Causes of graft loss over 10 years in csa treated patients
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Causes of Graft Loss over 10 Years in CsA-Treated Patients. Recurrent disease 6% . Other 3%. Acute Rejection 11% . PNF 5%. Vascular 8%. Death 27%. CAN 40%. Marcén R et al. Transplantation 2001; 72:57  62. Presentation techniques Some personal advice. I. Performance

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Causes of Graft Loss over 10 Years in CsA-Treated Patients

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Causes of graft loss over 10 years in csa treated patients

Causes of Graft Loss over 10 Years in CsA-Treated Patients

Recurrent

disease

6%

Other

3%

Acute

Rejection

11%

PNF

5%

Vascular

8%

Death

27%

CAN

40%

Marcén R et al. Transplantation 2001; 72:5762.


Presentation techniques some personal advice

Presentation techniquesSome personal advice

  • I. Performance

  • II. Manuscript

  • III. Slides


Presentation techniques some personal advice1

Presentation techniquesSome personal advice

  • I. Performance

  • II. Manuscript

  • III. Slides


I performance

I. Performance

  • Never turn your back on the audience

  • Always look at the audience

  • (and the laptop)


I performance1

I. Performance

  • Never turn your back on the audience

  • Always look at the audience

  • (and the laptop)

  • Never use the laser pointer

  • Always use your slides to make your point


Causes of graft loss over 10 years in csa treated patients1

Causes of Graft Loss over 10 Years in CsA-Treated Patients

Recurrent

disease

6%

Other

3%

Acute

Rejection

11%

PNF

5%

Vascular

8%

Death

27%

CAN

40%

Marcén R et al. Transplantation 2001; 72:5762.


Causes of graft loss over 10 years in csa treated patients2

Causes of Graft Loss over 10 Years in CsA-Treated Patients

Recurrent

disease

6%

Other

3%

Acute

Rejection

11%

PNF

5%

Vascular

8%

Death

27%

CVD

CNI-

nephrotox

CAN

40%

Marcén R et al. Transplantation 2001; 72:57-62.


Metabolic toxicities of immunosuppressive drugs

Metabolic Toxicities of Immunosuppressive Drugs

CsA = cyclosporine A; Tac = tacrolimus; Ster = corticosteroids;

SRL/EVL = sirolimus/everolimus; AZA = azathioprine

Adapted from Danovitch GM. Transplant Rev 2000; 14:65–81.


Metabolic toxicities of immunosuppressive drugs1

Metabolic Toxicities of Immunosuppressive Drugs

CsA = cyclosporine A; Tac = tacrolimus; Ster = corticosteroids;

SRL/EVL = sirolimus/everolimus; AZA = azathioprine

Adapted from Danovitch GM. Transplant Rev 2000; 14:65–81.


Metabolic toxicities of immunosuppressive drugs2

Metabolic Toxicities of Immunosuppressive Drugs

CsA = cyclosporine A; Tac = tacrolimus; Ster = corticosteroids;

SRL/EVL = sirolimus/everolimus; AZA = azathioprine

Adapted from Danovitch GM. Transplant Rev 2000; 14:65–81.


Metabolic toxicities of immunosuppressive drugs3

Metabolic Toxicities of Immunosuppressive Drugs

CsA = cyclosporine A; Tac = tacrolimus; Ster = corticosteroids;

SRL/EVL = sirolimus/everolimus; AZA = azathioprine

Adapted from Danovitch GM. Transplant Rev 2000; 14:65–81.


Metabolic toxicities of immunosuppressive drugs4

Metabolic Toxicities of Immunosuppressive Drugs

CsA = cyclosporine A; Tac = tacrolimus; Ster = corticosteroids;

SRL/EVL = sirolimus/everolimus; AZA = azathioprine

Adapted from Danovitch GM. Transplant Rev 2000; 14:65–81.


Daclizumab reduces the risk of biopsy proven acute rejection bpar

0.6

0.5

0.4

0.3

0.2

0.1

0

400

0

50

100

150

200

250

300

350

450

500

Daclizumab Reduces the Risk of Biopsy-Proven Acute Rejection (BPAR)

  • Cumulative incidence of first BPAR

  • Pooled analysis of 12-month data from two pivotal trials

Placebo (n=268)

116 events

Daclizumab (n=267)

74 events

Probability

p = 0.0001

(stratified

logrank test)

Time after transplantation (days)

Ekberg H et al. Transplant Int 2000; 13:151–9.


