Renal Disease in Rheumatoid Arthritis Unanonymous

Renal Disease in Rheumatoid Arthritis A Case-Based Discussion Case of M.M.   73F from Scotland, in Canada since 1967 Rheumatoid arthritis since 1995 – – – Symmetric polyarthritis – hands, elbows, shoulders, knees Treated with prednisone initially MTX 15mg/wk for the last 4 years Pleural effusions attributed to RA in past  EAM: – Past Medical History   Breast cancer in mid-90’s – R mastectomy and tamoxifen  DVT and PE ? Chronic lung disease – – 30 pack year smoking history, quit 1980s Evaluated for home O2 in last year   Osteoporosis Hyperlipidemia Past Medical History  Medications: – – – – MTX 15 mg po/wk Accupril 20 mg po OD Lipitor 10 mg po OD Actonel 35 mg po/wk Presenting History    At baseline health until ~ early Oct 2004 Mild thrombocytopenia (plt 124) – MTX discontinued ? Preceding URTI No fever SOBOE, dry cough, wheeze – – Presenting History  Admitted to Lakeridge hospital Oct 17 -22: – – Diffuse arthralgia, general malaise Noted to be dyspneic O2 sat: 93%, ABG: 7.46/40/67/29 CXR: ?interstitial lung disease vs. CHF CBC: Hb 118, plt 113, WBC 3.1, smear: N  Investigations: – – – Presenting History  Discharge diagnoses: – – Polyarthritis d/t RA – Celebrex Dyspnea d/t   Chronic lung disease– Spiriva, Advair, Flovent New onset atrial fibrillation - Coumadin  Discharge bloodwork: – – CBC: Hb 112, plt 114, WBC 3.4 Creatinine: 80 Presenting History  Nov 3 – Cardiology Clinic at SMH: – – Non-cardiac dyspnea Echo: Normal LV size and fxn, normal valves FVC 52%, TLC 57%, FEV1 51%, DLCO 55% Restriction: obesity, muscle weakness, early fibrosis likely d/t RA +/- MTX Obstruction: smoking  Nov 5 – Respirology Clinic at SMH: – – – Presenting History   Nov 9: Admitted to SMH for further w/u Admitting bloodwork: – – – CBC: Hb 111, plt 120, WBC 3.0 CR: 208 U/A: ptn 1.0g/L, 3+RBC, heme granular casts Bilateral pleural effusions L>R, basal atelectasis, ? Increased interstitial markings  CXR: – Physical Examination       General: obese, dyspneic, no distress Vitals: 126/80, 86, 22, sat: 93% RA Chest: bibasilar fine inspiratory crackles CVS and Abdo: normal MSK: 4 effused MCPs, 12 tender joints Derm: no rashes, no nail changes Problem List 1. 2. 3. 4. Dyspnea, hypoxemia Mild Pancytopenia Symmetric polyarthritis Acute Renal Failure – active sediment Clinical Focus • • Discuss the spectrum of renal disease in RA Re-consider the clinical case in light of the above discussion Renal Disease in RA    Not a “classical” organ manifestation of RA Clinically apparent renal involvement is common Incidence reports vary widely: – – 17% in prospective population-based study 52% in retrospective post-mortem study  Disease and treatment related variables Renal Disease in RA Disease Associated Medication Related Renal Involvement in Early RA   235 patients with newly diagnosed RA* Followed prospectively for mean 42 mo: Rise in Creatinine Persistent proteinuria Persistent hematuria Hematuria + proteinuria Hematuria + rise in Cr 12 (5%) 17 (7%) 31 (13%) 9 (3.8%) 3 (1.3%) *Koseki Y et al. Ann Rheum Disease 2001;60:327 Renal Involvement in Early RA  Rise in creatinine (N=12) – – – Drugs - 9  D-penicillamine, NSAIDS, ACEi, diuretics Dehydration – 2 Unknown -1   Improved with d/c drugs where possible In 3 cases, unresolved and unexplained Renal Involvement in Early RA  Persistent proteinuria (N=17) – Drug induced – 14   DMARDS - 13 – D-penicillamine, gold thiomalate, bucillamine NSAIDS – 1 – – – “Floating kidney” – 1 Chronic UTI – 1 Unknown – 1  Resolved in cases where drug was stopped Renal Involvement in Early RA  Persistent Hematuria (N=31) – – – Not found to be associated with drug use Associated with age at study entry Associated with disease activity?  