Acute Renal Failure Percy Pentecost MD

Objectives To understand: 3 major etiologies of ARF Pathophysiology of: prerenal ARF Postrenal ARF Intrarenal ARF Basic evaluation and treatment of ARF 2

Definitions Acute Renal Failure: abrupt and sustained decline in renal function resulting in an accumulation of nitrogenous waste products and uremic toxins Oliguria: Urine output less than 400 mL/ 24° Anuria: Urine output less than 100 mL/ 24° Azotemia: Increase in serum concentration of nitrogenous waste products 3

Incidence Community Acquired ARF: Hospital Acquired ARF: Prerenal70% of cases Mortality 7% Hospital Acquired ARF: 15-20% of ICU patients Ischemic or Toxic injury in 60% of these cases Mortality 50-70% 4

Risk Factors Advanced Age Preexisting Renal Disease Diabetes Cardiac Disease Liver Disease “Older Sicker Patients “Internal Medicine Patients” 5

3 Major Etiologies of ARF Prerenal “before the kidney” Postrenal “after the kidney” Intrarenal “within the kidney” 6

Prerenal ARF

Prerenal Factoids Very Common Often reversible within 24-48 hours Caused by renal hypoperfusion and decreased GFR Not associated with significant tubular injury… …unless sustained

Prerenal Causes Hypovolemia: Low Cardiac Output (real and effective): Hemorrhagic Shock, Dehydration, Liver Failure with Low Albumin Low Cardiac Output (real and effective): CHF, Drugs* Systemic Vasodilation: Sepsis, Drugs*, Hepatorenal Syndrome Renal Vasoconstriction: Renal Artery Stenosis, Embolism, or Disection 9

Prerenal--Drugs Changes in tone of afferent/ efferent arterioles will affect RBF and GFR ASA and NSAIDS cause this-------------------> ACEIs and ARBs cause this-------------------> 10

Prerenal Diagnosis Bun to Creatnine greater than 20 / 1 Classically FENa < 1% and Urine Sodium is low (<20) Kidneys avidly absorbing Na to increase perfusion pressure Urine Osms and SG are high Urine is concentrated Urine Sediment is bland (Minimal RBCs and WBCs) No tubular / glomerular injury or inflamation History suggests Nausea, vomiting, diarrhea, immobile with no access to water, etc… 11

Prerenal--Treatment Supportive Care Improve Renal Hemodynamics IVFs Minimize Nephrotoxic drugs Stop ACEi, NSAIDS Prevention Recognize Early 12

Postrenal ARF

Postrenal Failure Factoids 5% of all cases of acute renal failure Corrected within 1 week of onset prognosis excellent Persists > 12 weeks: interstitial fibrosis / tubular atrophy Irreversible Variable presentation: Anuria with complete obstruction Polyuria alternating with oliguria in partial obstruction Post-obstructive diuresis may lead to volume depletion 14

Postrenal Causes Urethral: Bladder: Ureters Urethral Stricture Clogged Foley BPH Bladder: Bladder Tumor Neurogenic Bladder Clots Ureters Stones Sloughed Papilla AAA Abdominal Cancers Abdominal Compartment Syndrome Retroperitoneal Fibrosis Lymphadenopathy Post Surgical

Postrenal Failure Diagnosis Clinical Suspicion Important—Who is going to get this? BUN/Cr ratio may be high (like in pre-renal) BUN diffuses back into system K may be high Type IV RTA UA with blood is common FeNa, Urine sodium, Urine Osms: normal Ultrasound Hydronephrosis Obstructing Lesion? Consider Noncontrast CT for stones 16

Postrenal Failure Treatment Put in Foley (or check for patency) Address Underlying Cause Urology Consult may be helpful Tumor? Stone removal? Watch for Post-obstructive Diuresis 17

Intrarenal ARF

Intrarenal--Causes Ischemic Tubular Injury (formerly ATN) Nephrotoxic Injury (Formerly ATN) Acute Interstitial Nephritis Intra-tubule Deposition/Obstruction Atheroembolic Thrombotic Microangiopathy Glomerulornephritis 19

Ischemic and Toxic Injury Intrarenal ARF Ischemic and Toxic Injury

Intrarenal Ischemic/Toxic Injury Phases Initiation Sustained Prerenal state (poor O2 delivery) Toxic Injury Extension and Maintenance Altered transport, adhesion, etc. Cell sloughing into tubule lumen Leukocytes, cytokines, etc. Now vascular blockage too... Recovery After insults are gone.... 21

Intrarenal Ischemic/Toxic Injury Diagnosis Prerenal Azotemia: BUN/Cr >20:1 Specific Gravity >1.020 FENA <1% Uosm > 500 Una <25 Bland Sediment Tubules working no signs of injury ATN / AKI: BUN/Cr ~10-15:1 Specific Gravity ~ 1.010 FENA >2% Uosm 300-350 Una > 40 Muddy Brown Casts Tubules injured and not working 22

