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

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 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 M Human 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’