Randomised comparison of two different immunosuppressive regimens on progression of arteriosclerosis in renal transplant patients.
Extension of NOCTX-study: Is progression of arteriosclerosis in ESRD patients inhibited by nocturnal hemodialysis or renal transplantation?

Cardiovascular disease is the leading cause of mortality both in patients with
end-stage renal disease (ESRD) as well as in renal transplant patients, during
the first 5 years after transplantation. The vascular abnormalities in ESRD are
especially characterized by arterial wall calcifications, whereas intimal
hyperplasia seen with *classic atherosclerosis* is less pronounced. These
calcifications are strongly associated with increased mortality. The exact
mechanism by which calcification develops is unknown, but there is a direct
relationship with increased serum calcium and serum phosphorus. With long and
frequent hemodialysis, such as nocturnal hemodialysis, and with renal
transplantation, calcium and phosphate values can be normalized. It is unknown
whether these treatments inhibit the progression of arterial calcification or
bring about regression of calcification.
Currently, little is known with regard to influences on aortic and coronary
calcification progression of different immunosuppressive regimens after
transplantation. The mTOR inhibitors are a relatively new class of
immunosuppressants, with a possible attenuating effect on intima proliferation
and atheroma formation. Furthermore, by their adequate immunosuppressive
properties, they allow for early withdrawal of calcineurin-inhibitors, that are
known to increase cardiovascular risk factors.
Therefore, as part of a study that compares the progression of coronary
calcification in different dialysis modalities in patients with end-stage renal
disease, it is of great additional importance also to study the effect of
different immunosuppressive regimens on this progression. Therefore we want to
compare in a randomised way the effect of a calcineurin-based immunosuppressive
regimen with an mTOR-based regimen on progression of coronary calcification on
renal transplant patients.
The results of this study will provide more insight in protection against
cardiovascular disease in renal transplant patients.

To compare in a prospective randomised way the effect of two different
immunosuppressive regimens - mTOR-based regimen or CNI-based regimen - on the
progression of coronary artery calcification in renal transplant patients
measured at baseline, 1, 2, and 3 years after transplantation.

Prospective randomized study as part of NOCTX-study. This study compares 2
groups of transplant patients, that are randomised at 3 months after renal
transplantation to one of two immunosuppressive regimens. Follow-up is
identical to the follow-up of the NOCTX-study.

Patients with ESRD, 18-75 yr, who undergo a living or postmortal transplant are
randomised at 3 months after transplantation to:
A: continuation with CNI-based immunosuppression
B: switch to mTOR-based immunosuppression.

The potential value of this study lies in gaining insight in the process of
artery calcification in patients with ESRD who undergo renal transplant.. On
theoretical grounds, it is plausible that progression is attenuated in patients
with a renal transplant, although some immunosuppressive drugs are known to
increase cardiovascular risk. However, no long-term data are available about
the effect of different immunosuppressive regimens on coronary calcification.
Therefore, modern immunosuppressive drugs could offer advantages regarding
progression of arteriosclerosis.
The risk and burden to the patient are formed in this study by:
- calcium score MSCT: as described above (7.3 Study procedures) multislice CT
is a very short procedure giving a low radiation dose (0.4-1.2 mSv);
- coronary MSCT: as described above (7.3 Study procedures) a coronary CT is
also a very short procedure with a low radiation dose (3-4 mSv) (NB for
comparison: a diagnostic abdominal CT scan delivers a dose of about 7-10 mSv);
- pulse-wave velocity: non-invasive measurement without risk;
- minor extra blood loss combined with routine venapunction.