Daclizumab reduces the risk of biopsy proven acute rejection bpar1

0.6

0.5

0.4

0.3

0.2

0.1

0

400

0

50

100

150

200

250

300

350

450

500

Daclizumab Reduces the Risk of Biopsy-Proven Acute Rejection (BPAR)

  • Cumulative incidence of first BPAR

  • Pooled analysis of 12-month data from two pivotal trials

Placebo (n=268)

116 events

Daclizumab (n=267)

74 events

Probability

p = 0.0001

(stratified

logrank test)

Time after transplantation (days)

Ekberg H et al. Transplant Int 2000; 13:151–9.


I performance2

I. Performance

  • Never turn your back on the audience

  • Always look at the audience

  • Never use the laser pointer

  • Always use your slides to make your point

  • Always time your performance at home

  • 3 - 7 - 10 - 20 minutes sharp


I performance3

I. Performance

  • Never turn your back on the audience

  • Always look at the audience

  • Never use the laser pointer

  • Always use your slides to make your point

  • Always time your performance at home

  • Always prepare your opening sentences


Opening sentence

Opening sentence

You will always be nervous:

Sit in the front - look back

Prepare your opening sentence

- the rest will come by itself


Opening sentence1

Opening sentence

You will always be nervous:

Sit in the front - look back

Prepare your opening sentence

- the rest will come by itself

Mr chairman, ladies and gentlemen! (.)

For many years (.)

steroids have been the backbone (.)

of our manitenance IS (.)

Now is the time to challenge them (.)


Opening sentence2

Opening sentence

You will always be nervous:

Sit in the front - look back

Prepare your opening sentence

- the rest will come by itself

Members and guests (.)

I thank the organizers for inviting me (.)

and I thank all of you for joining us (.)

in this symposium tonight (.)

Do not repeat the title of your talk


Presentation techniques some personal advice2

Presentation techniquesSome personal advice

  • I. Performance

  • II. Manuscript

  • III. Slides


Ii manuscript

II. Manuscript

  • Never read a manuscript of your talk

  • Always use your slides as the manuscript


Symphony study design

150-300 ng/ml for 3 months

100-200 ng/ml thereafter

A

Normal dose CsA

MMF

Steroids

50–100 ng/ml

Daclizumab

Low dose CsA

B

MMF

Steroids

3-7 ng/ml

Daclizumab

Low dose TAC

C

MMF

Steroids

4-8 ng/ml

Daclizumab

Low dose SRL

D

MMF

Steroids

SYMPHONY Study Design

6 mo

12 mo

Tx

Ekberg H et al Am J Transpl 2006, 6 (suppl 2), #49; 83.


Symphony study

Symphony study

Main inclusion criteria

  • Renal transplant recipients 18  75 years

  • Single-organ, kidney

  • Living or deceased donors

Main exclusion criteria

  • Panel reactive antibodies > 20%

  • Cold ischaemic time > 30 hours

  • History of malignancy


Ii manuscript1

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

II. Manuscript


Calculated gfr cockcroft gault

p=0.0014

p<0.0001

p<0.0001

Calculated GFR(CockcroftGault)

100

90

80

Normal-dose CsA

65

70

59

Low-dose CsA

57

57

60

Low-dose TAC

GFR (Cockcroft Gault) (ml/min)

50

Low-dose SRL

40

30

20

10

0

12 months post-Tx

Ekberg H et al Am J Transpl 2006, 6 (suppl 2), #49; 83.


Causes of graft loss over 10 years in csa treated patients

High Prevalence of

Subclinical Rejection (SCR)

  • Prevalence SCR

  • 1 mo61 %

  • 3 mo46 %

  • 1 yr26 %

80

60

Prevalence (%)

40

Acute rejection

SCR (acute)

20

SCR (borderline)

0

10

0.1

0.25

0.5

1

2

3

4

5

6

7

8

9

Time after transplantation (years)

Nankivell BJ et al. N Engl J Med 2003; 349:232633.


Ii manuscript2

II. Manuscript

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

  • Never start with comments


Ii manuscript3

II. Manuscript

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

  • Never start with comments

    • let comments come last

    • make one extra slide


Calculated gfr cockcroft gault1

p=0.0014

p<0.0001

p<0.0001

Calculated GFR(CockcroftGault)

100

90

80

Normal-dose CsA

65

70

59

Low-dose CsA

57

57

60

Low-dose TAC

GFR (CockcroftGault) (ml/min)

50

Low-dose SRL

40

30

No significant

difference between

CsA and Low-CsA

20

10

0

12 months post-Tx

Ekberg H et al Am J Transpl 2006, 6 (suppl 2), #49; 83.


