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case 3. Granulomatous interstitial nephritis case 3. Granulomatous interstitial nephritis

Vazquez Martul Eduardo.MDVazquez Martul Eduardo.MDCoruña .SpainCoruña .Spain

Case history

A male 59 years old with previous history of pulmonary disease with diagnostic of sarcoidosis three years before (dec 2005), with mediastinic and interstitial pulmonary affectation. No history of renal dysfunction was detected at that moment.The Crp was 1.3 mg/dl . Corticoid treatment was supplied with improvement of lung symptoms.November 2009, he was hospitalized because it was detected in a routine analysis a deterioration of renal function with a Crp 3.4mg/dl. The patient only reported malaise without urinary symptoms since one month before. No fever, thoracic, lumbar pain or dermatologic alteration was detected. The BT was 120/80. He denied intake of any antibiotic or anti-inflammatory treatment.Hemogramme: erythrocites: 4.56,leucocyte:6.130, lymphocyte 21%, monocyte 11%, neutrophil 3.780, glucose 90mg, urea 977, total bilirrubin 0.6 mg., uric acid 8 mg, calcium 11, P 3.9, Na 138, K 4.6 urea 80 mg, cholesterol 182mg, triglyceride 180 mg.Urine analysis: sediment normal, no hematuria., no proteinuria.Density 1.010.

Painting. Uroscopia. David Teniers, XVII CENTURYArt´s Museum. Brussels

Preliminary Diagnostic Preliminary Diagnostic guide-linesguide-lines

59 year old maleWith mediastinic and lung nodular affectationRapid deterioration of renal function

ANCA DISEASE.Granulomatosis with polyangiitis

ANTI-GBM GLOMERULONEPHRITIS

Tubulointerstitial disease; SARCOIDOSIS

A kidney biopsy was indicated

Granulomatous nodules

Tubular destruction

Lymphoide cellular infiltrationEosinoph leucocytesHistiocytes

HISTOPATHOLOGIC DIAGNOSIS

1. GRANULOMATOUS TUBULOINTERSTITIAL NEPHRITIS

EPITHELIOID GRANULOMAS COMPATIBLE WITH SARCOIDOSIS.

RENAL GRANULOMATOSES

DRUG INDUCED INFECTION :TUBERCULOSIS

VASCULITIDES SARCOIDOSIS

Clinical and laboratory features at presentation in patients with AIN Features

Acute renal failure 100%Acute renal failure requiring dialysis 40%Arthralgias 45%Fever 36%Skin rash 22%Eosinophilia (4500 eosinophils per mm3) 35%Microhematuria 67%Gross hematuria 5%Leukocyturia 82%Non-nephrotic proteinuria 93%Nephrotic-range proteinuria 2.5%Complete nephrotic syndrome 0.8%

From Praga M, Gonzalez E. Acute interstitial nephritisKidney Int 2010;77:956

Table 1 | Etiology of biopsy-proven AIN

• Drugs (47.5% of AIN) Antibiotics: ampicillin,cephalosporins,ciprofloxacin, cloxacillin, methicillin, penicillin,rifampicin, sulfonamides, vancomycin.NSAIDsOther: allopurinol, acyclovir, famotidine,furosemide, omeprazole, phenytoin

• Infections (5–10%)• Bacteria: Brucella, Campylobacter, Escherichia coli, Legionella, Salmonella, Streptococcus,Staphylococcus, Yersinia•. Viruses: cytomegalovirus, Epstein–Barr,hantavirus, human immunodeficiency virus, polyomavirusOther: Leptospira, Mycobacterium tuberculosis,Mycoplasma, Rickettsia, Schistosoma, Toxoplasma

Idiopathic (5–10%) Anti-TBMTINUAssociated with systemic diseases (10–15%)Sarcoidosis, Sjogren, systemic lupus erythematosus.

Abbreviations: AIN, acute interstitial nephritis; NSAID, nonsteroidal anti-inflammatorydrug; TBM, tubular basement membrane; TINU, tubulointerstitial nephritis and

From Praga M, Gonzalez E. Acute interstitial nephritisKidney Int 2010;77:956

Tuberculosis

Sarcoidosis : Differential diagnostic

Zhiel-Nielsen

¡¡¡Attention!!! fever can be present in sarcoidosis

Granulomatous Interstitial nephritis: Granulomatous Interstitial nephritis: differential diagnosisdifferential diagnosis

Cases associted with lymphoid infiltration and uveitis TINU syndrome Cases without granuloma

Granulomatous vasculitis

Sarcoidosis and

Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis.Agrawal V, Crisi GM, D'Agati VD, Freda BJ.Am J Kidney Dis. 2012 Feb;59(2):303-8. Epub 2011 Dec 15.

Rapid Progresive Renal failure Berner Bet al. Med klin 1999,94.690

Acute renal failure and Interstitial Acute renal failure and Interstitial nephritis: differential diagnosisnephritis: differential diagnosis

Light Chain deposit disease

Giant cellGiant cell: DIFFERENTIAL DIAGNOSIS: DIFFERENTIAL DIAGNOSIS

kappa

Uric acid cast

Granulomatous interstitial nephritis is a rare condition whose pathogenesis is poorly understood. 0.5- 1.5 THE RENAL BIOPSIES

Of 203 renal biopsies performed between 1974 to 1994 in which interstitial nephritis was the predominant change, granulomata occurred in 12.

Sarcoidosis accounted for granulomatous inflammation in three patients Hum Pathol. 1995 Dec;26(12):1347-53.Granulomatous interstitial nephritis.Viero RM, Cavallo T.

