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Nephropathology Slide seminar case 3. Granulomatous interstitial nephritis. Vazquez Martul Eduardo.MD Coruña .Spain. Painting. Uroscopia. David Teniers, XVII CENTURY Art´s Museum. Brussels. Case history

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Nephropathology slide seminar case 3 granulomatous interstitial nephritis

NephropathologySlide seminar case 3. Granulomatous interstitial nephritis

Vazquez Martul Eduardo.MDCoruña .Spain


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

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.


Preliminary diagnostic guide lines
Preliminary Diagnostic guide-lines

  • ANCA DISEASE.

  • Granulomatosis with polyangiitis

  • ANTI-GBM GLOMERULONEPHRITIS

  • Tubulointerstitial disease; SARCOIDOSIS

59 year old male

With mediastinic and lung nodular affectation

Rapid deterioration of renal function

A kidney biopsy was indicated


Granulomatous nodules

Tubular destruction


Lymphoide cellular infiltration

Eosinoph leucocytes

Histiocytes




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 nephritis

Kidney Int 2010;77:956


  • Table 1 | with AIN FeaturesEtiology of biopsy-proven AIN

  • Drugs (47.5% of AIN) Antibiotics: ampicillin,cephalosporins,

  • ciprofloxacin, cloxacillin, methicillin, penicillin,

  • rifampicin, sulfonamides, vancomycin.

  • NSAIDs

  • Other: 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, polyomavirus

  • Other: Leptospira, Mycobacterium tuberculosis,

  • Mycoplasma, Rickettsia, Schistosoma, Toxoplasma

  • Idiopathic (5–10%)

  • Anti-TBM

  • TINU

  • Associated with systemic diseases (10–15%)

  • Sarcoidosis, Sjogren, systemic lupus erythematosus.

  • Abbreviations: AIN, acute interstitial nephritis; NSAID, nonsteroidal anti-inflammatory

  • drug; TBM, tubular basement membrane; TINU, tubulointerstitial nephritis and

From Praga M, Gonzalez E. Acute interstitial nephritis

Kidney Int 2010;77:956


Sarcoidosis : Differential diagnostic with AIN Features

Tuberculosis

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

Zhiel-Nielsen


Granulomatous interstitial nephritis differential diagnosis
Granulomatous Interstitial nephritis: differential diagnosis with AIN Features

  • Cases associted with lymphoid infiltration

    and uveitis TINU syndrome

  • Cases without granuloma


Granulomatous vasculitis with AIN Features

Renalsarcoidosis 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.

Sarcoidosis and

Rapid Progresive Renal failure

Berner Bet al. Med klin 1999,94.690


Acute renal failure and Interstitial nephritis: differential diagnosis

Giant cell: DIFFERENTIAL DIAGNOSIS

kappa

Light Chain deposit disease


Uric acid cast diagnosis


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: 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.

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 wasseverely 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),


  • Renal of 44 cases]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

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

  • Thirty-seven patients presented noncaseating granulomatous interstitial nephritis

  • and 10 presented interstitial nephritis without granulomas.

  • All but one presented ARF

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


SARCOIDOSIS of 44 cases]

AND

KIDNEY

INTERSTITIAL

GRANULOMATOUS

NEPHRITIS

HYPERCALCEMIE

(2-20%)

ARF

TINU syndrome associated

Bilateral kidney pseudotumor

Vicente A, Acebal Blanco MM.

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

Nefrocalcinosis

Nephrolitiasis (1-14%)

  • GLOMERULAR

  • GN membranosa

  • GN membrano-

  • Proliferativa

  • GN mesangial IgA

  • Nefropatía por

  • cambios mínimos

  • GEFS

  • Vasculitis sistemica

proteinuria

CKD


CD68 of 44 cases]

SARCOIDOSIS

Pathogenesis??

CD68

CD5

CD5

CD20


PATHOGENESIS: SARCOIDOSIS of 44 cases]

II

GENES:DRB1/DQB1

Lower levels TGF-beta1

DPB1 gene

calcitrol

FIBROSIS

hypercalcemis

RESOLUTION

Chronic KD

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


General concepts and summary
General concepts and summary of 44 cases]

  • Sarcoidosis is a multisystemic disease of unknown etiology.

  • 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% but very infrequent in routine biopsies (less 1.5%)

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

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

  • A good response to treatment with corticosteroids

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

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

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

  • Postransplant recurrence is observed in 27%.




  • Selected References of 44 cases]

  • Granulomatous interstitial nephritis. Vieiro RM, Cavallo T.

  • Human Pathol. 1995,26: 1347-53

  • Granulomatous interstitial nephritis in an extrapulmonary sarcoidosis

  • Utas C, and al.Clin Nephrol 1.999,25:252

  • Renal 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 ,2:222-230

  • 18 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


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