Evaluation of CAF22 After Renal Transplantation
Condition: Kidney Transplantation; Delayed Graft Function
MeSH terms: Delayed Graft Function
Study type: Observational

Summary: 
      Established markers of kidney function, such as creatinine, have considerable limitations in
      the diagnosis of delayed graft function (DGF) after kidney transplantation (KT). Indeed,
      creatinine does not accurately reflect minor changes of renal function as its levels change
      only upon significant fluctuations of the latter. CAF22 is a molecule which arises from the
      degradation of a larger protein and it is proposed to be a reliable and more sensitive marker
      of renal function. This study aims to further clarify this issue by measuring blood and urine
      concentrations of CAF22 and comparing them with creatinine levels before and after KT.

      The main assumption is that blood CAF22 levels could serve as a more sensitive kidney
      function biomarker than creatinine post-KT to detect DGF.
    

Detailed description: 
      Background

      Kidney transplantation (KT) is the most appropriate therapy of end stage renal disease
      (ESRD). While the number of kidney donors remained stable during the last decade the number
      of patients waiting for a kidney transplantation are rapidly increasing resulting in
      utilization of an increasing numbers of marginal renal transplants. These kidneys show a
      relatively high percentage of delayed graft function (DGF), which complicates post-transplant
      management and increases both the duration of initial hospitalization and the cost of
      transplantation.

      Exact measurement of glomerular filtration rate (GFR) is complex in the clinical setting and
      thus GFR is usually estimated from serum creatinine levels through creatinine-based equations
      such as the MDRD or the CKD-EPI equations. Particularly, this is the case in kidney
      recipients with DGF, in whom creatinine levels remain high and they have to undergo dialysis.
      Creatinine is dialyzable, so that it cannot reflect the actual renal function in this setting
      due to fluctuations of its levels. Thus there is emergent need for a more accurate renal
      biomarker.

      CAF22 is the C-terminal 22 kDa domain of agrin. Agrin is cleaved by its specific protease
      neurotrypsin at two distinct sites, whereas cleavage at the beta site generates a 22 kDa
      C-terminal fragment (CAF22). In the kidney agrin is part of the basal lamina, where it is the
      major contributor of the anionic potential of the glomerular basement membrane (GBM). There
      are indices for a proteolytic activity selectively shedding the C-terminal part of agrin of
      the GBM. Recently, a 19-fold increase of CAF22 levels in ESDR was observed, which was reduced
      in patients receiving KT, qualifying CAF22 as effective renal function marker. Additionally,
      current data support that CAF22 levels are not influenced by inflammatory processes, steroids
      or by hemodialysis with a standard dialysis membrane.

      Objective

      Primary:

      - to compare CAF22 versus creatinine as biomarkers for DGF prediction in patients undergoing
      kidney transplantation

      Secondary:

        -  to evaluate the kinetics of CAF levels related with the graft function outcomes
           "immediate graft function (IGF)" and "delayed graft function (DGF)"

        -  to elucidate whether CAF can make estimations on the required hemodialysis days of
           patients with delayed graft function

      Methods

      Research project with humans associated with the collection of biologic material and
      health-related data. Prospective, observational trial.

      All patients will be screened consecutively before undergoing kidney transplantation (KT).

      All participants will undergo blood and urine sampling for estimation of CAF22 levels once
      before KT, once daily during the first 7 days after KT as well as at 2, 4 and 12 weeks after
      KT. Blood and urine sampling for CAF22 will be performed during routine follow-up sampling.
    

Intervention name(s): Blood and urine sampling
Intervention type(s): Other
Intervention description(s): Blood and urine sampling (in the context of routine sampling)
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with end stage renal disease (ESRD) planned to undergo kindey transplantation in
        Bern University Hospital will be screened consecutively, informed and asked for written
        inform consent.
      
Biospecimen description: 
      Serum, urine
    
Keywords: Kidney Transplantation; Delayed Graft Function; C-terminal fragment of agrin; Dialysis