Evaluation of the Outcomes of Kidney Biopsies in Deceased Donors in the Emilia-Romagna Region (KT-BX-RER Stud)

The KT-BX-RER Study is a multicenter observational cohort study, with both retrospective and prospective components, designed to evaluate pre-implant kidney biopsies from deceased donors in the Emilia-Romagna Region and to compare findings between donors after circulatory death (DCD) and donors after brain death (DBD).

Chronic kidney disease affects 10-15% of the global population, and kidney transplantation is considered the most effective treatment for end-stage renal disease. Because the demand for donor organs exceeds their availability, the use of kidneys from DCD donors has increased. However, DCD donation is associated with prolonged warm ischemia time and ischemia-reperfusion injury, which may lead to thrombotic microangiopathy (TMA), acute tubular necrosis (ATN), delayed graft function (DGF), or primary non-function (PNF).

Kidney quality is currently assessed through pre-transplant biopsy using the Karpinski score. Since this score does not specifically evaluate TMA, the Emilia-Romagna Transplant Reference Center and Pathology Department integrated additional morphological parameters derived from the Banff classification, including assessment of TMA and ATN as indicators of ischemia-reperfusion injury.

The Emilia-Romagna Region has extensive experience with controlled DCD programs and represents a large proportion of Italian DCD activity. The study aims to provide evidence that may improve the interpretation of pre-implant biopsy findings and clarify the role of biopsy assessment in DCD kidney transplantation.

The primary objective is to determine whether there is a difference, and to what extent, in the presence of TMA and ATN in pre-implant kidney biopsies from DCD donors compared with DBD donors. Outcomes include presence, percentage, and severity (mild, moderate, severe) of TMA and ATN measured at the time of organ pre-implant assessment.

Secondary objectives include:

Comparing the prevalence of different ATN groups between DCD and DBD donors. Comparing epidemiological and transplant outcome data between DCD and DBD transplantation.

Evaluating whether the relationship between TMA and transplant outcomes is modified by donor type (DCD versus DBD).

Secondary outcome measures include:

Histological findings of pre-implant biopsies, including Karpinski score components.

Graft survival. Causes of graft loss. Recipient survival. Causes of death. Post-transplant complications. DGF and PNF. Post-transplant renal function assessed by estimated glomerular filtration rate (eGFR).

Study Design This is a retrospective and prospective multicenter cohort study involving transplant centers in Bologna, Parma, and Modena. All eligible DCD and DBD donors from Emilia-Romagna between 1 January 2017 and 31 December 2024 will be included retrospectively, while donors from 1 January 2025 to 31 December 2027 will be enrolled prospectively. Only kidneys from Emilia-Romagna donors whose biopsies were evaluated by the Pathology Department of the IRCCS Azienda Ospedaliero-Universitaria di Bologna will be included.

Kidney transplant recipients aged over 18 years who received kidneys from these donors will also be enrolled. Recipients transplanted through the national excess, highly immunized, or DECK allocation programs will be excluded. No additional treatments, examinations, or procedures beyond routine clinical practice are required.

Sample Size and Duration For the primary endpoint, the study assumes a TMA prevalence of 2% among DBD donors and 5% among DCD donors. A sample size of 1,677 subjects provides approximately 80% statistical power to detect this difference.

The overall study duration is nine years, consisting of:

36 months of enrollment, 60 months of follow-up, 12 months of data analysis. Data Collection and Analysis

Clinical data will be collected in pseudonymized form through an electronic case report form managed on the REDCap platform. Recipient follow-up will occur according to routine clinical practice, with assessments at 3, 6, 12, 24, and 36 months after transplantation. Variables include immunological characteristics, immunosuppressive therapy, DGF, PNF, creatinine levels, complications, and survival.

The primary analysis will use multiple logistic regression with TMA as the outcome and donor type (DCD versus DBD) as the exposure variable, adjusting for donor and recipient characteristics. Secondary analyses will use regression models, Cox proportional hazards models, competing-risk models, and mixed linear models, depending on the outcome evaluated. Effect modification by donor type in the association between TMA and transplant outcomes will also be assessed.

Ethical and Administrative Aspects Written informed consent will be obtained from transplant recipients. Because organ donors are deceased, consent cannot be obtained from them. For retrospective recipient data, consent will be sought during follow-up visits; under specific circumstances i