In our experience since 1978 up to now (3.000 kidney biosies) only two cases

Granulomatous interstitial nephritis (GIN) are identified in 0.5 to 1,3% of all renal biopsies.20% in prviously diagnosed sarcoide patients

The study population included 25 men and 19 women with a mean age of 56 years

Renal function was severely impaired (mean creatinine clearance 24mL/min) in 43 patients. Proteinuria was observed in 77% The most common diagnosis was sarcoidosis (25%, n = 11), followed by drug-induced GIN (9%, n = 4), tuberculosis (6,8%, n=3),

Granulomatous interstitial nephritis: A retrospective study of 44 cases]

.Pasquet F, Chauffer M, Karkowski L, Debourdeau P, Mc Grégor B, Labeeuw M, Laville M, Pavic M.

Rev Med Interne. 2010 Oct;31(10):670-6.

French Sarcoidosis Group. (30 male/17 female, M/F ratio: 1.76).

• Fifteen of 47 (32%) patients had hypercalcemia (>2.75 mmol/L).

•Thirty-seven patients presented noncaseating granulomatous interstitial nephritis and 10 presented interstitial nephritis without granulomas.

•All but one presented ARF

•Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients.Mahévas M, Lescure FX, Boffa JJ, Delastour V,et al.Medicine (Baltimore). 2009 Mar;88(2):98-106

HYPERCALCEMIE(2-20%)

INTERSTITIAL GRANULOMATOUS

NEPHRITIS

GLOMERULAR• GN membranosa• GN membrano-

Proliferativa• GN mesangial IgA

• Nefropatía por cambios mínimos

• GEFS• Vasculitis sistemica

SARCOIDOSIS AND KIDNEY

NefrocalcinosisNephrolitiasis (1-14%)

TINU syndrome associated

proteinuria

ARF

Bilateral kidney pseudotumor Vicente A, Acebal Blanco MM.

Arch Esp Urol. 2012 Jul;65(6):629-.

CKD

CD68

CD68

CD5CD5

CD20

SARCOIDOSISPathogenesis??

Sato H,Woodhead FA,AhmadT et al. Hum Mol Genet, 2010.19.4100

GENES:DRB1/DQB1

II

Lower levels TGF-beta1

PATHOGENESIS: SARCOIDOSIS

hypercalcemis

calcitrol

DPB1 gene

FIBROSISChronic KDRESOLUTION

SSarcoidosis is a multisystemic disease of unknown etiology.arcoidosis is a multisystemic disease of unknown etiology.

It is characterized by the presence of non- caseating epitelioid granulomas in various organs.It is characterized by the presence of non- caseating epitelioid granulomas in various organs.

Renal disease is common in previously sistemic sarcoidosis up to 20%Renal disease is common in previously sistemic sarcoidosis up to 20% but very infrequent in routine but very infrequent in routine biopsies (less 1.5%)biopsies (less 1.5%)

It is necessary to mark out that It is necessary to mark out that GIN is not pathognomonic of sarcoidosisGIN is not pathognomonic of sarcoidosis : being also present in drug reactions, : being also present in drug reactions, mycobacterial and fungal infections and in granulomatosis vasculitis.mycobacterial and fungal infections and in granulomatosis vasculitis.

Most renal disease related to sarcoidosis is due to Most renal disease related to sarcoidosis is due to hypercalciuria and nephrocalcinosishypercalciuria and nephrocalcinosis is the most common disease. is the most common disease.

A good response to treatment with corticosteroids A good response to treatment with corticosteroids

End-stage renal disease from sarcoidosis is usually due to hypercalcemiaEnd-stage renal disease from sarcoidosis is usually due to hypercalcemia , renal stones and obstructive uropathy, renal stones and obstructive uropathy

Cases associated with vasculitis, lymphoid interstitial nphritis (TINU S)Cases associated with vasculitis, lymphoid interstitial nphritis (TINU S)

The association between any form of glomerulonephritis and sarcoidosis is fortuitous The association between any form of glomerulonephritis and sarcoidosis is fortuitous

Postransplant recurrencePostransplant recurrence is observed in 27%. is observed in 27%.

General concepts and General concepts and summarysummary

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Selected ReferencesGranulomatous interstitial nephritis. Vieiro RM, Cavallo T. Human Pathol. 1995,26: 1347-53Granulomatous interstitial nephritis in an extrapulmonary sarcoidosisUtas C, and al.Clin Nephrol 1.999,25:252Renal disease in sarcoidosis. Curhan GC edit. Burton D Rose and G. Rizzato.2012 www.uptodate.Frequency of kidney disease in chronic sarcoidosis.Bergner R, Hoffmann M, Waldherr R, Uppenkamp M.Sarcoidosis Vasc Diffuse Lung Dis. 2003 Jun;20(2):126-32.Renal failure in sarcoidosis].Sadek BH, Sqalli Z, Al Hamany Z, Benamar L, Bayahia R, Ouzeddoun N.Rev Pneumol Clin. 2011 Dec;67(6):342-6.Granulomatous interstitial nepritis.- Nicola Joss et al.,CJASN 2007 ,2:222-23018 cases: 5 associated with sarcoidosis.Granulomatous interstitial nephritis: A retrospective study of 44 cases] Pasquet F, Chauffer M, Karkowski L, Debourdeau P, Mc Grégor B, Labeeuw M, Laville M, Pavic M.Rev Med Interne. 2010 Oct;31(10):670-6. . Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients. Mahévas M, Lescure FX, Boffa JJ, Delastour V,et al.Medicine (Baltimore). 2009 Mar;88(2):98-106