Characterisation tissue-resident cells in donor and native kidneys

Kidney transplantation is the preferred type of renal replacement therapy for
patients suffering from end-stage renal disease. However, long-term renal
allograft survival is compromised by chronic rejection, being one of the most
frequent causes of progressive loss of renal allograft function.
Recent studies have revealed that the cellular part of the immune system is
involved and the degree of inflammation is the predominant predictor of graft
loss. Little is known with respect to which immune cells and mechanisms
eventually contribute to loss of the renal allograft.
Large numbers of intrarenal immune cells need to be obtained for detailed
characterization of phenotype and function of immune cells within the graft
Different methods for obtaining immune cells will be compared with respect to
yield using renal tissue obtained from failed renal allografts and healthy
native kidney tissue. In addition, phenotype as well as function of immune
cells of failing renal allografts will be compared to that of healty native
kidneys.

The primary objective of this study is to develop a method by which large
numbers of immune cells can eventually be obtained from a kidney biopsy to
study phenotype and function of immune cells and unravel mechanisms
contributing to loss of renal allograft function.
For this, we will use kidney tissue obtained from a failed renal allograft and
native kidney and compare yield of immune cells for different methods. In
addition, we will compare phenotype and function of immune cells present within
a failed renal allograft to immune cells present within a healthy piece of the
native kidney.

Subjects undergoing a transplantectomy or nephrectomy, will be asked to give
informed consent for using part of their transplanted/native kidney and one
additional blood donation for scientific research.
Different methods will be compared with respect to yield of intrarenal immune
cells. One of these methods uses peripheral blood mononuclear cells of the
patient to induce proliferation of intrarenal immune cells.
In addition, phenotype and function of the obtained immune cells isolated from
a failed renal allograft will be compared to that from a piece of healthy
native kidney.

For this research we will make use of (remaining) kidney material obtained
following a transplantectomy or nephrectomy and one additional blood donation
(2 heparin tubes a 10 mL blood=20 mL of blood) at the time of routine blood
withdrawal by experienced personnel.
The burden for the patient is therefore minimal and no additional risks are
involved when participating in this study.