Causes of Graft Loss over 10 Years in CsA-Treated Patients Recurrent disease 6% Vascular 8% PNF 5% Acute Rejection 11% Other 3% CAN 40% Death 27% Marcén R et al. Transplantation 2001; 72:57  62.

Presentation techniques Some personal advice I. Performance II. Manuscript III. Slides

Presentation techniques Some personal advice I. Performance II. Manuscript III. Slides

I. Performance Never turn your back on the audience Always look at the audience (and the laptop)

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 Patients Recurrent disease 6% Vascular 8% PNF 5% Acute Rejection 11% Other 3% CAN 40% Death 27% Marcén R et al. Transplantation 2001; 72:57  62.

Causes of Graft Loss over 10 Years in CsA-Treated Patients Recurrent disease 6% Vascular 8% PNF 5% Acute Rejection 11% Other 3% CAN 40% Death 27% Marcén R et al. Transplantation 2001; 72: CVD CNI- nephrotox

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 Drugs ComplicationCsATacSterMMFSRLDZB/ BAS Nephrotoxicity Hypertension Hyperlipidaemia+?+-+- Diabetes Haematologic toxicity---++-

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 Drugs ComplicationCsATacSterMMFSRLDZB/ BAS Nephrotoxicity Hypertension Hyperlipidaemia+?+-+- Diabetes Haematologic toxicity---++-

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 Drugs ComplicationCsATacSterMMFSRLDZB/ BAS Nephrotoxicity Hypertension Hyperlipidaemia+?+-+- Diabetes Haematologic toxicity---++-

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 Drugs ComplicationCsATacSterMMFSRLDZB/ BAS Nephrotoxicity Hypertension Hyperlipidaemia+?+-+- Diabetes Haematologic toxicity---++-

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 Drugs ComplicationCsATacSterMMFSRLDZB/ BAS Nephrotoxicity Hypertension Hyperlipidaemia+?+-+- Diabetes Haematologic toxicity---++-

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 Ekberg H et al. Transplant Int 2000; 13:151–9. Daclizumab (n=267) 74 events Placebo (n=268) 116 events Time after transplantation (days) Probability p = (stratified logrank test)

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 Ekberg H et al. Transplant Int 2000; 13:151–9. Daclizumab (n=267) 74 events Placebo (n=268) 116 events Time after transplantation (days) Probability p = (stratified logrank test)

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 minutes sharp

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 You will always be nervous: Sit in the front - look back Prepare your opening sentence - the rest will come by itself

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 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 advice I. Performance II. Manuscript III. Slides

II. Manuscript Never read a manuscript of your talk Always use your slides as the manuscript

SYMPHONY Study Design Tx 6 mo 12 mo Daclizumab Low dose CsA MMF Steroids B 50–100 ng/ml Low dose SRL D MMF Steroids Daclizumab 4-8 ng/ml Low dose TAC MMF Steroids Daclizumab 3-7 ng/ml C ng/ml for 3 months ng/ml thereafter Normal dose CsA MMF Steroids A Ekberg H et al Am J Transpl 2006, 6 (suppl 2), #49; 83.

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. Manuscript Never read a manuscript Always use your slides as the manuscript Always describe your slide immediately

months post-Tx GFR (Cockcroft Gault) (ml/min) Calculated GFR (Cockcroft  Gault) p< p= p< Normal-dose CsA Low-dose CsA Low-dose TAC Low-dose SRL Ekberg H et al Am J Transpl 2006, 6 (suppl 2), #49; 83.

Prevalence (%) Time after transplantation (years) Acute rejection SCR (acute) SCR (borderline) Prevalence SCR 1 mo61 % 3 mo46 % 1 yr26 % Nankivell BJ et al. N Engl J Med 2003; 349:2326  33. High Prevalence of Subclinical Rejection (SCR)

II. Manuscript Never read a manuscript Always use your slides as the manuscript Always describe your slide immediately Never start with comments

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

months post-Tx GFR (Cockcroft  Gault) (ml/min) Calculated GFR (Cockcroft  Gault) p< p= p< Normal-dose CsA Low-dose CsA Low-dose TAC Low-dose SRL No significant difference between CsA and Low-CsA Ekberg H et al Am J Transpl 2006, 6 (suppl 2), #49; 83.

