Nausea, vomiting, SOB x 1 week • Sore throat 3 weeks ago • Cr 300

  27. What do you think is going on? What would you like to order?

  28. 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?

  29. Intrinsic Renal Failure • Tubular Disease • Glomerular Disease • Interstitial Disease • Vascular Disease

  30. 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)

  31. Work-Up • ASO Titer • Renal biopsy • ASA / ANCA / serologies • Anti-GBM antibodies • Medication Hx • CT Scan

  32. 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%

  33. 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

  34. Case 3 Summary Intrinsic Renal Failure: Glomerulonephritis • BUN:Cr <20 • FeNa <1% • Urine osmolality >500 • Urinalysis: RBC, RBC casts, protein

  35. 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?

  36. 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.

  37. 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!

  38. 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)

  39. What is going on?

  40. 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

  41. Nephrotoxins Drugs that alter blood flow • NSAIDs, ACEI, cyclosporine, tacrolimus, contrast, amphotericin B, interleukin-2 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

  42. What puts Mr. Dye at risk for renal failure? (i.e. What are the risk factors for contrast-induced renal failure?)

  43. 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

  44. How can you prevent contrast-induced renal failure?

  45. 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.

  46. What if Mr. Dye had just been started on his ACE inhibitor? What condition would you be concerned about?

  47. ACE Inhibitors • Dilate postglomerular capillaries -> increase renal blood flow and decrease GFR -> natural increase in serum Cr 10-20% • ARF after ACEI initiation -> bilateral renal artery stenosis • ARBs may also cause ARF • Check Cr, lytes 2 weeks after starting ACE

  48. NSAIDs / COX Inhibitors • Risk Factors for Renal Failure: • Age • Chronic Renal Failure • CHF • DM • Hypovolemia • Diuretics • ACEI

  49. Aminoglycosides • Trough concentration is relevant • Once daily dosing can reduce toxicity

  50. 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

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