Research Group

  • Dr Michael Eikmans, Principal Investigator
  • Prof. Frans Claas, Co-applicant
  • Prof. Hans de Fijter, Research Associate
  • Dr. Dave Roelen, Research Associate
  • Dr. Ingeborg Bajema, Research Associate
  • Prof. Cees van Kooten, Research Associate
  • Dr., Sebastiaan Heidt, Research Associate
  • Mathijs van de Vrie, Research Associate
  • Prof. Luuk Hilbrands, Research Associate
  • Prof. Caner Süsal, Research Associate
  • Geert Haasnoot, lab technician
  • Jacqueline Anholts, Research Associate


  • Leiden University Medical Center, Leiden, The Netherlands


  • Noninvasive detection of kidney allograft rejection in urine and blood by integrating novel molecular tools into a combined biomarker strategy

In kidney transplantation, acute rejection poses a risk factor of graft loss. The biopsy is the golden standard for diagnosis, but it associated with side effects for the patient. Noninvasive sources of material allow immunomonitoring at multiple time points after transplantation. Molecular alterations are expected to precede graft injury and dysfunction. The goal is to use novel molecular tools in urine and peripheral blood as biomarkers of acute rejection, and integrate these into a broader set of analytes. We aim to:

1) test whether the novel molecular parameters are diagnostic of acute rejection. These are:
a) urinary microRNAs
b) cell-free donor DNA in the recipient's plasma
2) compare the discriminative value with that of other parameters of immunity and graft damage.
3) test which multi-parameter approach is the most discriminative and predictive of acute rejection and long-term prognosis.

In a cross-sectional approach of two transplant centers, samples taken during (biopsy-supported) acute rejection from 116 patients will be compared to samples taken due to other causes of acute graft dysfunction (n = 91) and during stable graft function. In a longitudinal approach, 34 patients with acute rejection and 55 patients with no rejection will be studied before transplantation and thereafter.
Primary outcome is presence of acute rejection. Therapy-sensitivity to anti-rejection treatment and graft outcome are secondary outcome parameters. We will apply expression profiling of microRNAs in urinary sediments, and determine ratios of donor to recipient DNA in the plasma. Other analytes will be analyzed in serum (sCD30) and in urine supernatant (KIM-1, NGAL, sHLA), along with mRNA transcripts in urinary sediments and blood cells. Statistical analyses will provide information on which combination of tests offers the best discriminative and predictive value.
Availability of suitable markers will facilitate decisions on whether a biopsy should be taken, and may have implications for future therapeutic decision-making.

Progress Report