Prevalence (%) Time after transplantation (years) Acute rejection SCR (acute) SCR (borderline) Prevalence SCR 1 mo61 % 3 mo46 % 1 yr26 % Nankivell BJ et al. N Engl J Med 2003; 349:2326  33. High Prevalence of Subclinical Rejection (SCR)

High risk for AR after CNI w/d Lower risk Prevalence (%) Time after transplantation (years) Acute rejection SCR (acute) SCR (borderline) Prevalence SCR 1 mo61 % 3 mo46 % 1 yr26 % Nankivell BJ et al. N Engl J Med 2003; 349: High Prevalence of Subclinical Rejection (SCR)

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 listen to you at the same time - > Competition

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

Methods Acute Rejection Biopsy-proven Treated patients Within 6 mo. Excluding Borderline

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 First, say what you are going to tell us Then tell us Finally, say what you have told us This is a study that shows the benefit of steroid withdrawal … the study… In conclusion, this study has shown the benefit of steroid withdrawal.

Chapters Divide your talk into chapters 1. Background 2. Aim 3. Method 4. Results 5. Conclusion

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 slides = 7 minutes

Presentation techniques Some personal advice I. Performance II. Manuscript III. Slides

Never apologize for a busy slide - discard it! Never say ’as you can see’ -it means nobody can see!

Table 2. Multivariate Risk Estimates for Endpoint of Overall Graft Loss* Variable* [Reference Group] Hazard Estimate95% Confidence IntervalP Value Cyclosporine [Tacrolimus] 0.979(0.861, 1.112).7428 MMF [No antiproliferative medication] 0.794(0.661, 0.953).0133 Cold Ischemia time >37 hours [Ischemia time <12 hours] 1.451(1.034, 2.036).0315 PRA level >30 [PRA level = 0] 1.337(1.110, 1.610) HLA-A mismatch [0 HLA-A mismatches] 1.382(1.106, 1.727) HLA-A mismatches [0 HLA-A mismatches] 1.506(1.202, 1.887) HLA-DR mismatches [0 HLA-DR mismatches] 1.359(1.123, 1.645).0017 Recipient African American [Recipient Caucasian] 1.403(1.212, 1.625)<.0001 Recipient age [Recipient age 18-35] 1.503(1.214, 1.860).0002 Recipient age 65+ [Recipient age 18-35] 1.702(1.330, 2.177)<.0001 Primary recipient diagnosis: polycystic kidneys [Glomerular diseases] 0.514(0.375, 0.704)<.0001 Primary recipient diagnosis: diabetes [Glomerular diseases] 1.308(1.073, 1.593).0078 *Table displays main variable of interest and significant (α <.05) covariates in the model. This is actually a slide that was used in a congress

Multivariate risk estimates for graft loss Variable [Reference Group] Hazard Estimate 95% Confidence Interval P Value CsA [vs Tac] 0.979(0.861, 1.112).7428 MMF [vs None] 0.794(0.661, 0.953).0133 CIT >37 hours [vs <12 hours] 1.451(1.034, 2.036).0315 PRA level >30 [vs PRA level = 0] 1.337(1.110, 1.610) HLA-A MM [vs 0 HLA-A MM] 1.382(1.106, 1.727) HLA-A MM [vs 0 HLA-A MM] 1.506(1.202, 1.887) HLA-DR MM [vs 0 HLA-DR MM] 1.359(1.123, 1.645).0017 Somebody et al ATC 2004

Multivariate risk estimates for graft loss Variable [Reference Group] Hazard Estimate 95% Confidence Interval P Value CsA [vs Tac] 0.979(0.861, 1.112).7428 MMF [vs None] 0.794(0.661, 0.953).0133 CIT >37 hours [vs <12 hours] 1.451(1.034, 2.036).0315 PRA level >30 [vs PRA level = 0] 1.337(1.110, 1.610) HLA-A MM [vs 0 HLA-A MM] 1.382(1.106, 1.727) HLA-A MM [vs 0 HLA-A MM] 1.506(1.202, 1.887) HLA-DR MM [vs 0 HLA-DR MM] 1.359(1.123, 1.645).0017 Somebody et al ATC 2004

Multivariate risk estimates for graft loss Variable [Reference Group] Hazard Estimate 95% Confidence Interval P Value CsA [vs Tac] 0.979(0.861, 1.112).7428 MMF [vs None] 0.794(0.661, 0.953).0133 CIT >37 hours [vs <12 hours] 1.451(1.034, 2.036).0315 PRA level >30 [vs PRA level = 0] 1.337(1.110, 1.610) HLA-A MM [vs 0 HLA-A MM] 1.382(1.106, 1.727) HLA-A MM [vs 0 HLA-A MM] 1.506(1.202, 1.887) HLA-DR MM [vs 0 HLA-DR MM] 1.359(1.123, 1.645).0017 Somebody et al ATC 2004

