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 • 2007-2010: recurrent hemoptoe presenting a cystic lesion at the Right Upper Lobe of the Lung.
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
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.
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
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.
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.
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
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.
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.
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.
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
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’