Presentation is loading. Please wait.

Presentation is loading. Please wait.

Management of disease recurrence after renal transplantation

Similar presentations

Presentation on theme: "Management of disease recurrence after renal transplantation"— Presentation transcript:

1 Management of disease recurrence after renal transplantation
Patrick Niaudet Néphrologie Pédiatrique Centre de référence des maladies rénales génétiques Hôpital Necker-Enfants Malades, Paris ESPN, September 2008

2 Recurrence of primary disease
Recurrence frequency Graft loss SRNS with FSGS 30% 40-50% MPGN Type I 20-30% 30-40% Type II 80-100% 20% Membranous nephropathy 10% 40% IgA nephropathy 15-30% SHP nephritis <1% Systemic vasculitis 10-20% <5% SLE < 2% rare Anti-GBM disease < 5% 50% D+HUS exceptionnal Atypical HUS 30-50% >50% Amyloidosis 25 % Primary hyperoxaluria 100% 80%

3 Recurrence of nephrotic syndrome after renal transplantation
Occurs in about 30% of patients with SRNS and FSGS Extremely low rate of recurrence in genetic forms of the disease Proteinuria is most often of rapid onset

4 Recurrence of nephrotic syndrome after renal transplantation
Risk factors for recurrence : duration of disease shorter than 3 years disease starting after the age of 6 years diffuse mesangial proliferation on initial biopsy recurrence on a previous graft Graft failure occurs in 60% of patients with recurrence CsA does not prevent recurrence but improves graft survival

5 Recurrence of nephrotic syndrome according to the age at onset of disease
% with recurrence age > 6 years 54 age < 6 years 22 (p < 0.01) age < 3 years (n=41) 7 age < 1 year (n=15) Enfants Malades

6 Removal of circulating factor lowers protein excretion in recurrent NS
h a n g e 1 Pu P r o t e i n a b s o r p t i o n 8 6 4 2 Prett Tt Day 7 Day 15 Dantal et al, NEJM 1994, 330: 7

7 Prophylactic plasma exchanges
Recurrence in 4 of 6 pts in the non prophylactic group Recurrence in 5 of 15 pts in the prophylactic group 7 recurrent pts received PE with remission in 6 (Ohta et al, Transplantation, 2001)

8 Plasma exchanges plus cyclophosphamide
Dall’Amico et al (AJKD, 1999) Sucessfull in 9 of 11 children Persistent remission in 7 with a follow-up of 32 months Cheong et al (NDT, 2000) Complete remission in 3/6 Partial remission in 3/6

9 Rituximab failed to improve nephrotic syndrome in four adult renal transplant patients with early recurrent FSGS refractory or dependent on plasmapheresis Yabu JM et al AJT 2008; 8: 222-7

10 Intravenous CsA for recurrent nephrotic syndrome after RT
Between March 1991 and July 2007, recurrence has occurred in 22 grafts in 21 children CsA was immediately administered IV, at an initial dose of 3 mg/kg/d and the dose was adjusted in order to maintain whole blood levels above 250 ng/ml Plasma exchanges, 2 to 10 sessions, in 9 patients Enfants Malades

11 Intravenous CsA for recurrent nephrotic syndrome after RT
One pt with delayed recurrence (day 18) did not respond to IV CsA + PE Among the 21 early recurrences (within the first week) : 1 pt did not respond to IV CsA + PE 3 pts showed partial remission (proteinuria without nephrotic syndrome) after IV CsA + ACEI 17 pts (77%) entered into complete remission within 20 days (D12 to D40) with CsA alone in 11 cases with CsA + PE in 7 cases 11 of the 17 pts are still in CR 1 to 14 years later

12 Recurrence of NS after RT
Seems to be mediated by a circulating 50-kD plasma protein, which is bound to Ig Identification of the protein ? Clinical usefullness of the presence of the « permeability » factor ? Living donor or cadaveric donor ? Best therapy Plasma exchanges ± cyclophosphamide IV cyclosporine ± plasma exchanges Others ?