CRP higher in those with persistent hematuria than those in whom hematuria resolved  Most had hematuria at study entry and were NOT thoroughly investigated Renal Involvement in Early RA   Renal disease in early RA is common – Hematuria>proteinuria>rise in creatinine  Proteinuria and renal insufficiency are usually drug-induced and resolve with drug cessation Hematuria may be the exception – Causes and outcomes are not clear Renal Biopsy Findings in RA    110 patients with RA* Average duration of disease = 11 years Indications for biopsy: – – – – – Isolated proteinuria – 37 Isolate hematuria – 30 Hematuria + proteinuria – 21 Nephrotic syndrome - 21 Acute renal failure – 1 *Helin HJ et al. Arthritis and Rheum 1995; 38:242 Renal Biopsy Findings in RA Histopathology Mesangial GN Renal amyloidosis Membranous GN Focal proliferative GN Minimal change GN No. of patients 40 33 19 4 3 AIN Arteriosclerosis DM glomerulosclerosis Normal 1 2 2 6 Renal Biopsy Findings in RA   Mesangial GN, N=40: Presentations: – – – Isolated hematuria most common - 20 Hematuria with proteinuria – 12 Proteinuria - 8   8 had predominance of IgA = Buerger’s Renal function generally preserved at presentation and at 42 months Renal Biopsy Findings in RA   Amyloidosis, N=33 Presentations: – – – Nephrotic syndrome - 16 Proteinuria - 12 Renal function abnormal in 60%  Duration RA averaged 17.2 years Renal Biopsy Findings in RA   Membranous, N=19 Presentations: – – – Proteinuria - 13 Hematuria - 3 Proteinuria + hematuria - 3 Gold 12, D-penicillamine 5, auranofin 1   Causes: – Duration RA averaged 3.8 years Renal Biopsy Findings in RA   Focal Segmental GN, N=4 Presentations: – – – Systemic rheumatoid vasculitis with ARF - 2 Hematuria + proteinuria -1 Nephrotic syndrome (associated with gold) -1 Summary of Renal Disease in RA  Disease-Associated: –  Medication-Related: – – – – – – ?Hematuria Mesangial GN Amyloidosis Focal segmental GN Proteinuria  D-penicillamine NSAIDS NSAIDS, analgesics D-Penicillamine Gold Gold Renal Insufficiency  AIN, CIN  – Membranous GN   – Minimal Change  Summary of Renal Disease in RA   Most common presentations of renal disease in RA are isolated abnormalities on urinalysis Nephrotic syndrome occurs more commonly in longstanding active disease – related to amyloidosis  Acute renal failure is an uncommon presentation – Suspect in patients with rheumatoid vasculitis Summary of Renal Disease in RA  Mesangial GN is most common lesion on biopsy in patient with RA – Prognosis is generally good  Renal lesions cannot be predicted based on clinical presentation – – Presenting features non-specific, overlapping Renal biopsy often required to guide treatment Back to the Case of M.M. 1. 2. 3. 4. Dyspnea, hypoxemia Mild Pancytopenia Symmetric polyarthritis Acute Renal Failure – active sediment Investigations  CT thorax: – traction bronchiectasis at bases, moderate emphysema, atelectasis+/-consolidation, effusions; moderate pericardial effusion NO alveolar blood BAL: occasional PMN, no bacteria, AFB and cultures negative  Bronchoscopy: – –  Dx: emphysema, early fibrosis d/t RA Investigations       Reticulocytes: 20 Normal B12 and folate Smear: no fragments Bilirubin, haptoglobin normal Fe 4, TIBC 34, Sat 12% Bone Marrow Aspirate: – anemia of chronic disease, adequate WBC and plt precursors Investigations  Bloodwork and serology: – – – – – – – – ESR 79, blood cultures negative x 2 RF = 31 ANA = 1:640, homogeneous ds DNA (Crithidia) – negative ds DNA (ELISA) – pending ENA – pending C3, C4 - low Cryoglobulins - pending Investigations  Synovitis at multiple sites: – – – – Symmetric involvement Hands: MCP, DIP Shoulders Knees   No deformity Xrays: no erosions Investigations  24h urine collection: – – GFR: 16ml/min Protein: 760mg/d      US abdo: echogenic cortices, no hydro Serum protein electrophoresis: no M-band Immunoquantitation: elevated IgG, IgA Urine Bence-Jones protein: negative ANCA, GBM negative Conclusions  Renal Biopsy – – Mesangial proliferative GN + ATN changes IF: immune complexes within mesangium, predominantly IgG Mesangial proliferative GN related to RA Pulse solumedrol, prednisone 100 mg po OD   Final diagnosis: – Treatment: – Is it really that simple?  Non-erosive arthritis, pericardial effusion, high titre ANA, low complements – Underlying diagnosis?  Clinical presentation of ARF with mesangial proliferation on biopsy – Acute on chronic insult? DDx:  Clinical presentation: – –  Renal lesion: – – – – – SLE Cryoglobulinemia RA with vasculitis Hypersensitivity reaction Post-infectious – – – RA SLE Post-infectious Hypersensitivity IE