9-1. kidney transplantation in children. pierre cochat (eng)
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Kidney transplantation in children
[email protected] de référence des maladies rénales raresUniversité de Lyon
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The very first kidney transplantation in humans has been performed in
A. Mumbai, India, 1915B. Chicago, USA, 1912C. Moskow, Russia, 1909D. Lyon, France, 1906E. London, UK, 1903
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Pig-to-man kidney transplantation…Vascular anastomosis to the humeral vessels!
Jaboulay Lyon Medical 1906
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The first kidney transplantation in humans has been performed in
A. Mumbai, India, 1915B. Chicago, USA, 1912C. Moskow, Russia, 1909D. Lyon, France, 1906E. London, UK, 1903
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What is the lower age limit for kidney Tx?
A. BirthB. 6 monthsC. 1 yearD. 2 yearsE. 3 years
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Indication for kidney transplantation
Children with irreversible renal failure
Minimal age: 6 to 12 mos Minimal BW: 5 to 10 kg
Relative contraindications ABO incompatibility Malignancy within the previous 12 months Active viral infection: HIV, VHB, VHC Active systemic disease: HUS, SLE, RPGN, vasculites, etc. Multiorgan failure, severe brain damage, etc.
According to localexperience & guidelines
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Age Premature baby – Birth – 6 mos – 12 mos – 18 mos – 2 yrs
PD
HD
Tx
Options according to age at start of RRT
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Peritoneal dialysis1000 g
Transplantation6 mos – 5.4 kg
Hemodialysis5 mos – 4.8 kg
RRT options1st yr of life
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NAPRTCS 2010
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What is the lower age limit for kidney Tx?
A. BirthB. 6 monthsC. 1 yearD. 2 yearsE. 3 years
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What is the part of pediatrics among all kidney Tx?
A. 1%B. 2.5%C. 5%D. 7.5%E. 10%
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Kidney transplantation activity in Europe Cochat Comprehensive Pediatric Nephrology 2008
Country Total Nb of Tx Tx in children (%)
Croatia 109 4 (3.66%)
Czech Republic 427 15 (3.51%)
France 2423 81 (3.34%)
Germany 2478 117 (4.72%)
Israel 94 21 (22.3%)
Italy 1746 58 (3.32%)
Lithuania 63 2 (3.17%)
Netherlands 420 14 (3.33%)
Norway 256 9 (3.51%)
Poland 1067 38 (3.56%)
Spain 2057 68 (3.31%)
Sweden 372 13 (3.49%)
Turkey 665 59 (8.87%)
UK 1516 128 (8.44%)
Serbia 67 3 (4.47%)
Average % Tx in
children
4.5 %
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What is the part of pediatrics among all kidney Tx?
A. 1%B. 2.5%C. 5%D. 7.5%E. 10%
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What is the main cause of ESRD in children < 5 yrs?
A. CAKUTB. Steroid resistant nephrotic syndromeC. Inherited renal diseasesD. Hemolytic uremic syndromeE. Chronic pyelonephritis
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Wühl Clin J Am Soc Nephrol 2013
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What is the main cause of ESRD in children < 5 yrs?
A. CAKUTB. Steroid resistant nephrotic syndromeC. Inherited renal diseasesD. Hemolytic uremic syndromeE. Chronic pyelonephritis
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What are the 2 critically important outcomes in kidney Tx?
A. Patient survivalB. Blood pressureC. Graft survivalD. Acute rejectionE. Graft function
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ERA-EDTA ERBP in press H
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What are the 2 critically important outcomes in kidney Tx?
A. Patient survivalB. Blood pressureC. Graft survivalD. Acute rejectionE. Graft function
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Preemptive kidney Tx
A. Is used for an average 25% of the pediatric populationB. Is associated with a greater risk of nonadherenceC. Can be proposed irrespective of the primary diseaseD. Provides the same survival than in dialysis childrenE. Relies on local facilities
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% Preemptive Tx in EuropeCochat Comprehensive Pediatric Nephrology 2008
0 10 20 30 40 50
SerbiaIsrael
Czech RepTurkey
Germany FranceCroatia
SpainUK
USANetherlands
NorwaySweden
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Transplant characteristics in USA NAPRTCS 2007
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The best option for RRT in children is preemptive TxDialysis should be limited to those children who cannot benefit from preemptive Tx
Advantages Avoids dialysis (school attendance, social and family life) Avoids vascular/peritoneal access Better results than non-preemptive Tx Cost effectiveness
Drawbacks Timing for putting the patient on the waiting list? Increased risk of non-adherence?
