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Do we still need corticosteroids for maintenance immunosuppression after renal transplantation ? Luca Dello Strologo Bambino Gesù Childrens Hospital Institute.

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Presentation on theme: "Do we still need corticosteroids for maintenance immunosuppression after renal transplantation ? Luca Dello Strologo Bambino Gesù Childrens Hospital Institute."— Presentation transcript:

1 Do we still need corticosteroids for maintenance immunosuppression after renal transplantation ? Luca Dello Strologo Bambino Gesù Childrens Hospital Institute for Scientific Research Rome Italy

2 Steroids side effects Growth impairment Growth impairment Fluid and electrolyte abnormalities Fluid and electrolyte abnormalities Hypertension Hypertension Hyperglycemia Hyperglycemia Increased susceptibility to infection Increased susceptibility to infection Osteoporosis Osteoporosis Myopathy Myopathy Behavioural disturbances Behavioural disturbances Cataracts Cataracts Possible risk of peptic ulcers Possible risk of peptic ulcers Characteristic habitus including Characteristic habitus including fat redistribution fat redistribution striae striae ecchymoses ecchymoses acne acne hirsutism hirsutism

3 CNI side effects TACCsA Nephrotoxicity+++++ Neurotoxicity+++ Diabetes+++ Hypertension+++++ Hyperlipidemia±++

4 CNI: Minor side effects Side Effect CsA(%)TAC(%) Acne103 CsA > TAC Alopecia CsA < TAC Anaemia CsA = TAC GUM Hyperplasia CsA > TAC Hirsutism Pruritus CsA < TAC Tremor Drugs :

5 Which poison is worse?

6 Steroids side effects Growth impairment Growth impairment Fluid and electrolyte abnormalities Fluid and electrolyte abnormalities Hypertension Hypertension Hyperglycemia Hyperglycemia Increases susceptibility to infection Increases susceptibility to infection Osteoporosis Osteoporosis Myopathy Myopathy Behavioural disturbances Behavioural disturbances Cataracts Cataracts Possible risk of peptic ulcers Possible risk of peptic ulcers Characteristic habitus including Characteristic habitus including fat redistribution fat redistribution striae striae ecchymoses ecchymoses acne acne hirsutism hirsutism

7 tp 153 tp 38 pts older than pts older than with syndromes associated with poor growth (cystinosis, Laurence Moon Biedl, other genetic syndromes, etc.) 23 with syndromes associated with poor growth (cystinosis, Laurence Moon Biedl, other genetic syndromes, etc.)

8 ,0 -1,9 -1,8 -1,7 -1,6 -1,5 -1,4 -1,3 -1,2 -1,1 -1,0 -0,9 SDS for Height post-transplant follow up, months

9 ,0 -1,9 -1,8 -1,7 -1,6 -1,5 -1,4 -1,3 -1,2 -1,1 -1,0 -0,9 Height SDS Time post-transplant (months) n:51 n:42

10 ,5 -3,0 -2,5 -2,0 -1,5 -1,0 -0,5 0,0 0,5 HSDS months, post transplantation < 7 years of age at transplant > 7 years of age at transplant

11 age at transplantation period of transplantation p: n.s.

12 Height SDS Time post-transplant (months) Patients < 7 years of age at tp

13 ,6 -2,4 -2,2 -2,0 -1,8 -1,6 -1,4 -1,2 -1,0 -0, Height SDS Time post-transplant (months) Patients > 7 years of age at tp

14 P<0.001 P: Post transplant years Time to alternate day steroids

15 % post-transplant follow up, days ALG + azathioprine basiliximab + MMF Rejection free rate N: 75 N: 45

16

17 Am J Transplant 2008; 8: 574–585

18 Am J Transpl 2008; 8: 307–316 Rejection treatment: 500 – 1000 mg ev for three days

19 Long term outcome without steroids 1992: significant worse outcome 5 year after withdrawal 1992: significant worse outcome 5 year after withdrawal (Sinclair Can Med Assoc J:147(5) ) 2005: outcome comparable to historical cohort (different drugs!) 2005: outcome comparable to historical cohort (different drugs!) (Matas Am J transplant 5:2473-8)

20 osteopenia Similar bone density 3 months after transplantation (low dosage steroid vs no steroid) (Transpl int :82-7) Similar bone density 3 months after transplantation (low dosage steroid vs no steroid) (Transpl int :82-7) Very mild benefit on the lumbar spine after one year (Transplantation ) Very mild benefit on the lumbar spine after one year (Transplantation )

21 CNI nephrotoxicity

22 ml/min/1.73 m 2 follow up, months Dello Strologo et al Pediatr Nephrol :561-5 Renal function in CsA treated heart transplanted children

23 CNI minimization protocols pts MMF + steroids and stop or reduce CsA or TAC (Weir: Am J Nephrol. ;24 :379-86) pts MMF + steroids and stop or reduce CsA or TAC (Weir: Am J Nephrol. ;24 :379-86) 2004: 110 pts CsA + Everolimus + steroids (Nashan Transplantation Nov 15;78(9): ) 2004: 110 pts CsA + Everolimus + steroids (Nashan Transplantation Nov 15;78(9): ) 2007: 1645 pts: MMF + steroids and low dose CsA/TAC or sirolimus (Ekberg New Engl J Med 357: ) 2007: 1645 pts: MMF + steroids and low dose CsA/TAC or sirolimus (Ekberg New Engl J Med 357: ) 2007: 536 pts: MMF + steroids + CsA minimization (Ekberg Am J Transpl 7: 560–570) 2007: 536 pts: MMF + steroids + CsA minimization (Ekberg Am J Transpl 7: 560–570) 2008: 19 children everolimus + CsA +steroids (Ettenger Pediatr Transplantation 12: 456– : 19 children everolimus + CsA +steroids (Ettenger Pediatr Transplantation 12: 456–463

24 nephrotoxicity Animal models suggest prednisone may protect from CNI-induced nephrotoxicity (Exp. Nephrol :61-8) Animal models suggest prednisone may protect from CNI-induced nephrotoxicity (Exp. Nephrol :61-8) A randomized study in humans showed a lower incidence of CNI-induced nephrotoxicity in patients on steroid maintenance (n:34) vs patients with early steroid withdrawal (n:35) (Surgery :364-71) A randomized study in humans showed a lower incidence of CNI-induced nephrotoxicity in patients on steroid maintenance (n:34) vs patients with early steroid withdrawal (n:35) (Surgery :364-71)

25 nephrotoxicity CNI + MMF CNI + MMF PSI + low dose (or without) CNI + steroid PSI + low dose (or without) CNI + steroid Which kidney will last longer? Which kidney will last longer?

26 summary IS is needed to protect the graft IS is needed to protect the graft All IS drugs have side effects All IS drugs have side effects Steroids provide a low rejection rate even when used to a low dose Steroids provide a low rejection rate even when used to a low dose Rejections are treated with high dosages of steroids Rejections are treated with high dosages of steroids Steroids are used in a wide range of diseases and we have learned to manage their toxicity. Steroids are used in a wide range of diseases and we have learned to manage their toxicity.

27 conclusions We should aim at a steroid-free IS in the future We should aim at a steroid-free IS in the future Currently, low doses of steroids on alternate day are effective and have limited side effects. Currently, low doses of steroids on alternate day are effective and have limited side effects. Steroids allow to minimize the dosages of the other immunosuppressive drugs Steroids allow to minimize the dosages of the other immunosuppressive drugs


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