Download - Challanges in Pediatric Renal Transplant 2
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One year old child 6 Kg
Performing hemodialysis.
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It is not Easy to Get Along that Early
without Kidneys
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Because children are constantly
growing and developingtechnical, metabolic,
immunologic, and psychological
factors exist that are unique to
children having kidney
transplantation, and must be
considered.
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Aplastic, hypoplastic, or dysplastic kidneys
Obstructive uropathy
Reflux nephropathy
Focal segmental glomerulosclerosis
Systemic immunological disease
Chronic glomerulonephritis
Hemolytic uremic syndrome
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Polycystic kidney disease
Congenital nephrotic syndrome
Medullary cystic disease
MPGNType II
MPGNType I
OTHER DISEASES
Diabetic glomerulonephritis
Sickle cell nephropathy
Unknown
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Growth retardation.Infections.
Non adherence to therapy.
Renal allograft dysfunction.
Long term kidney allograft
survival.
Immune suppression regimen.
Some technical aspects.Side effects .
Long term out come.
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Growth retardation is common in childrenand adolescents with chronic kidney disease
(CKD).
The etiology is multifactorial and includes: malnutrition due to uremic anorexia,
acidosis, alterations in calcium and phosphate
metabolism,
and alteration in the growth hormone-insulin-like growth factor axis
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One of the goals of successful pediatric renal
transplantation is the attainment of optimalfinal adult height.
Although height standard deviation scores of
pediatric renal transplant recipients have
steadily improved over the past 2 decades,
growth in many children despite targeted
therapeutic efforts remains suboptimal aftertransplantation
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Several factors have been shown to affect the
growth rates of children after renaltransplantation, but the most important are
Age at time of transplantation,
Allograft function,
And corticosteroid therapy.
Age: younger recipients exhibitthe greatest immediate catch-up growth
; catch-up growth occurs primarily
in recipients < 6 years of age at transplantationGraft function: elevated SCr concentration
and decreased GFR have been correlated with
a reduction in height and growth velocity.
Corticosteroids:
are known to adversely affect growth in children
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Infection now exceeds rejection as a causeof hospitalization of pediatric renal
transplant recipients in the first 2 years
post-transplantation.
The youngest children (aged 0-1 years) at
time of transplantation had significantly
higher rates of infection requiring
hospitalization , for bacterial and viral
infection compared with children > 12
years
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Infection-related hospitalization rates were
highest for pediatric kidney transplantrecipients.
Urinary tract infection (UTI) is a major causeof morbidity .
graft function deteriorated at a significantly
faster rate in patients with recurrent UTIs thanin those without recurrent UTIs at 4 years
post-transplantation
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Adolescents have the highest rate of 1-yeargraft survival of any age group, but long-term
transplant outcomes in this age group aredisappointing.
The most important challenge to long-term
survival in children following transplantationis the management of non adherence andother adolescent issues.
A major cause of late graft failure inadolescents is medication noncompliance.Medication noncompliance has been shownto be more than 4 times greater in adolescents
than in adults.
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Important milestones during the transition fromchildhood to adulthood include:
Becoming autonomous and eventually fullyindependent.
But almost paradoxically the cognitive skillsand intellectual maturation of adolescents arelimited, particularly in those with chronicdiseases .
Adolescents struggle with abstract thinking,including conceptualization of futureconsequences of present actions, which leads torisk-taking behaviors, including non adherence
with medications.
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A
s a group, the immunosuppressiveagents used to prevent acute rejection
and preserve kidney function in renal
Alter physical appearance,
Cause serious mental and psychosocial
problems,
Compromise quality of life
side effects
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Corticosteroids
CSA
TAC
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Gingival overgrowth in a transplant recipient taking CSA.
The accumulation of collagen seen in gingival overgrowth,
thought to occur as a result of CSA-induced inhibition of
collagenolytic activity within the gingival tissues, is disfiguring
and contributes to periodontal disease.
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Medication noncompliance is a leading cause
of morbidity in pediatric transplant recipients.
Stopping or markedly under dosing
immunosuppression even once for anextended period of time may allow the
irreversible process of chronic rejection to
begin.
Once this process begins, even if compliance
is perfect thereafter, the process is not likely
to be reversible
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Although the age group most commonlyassociated with increased risk for graft failure
is infancy, a less recognized high-risk age
group is adolescence.