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Preemptive kidney Tx
A. Involves an average 25% of the pediatric populationB. Is associated with a greater risk of nonadherenceC. Can be proposed irrespective of the primary diseaseD. Provides the same survival than in dialysis childrenE. Relies on local facilities
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In Europe, the average rate of living donation for children is
A. 15%B. 20%C. 25%D. 30%E. 40%
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% Living (related) donors in pediatric kidney TxCochat Comprehensive Pediatric Nephrology 2008
0
20
40
60
80
100
Czech
Rep
Spain
Poland
Israe
l
France
German
y
Croati
a UK
Nether
lands
USA
Switzerl
and
Turke
ySerb
ia
Scand
inavia
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In Europe, the rate of living donation for children is
A. 15%B. 20%C. 25%D. 30%E. 40%
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In the post-operative period after cadaver Tx,
A. The use of 20% mannitol is recommendedB. The use of dopamine at ‘renal’ dose enhances diuresisC. Urinary bladder catheter can be removed after 3 daysD. IV wide-spectrum antibiotics should be given for 1 weekE. A 2-week strict isolation period is mandatory
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ERA-EDTA ERBP in press H
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In the post-operative period after cadaver Tx,
A. The use of 20% mannitol is recommendedB. The use of dopamine at ‘renal’ dose enhances diuresisC. Urinary bladder catheter can be removed after 3 daysD. Antibiotic prophylaxis should be given for 1 weekE. A 2-week strict isolation period is mandatory
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The current rate of acute rejection in kidney Tx is:
A. 3%B. 13%C. 23%D. 33%E. 43%
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The issue of AREH
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NAPRTCS 2010
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The current rate of acute rejection in kidney Tx is:
A. 3%B. 13%C. 23%D. 33%E. 43%
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In children, the main cause of graft failure is:
A. Vascular thrombosisB. Recurrence of the primary diseaseC. Acute rejectionD. Chronic rejectionE. PTLD
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NAPRTCS 2007
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In children, the main cause of graft failure is:
A. Vascular thrombosisB. Recurrence of the primary diseaseC. Acute rejectionD. Chronic rejection (high rate of non-adherence)E. PTLD
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In children, the risk of metabolic syndrome at 1 yr post-Tx is:
A. 5 to 10%B. 15 to 20%C. 25 to 30%D. 35 to 40%E. 45 to 50%
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Metabolic syndrome in children after renal Tx
Reversal of metabolic abnormalities depends on post-Tx GFR But immunosuppressive drugs cause metabolic abnormalities
Atherosclerotic dyslipidemia Insulin resistance Risk of new-onset diabetes after Tx
Prevalence in children 1 year post-Tx: 35 to 40% (mostly de novo) Major role of glucocorticoids Falls to 5% in the absence of steroids
Greater risk of Lower graft survival Lower GFR Left ventricular hypertrophy
Litwin Pediatr Nephrol 2013
Hos
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Cla
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1
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In children, the risk of metabolic syndrome at 1 yr post-Tx is:
A. 5 to 10%B. 15 to 20%C. 25 to 30%D. 35 to 40% with steroid-based immunsuppressionE. 45 to 50%
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In children, the risk of metabolic syndrome at 1 yr post-Tx is:
A. 5 to 10% without corticosteroidsB. 15 to 20%C. 25 to 30%D. 35 to 40%E. 45 to 50%
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Antibody-mediated rejection
A. Is associated with serum donor-specific antibodiesB. Can be treated by high-dose methylprednisoloneC. Involves complement activation and endothelial injuryD. Is characterized by peritubular capillary C4d staining E. Has better outcomes than cellular acute rejection
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Humoral [antibody-mediated] rejection
Diagnosis Circulating anti-HLA Ab Protocol biopsy (C4d) Graft dysfunction
Post Tx anti-HLA antibodies DSA, donor specific antibodies
Blood transfusion Pregnancy Retransplantation
DR matching
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Pathology
Pericapillary inflammation C4d+ on peritubular capillaries
Courtesy Dr F Dijoud Lyon 2011
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Impact of donor-specific anti-HLA antibodiesH
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Loupy Nat Rev Nephrol 2012; Everly Transplantation 2013
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Antibody-mediated rejection
A. Is associated with serum donor-specific antibodiesB. Can be treated by high-dose methylprednisoloneC. Involves complement activation and endothelial injuryD. Is characterized by peritubular capillary C4d staining E. Has better outcomes than cellular acute rejection
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In children, these diseases have a 80 to 100% risk of recurrence in the renal graft
A. Focal segmental glomerulosclerosisB. Atypical HUS with factor H mutationC. Primary hyperoxaluria type 1D. Lupus nephritisE. MPGN type 2
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Recurrent renal diseases: an overview
Recurrence of the full primary renal diseaseHigh risk of graft loss Low risk of graft loss Late risk of graft loss
Primary hyperoxaluria type 1 IgA nephropathy Type 1 diabetes
Steroid resistant NS / FSGS Lupus nephritis Sickle cell disease
Atypical HUS ANCA-associated GN
Membranoproliferative GN
Membranous nephropathy
Recurrence of specific features Alloimmunization
Nephrin, PodocinAlport syndrome
Urinary tract malformationsPosterior urethral valves
Different from recurrenceDe novo renal diseases
Membranous GN, TMASpecific deposits
Cystinosis, Fabry
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Recurrence rate after the 1st renal Tx
Cochat Current Pediatr Rep 2013
Primary disease Recurrence rate (%) Graft loss to recurrence (%)
SRNS/FSGS 14-50 (average 30) 40-60
Atypical HUS 17 (MCP) – 90 (CFH-CFI) 10 (MCP) – 85 (CFH-CFI)
Typical HUS 0-1 0-1
MPGN type 1 30-77 17-50
MPGN type 2 66-100 25-61
Lupus nephritis 0-30 0-5
IgAN (Berger disease) 32-60 3-7
Henoch Shönlein nephritis 31-100 8-10
Primary hyperoxaluria type 1 90-100 80-100
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Graft survival according to primary diseaseH
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van Stralen Nephrol Dial Transplant 2013
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Among 100 patients with SRNS…
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~10% will be steroid resistant
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One third are genetic Another third will recur post-Tx
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Treatment options for recurrent FSGS
High-dose iv CsA
Plasmapheresis/immunoadsorption With or without iv CsA With or without cyclophosphamide instead of MMF/Aza
Rituximab?
