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
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
ANCA DISEASE.
Granulomatosis with polyangiitis
59 year old male
With mediastinic and lung nodular affectation
Rapid deterioration of renal function
ANTI-GBM GLOMERULONEPHRITIS
Tubulointerstitial disease;
SARCOIDOSIS
A kidney biopsy was indicated
Granulomatous nodules
Tubular destruction
Lymphoide cellular infiltration
Eosinoph leucocytes
Histiocytes
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 nephritis
Kidney 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.
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
Tuberculosis
¡¡¡Attention!!! fever can be present in sarcoidosis
Zhiel-Nielsen
Granulomatous Interstitial nephritis:
differential diagnosis
Cases associted with lymphoid infiltration
and uveitis TINU syndrome
 Cases without granuloma
Granulomatous vasculitis
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.
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
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 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),
•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
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
AND
KIDNEY
HYPERCALCEMIE
(2-20%)
INTERSTITIAL
GRANULOMATOUS
NEPHRITIS
ARF
TINU syndrome associated
Bilateral kidney pseudotumor
Vicente A, Acebal Blanco MM.
Arch Esp Urol. 2012 Jul;65(6):629-.
Nefrocalcinosis
Nephrolitiasis (1-14%)
CKD
GLOMERULAR
• GN membranosa
• GN membranoProliferativa
• GN mesangial IgA
• Nefropatía por
cambios mínimos
• GEFS
• Vasculitis sistemica
proteinuria
CD68
SARCOIDOSIS
Pathogenesis??
CD68
CD5
CD20
CD5
PATHOGENESIS: SARCOIDOSIS
II
GENES:DRB1/DQB1
Lower levels TGF-beta1
DPB1 gene
calcitrol
hypercalcemis
FIBROSIS
RESOLUTION
Chronic KD
Sato H,Woodhead FA,AhmadT et al. Hum Mol Genet, 2010.19.4100
General concepts and
summary

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%.
Hercules light House. Coruña. Galizia.Spain
THANK YOU… AND SEE YOU IN LISBONE
Selected References
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