Adolescents also had a significantly higher
percentage of late acute rejection episodes
and a lower rate of rejection reversal
compared with other age groups.
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There are many causes of renal dysfunction inpediatric renal transplant recipients. Likewise,the allograft can undergo a variety ofmorphologic changes during the progressionfrom injury to dysfunction.
Acute antibody-mediated and cell-mediated rejection,
Drug toxicity from CNIs,
Chronic allograft nephropathy (CAN),Viral infection,
And post-transplant lymphoproliferative
disease are
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Although short-term kidney allograft survivalrates have improved dramatically, long-term
survival has not kept pace due to the nearly
universal development of CAN.
Chronic allograft nephropathy (CAN) is
irreversible and is the single most important
factor for allograft dysfunction and loss in
children.
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Chronic allograft nephropathty
10 years
Immunologic Nonimmunologic
eg, rejection
, inadequate immunosuppression,
viral infection
eg, reperfusion injury,
increased ureteral pressure,
hypertension,
hyperfiltration,
ischemia,
proteinuria,
CNI toxicity
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Clinically, CAN is characterized by :
Worsening renal function (slowly
progressive decrease in the GFR),De novo or aggravated hypertension,
And worsening proteinuria .
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Reliance on SCr can underestimate the
severity and rate of decline in renal function,
particularly when the GFR is 30 to 70
mL/min (which is the case for most kidneytransplant recipients).
Proteinuria (new-onset, > 0.5 g/24 h, orworsening) should raise the suspicion of
CAN
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Investigators evaluated
transplant protocol biopsies
from 280 patients with stable SCr levels
and determined that
SCr and estimatedGFR are poor
predictors of early histopathologicchanges that precede CANinrenal allograft biopsies.
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A renal allograft affected by chronic allograft nephropathy shows loss of
normal architecture with interstitial chronic inflammation, tubular atrophy,glomerular collapse, and global sclerosis but without tubulitis or arteritis.
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Renal function within
the first year of
transplantation wasthe most important
predictor of kidney
graft survival
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Although the occurrence of acute rejection isthe strongest predictor for the development of
chronic rejection.
1-year SCr and delta creatinine values, not
clinical acute rejection episodes, predicted
long-term renal graft survival.
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In the setting of acute rejection,
it is thepreservation of renal function that
is more important for graft survival.
That recent improvements in graft half-life
can be attributed to better preservation of
renal function within the first year post-transplantation
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Conversion from a CSA-based to a TAC-based
immunosuppression regimen has been
associated with
Stabilization of renal function, compared with agradual deterioration of graft function in patients whoremained on CSA
Sustained reduction in systolic and diastolic bloodpressure
Sustained improvement in serum lipid profile (totalcholesterol, LDL-C, and triglycerides)
Reduced Framingham risk score
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RECURRENT RENAL DISEASEPrimary hyperoxaluria
IgA nephropathyMembranous glomerulonephritis
Diabetes mellitus
Cystinosis
Amyloidosis
Focal segmental glomerulosclerosis
Alports, crescentic glomerulonephritis, vasculitis
Haemolytic uraemic syndrome
Systemic lupus erythematosus
Mesangiocapillary glomerulonephritis
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As pediatric recipients
are likely to require
re-transplantation during their lifetime,every effort should be made
to minimize HLA mismatches
to reduce the risk of future sensitization
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The implantation of an adult kidney into a
paediatric recipient requires close cooperation
between the surgical and anaesthetic teams.
Meticulous attention needs to be paid to the
child's intravascular volume status.
When the aortic and inferior vena cava
clamps are released, the transplanted organ
and lower extremities fill with blood,potentially resulting in severe hypovolaemia
unless adequate volume loading has taken
place.
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Fluids and electrolyte balance
Urine output and insensible losses are replaced initiallywith 2.5% glucose/0.45% saline, volume for volume on an
hourly basis.
Plasma electrolytes are checked at 2-4 hourly intervals for
the first 12 to 24 hours and replacement fluids should be
adjusted according to these results.
Central venous pressure (CVP) monitoring is mandatory
and the CVP should be maintained at 5-10cmH2O in the
spontaneously breathing patient, with intravenous normal
saline or by the administration of an alternative colloid to
correct hypovolaemia.
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