1. Case Conference

2. History 56 year old African American female Was transferred from outlying hospital for:  B/L LE infected ulcers (due to heating pad) and possible amputation.  Increased output from tracheostomy.  Outpatient HD set up. She was recently started on HD at outlying facility.

3. Previous Hospitalization She went at outlying facility in early Aug with shortness of breath and generalized edema. Diagnosed with Acute on chronic systolic heart failure. She also developed Acute Kidney Injury and was started in HD for fluid removal. From reviewing the records, We found a CT scan Abdomen from July which was done due to gross hematuria. Kidneys, ureters and bladder was normal in that.

4. Creatinine trend HD DC Baseline Creatinine: 0.9

5. Past Medical History: Complicated CABG surgery in 2011 with prolonged intubated and subglottic stenosis s/p tracheostomy. DM Ischemic Cardiomyopathy COPD Social History: Non smoker, non drinker. Family History: Positive for DM and HTN. Sister had HIV related renal disease (was on HD).

6. Medications Amiodarone 200mg QD Metoprolol 50 mg QD Metformin Omeprazole Iron sulfate Insulin Furosemide 40 mg BID Digoxin 125 mcg QD Imdur Ibuprofen (3-4 times a month 800 mg)

7. Exam BP 89/56 | Pulse 89 | Temp 98.2 °F | Resp 15 | Wt 120.9 kg | SpO2 94% Body mass index is 43.02 kg/(m^2). Constitutional: well developed, well nourished, in no apparent distress Neck: tracheostomy present Lungs: decreased breath sounds at bases Cardiac: regular rate and rhythm, S1, S2 normal, no murmur, click, rub or gallop Abdomen/GI: soft, non-tender; bowel sounds normal; no masses, no organomegaly Extremities: b/l LE bandaged due to wounds. Wounds were deep and foul smelling. Skin: no rash

8. Labs 138972398 3.8272.12 Calcium: 8.8, Phos 3.0 T. Protein: 6.4, Albumin: 2.4 7.0 11.5 225 37.2 UA showed pH: 6.5, Sp Gr: 1.015, Protein: 30, WBCs: 392, RBCs: 11, No casts Urine Protein/Crt: 0.4 gm/gm

9. Differential Diagnosis Prerenal: Decreased kidney perfusion sec to severe systolic heart failure (EF <10%), sepsis related hypotension Renal:  GN: FSGS, IgA nephropathy, Post infectious, Vasculitis, amyloidosis due to chronic infection, HIV, Hep C membranoprofilerative, DM, Anti-GBM disease  AIN sec to recent antibiotics.  ATN from long standing hypotension. Postrenal

10. Follow up Labs Anti ds DNA, C-ANCA, P-ANCA, HIV, Hep Panel: negative ANA: 1:80 Nucleolar Haptoglobin: 179. LDH: 258 Kappa/Lambda: 1.42 normal C3, C4: Normal SPEP/UPEP: negative Urine Eosinophils: None US Kidneys: No evidence of obstructive lesion or other concerning abnormality of the kidneys.

11. Anti-GBM Antibody (9/25/13): Positive: 49 (By ELISA) <19 AU/ML..................... Negative 20-25 AU/mL................. Equivocal 26 AU/mL or Greater...... Positive Repeat one was done on 10/1/13: Positive: 32

12. Progress During her Hospitalization, We started her on diuretics. She didnt receive any Dialysis since admission. She was also diagnosed with LV thrombus and is on anticoagulation.

13. Questions Does our patient has Anti-GBM disease or the positive anti-GBM Ab is a false positive test? Should we proceed for biopsy? If biopsy is positive, Should we consider treatment? Do we treat patients with positive Anti-GBM but normal renal function?

14. Anti-GBM Antibody Disease Anti-GBM antibody disease is a disorder in which circulating antibodies are directed against an antigen intrinsic to the glomerular basement membrane (GBM), thereby resulting in acute or rapidly progressive glomerulonephritis that is typically associated with crescent formation.

15. Type IV Collagen N Engl J Med 2003; 348:2543-2556, June 19, 2003

16. N Engl J Med 2003; 348:2543-2556June 19, 2003

17. Clinical Presentation Young men in late 20s and in men and women over 60 years of age. In the younger age group, the disease is usually eruptive, with hemoptysis, anemia, cough, fever, dyspnea, hematuria, non- nephrotic proteinuria, and red-cell casts. CXR shows diffuse alveolar infiltrates. Goodpasture's syndrome is generally detected earlier in patients who present with lung hemorrhage, and such patients may do better than those who present with silent renal injury alone. Presentation with oliguria is a particularly bad sign

18. Diagnosis Blood Tests: Antiglomerular basement membrane antibodies Based on diagnostic case-control study. 103 serum samples were analyzed. 34 serum samples from 19 patients with anti-GBM antibody disease. 41 serum samples from disease controls (22 with Wegener granulomatosis, 15 with microscopic polyangiitis, 1 with Churg-Strauss syndrome, 2 with SLE, 1 with idiopathic pulmonary fibrosis) 28 samples from healthy controls Nephrol Dial Transplant 2006 Feb;21(2):397 full-text

19. Results Nephrol Dial Transplant 2006 Feb;21(2):397 full-text

20. Western Blot Western blot screening for antibody against the human Goodpasture antigen (alpha- 3(IV) NC1) Urine tests: Active urine sediment with red blood cells, white blood cells, and red blood cell casts occurs with glomerulonephritis Hematuria Non-nephrotic range proteinuria

21. Treatment

22. Positive Anti-GBM antibody JASN November 1, 1999 vol. 10 no. 11 2446-2453

23. Case Reports Diabetic nephropathy with interstitial nephritis presenting with a false-positive anti-GBM antibody. Clin Nephrol. 2002 May;57(5):381-5 An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies. Am J Kidney Dis. 2005;45(4):743. A Friday afternoon case of apparent anti-glomerular basement nephritis. (The blocking reagent of the ELISA kit from Imtec contained bovine serum albumin, suggesting the reason for the false-positive result) Nephrology Dialysis Transplantation Volume 21, Issue 8Pp. 2328-2330

24. Do we treat patients with positive Anti-GBM but normal renal function?

25. Anti-glomerular basement membrane (GBM)-antibody- mediated disease with normal renal function Nephrol Dial Transplant. 1998 Apr;13(4):935-9.

26. All got same treatment: patients with no renal impairment survived with normal creatinine and no need for dialysis. Patients with renal impairment are on either dialysis or got renal transplant.

27. Br Med J (Clin Res Ed). 1986 February 1; 292(6516): 301–304.

28. Clinical analysis of anti glomerular basement membrane disease with normal renal function Total no. of patients: 35 (6 with normal renal function) 5/6 had microhematuria and proteinuria 4/6 patients had linear deposition in immunofloresence. 5/6 got treatment with immunosuppresives and plasmapheresis These 6 patients with normal renal function were followed up for 12- 133 months, among whom 4 patients achieved complete remission and 2 had mild proteinuria and microhematuria. 2011 Aug;33(4):432-5. doi: 10.3881/j.issn.1000-503X.2011.04.016.

29. How should we manage our patient?