Kidney transplantation is generally safe and effective for treating end-stage renal disease in patients with cystinosis. Studies have shown good patient and graft survival rates comparable to or better than other transplant recipients. Outcomes have also improved over time, with lower acute rejection rates and higher graft function. However, lifelong cysteamine therapy is still needed after transplant to prevent systemic complications from cystine accumulation in other organs.

1. Kidney Transplantation
in Cystinosis
Mitra Basiratnia
Ped nephrologist
SUMS

2. Introduction
 Cystinosis is a rare autosomal recessive lysosomal disorder
with an estimated incidence of 1 per 100 000 to 200 000 live
births
 The gene responsible for the disease, CTNS, was identified in
1998
 Kidney involvement is the most serious clinical event,
because it leads to end stage renal disease (ESRD) before the
age of 20 in more than 90 % of patients
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3. Introduction
 Systemic treatment with cysteamine, delays the time
between diagnosis and the onset of ESRD, but is not
sufficient to prevent it.
 Renal transplantation is the best therapeutic option for
ESRD in young patients
 Few studies have investigated the safety and efficacy of
kidney transplantation in cystinosis patients
3

4.  Between 1976 and 1989, 22 children (11 females, 11 males)
with nephropathic cystinosis received 28 renal allografts
 None of the patients had ever been treated with cystine-
depleting agents before and after TX
 Patient and graft survival did not differ from non-cystinotic
children.
 There is a need for a specific metabolic treatment for
cystinosis starting at early age and possibly persisting after
transplantation.
4

5. 5

6. ⦁ They assessed 15 cystinotic patients with renal TX (1375-1385)
⦁ Mean F.up was 43mo /mean age at TX was 8 years (2-13)
⦁ Four years patient and graft survival was 100% and 86.7%,
respectively.
⦁ The cause of graft loss was vascular insult in 2 patients.
⦁ Mean age at TX was lower in comparison to other studies ( 8 years
VS 9 years)
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7.  441 kidney transplants performed in 362 cystinotic patients
younger than 31 years between 1987 and 2017
 three equal eras (1987‐1997, 1998‐2007, and 2008‐2017) to assess
changes in outcomes
 Eras 2 and 3 had lower risk of acute rejection
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8. Eras 2 and 3 had higher 5‐year mean GFR
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9.  Five‐year graft survival was similar across eras, but 5‐year
patient survival was higher for era 2
 Age at ESRD, acute rejection, GFR at 5 years, and patient
survival improved over time.
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10.  Data of renal transplantation (n = 31) in 30 adult patients with
cystinosis in 5 French university transplant centers between
1980 and 2013
 A control cohort of 93 patients was matched for age, graft date,
living/deceased donor status and transplant center
 Median age at transplantation was 20.4 years (7–36.5).
 At transplantation, all patients with cystinosis had corneal
cystine deposits, 3 had diabetes and 7 had hypothyroidism.
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11.  Graft survival was better in patients with cystinosis than in
control patients (p = 0.013).
 Graft survival at 5 and 10 years was 92.0 and 86.5 % in
cystinosis group, respectively, and 86.0 % and 72.0 % in
control group.
 Multivariate analysis confirmed that cystinosis was an
independent protective factor for graft survival
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12.  Specific complications of cystinosis occurred during follow up:
diabetes mellitus (n = 4), hypothyroidism (n = 1), liver
involvement (n = 1), neurologic involvement (n = 2).
 Proportion of post-transplant diabetes mellitus (PTDM) was not
statistically different in cystinosis group compared to control
group
 They concluded that Renal transplantation appears to be safe
with excellent long-term outcomes in patients with cystinosis.
12

13. Kaplan-Meier analysis of graft survival during
follow up.
13

14. Protective and pejorative factors for graft survival
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15. Graft outcome
 In pediatric cohorts, the outcome of kidney transplantation in
patients with cystinosisis generally better than that for other
patients undergoing transplantation
 ERA/EDTA registry showed that 5-year graft survival was better
in 245 cystinosis patients compared to 490 control children
undergoing kidney transplantation for another cause (94.0 %
versus 84.0 %, respectively)
 Australian and New Zealand (ANZDATA) registry showed the
10-year survival of first transplant recipients with cystinosis (n
= 44) was 86% at the era of cysteamine therapy
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16.  the rate of patient survival was excellent (97.0 % at 10 years)
 One patient died after 51 months of follow-up, because of a car
accident
 at the era of cysteamine, none of the deaths was related to
cystinosis or chronic kidney disease
 In the opposite, in the early group (no cysteamine) of the
ANZDATA study, the majority of deaths were cystinosis or
chronic kidney disease related
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17. 17
preliminary unpublished data suggest that the
mTORC1 pathway is down-regulated in cystinosis
patients, which may explain the very good longer
outcome of renal transplantation in these individuals
and the previously suggested better immune tolerance
of patient with cystinosis

18. protocol biopsy
 A protocol biopsy was performed one year after transplantation
in 13 patients with cystinosis
 Cystine crystals were observed in the renal biopsy from only
one patient
 the patient had a functional graft 22 years after transplantation
(serum creatinine level 182 μM).
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19. Kidney transplant biopsy showing cystine
crystal into recipient mononuclear cells
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20.  Proximal tubular disease does not occur in the transplanted
kidney because cystine lysosomal efflux transport system
is functional in the engrafted kidney
 retention of a native kidney can result in the persistence of
renal tubular Fanconi syndrome
 protocol biopsies have shown that cystine crystals may be
deposited within the interstitial tissue and less frequently
within glomeruli without any clinical or biological
manifestations.
 These crystals are present in the host’s own mononuclear
cells
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21. Complications of cystinosis after renal
transplantation
 Renal transplantation does not correct the systemic metabolic
defect of cystinosis
 Cystine accumulate in most organs and will lead to late
systemic complications.
 Those over the age of 30 were usually doing poorly, although
many were still working
 Lack of prolonged compliance with cysteamine therapy may
have been a major cause of these problems
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22.  Diabetes can develop a long time after transplantation, and
doesn’t seem to be related t immunosuppressive regimen.
 The use of a cystine-depleting cysteamine by all patients
probably limits the risk of cystinosis-related diabetes
 Immunosuppressive maintenance treatment regimens should
be equivalent between patients with or without cystinosis,
because the potential risk of diabetes after transplantation is
not sufficient to necessitate specific treatment in patients with
cystinosis
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23.  Neurological complications consisted in progressive distal
myopathy in two patients, leading to interdigital amyotrophy
 It is estimated that depletion of excess cystine from muscle
requires 4 to 11 years of therapy.
 One patient presented 3 years after transplantation with
behavioral disorder without any motor or sensitive deficiency.
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24.  Another patient with hepatic involvement presented with
cholestasis
 Corneal transplantation was performed in two patients
during follow up
 One patient developed PTLD, successfully treated with
chemotherapy.
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25. “
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All patients who developed cystinosis complications
had cystine leukocyte content above 2 at the time of
the complication

26. CONCLUSION
 Long-term outcome of cystinosis patients undergoing
renal transplantation is excellent.
 Renal transplant recipients with cystinosis have a better
long-term outcome than other renal transplant recipients
 Kidney transplant outcomes for children and young
adults with cystinosis have improved over the last three
decades.
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