Causes of graft loss over 10 years in csa treated patients

High Prevalence of

Subclinical Rejection (SCR)

  • Prevalence SCR

  • 1 mo61 %

  • 3 mo46 %

  • 1 yr26 %

80

60

Prevalence (%)

40

Acute rejection

SCR (acute)

20

SCR (borderline)

0

10

0.1

0.25

0.5

1

2

3

4

5

6

7

8

9

Time after transplantation (years)

Nankivell BJ et al. N Engl J Med 2003; 349:232633.


Causes of graft loss over 10 years in csa treated patients

High Prevalence of

Subclinical Rejection (SCR)

  • Prevalence SCR

  • 1 mo61 %

  • 3 mo46 %

  • 1 yr26 %

80

High risk for AR after CNI w/d

Lower risk

60

Prevalence (%)

40

Acute rejection

SCR (acute)

20

SCR (borderline)

0

10

0.1

0.25

0.5

1

2

3

4

5

6

7

8

9

Time after transplantation (years)

Nankivell BJ et al. N Engl J Med 2003; 349:2326-33.


Ii manuscript4

II. Manuscript

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

Why is this so important?

Because the audience cannot

read your slide and listento you at the same time

- > Competition


Ii manuscript5

II. Manuscript

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

- > Competition

TV news + kids

TV news + Radio news


Ii manuscript6

II. Manuscript

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

  • Always send on one channel at the time

So read your text with them first

then give your comments

TV news first, then radio


Methods

Methods

  • Acute rejection was defined as biopsy-proven and treated events within 6 months after transplantation excluding borderline cases


Methods1

Methods

  • Acute Rejection

    • Biopsy-proven

    • Treated patients

    • Within 6 mo.

    • Excluding Borderline


Ii manuscript7

II. Manuscript

  • Never read a manuscript

  • Always use your slides as the manuscript

  • Always describe your slide immediately

  • Send on one channel at the time

  • Always use a strategy

  • (chapters, line of thoughts)


Strategy

Strategy

This is a study that shows the benefit

of steroid withdrawal

… the study…

In conclusion, this study has shown

the benefit of steroid withdrawal.

  • First, say what you are going to tell us

  • Then tell us

  • Finally, say what you have told us


Chapters

Chapters

  • Divide your talk into chapters

    • 1. Background

    • 2. Aim

    • 3. Method

    • 4. Results

    • 5. Conclusion


Chapters1

Chapters

  • Divide your talk into chapters

    • 1. Background- 2 slides

    • 2. Aim- 1 slide

    • 3. Method- 2 slides

    • 4. Results- 3 slides

    • 5. Conclusion- 1 slide

    • 8 - 10 slides = 7 minutes


Presentation techniques some personal advice3

Presentation techniquesSome personal advice

  • I. Performance

  • II. Manuscript

  • III. Slides


Iii slides

III. Slides

  • Never apologize for a busy slide

    • - discard it!

  • Never say ’as you can see’

    • it means nobody can see!


  • Causes of graft loss over 10 years in csa treated patients

    Table 2. Multivariate Risk Estimates for Endpoint of Overall Graft Loss*

    This is actually a slide

    that was used in a congress

    *Table displays main variable of interest and significant (α < .05) covariates in the model.


    Causes of graft loss over 10 years in csa treated patients

    Multivariate risk estimates for graft loss

    Somebody et al ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Multivariate risk estimates for graft loss

    Somebody et al ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Multivariate risk estimates for graft loss

    Somebody et al ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Multivariate risk estimates for graft loss

    Somebody et al ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Multivariate risk estimates for graft loss

    Somebody et al ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Creatinine levels

    in posttransplant periods by CNI

    Kaplan and Meier-Kriesche ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Creatinine levels

    in posttransplant periods by CNI

    Kaplan and Meier-Kriesche ATC 2004


    Causes of graft loss over 10 years in csa treated patients

    Creatinine levels

    in posttransplant periods by CNI

    Kaplan and Meier-Kriesche ATC 2004


    Iii slides1

    III. Slides

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides


    Daclizumab reduces the risk of biopsy proven acute rejection bpar2

    0.6

    0.5

    0.4

    0.3

    0.2

    0.1

    0

    400

    0

    50

    100

    150

    200

    250

    300

    350

    450

    500

    Daclizumab Reduces the Risk of Biopsy-Proven Acute Rejection (BPAR)

    • Cumulative incidence of first BPAR

    • Pooled analysis of 12-month data from two pivotal trials

    Placebo (n=268)

    116 events

    Daclizumab (n=267)

    74 events

    Probability

    p = 0.0001

    (stratified

    logrank test)

    Time after transplantation (days)

    Ekberg H et al. Transplant Int 2000; 13:151–9.


