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

Clinical History: Background  Man  53 year  Ethyl ++, smoking cigars/day  1994: T3N0M0 Spinocellular Carcinoma of the glottis  : 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 ^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: ^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

AG Methanamine x10

CONGORED x25

CONGORED X 10

PAS x40

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.

C3 Deposition at capillary wall

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 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 M Human Pathology 2008, 39, , 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’