Application of mesenchymal stem cells in patients with end-stage renal disease

The only treatments for patients with end-stage renal disease (ESRD) are
dialysis and kidney transplantation. Dialysis, however, severely impairs
quality of life, while kidney transplantation is limited by donor-shortage.
Furthermore, ischemia-reperfusion injury and nephrotoxic effects of
immunosuppressive medication impair kidney-graft function. Mesenchymal stem
cells (MSC) have tissue regenerative and immunosuppressive properties that may
prolong the life span of diseased kidneys and alleviate the need for
immunosuppressive drugs after kidney transplantation. In this phase I study we
aim to examine the safety and feasibility of infusion of culture-expanded,
autologous adipose tissue-derived MSC (ASC) in ESRD patients before kidney
transplantation and examine clinical and mechanistic parameters to pave the way
for efficacy trials in ESRD and kidney transplant patients.

The primary objective of the study is:
- to establish the safety and feasibility of infusion of escalating doses of
autologous ASC in end-stage renal disease patients.

Secondary objectives are:
- to determine the effect of ASC infusion on kidney function
- to detect immunological and regenerative markers after ASC infusion
- to determine the optimal time frame of the effects of ASC infusion

This is a randomized, blind placebo-controlled intervention study. ASC will be
isolated from abdominal subcutaneous adipose tissue of end-stage renal disease
patients with glomerular filtration rate between 15 and 25 that are planned for
living (un)related kidney transplantation. ASC are expanded ex vivo and
intravenously infused in escalating doses. Every patient will receive a single
infusion of ASC.

We will include sixteen subjects. Twelve subjects will receive a single
intravenous infusion of ASC. Doses of ASC will escalate from 0.33x106, 1x106 to
3x106 ASC/kg body weight. Four subjects will receive placebo (infusion liquid
without cells).

A small amount (1-4 grams) of abdominal subcutaneous adipose tissue will be
removed under local anaesthesia. Two months later, ASC will be infused via an
intravenous catheter. Subjects will stay in the hospital for observation for 3
hours. After infusion, subjects will undergo non-invasive clinical examinations
on day 1, 3, 7, and 21. During the study, seven times 25 ml of blood will be
collected. Subjects will visit the hospital six times.
This is a phase 1 study focussed on safety and tolerability. Although studies
in other patient groups suggest that infusion of ASC is safe, there is a risk
for the incidence of oppurtunistic infections or viral reactivations. Subjects
will be screened for microbiological and viral infections before participation
in the study. No direct benefits for the participants may be expected at this
stage. However, succesful completion of this study may lead to follow-up
studies that are designed to test efficacy. As a group, ESRD patients may
therefore benefit from this study.