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1 Enterprise Interest None
2 29th Congress of The European Society of Pathology Amsterdam- Sep 2017 ESP Nephropathology Working Group Infectious Tubulointerstitial Diseases Wesam Ismail, MD Assistant Professor of Pathology Pathology Department, Beni Suef University EGYPT
3 Tubular Injury/ Tubulointerstitial Diseases Tubular and interstitial diseases are considered as one entity Wide variety of renal and systemic diseases Primary or secondary Correlates with renal function Clinical Nephrology, Johnson & Feehally, 2000
4 Infections
5 Global Examples of Emerging and Re-emerging Infections Nature Jul 8;430(6996):242-9
6 A Challenge Infection-Related Kidney Disease Glomerular Tubulointerstitial Vascular (very rare) Patterns of Injury: Glomerular: Acute GN, MesPGN, MPGN, MGN, TMA, Crescentic GN, Collapsing Glomerulopathy, AA, rarely Fibrillary GN Tubulointerstitial: Acute TIN, Chronic TIN, Granulomatous TIN Organism: Bacterial, Viral, Fungal, Protozoal & Parasitic Variable Clinical presentation
7 Infectious Tubulointerstitial Diseases Acute/Chronic/Granulomatous Type of infiltrate may provide a clue to the underlying etiology Neutrophils Eosinophils Lymphoplasmacytic Extent of tubulitis varies ATI or AIN?????
8 Acute Pyelonephritis (APN)/Acute Bacterial Nephritis Commonest organism: E.Coli(serotypes O, K, and H) Other: Proteus, Klebsiella, Enterobacter, Pseudomonas, Streptococcus faecalis Predisposing Factors: - Obstruction, Reflux, Calculi - Diabetes, Pregnancy - Transplantation, Immunosuppression
9 Pathogenesis of UTI Bacterial Factors: Virulence Adhesion & Motility (P & Type 1 fimbriae) Toxin production Intracellular communities Quiescent intracellular reservoirs (QIS) Host Factors: Antibodies against Bacteria ph (vaginal flora) Tamm-Horsfall proteins CXCR1 gene polymorphisms Neutrophils Innate immunity TLR4, IL8
10
11 Same pathology - Fungal (candida, aspergillosis, mucormycosis) - Nocardiosis (immunocompromised)
12 Acute Pyelonephritis (APN)/Acute Bacterial Nephritis Complications Perinephric abscess, septicemia Emphysematous pyelonephritis: gas forming bacteria Persistent infection/ recurrent episodes Chronic pyelonephritis D.D: Tubulointerstitial Nephritis, Primary FSGS, Hypertensive Renal Disease
13 Variants of chronic pyelonephritis Xanthogranulomatous Pyelonephritis: Often unilateral, mass lesion with abundant foamy macrophages & Frequent granulomas Malakoplakia: Michaelis Gutmann bodies Megalocytic interstitial nephritis: Rare, Extensive interstitial histiocytic infiltrate with abundant granular eosinophilic cytoplasm, sparing of the tubules D.D: Renal cell carcinoma
14
15 Nephrectomy of a diabetic patient with clinical diagnosis of???emphysematous pyelonephritis ALECT2
16 Case 1 A female 48 years old, presented with acute renal failure, fever, night sweats and peripheral neuropathy screatinine :12mg/dl, protein/creatinine ratio: 900mg/gm No history of diabetes or hypertension Reported brucella infection 6 month prior to presentation upon which she received treatment which she stopped prematurely Serology for brucella was positive
17
18 Renal involvement in Brucellosis is rare No fungal infection was detected Ziehl-Neelsen (acid-fast bacteria) stain negative
19 Tuberculosis After decline for almost 3 decades, TB is increasing (HIV, transplantation) Genitourinary TB accounts for 30% of extrapulmonary TB in developed countries and is probably more in developing countries D.D Tuberculoid leprosy (GN & AA amyloid more common) -Fungal: Histoplasmosis, Blastomycosis, Coccidioidomycosis, crytococcosis
20 A 13 year old boy with secondary genitourinary TB
21 Case 2 A 55 year old male who presented with low grade fever, dysuria, flank pain and tenderness, along with a slight rise in serum creatinine Patient has a high grade non-invasive urothelial carcinoma upon which he received recently intravesical BCG
22 BCG granulomatous interstitial nephritis Granulomatous inflammation of kidney due to intracavitary BCG for treatment of in situ urothelial carcinoma Asymptomatic granulomatous inflammation of renal pelvis in 25% of patients treated with BCG BCG nephritis in around 2% of patients Ziehl-Neelsen (acid-fast bacteria) stain negative
23 Differential Diagnosis (other than infections) Sarcoidosis Drug Induced (+ eosinophils)
24 Leptospirosis Leptospira are nephrophilic, Primary injury of the PCT is regarded as the hallmark of renal injury Acute Tubular Necrosis Interstitial hemorrhage may occur (Early neutrophils) Interstitial Nephritis (mainly monocytes & lymphocytes DD: Viral or Ricketssial Infection
25
26 Cytomegalovirus infection (CMV)
27 Cytomegalovirus infection (CMV)
28 Polyoma Virus Nephropathy (PVN)/ BK virus nephropathy Immunocompromised host, Rare in recipients of organs other than kidney Predominant medullary inflammation raises PVN suspicion
29
30
31 Polyoma Virus Nephropathy (PVN) Type I Type II Type III Type IV Courtesy of Volker Nickeleit
32 Polyoma Virus Nephropathy (PVN) SV40
33 Banff Consensus Recommendations 2009 PVN staging focuses on 3 disease phases: very early (stage A) florid/acute (stage B) chronic (stage C) In addition to evaluation of the viral load
34 ? Adenovirus
35 Epstein-Barr Infection (EBV) Post-Transplant lymphoproliferative Disorders (PTLD) CD20
36 Hanta Viruses Emerging Zoonosis Rodent-borne pathogens. New hosts are being discovered Endemic areas (Europe, Eurasia & eastern Russia) and distribution seems to expand (new cases in Africa) New World hantaviruses causing hantavirus cardiopulmonary syndrome (HCPS) and Old World hantaviruses causing hemorrhagic fever with renal syndrome (HFRS) Mainly vascular alterations and leakage leads to organ failure
37 Hanta Viruses Emerging Zoonosis Five stages of the disease : febrile,hypotensive, oliguric, diuretic and convalescence Only one third of patient s follow this course Variable clinical presentations Glomeruli:? Mesangial proliferation
38 Infectious Tubulointerstitial Diseases Can be a challenging diagnosis The exact incidence of is unknown Few biopsies in TIN and Very few biopsies in AKI Morphology is variable and often similar with varied mechanisms With the emergence of new infections and the re-emergence of old ones with different strains, we might be one step behind No ideal classification should take into account: clinical, etiological, pathological and pathogenetic mechanisms
39 Thank you For your Attention
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