Intrarenal Ischemic/Toxic Injury Toxins Partial List Aminoglycosides Amphotericin B Iodinated contrast Cisplatin Heme pigments Hemolysis rhabdomyolysis Notes From ischemic or due to contrast onset is rapid. From aminogylcosides onset often delayed As a general rule, toxic injury is dose dependent Aminoglycosides may be less toxic given daily 23

Intrarenal Ischemic/Toxic Injury Treatment Remove the insult Supportive Watch / Replace Electrolytes Maintain fluid balance 24

Intrarenal ARF AIN

AIN Factoids AIN = Acute Interstitial Nephritis Hypersensitivity drug reaction most common cause 26

AIN Drugs Drugs associated with AIN: More drugs associated with AIN: Beta-lactam antibiotics Sulfonamides Vancomycin Ciprofloxacin Rifampin Acyclovir Captopril Aspirin NSAIDS Diuretics More drugs associated with AIN: Polymyxin Erythromycin Indinavir Alpha-interferon Cimetidine Allopurinol Azathioprine Diazepam Tetracycline Phenobarbital Clofibrate Carbamazepine Sulfinpyrazone Phenindione 27

AIN Drug Factoids Original reports on methicillin-associated AIN reported occurrence after 10-20 days of drug therapy Currently, reported to occur after 7-14 days of therapy Can occur within 2-3 days after re-exposure to particular drug Can occur de novo in response to previously tolerated drug (e.g. NSAIDs) 28

AIN Diagnosis “Classic” presentation (less than 30% of patients) Elevated Cr Fever Rash Eosinophiluria Clinical suspicion is important Renal biopsy is gold standard 29

AIN Treatment Supportive Discontinue potentially offending drugs May need Renal Consult: Steroids may help (no RCTs to support) Window of therapy for steroids is 7-14 days after onset of azotemia Plasmapheresis if anti-tubular basement membrane ABs on biopsy Prognosis: Usually reversible if drug stopped quickly (1 week) 30

Intrarenal ARF Tubular Obstruction

Tubular Obstruction 32 Pathophysiology: Drugs/compounds precipitate in tubules Form obstructing crystals A Partial List: Methotrexate Intravenous acyclovir Sulfadiazine Indinavir Ethylene glycol toxicity Calcium oxalate crystals Urate crystal nephropathy After cancer chemotherapy Light chains in Multiple Myeloma 32

Tubular Obstruction Diagnosis Elevated Uric Acid (Post Chemotherapy) SPEP/UPEP (Multiple Myeloma) Medication List History 33

Tubular Obstruction Treatment Prevention Best Cure Adequate Volume Specific Therapies in some instances Theophyline for Cisplatin Supportive 34

Intrarenal ARF Atheroembolic

Atheroembolic Pathogenesis Sometimes occurs spontaneously Anticoagulation may precipitate it Usually after manipulation of aorta Surgery Angiography Embolization of cholesterol into arterioles and glomerular capillaries inflammatory cell infiltrate ischemic tubular injury 36

Atheroembolic Diagnosis Cutaneous manifestations: Livedo reticularis, digital infarcts Other organs involves: bowel ischemia, CNS disturbance Eosinophilia Low C3 levels (in some patients—15%) Elevated ESR History 37

Atheroembolic Treatment Supportive Treat diabetes, hypertension, dyslipidemia Discontinue Anticoagulents Management of vascular risk factors Prognosis traditionally thought to be poor comorbid cardiovascular disease 38

Thrombotic Microangiopathy Intrarenal ARF Thrombotic Microangiopathy

Thrombotic Microangiopathies Etiology Pathophysiology: Clotting cascade imbalance Small vessel blockage and ischemia Multiple Precipitating factors DIC TTP Infectious Diarrhea (Ecoli 0157, Shiga Toxin) SLE HIV Drugs 40

Thrombotic Microangiopathies Diagnosis/Treatment Low Platelets on CBC RBC fragments on peripheral smear Clotting cascade imbalance Small vessel ischemia Multiple Precipitating factors DIC TTP Infectious Diarrhea (Ecoli 0157, Shiga Toxin) SLE HIV 41

Acute Glomerulonephritis Intrarenal ARF Acute Glomerulonephritis

Glomerulonephritis Pathogenesis Deposition of complexes in glomeruli Cause damage and inflammation Many Precipitating Factors Bacterial infection Group A Strep Viral Infection URI Hep C Rheumatalogic Disease SLE Vasculitis 43

Glomerulonephritis Diagnosis Urinalysis with “Active Sediment” RBCs and WBCS Dysmorphic RBCs RBC and WBC Casts C3 levels Low (C3 represents intrinsic and extrinsic pathway) ASO titer (post streptococcal) Hepatitis Panel (Hep C) Skin Biopsy (IgA Nephropathy and vasculitis) RF, ANA, ANCAs, etc. (SLE, vasculitis, etc.) Renal Biopsy 44

Glomerulonephritis Treatment Treat Infections “breaks the cycle” Treat Underlying Diseases Steroids and/or Cyclophosphamide Renal and Rheumatology Consults 45

Questions? 46