Multivariate risk estimates for graft loss Variable [Reference Group] Hazard Estimate 95% Confidence Interval P Value CsA [vs Tac] 0.979(0.861, 1.112).7428 MMF [vs None] 0.794(0.661, 0.953).0133 CIT >37 hours [vs <12 hours] 1.451(1.034, 2.036).0315 PRA level >30 [vs PRA level = 0] 1.337(1.110, 1.610) HLA-A MM [vs 0 HLA-A MM] 1.382(1.106, 1.727) HLA-A MM [vs 0 HLA-A MM] 1.506(1.202, 1.887) HLA-DR MM [vs 0 HLA-DR MM] 1.359(1.123, 1.645).0017 Somebody et al ATC 2004

Multivariate risk estimates for graft loss Variable [Reference Group] Hazard Estimate 95% Confidence Interval P Value CsA [vs Tac] 0.979(0.861, 1.112).7428 MMF [vs None] 0.794(0.661, 0.953).0133 CIT >37 hours [vs <12 hours] 1.451(1.034, 2.036).0315 PRA level >30 [vs PRA level = 0] 1.337(1.110, 1.610) HLA-A MM [vs 0 HLA-A MM] 1.382(1.106, 1.727) HLA-A MM [vs 0 HLA-A MM] 1.506(1.202, 1.887) HLA-DR MM [vs 0 HLA-DR MM] 1.359(1.123, 1.645).0017 Somebody et al ATC 2004

CyclosporineTacrolimus Follow-Up Period Standard Deviation Mean 6 mo yr yr yr yr yr Kaplan and Meier-Kriesche ATC 2004 Creatinine levels in posttransplant periods by CNI

CyclosporineTacrolimus Follow-Up Period Standard Deviation Mean 6 mo yr yr yr yr yr Kaplan and Meier-Kriesche ATC 2004 Creatinine levels in posttransplant periods by CNI

CyclosporineTacrolimus Follow-Up Period Standard Deviation Mean 6 mo yr yr yr yr yr Kaplan and Meier-Kriesche ATC 2004 Creatinine levels in posttransplant periods by CNI

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 (BPAR) Cumulative incidence of first BPAR Pooled analysis of 12-month data from two pivotal trials Ekberg H et al. Transplant Int 2000; 13:151–9. Daclizumab (n=267) 74 events Placebo (n=268) 116 events Time after transplantation (days) Probability p = (stratified logrank test)

Daclizumab Prevents Acute Rejection Pooled analysis at 12-mo. from two pivotal trials Ekberg H et al. Transplant Int 2000; 13:151–9. Daclizumab (n=267) Placebo (n=268) Time after tx (days) Probability p =

III. Slides Never apologize for a busy slide Never say ’as you can see’ Always use simple slides Think about key words

Conclusion Kaplan and Meier-Kriesche ATC 2004 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.

Conclusion Kaplan and Meier-Kriesche ATC 2004 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.

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

Conclusion Kaplan and Meier-Kriesche ATC 2004 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. Not good

Conclusion Kaplan and Meier-Kriesche ATC 2004 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.

Conclusion Kaplan and Meier-Kriesche ATC 2004 For both LD transplants and CD paired kidneys, there was no difference in 5-year graft or 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.

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 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 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 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. 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 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: 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 Interstitial fibrosis and CAN translates into differences in GFR and graft survival: Baboolal K, et al. Kidney Int 2002;61:686–96 GFR 12 mo.24 mo. CsA5348 Tacrolimus66 P-value0.05

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 GFRGraft survival 12 mo.24 mo.12 mo.24 mo. CsA534892%88% Tacrolimus66 100%96% P-value0.05

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 GFRGraft survival 12 mo.24 mo.12 mo.24 mo. CsA534892%88% Tacrolimus66 100%96% P-value0.05 Colours to simplify

A Meta-Analysis of steroid withdrawal trials Kasiske et al, JASN 2000 Acute rejection (9 studies, n=1461)  %95% CIp _________________________________________ AR after SRW  17 <0.001 _________________________________________ Graft survival (9 studies, n=1899) RR95%CI _________________________________________ RR graft failure  1.67<0.012 _________________________________________

A Meta-Analysis of steroid withdrawal studies Acute Rejection (9 studies; n=1,461) %% 95% CIp Acute Rej14 10  17 <0.001

A Meta-Analysis of steroid withdrawal studies Acute Rejection (9 studies; n=1,461) %% 95% CIp Acute Rej14 10  17 <0.001 Graft Survival (9 studies, n=1,899) RR95% CIp Graft Loss  1.67 <0.012

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

Presentation techniques Some personal advice I. Performance II. Manuscript III. Slides

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. 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. 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. 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. 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. 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

Always be yourself - take advantage of your personal talents Enjoy!

Thank you for your attention