Case study: acute renal failure

1. Case study: acute renal failure Bruce R. Wall, MD, FACP 4/3/06 Renal resident conference

2. 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

3. 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

4. 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

5. 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

6. Amitriptyline Aspirin 81 mg Atorvastatin Clonidine TTS Plavix Iron Lisinopril Metoprolol Protonix Morphine SL nitroglycerin Vitamin K Centrum ALLERGY:Voltaren (nausea) Medications:

7. 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

8. 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

9. 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

10. Additional information • Any additional history required? • Any additional physical exam? • Labs pending: repeat 24hr urine, complements, myeloma markers, lupus markers, vasculitis markers

11. Differential diagnosis: • This slide intentionally left blank

12. 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

13. “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

14. 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

15. 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

16. 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)

17. Lab profile

18. Renal biopsy • Indication • Risk • Solitary kidney? • Complications • Follow up monitoring

19. Additional serology • Anti GBM negative • ANA 1:40 speckled • P–ANCA 1:32 with positive MPO (Myeloperoxidase IgG) of 55 units

20. biopsy

26. 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.

27. Overview to classification of RPGN

28. 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)

29. 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

30. 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)

31. 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?

32. Lab profile