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

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 Potassium Chloride BUN creatinine Glucose bicarbonate calcium albumin cholesterol 225

9. Labs: continued CXR - borderline cardiomegaly
Urinalysis: yellow hazy SG pH 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:
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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 Date BUN Creatinine 2/13/06 34 2.6 2/27/06 40 4.0 3/14/0650
6.3
3/20/06 55
7.2
3/26/06 86
8.0
3/30/06 85
7.3
4/02/06 90
6.0

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 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 Date BUN Creatinine 2/13/06 34 2.6 2/27/06 40 4.0 3/14/0650
6.3
3/20/06 55
7.2
3/26/06 86
8.0
3/30/06 85
7.3
4/02/06 90
6.0