13 Atypical HUS Mutations in genes of the complement pathway (50%)
Anti-CFH antibodies Von Willebrand factor cleaving protease deficiency (ADAMTS13 gene mutation) Defects of vitamine B12 metabolism Idiopathic autosomal recessive disease Idiopathic autosomal dominant disease

14 Atypical HUS : French Pediatric Registry
Mutation CFH IF MCP No N (46) 10 (22%) 6 (13%) 7 (15%) 22 (48%) Outcome Death 2 1 ESRD 6 (Sellier-Leclerc et al, JASN 2007)

15 Atypical HUS : posttransplant course
24 grafts in 15 patients 12 graft failures during the first year (50%) 8 from thrombosis 3 from recurrence 1 from CMV 4 graft failures later (recurrence in 2, rejection in 2) 2 functioning grafts at 2yr despite recurrence 6 grafts with good outcome 5 to 15 yr later (Sellier-Leclerc, JASN 2007)

16 Atypical HUS : recurrence after RT
Mutation CFH IF MCP No Nb pts 34 8 10 20 Recurrence 76% 88% 20% 30% Graft loss (from recurrence at 1yr) 81% 100% 1/2 83% Richards 2003 ; Fremeaux-Bacchi 2004, 2006, 2007 ; Kavanagh 2005 ; Bresin 2005 ; Caprioli 2006 ; Heinen 2006 ; Venables 2006 ; Nilsson 2007 ; Geelen 2007 ; Sellier-Leclerc 2007

17 Possible therapy FFP ± PE Eculizumab (monoclonal antibody)
Binds to C5, inhibiting its clivage to C5a and C5b Prevents the release of C5a and the formation of C5b-C9 Reduces transfusion requirements in paroxysmal noctural hemoglobinuria (lack of GPI-linked-proteins that protect cells from complement-mediated attack)

18 Atypical HUS with CFH mutation : results of liver transplantation
Initial experience with combined L+K (2) or L (1) but no plasma therapy : 2 deaths and 1 with neurological sequellae (Remuzzi, Cheong) Combined L+K with extensive plasma therapy : children with excellent outcome and no recurrence (Saland, Jalanko) PE with FFP before surgery FFP ± PE during surgery Anticoagulation after surgery

19 Consensus Conference (Bergame, Dec 2007) Indications for combined liver-renal or isolated liver transplantation CFH mutation First graft lost from recurrence Another family member with the same mutation and who lost a graft from recurrence Patient with a mutation reported to be associated with graft loss from recurrence Not enough data for HUS associated with other complement mutations

20 Conservative treatment of primary hyperoxaluria
High fluid intake over 24h : 3l/m2 Solubilization of calcium oxalate : potassium citrate AGT coenzyme : Pyridoxine [G170R] Avoid surgical removal of calculs Low oxalate diet Oxalobacter formigenes (OxabactTM : 2 x 107 UFC/d) : ongoing trial

21 Evolution of GFR in children with PH1 under conservative treatment
200 180 160 140 120 100 GFR (Schwartz formula) mL/mn/1.73m2 80 GFR at initiation : 92 ml/mn At last examination Stable GFR 19/27pts Decreased GFR 8/27pts ESRF 4/27pts 60 40 20 24 48 72 96 120 144 168 192 216 240 time (months) (Société de Néphrologie Pédiatrique)

22 Extra renal complications in PH1
Oxalate accumulates in tissues when plasma oxalate reaches 50mol/l 4 to 8 mmol of oxalate are produced every day bone disease retinal deposits with amblyopia conduction system abnormalities cardiomyopathy artery calcifications and ischemia livedo reticularis , gangrene polyneuritis

23 Transplantation strategy (P. Cochat)
Liver + kidney Liver then kidney Kidney Liver Infantile (ESRF<2yr) Second choice First choice X GFR to 60 mL/min ? GFR to 40 mL/min ? If Vit B is active and G170R mutation GFR<20 mL/min

24 Management of primary hyperoxaluria
The best treatment of oxalosis is conservative and preventive when possible A careful protocol must be applied and maintained for preventing recurrence on the graft The most important point is to maintain high urine output after renal transplantation (low oxalate concentration) Dialysis is indicated only in case of oliguria

25 24 h Oxaluria in 3 children after liver/ kidney transplantation
µmol/ day 250 500 750 1000 1250 1500 1750 2000 2000 1500 1000 500 Days post grafting

26 Evolution of extra renal complications after liver-kidney transplantation
Bone disease improves very slowly but complete healing was reported after several years Toussaint et al Am J Kidney Dis Conduction system abnormalities and cardiomyopathy may rapidly be reversed after some weeks Rodby et al. Am J Med Fyfe et al. Am J Cardiol

27 Conclusion Recurrent disease in a renal transplant remains an important cause of chronic allograft dysfunction and graft failure Patients and their families should be informed of the recurrence risk, potential therapeutic options and prognosis The indication of retransplantation when a primary graft has been lost to recurrence is a difficult issue

Download ppt "Management of disease recurrence after renal transplantation"

Similar presentations

Ads by Google