Assessment of sympathetic reinnervation of the kidney allograft
with 123I-MIBG scintigraphy.
(RENnervate study).

A number of renal transplant recipients have excellent functioning grafts for
many years after transplantation. Most obvious this is due to immunological
factors, infection rates and comorbidity. However, it is unclear whether renal
nerve regrowth in the allograft might influence graft survival. Due to the
explantation process, the renal allograft is entirely denervated at time of
transplantation.
In years after transplantation, it is unknown to what extend and when
regeneration of renal sympathetic nerves after transplantation occurs.

Assessment of the sympathetic nerve activity (SNA) can be determined by
peroneus microneurography or catecholamine levels in plasma. However, these
methods are indirect, invasive and impractical and do not supply information
about regional sympathetic nerve activity.
123I-metaiodobenzylguanidine (123I-MIBG) is a radio-labeled analogue of
noradrenaline and is taken up by presynaptic nor-adrenaline transporters and
thereby it can provide an estimate of sympathetic activity. 123I-MIBG
scintigraphy has shown to offer prognostic information in patients with heart
failure.
Since kidney transplantation is the only durable therapy for end stage renal
disease, allograft nephropathy remains an important clinical problem. Various
lines of evidence suggest that sympathetic denervation of the allograft plays a
role in the pathogenesis of allograft nephropathy.
Due to the explantation process, the renal allograft is entirely denervated at
time of transplantation. There is histological evidence that after
transplantation there is re-innervation of the allograft. However, up to 2,5
years after transplantation such reinnervation has been shown not to be of
functional significance. Reinnervation is a potential therapeutic aim to
prevent allograft nephropathy.
We hypothesize that allograft sympathetic reinnervation is a slow process which
takes >10 years to reach functional capacity.

If there is a >7.5% difference in washout-rate n the kidney graft compared to
the mediastinum, we assume that this implicates reinnervation of the graft. We
assume that if renal re-innervation occurs, 123I-MIBG uptake will be higher in
patients with an older renal allograft compared to recent transplanted
allografts that show decreased or lack of 123I-MIBG uptake.Therefore, patients
with a graft in situ for > 10 years will be studied initially.A negative
control group is studied, consisting of n=6 oliguric/anuric patients 0-6 weeks
after kidney transplantation with one or both native kidneys in situ.

To assess renal sympathetic reinnervation in the kidney allograft by 123-I-MIBG
scintigraphy.

We propose an observational pilot study with n=6 renal transplant patients with
a functioning allograft in situ for 6-18 months, n=6 kidney transplant patients
with an allograft for > 4* but <7 years in situ and n=6 with their allograft
in situ >10 years and a negative control group is studied consisting of n=6
oliguric/anuric patients 0-6 weeks after kidney transplantation with one or
both native kidneys in situ.


All patients will undergo 123I-MIBG scintigraphy. They will receive 185 MBq of
123I-MIBG intravenously.
Subsequently at 15 min and 4 hrs and 24 hours post injection planar images are
made in combination with SPECT at 4 an 24 hours post injection. The SPECT
acquisition is combined with a low dose CT-scan of the abdomen (without
intravenous contrast) to relate the 123I-MIBG uptake to anatomical structures.
All six patients with a graft in situ for > 10 years will be studied initially.

- The risk of the venous canulation (for the 123I-MIBG scintigraphy) is
haematoma formation, and infection.
- Time burden: patients with a kidney transplant attend their nephrologist on
average 4 times a year. The number of extra (outpatient) clinic visits for
participation in this study is approximately 3.5hours.
- There are no known risks to the extra blood pressure measurements.
- The complete radiation exposure due to 123I-MIBG amounts to 8.0 mSv which is
an intermediate risk according to the category IIb of the ICRP (rapport
ICRP62).