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Interstitial nephritis associated with PostInfectious GN

Interstitial nephritis associated with PostInfectious GN. PRAET MARLEEN , MD, PhD UNIVERSITY HOSPITAL GHENT. Clinical History: Background. Man 53 year Ethyl ++ , smoking 10-12 cigars/day 1994: T3N0M0 Spinocellular Carcinoma of the glottis

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Interstitial nephritis associated with PostInfectious GN

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  1. Interstitial nephritis associated with PostInfectious GN PRAET MARLEEN , MD, PhD UNIVERSITY HOSPITAL GHENT

  2. Clinical History: Background • Man • 53 year • Ethyl ++ , smoking 10-12 cigars/day • 1994: T3N0M0 Spinocellular Carcinoma of the glottis • 2007-2010: recurrent hemoptoe presenting a cystic lesion at the Right Upper Lobe of the Lung.

  3. Clinical History: Recent • 04/10/2011: lobectomie • Histology:        Pachypleuritis met underlying scar of the pulmonary parenchyma. Bronchiectasy and chronic inflammation. No malignancy.     • Follow up: hydropneumothorax with infection: crp 15 mg/dL, WBC 19000 10^3/µL, fever 39°C, sputum: H.Influenza

  4. Admission in Emergency 3 weeks after lobectomy • Acute renal failure: - Creatinin 4,21 mg/dl - Proteinuria 4.3g/L - Macroscopic hematuria - Oliguria - WBC: 21700 10^3/µL - CRP 10.6 mg/dl • Normal temperature, normal BP • Renal biopsy.

  5. AgMethanamine x 4 Kidney biopsy containing 30 glomeruli: 4 glomeruli are completely sclerosed. 7 glomeruli undergo proliferative changes with crescent formation surrounding the glomeruli segmentally or globally. Glomeruli, tubuli and interstitium are infiltrated by neutrophils. No vasculitis

  6. AG Methanamine x10

  7. CONGORED x25

  8. CONGORED X 10

  9. PAS x40

  10. Differential Diagnosis • (Focal) crescentic glomerulonephritis post infection (PIGN). • Microangiopathic vasculitis with crescentic glomerulonephritis: ANCA-associated systemic vasculitides (Wegener, microscopic polyangitis, Churg- Strauss) • Sepsis with combined interstitial and glomerular changes.

  11. Immunofluorescence Findings • Ig G, Ig A, Ig M, C1Q: negative IF findings • Kappa, Lambda: negative IF findings • C3: strong granular staining at capillary wall 3+ SUGGESTED DIAGNOSIS: Post infectious glomerulonephritis with crescent formation in < 50% of the glomeruli. IF findings consistent with previous infection.

  12. C3 Deposition at capillary wall

  13. ORIGIN OF INFECTION • 2 possibilities: - Hydropneumothorax with infectious agent: H. Influenzae was found in the sputum. - Bronchiectasy with ulcerative inflammation and presence of germs: however no infectious agent was cultivated

  14. Treatment of the patient Original clinical diagnosis: vasculitis: plasmapheresis, cyclophosphamide, high dosed steroids. Creat levels up tot 6. 65 mg/dl. However: ANCA: negative, anti GBM: negative Switch of treatment after IF findings: stop plasmapheresis, stop cyclophosphamide: Instead: intravenous AB, steroids, dialysis. Creat level is decreasing with recovery of the patient.

  15. Discussion Glomerulonephritis and infection • - is primarily a childhood disease occuring after upper respiratory infection(5-10 %) or impetigo (25%) (Streptococcus A, beta – hemolytic, serotypes 12, 49) • - in older patients: less well known • Male/female ratio 2.8:1 • Immunocompromised background is present in 61 %, most often diabetes or malignancy • Infectious agent most often found: staphylococcus (46%), streptococcus (16%) and unusual gram- negative organisms.

  16. Discussion • Glomerulonephritis and infection: • IF findings in PIGN: IgG and C3, or C3 only • IgA dominant PIGN: strong association with staphylococcal infections of the skin with diabetes as a major risk. This variant of APIGN should be distinguished from the classic IgA nephropathy(Haas MHuman Pathology 2008, 39, 1309-1316,Nasr S, D’Agati Nephron Clin Pract 2011, 119, 18-26) • EM findings: classical PIGN: large subepithelial deposits (humps). APIGN: often no subepithelial deposits with varied findings (subendothelial, mesangial). Our patient: NO glomeruli in EM material.

  17. DISCUSSION • Glomerulonephritis and infection in our patient: no definite infectious agent revealed • But “immunocompromised”: alcoholism • NASR. ET AL.: Acute Postinfectious Glomerulonephritis in the Modern Era. Medicine, 87:21-32, 2008

  18. NASR. ET AL.: Acute Postinfectious Glomerulonephritis in the Modern Era. Medicine, 87:21-32, 2008 • ‘In Western Europe, alcoholism had become the most important risk factor for Acute Postinfectious Glomerulonephritis’ • Upper respiratory tract > skin > lung > endocarditis > teeth • 56% complete remission • 4-17% requiring renal replacement therapy • ‘Evidence supporting the use of steroid therapy for postinfectious crescentic GN is largely anecdotal’

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