Evaluation of Serum and Urinary C-terminal Agrin Fragment-22 (CAF22) as Novel Renal Function Marker in Kidney Transplant Recipients - A Prospective Observational Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 99
- Locations
- 2
- Primary Endpoint
- Delayed graft function (DGF) defined as the requirement of dialysis within 7 days after transplantation
Study Overview
Brief 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
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years old
- •Written informed consent
- •All patients planned to undergo kidney transplantation
- •Exclusion Criteria
- •Age <18 years old
- •Pregnancy
- •Other individuals especially in need of protection (according to the Swiss Academy of Medical Sciences)
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Delayed graft function (DGF) defined as the requirement of dialysis within 7 days after transplantation
Time Frame: 7 days
Secondary Outcomes
- Need for hemodialysis(7 days)
- Hemodialysis duration (in days)(7 days)
- Immediate graft function (IGF)(7 days)