    Daclizumab prevents acute rejection

    0.6

    0.5

    0.4

    0.3

    0.2

    0.1

    0

    400

    0

    50

    100

    150

    200

    250

    300

    350

    450

    500

    Daclizumab Prevents Acute Rejection

    Pooled analysis at 12-mo. from two pivotal trials

    Placebo (n=268)

    Daclizumab (n=267)

    Probability

    p = 0.0001

    Time after tx (days)

    Ekberg H et al. Transplant Int 2000; 13:151–9.


    Iii slides2

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides

    • Think about key words

    III. Slides


    Conclusion

    Conclusion

    For both LD transplants and CD paired kidneys, there was no difference in 5-year graft or patient survival to be found between primary CsA or tacrolimus therapy. There is some evidence that tacrolimus may be associated with improved renal function as compared to CsA.

    Kaplan and Meier-Kriesche ATC 2004


    Conclusion1

    Conclusion

    • For both LD transplants and CD paired kidneys, there was no difference in5-year graftor patient survival to be found between primary CsA or tacrolimus therapy.

    • There is some evidence that tacrolimus may be associated with improved renal function as compared to CsA.

    Kaplan and Meier-Kriesche ATC 2004


    Iii slides3

    III. Slides

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides

    • Always write like a poet - think key words


    Conclusion2

    Conclusion

    • For both LD transplants and CD paired kidneys, there was no difference in5-year graftor patient survival to be found between primary CsA or tacrolimus therapy.

    • There is some evidence that tacrolimus may be associated with improved renal function as compared to CsA.

    Not good

    Kaplan and Meier-Kriesche ATC 2004


    Conclusion3

    Conclusion

    For both LD transplants and DD paired kidneys (.)

    there was no difference (.)

    in 5-year graft or patient survival (.)

    to be found between CsA or tacrolimus therapy.

    Poetry

    There is some evidence (.)

    that tacrolimus may be associated (.)

    with improved renal function as compared to CsA.

    Kaplan and Meier-Kriesche ATC 2004


    Conclusion4

    Conclusion

    For both LD transplants and CD paired kidneys,

    there was no difference

    in5-year graftor patient survival

    to be found between CsA or tacrolimus therapy.

    Poetry

    Key words

    There is some evidence

    that tacrolimus may be associated

    with improved renal function as compared to CsA.

    Kaplan and Meier-Kriesche ATC 2004


    Conclusionary remarks conversion from cni to mmf maintenance monotherapy

    Conclusionary Remarks: Conversion from CNI- to MMF- Maintenance-Monotherapy

    • Long-term observations of patients converted from CNI-to MMF-monotherapy confirm our previous early experience with this kind of an i.s. maintenance therapy as an efficacious and safe treatment after cadaveric kidney transplantation, - in particular:

    • Early amelioration of renal allograft function as well as early reduction of recipients´ high atherogenic profile (=improvement of hypertension and high blood lipids!) are not only being maintained over the years (3,4 y) after conversion but tend to improve further later on;

    • There is no evidence of late subclinically-ongoing acute rejection events as demonstrated by protocol biopsies taken 2 years after conversion in about 50 % of the patients;

    • Long-term amelioration of recipients´ atherogenic profile may let assume a reduction in morbidity and mortality due to late cerebro-cardio-vascular accidents and, thus, may contribute to an improved life expectancy of kidney-transplanted patients. Indeed,5 years after the start of the trial,there is already a trend for improved patient survival (= no patient death so far.)

    Senior Lecturer at a Course


    Conversion from cni to mmf monotherapy

    Conversion from CNI to MMF Monotherapy

    • MMF monotherapy was safe and effective

    • Continued improvement of hypertension and hyperlipidemia after CNI withdrawal

    • No subclinical rejection at 2 years

    • Improved patient survival due to less CVD


    Conversion from cni to mmf monotherapy1

    Conversion from CNI to MMF Monotherapy

    • MMF monotherapy was safe and effective

    • Continued improvement of hypertension and hyperlipidemia after CNI withdrawal

    • No subclinical rejection at 2 years

    • Improved patient survival due to less CVD

    Much better - but no Poetry

    No Key Words

    No spacing between paragraphs


    Conversion from cni to mmf monotherapy2

    Conversion from CNI to MMF Monotherapy

    • MMF monotherapy was safe and effective

    • Continued improvement of hypertension and hyperlipidemia after CNI withdrawal

    • No subclinical rejection at 2 years

    • Improved patient survival due to less CVD


    Iii slides4

    III. Slides

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides

    • Always write like a poet - think key words

    • Always use animation to simplify

    • (not to impress)


    Binet i et al polyomavirus disease under new immunosuppressive drugs transplantation 1999 67 928

    Binet I et al ; Polyomavirus disease under new immunosuppressive drugsTransplantation 1999 ; 67: 928

    Retrospectiv analysis of 616 Tx from 8595

    No polyoma virus infection

    From 9598; 5 cases with polyoma (% ??)

