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Il cane leishmaniotico nefropatico: quando non effettuare terapia leishmanicida Andrea Zatelli DMV Medical Consultancy Services – Malta [email protected] Bari 12 Novembre 2017 Bari 12.11.2017

Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

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Page 1: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Il cane leishmaniotico nefropatico:

quando non effettuare terapia leishmanicida

Andrea Zatelli DMV Medical Consultancy Services – Malta [email protected]

Bari 12 Novembre 2017 Bari 12.11.2017

Page 2: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

www.gruppoleishmania.org

Bari 12.11.2017

Page 3: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Canine Leishmaniasis Bari 12.11.2017

Page 4: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

CanL Bari 12.11.2017

Page 5: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Immune-mediated glomerular damage

Associated with IC deposition in the glomeruli

IC = Ab (seroconversion) + Ag (leishmania)

PROTEINURIA

Bari 12.11.2017

Page 6: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Subepithelial – BM thickening and minimal inflammatory cell infiltration. Proteinuria may be severe

Subendothelial – recruitment inflammatory cells and

BM thickening. Moderate proteinuria Mesangial – hypercellularity and mesangial matrix

accumulation. May be asymptomatic

Leishmaniasis and glomerular damage Bari 12.11.2017

Relatore
Note di presentazione
The location of the IC deposition determines the histologic changes abserved and the severity of glomerular disfunction and degree of proteinuria
Page 7: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

High IFA/ELISA – Normal renal function, perfect clinical condition

Low IFA/ELISA – Normal renal function, perfect clinical condition

High IFA/ELISA – Azotemia, proteinuria, anemia, hypertension….

Low IFA/ELISA – Azotemia, proteinuria, anemia, hypertension….

Symptomatic Vs Asymptomatic Bari 12.11.2017

Relatore
Note di presentazione
The location of the IC deposition determines the histologic changes abserved and the severity of glomerular disfunction and degree of proteinuria
Page 8: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Therapy? Bari 12.11.2017

Page 9: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

IC in the glomerulus

1. Ag-Ab equivalence - Soluble circulating IC are

trapped in the glomerulus

2. Ab excess – IC tends to be large and insoluble

and are removed by phagocytic cells

3. Ag excess – IC do not readily bind complement

and are less likely to produce immunological

injury

Bari 12.11.2017

Relatore
Note di presentazione
In course of a type III reaction, the complexes formed between a monoclonal Ab and its Ag or the complex formed between a polyclonal Ab and a hapten are soluble. However the complexes between polyclonal Ab or myxtures of monoclonal Ab and a large Ag often lead to the formation of an insoluble precipitate (the so-called precipitin reaction)
Page 10: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Precipitin reaction Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 11: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Precipitin reaction

.

.

Dep

ositi

on

Phag

ocyt

osis

No

inju

ry

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 12: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Precipitin reaction

Ag/Ab

˃1 =1 ˂1

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 13: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Therapy (leishmanicidal)

Increased Ag concentration

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 14: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Therapy (leishmanicidal)

Increased Ag concentration

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 15: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Therapy (leishmanicidal)

Increased Ag concentration

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 16: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Therapy (leishmanicidal)

Increased Ag concentration

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 17: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Case #1 - MAX

•Mixed breed, 7 yrs old, castrated male

•Indoor and outdoor, Malta

•Depressed, BCS 2/5

Bari 12.11.2017

Page 18: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Case #1 - MAX Bari 12.11.2017

Page 19: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Case #1 - MAX Bari 12.11.2017

Page 20: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

IFA Leishmania 1:640

Case #1 - MAX Bari 12.11.2017

Page 21: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Case #1 - MAX

•Depressed, BCS 2/5

•Hypoalbuminemia, Hyperglobulinemia

•Increased creatinine

•Anemia

•Thrombocytopenia

•Serology + parasite

Bari 12.11.2017

Page 22: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Therapy? Bari 12.11.2017

Page 23: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 1,9 mg/dl Day 0

? Case #1 - MAX Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 24: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 1,9 mg/dl

Creatinine 2,7 mg/dl

Day 0

Case #1 - MAX Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 25: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 1,9 mg/dl

Creatinine 2,7 mg/dl

Creatinine 1,6 mg/dl

Day 0

Case #1 - MAX Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 26: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 2,6 mg/dl Day 0

Case #2 Toby

? Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 27: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 2,6 mg/dl

Creatinine 2,2 mg/dl

Day 0

Case #2 Toby Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 28: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 2,6 mg/dl

Creatinine 2,2 mg/dl

Creatinine 1,8 mg/dl

Day 0

Case #2 Toby Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 29: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 1.4 mg/dl Day 0

Case #3 Jack ? Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 30: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

1 2 3

5 25 30

CHECK CHECK

Creatinine 1.5 mg/dl Day 0

Case #3 Jack

Creatinine 2,9 mg/dl

8

CHECK

Creatinine 3,8 mg/dl

Bari 12.11.2017

Relatore
Note di presentazione
The amount of precipitate that is recovered when an increasing amount of Ag is added to a constant amount of Ab follow a typical pattern. The amount of Ab precipitated increases with the amount of Ag (zone 1) up to a maximum (zone 2), after which further increase in the amount of Ag leads to a decrease in the amount af Ab precipitated (zone3)
Page 31: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Helpful tips

1. Seroconversion (TEST)

2. Ic & clinical manifestation

3. Precipitin reaction (Ag/Ab)

4. AKI Vs CKD Vs AKI on CKD?

5. Nephrotoxicity?

Bari 12.11.2017

Relatore
Note di presentazione
In course of a type III reaction, the complexes formed between a monoclonal Ab and its Ag or the complex formed between a polyclonal Ab and a hapten are soluble. However the complexes between polyclonal Ab or myxtures of monoclonal Ab and a large Ag often lead to the formation of an insoluble precipitate (the so-called precipitin reaction)
Page 32: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Il cane leishmaniotico nefropatico:

quando non effettuare terapia leishmanicida?

Bari 12.11.2017

Relatore
Note di presentazione
In course of a type III reaction, the complexes formed between a monoclonal Ab and its Ag or the complex formed between a polyclonal Ab and a hapten are soluble. However the complexes between polyclonal Ab or myxtures of monoclonal Ab and a large Ag often lead to the formation of an insoluble precipitate (the so-called precipitin reaction)
Page 33: Role of pathogens in glomerulonephritis · Precipitin reaction Ag/Ab ˂1 =1 ˃1. Bari 12.11.2017. The amount of precipitate that is recovered when an increasing amount of Ag is added

Bari 12.11.2017