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Case study: acute renal failure Bruce R. Wall, MD, FACP 4/3/06 Renal resident conference Patient P B 80 yo white female with history of HBP for 20 years, and previous Left hemispheric CVA CC: “Doc, I was playing bridge 2 weeks ago…” Known lumbosacral spine stenosis/listhesis with increasing back pain and loss of strength in lower legs 1 week of nausea and vomiting with minimal abd pain Two year history of ibuprofen use; recent conversion of naprosyn for 1 month… No abd distension; no hematemesis; occasional pink tinged sputum, while on Plavix Conversion to Ultram, then narcotics, which caused constipation H & P continued No previous documentation of creat in caregate; current creat 2.5 to 3.5mg% Iron deficiency anemia documented; negative colonscopy 1 year ago GI consulted for nausea, vomiting, anemia after naprosyn exposure; EGD WNL Renal consulted for ARF? CRF? Lower leg weakness, poor gait, and GI symptoms were her main concerns PAST HISTORY Hypertension 20 yrs Coronary artery stent 2002 CVA with mild expressive aphasia Anemia CKD Diverticulae and internal hemorrhoids Lumbar stenosis, moderate, at L3-4 Cholecystectomy, appy, & TAH History: continued FH: HBP, CVA & ASCVD at young age SH: remote smoker, very active, no ETOH ROS: ataxia with abnormal gait, requiring walker; GI symptoms; no history of CHF; no nephrolithiais, no endocrinopathy, no diabetes; able to drive Medications: Amitriptyline Aspirin 81 mg Atorvastatin Clonidine TTS Plavix Iron Lisinopril Metoprolol Protonix Morphine SL nitroglycerin Vitamin K Centrum ALLERGY:Voltaren (nausea) Physical exam 140/88 90 14 afebrile Awake, alert, preserved muscle mass; HEENT: minimal facial asymmetry NECK: no nodes, chronic stiffness LUNGS: no hemoptysis; no rales COR: RRR, no murmur, no gallop ABD: soft, benign, no hepatomegaly GU: positive stool occult blood, no mass EXT: impressive 3+ edema; no purple toes NEURO: expressive aphasia; abnormal gait; no hyperreflexia Laboratory exam Hgb 9gms; normocytic; plts WNL Serum iron 20, ferritin 325, sat 18% Nomal LFT’s and normal coags Sodium 128 Potassium 5.1 Chloride 100 BUN 34 creatinine 2.8 Glucose 100 bicarbonate 23 calcium 7.6 albumin 2.7 cholesterol 225 Labs: continued CXR - borderline cardiomegaly Urinalysis: yellow hazy SG 1.01 pH 5 large blood negative ketones RBC 25/HPF WBC 35/HPF 2+protein Sonography: left 10.7cm, right 11.9cm “isoechoic with the liver” 24 hour urine: clearance 9ml/min; total protein = 1100mg per day Additional information Any additional history required? Any additional physical exam? Labs pending: repeat 24hr urine, complements, myeloma markers, lupus markers, vasculitis markers Differential diagnosis: This slide intentionally left blank Approach to kidney Acute vs chronic disease Nephritic vs nephrotic syndrome Glomerular disease:acute vs chronic GN Interstitial disease: infiltrative, AIN Renal artery disease: stenosis or emboli Obstructive disease: tubules, stones, retroperitoneum, BPH vs prostate CA “don’t fall in love with your first diagnosis…” TOXIC EFFECTS of NSAIDS – GI toxicity – upper and lower Modest worsening of chronic hypertension ARF – 2 different types CV effects – blocks beneficial effect ASA Hepatic injury Bone marrow toxicity – aplasia Anti-platelet effect – stop 5 days prior to surgery CNS changes – tinnitus Skin - TEN NSAID induced renal failure Hemodynamic mediated ARF: not a concern in normal individuals; yet patients with underlying GN, CKD, or hypercalcemia all need prostacyclin and PGE2 Patients with increased vasoconstrictors AII or NE – “states of volume depletion” CHF, cirrhosis, & DM are at greatest risk NSAID induced ARF Inhibition of PG by any NSAID in state of vasoconstriction may lead to reversible renal insufficiency or ARF Indocin, ibuprofen, and toradol most common causes COX II inhibition “reported” cause ARF Sulindac/clinoril less suppression & ARF AIN: allergic interstitial nephritis Fenoprofen and Indocin relatively common cause hematuria, pyuria, proteinuria; yet the full blown syndrome of fever,rash, eosinophilia is extremely uncommon Nephotic range proteinuria is reported Biopsy is uncommon since pts improve Prednisone not helpful (retrospective) Lab profile Date 2/13/06 2/27/06 3/14/06 3/20/06 3/26/06 3/30/06 4/02/06 BUN 34 40 50 55 86 85 90 Creatinine 2.6 4.0 6.3 7.2 8.0 7.3 6.0 Renal biopsy Indication Risk Solitary kidney? Complications Follow up monitoring Additional serology Anti GBM negative ANA 1:40 speckled P–ANCA 1:32 with positive MPO (Myeloperoxidase IgG) of 55 units biopsy Overview to classification of RPGN RPGN is the syndrome; crescentic GN is the pathologic entitiy Crescent formation is a nonspecific response to injury of glomerular capillary wall >80% crescents present -- severe ARF Types of crescentic GN: type I: anti-GBM disease type II: immune complex disease type III: pauci-immune disease Pauci-immune present with necrotizing GN with few or no immune deposits by IF or EM. Majority of patients with renal-limited vasculitis are P-ANCA positive with 75% MPO positive. Overview to classification of RPGN Spectrum of ANCA Described in 1982 Technical issues: indirect IF assay is more sensitive & ELIZA more specific C-ANCA pattern staining is diffuse @ cytoplasm (most are PR3 positive) P-ANCA stains around the nucleus, (most are MPO positive) Clinical applications of ANCA Is a positive result a “true positive?” Yes, if ELIZA (+), fairly good PPV. Does (-)ANCA exclude ANCA vasculitis? No, since 40% test (-) in Wegener’s. Does presence of (+)ANCA establish the diagnosis (no biopsy required)? No, tissue confirmation is standard. Does rising ANCA titer correlate with flare? No, not a reliable indicator of disease. Does persistant (-)ANCA mean quiescence? No Disease associations ANCA are associated with may cases of WG, MPA,Churg-Strauss syndrome, “renal-limited vasculitis” and certain drug-induce syndromes (PTU, hydralazine, minocycline) therapy Initial dosing with 1000mg solumedrol for 3 days Intravenous cyclophosphamide every month has less toxicity than PO Once in remission, consider PO imuran, methotrexate, or ENBREL? Lab profile Date 2/13/06 2/27/06 3/14/06 3/20/06 3/26/06 3/30/06 4/02/06 BUN 34 40 50 55 86 85 90 Creatinine 2.6 4.0 6.3 7.2 8.0 7.3 6.0