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Rituximab375 mg/m² x 1-6
Sethna J Transplantation 2011
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aHUS - Transplantation
Biological defect % of aHUS % disease recurrence % graft lossADAMTS-13 deficiencyFactor H mutation 20-30 50-100 75-95Anti-factor H antibodies 5-10MCP/CD46 mutation 10-15 20Factor I mutation 10-15 80-100 100Factor B mutation <5 100C3 mutation 5-10 50THBD (thrombomodulin) mutation <5 5No gene mutation 30-40 60 85
aHUS is responsible for 2 to 5 % of children with ESRDOverall recurrence rate: 50-60%
Median time to recurrence: 30 days [0 day – 16 yrs]
Kavanagh Semin Thromb Hemostasis 2010 - Loirat Pediatr Nephrol 2008 – Noris Am J Transplant 2010 – Sánchez-Corral Br J Haematol 2010
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Tx options in aHUS
Noris Am J Transplant 2010
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Eculizumab blocks terminal complement pathway
Lectin Alternative
C3 C3a
C3b
C5
Proximal
Terminal
Microorganisms Ag-Ab complexesConstitutive
Microorganisms
Figueroa Clin Microbiol Rev 1991 - Walport N Engl J Med 2001
C5b-9
C5a
C5b
Eculizumab
Proximal functions of complement remain intact Weak anaphylatoxin Immune complex and apoptotic
body clearance Microbial opsonization
Terminal complement activity is blocked
Eculizumab binds with high affinity to C5
Classical
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In children, these diseases have a 80 to 100% risk of recurrence in the renal graft
A. Focal segmental glomerulosclerosisB. Atypical HUS with factor H mutationC. Primary hyperoxaluria type 1D. Lupus nephritisE. MPGN type 2
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In pediatric kidney Tx, the risk of malignancy is:
A. Quite nullB. 1 to 3% at 3 yrsC. 4 to 5% at 3 yrsD. 5 to 7% at 3 yrsE. 7 to 9% at 3 yrs
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The issue of malignanciesH
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NAPRTCS 2010
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In pediatric kidney Tx, the risk of malignancy is:
A. Quite nullB. 1 to 3% at 3 yrsC. 4 to 5% at 3 yrsD. 5 to 7% at 3 yrsE. 7 to 9% at 3 yrs
![Page 64: 9-1. Kidney transplantation in children. Pierre Cochat (eng)](https://reader031.vdocuments.site/reader031/viewer/2022013100/547b38f5b4af9f7e728b47e1/html5/thumbnails/64.jpg)
In children with a functioning renal graft, growth
A. Returns to normal velocityB. Is retarded in 10 to 20% of patientsC. Depends on steroid exposureD. Depends on GFRE. Can be improved by the use of rhGH
![Page 65: 9-1. Kidney transplantation in children. Pierre Cochat (eng)](https://reader031.vdocuments.site/reader031/viewer/2022013100/547b38f5b4af9f7e728b47e1/html5/thumbnails/65.jpg)
Fine Pediatr Nephrol 2009
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Harambat Pediatr Nephrol 2009
![Page 67: 9-1. Kidney transplantation in children. Pierre Cochat (eng)](https://reader031.vdocuments.site/reader031/viewer/2022013100/547b38f5b4af9f7e728b47e1/html5/thumbnails/67.jpg)
In children with a functioning renal graft, growth
A. Returns to normal velocityB. Is retarded in 10 to 20% of patientsC. Depends on steroid exposureD. Depends on GFRE. Can be improved by the use of rhGH, if licenced
![Page 68: 9-1. Kidney transplantation in children. Pierre Cochat (eng)](https://reader031.vdocuments.site/reader031/viewer/2022013100/547b38f5b4af9f7e728b47e1/html5/thumbnails/68.jpg)
Thank you for your attention!