    All had prior rejections

    All switched from CsA to Tacro

    4 switched from Aza to MMF

    4 grafts are lost/1 has s-creat 302 mol/l


    Binet i et al polyomavirus disease under new immunosuppressive drugs transplantation 1999 67 9281

    Binet I et al ; Polyomavirus disease under new immunosuppressive drugsTransplantation 1999 ; 67: 928

    Retrospectiv analysis of 616 Tx

    From 198595: No polyoma virus infection

    From 199598: 5 cases with polyoma

    All had prior rejections

    All switched from CsA to Tacro

    4 switched from Aza to MMF

    4 grafts were lost


    Gfr and graft survival tacrolimus vs csa

    GFR and Graft Survival tacrolimus vs CsA

    • Interstitial fibrosis and CAN translates into differences in GFR and graft survival:

    Baboolal K, et al. Kidney Int 2002;61:686–96


    Gfr and graft survival tacrolimus vs csa1

    GFR and Graft Survival tacrolimus vs CsA

    • Interstitial fibrosis and CAN translates into differences in GFR and graft survival:

    Baboolal K, et al. Kidney Int 2002;61:686–96


    Gfr and graft survival tacrolimus vs csa2

    GFR and Graft Survival tacrolimus vs CsA

    • Interstitial fibrosis and CAN translates into differences in GFR and graft survival:

    Colours to simplify

    Baboolal K, et al. Kidney Int 2002;61:686–96


    A meta analysis of steroid withdrawal trials

    A Meta-Analysis of steroid withdrawal trials

    Acute rejection (9 studies, n=1461)

    %95% CIp

    _________________________________________

    AR after SRW 14 1017 <0.001

    _________________________________________

    Graft survival (9 studies, n=1899)

    RR95%CI

    _________________________________________

    RR graft failure1.381.081.67<0.012

    _________________________________________

    Kasiske et al, JASN 2000


    A meta analysis of steroid withdrawal studies

    A Meta-Analysis of steroid withdrawal studies


    A meta analysis of steroid withdrawal studies1

    A Meta-Analysis of steroid withdrawal studies


    Iii slides5

    III. Slides

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides

    • Always write like a poet - think key words

    • Always use animation to simplify

    • Always use colours to simplify

    • Always use the full area of the slide


    Demographics of old organ donors

    Demographics of old Organ Donors


    Demographics of old organ donors1

    Demographics of Old Organ Donors


    Presentation techniques some personal advice4

    Presentation techniquesSome personal advice

    • I. Performance

    • II. Manuscript

    • III. Slides


    I performance4

    I. Performance

    • Never turn your back on the audience

    • Always look at the audience

    • Never use the laser pointer

    • Always use your slides to make your point

    • Always time your performance at home

    • Always prepare your opening sentences


    I performance5

    I. Performance

    • Never turn your back on the audience

    • Always look at the audience

    • Never use the laser pointer

    • Always use your slides to make your point

    • Always time your performance at home

    • Always prepare your opening sentences


    Ii manuscript8

    II. Manuscript

    • Never read a manuscript

    • Always use your slides as the manuscript

    • Always describe your slide immediately

    • Always send on one channel at the time

    • Always use a strategy


    Ii manuscript9

    II. Manuscript

    • Never read a manuscript

    • Always use your slides as the manuscript

    • Always describe your slide immediately

    • Always send on one channel at the time

    • Always use a strategy


    Iii slides6

    III. Slides

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides

    • Always write like a poet - think key words

    • Always use animation to simplify

    • Always use colours to simplify

    • Always use the full area of the slide


    Iii slides7

    III. Slides

    • Never apologize for a busy slide

    • Never say ’as you can see’

    • Always use simple slides

    • Always write like a poet - think key words

    • Always use animation to simplify

    • Always use colours to simplify

    • Always use the full area of the slide


    Causes of graft loss over 10 years in csa treated patients

    Always be yourself

    - take advantage

    of your personal talents

    Enjoy!


    Causes of graft loss over 10 years in csa treated patients

    Thank you

    for your attention


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