Case study: acute renal failureBruce R. Wall, MD, FACP4/3/06Renal resident conference

Patient P B80 yo white female with history of HBP for 20 years, and previous Left hemispheric CVACC: Doc, I was playing bridge 2 weeks agoKnown lumbosacral spine stenosis/listhesis with increasing back pain and loss of strength in lower legs1 week of nausea and vomiting with minimal abd painTwo year history of ibuprofen use; recent conversion of naprosyn for 1 monthNo abd distension; no hematemesis; occasional pink tinged sputum, while on PlavixConversion to Ultram, then narcotics, which caused constipation

H & P continuedNo previous documentation of creat in caregate; current creat 2.5 to 3.5mg%Iron deficiency anemia documented; negative colonscopy 1 year agoGI consulted for nausea, vomiting, anemia after naprosyn exposure; EGD WNLRenal consulted for ARF? CRF?Lower leg weakness, poor gait, and GI symptoms were her main concerns

PAST HISTORYHypertension 20 yrsCoronary artery stent 2002CVA with mild expressive aphasiaAnemiaCKDDiverticulae and internal hemorrhoids Lumbar stenosis, moderate, at L3-4Cholecystectomy, appy, & TAH

History: continuedFH: HBP, CVA & ASCVD at young ageSH: remote smoker, very active, no ETOHROS: ataxia with abnormal gait, requiring walker; GI symptoms; no history of CHF; no nephrolithiais, no endocrinopathy, no diabetes; able to drive

Medications:AmitriptylineAspirin 81 mgAtorvastatinClonidine TTSPlavixIronLisinoprilMetoprololProtonixMorphine SL nitroglycerinVitamin KCentrum

ALLERGY:Voltaren (nausea)

Physical exam140/88 90 14 afebrileAwake, alert, preserved muscle mass;HEENT: minimal facial asymmetryNECK: no nodes, chronic stiffnessLUNGS: no hemoptysis; no ralesCOR: RRR, no murmur, no gallopABD: soft, benign, no hepatomegalyGU: positive stool occult blood, no massEXT: impressive 3+ edema; no purple toesNEURO: expressive aphasia; abnormal gait; no hyperreflexia

Laboratory examHgb 9gms; normocytic; plts WNLSerum iron 20, ferritin 325, sat 18%Nomal LFTs and normal coagsSodium 128 Potassium 5.1 Chloride 100 BUN 34 creatinine 2.8 Glucose 100 bicarbonate 23 calcium 7.6 albumin 2.7 cholesterol 225

Labs: continuedCXR - borderline cardiomegalyUrinalysis: yellow hazy SG 1.01 pH 5 large blood negative ketones RBC 25/HPF WBC 35/HPF 2+proteinSonography: left 10.7cm, right 11.9cm isoechoic with the liver24 hour urine: clearance 9ml/min; total protein = 1100mg per day

Additional informationAny 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 kidneyAcute vs chronic diseaseNephritic vs nephrotic syndromeGlomerular disease:acute vs chronic GNInterstitial disease: infiltrative, AINRenal artery disease: stenosis or emboliObstructive disease: tubules, stones, retroperitoneum, BPH vs prostate CA

dont fall in love with your first diagnosis TOXIC EFFECTS of NSAIDS GI toxicity upper and lowerModest worsening of chronic hypertensionARF 2 different typesCV effects blocks beneficial effect ASAHepatic injuryBone marrow toxicity aplasiaAnti-platelet effect stop 5 days prior to surgeryCNS changes tinnitusSkin - TEN

NSAID induced renal failureHemodynamic mediated ARF: not a concern in normal individuals; yet patients with underlying GN, CKD, or hypercalcemia all need prostacyclin and PGE2Patients with increased vasoconstrictors AII or NE states of volume depletion CHF, cirrhosis, & DM are at greatest risk

NSAID induced ARFInhibition of PG by any NSAID in state of vasoconstriction may lead to reversible renal insufficiency or ARFIndocin, ibuprofen, and toradol most common causesCOX II inhibition reported cause ARFSulindac/clinoril less suppression & ARF

AIN: allergic interstitial nephritisFenoprofen and Indocin relatively common cause hematuria, pyuria, proteinuria; yet the full blown syndrome of fever,rash, eosinophilia is extremely uncommonNephotic range proteinuria is reportedBiopsy is uncommon since pts improvePrednisone not helpful (retrospective)

Lab profile

Renal biopsyIndicationRiskSolitary kidney?ComplicationsFollow up monitoring

Additional serologyAnti GBM negativeANA 1:40 speckledPANCA 1:32 with positive MPO (Myeloperoxidase IgG) of 55 units

biopsy

Overview to classification of RPGNRPGN is the syndrome; crescentic GN is the pathologic entitiyCrescent formation is a nonspecific response to injury of glomerular capillary wall>80% crescents present -- severe ARFTypes of crescentic GN: type I: anti-GBM diseasetype II: immune complex diseasetype III: pauci-immune diseasePauci-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 ANCADescribed in 1982Technical issues: indirect IF assay is more sensitive & ELIZA more specificC-ANCA pattern staining is diffuse @ cytoplasm (most are PR3 positive)P-ANCA stains around the nucleus, (most are MPO positive)

Clinical applications of ANCAIs a positive result a true positive? Yes, if ELIZA (+), fairly good PPV.Does (-)ANCA exclude ANCA vasculitis? No, since 40% test (-) in Wegeners.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 associationsANCA are associated with may cases of WG, MPA,Churg-Strauss syndrome, renal-limited vasculitis and certain drug-induce syndromes (PTU, hydralazine, minocycline)

therapyInitial dosing with 1000mg solumedrol for 3 daysIntravenous cyclophosphamide every month has less toxicity than POOnce in remission, consider PO imuran, methotrexate, or ENBREL?

Lab profile