Background

Renal transplantation is an increasingly successful therapy as judged by progressive improvements in patient and graft survival for all types of renal transplantation over the last 20 years.

Much useful data has come from long-term follow up of transplant patients.  Transplant registries, for example UNOS [1] in the United States or ANZDATA [2] in Australasia, have provided invaluable information on very large patient cohorts.  The importance of early graft function on patient survival has been established [3,4], and death after graft loss has been associated with prolonged waiting time on dialysis, diabetes mellitus and acute rejection [4].  The impact of post transplant diabetes[5] and obesity[6] is emerging, as is the importance of addressing cardio-vascular risk factors amongst renal transplant recipients[7].

However most other studies have focussed on the transplant itself, collecting information prospectively from the day of transplantation, focussing on transplant-related parameters which influence graft survival.  Graft failure and death with a functioning graft are the usual end points of analysis.  Second and subsequent transplants are usually regarded as separate episodes. 

There are a number of limitations in this approach:
1. Registry datasets typically focus on numerical variables easily retrieved from clinical records.
2. The crucial issue of the impact of unsuccessful transplantation on long term outcome is poorly investigated since the patient who returns to dialysis is in most circumstances not under continuing assessment. 
3. The continuing burden of co-morbidity before, during and after transplantation is less well documented.
4. The complex interactions of multiple immunosuppressive agents and other medications, particularly any influence on long term co-morbidity, have not been well analysed.  Impact of immunosuppressive regimens has predominantly focussed on incidence of acute rejection and graft survival. Analysis is often on an ‘intention to treat’ basis. Major comorbidities which are of increasing concern include both cardiovascular disease and opportunistic infection. The latter in particular may assume increasing significance as the range and complexity of immunosuppressive regimens increases with the goal of minimising early acute rejection.
5. Quality of life or quality of health outcomes analysis typically identifies transplantation as superior to dialysis but studies with power adequate to investigate the influence of a wide range of co-morbidity and transplant-related variables are lacking.

Long-term follow-up of transplant recipients including those whose graft fails is currently scarce.

The STEPP study is an ambitious study designed to collect as much data as is possible in a retrospective study on treatment, events and outcomes in a cohort of renal transplant recipients.

The study is only possible because of the generous funding from a consortium of organisations and companies with an interest in Renal Transplantation.  It is therfore with thanks to Kidney Research UK, The Renal Association, The British Transplant Society, Roche Pharmaceuticals, Astellas Pharmaceuticals and Wyeth Pharmaceuticals that the study is possible.

Study Plan

The aim of the study is to collect as much biomedial data about patient and transplant outcomes in all patients who had a first renal transplant in any of the five participating centres between 01-01-1992, and 31-12-2004.  Patients less than 18 years old on the date of transplant, or who only attended the transplant centre for the first time to be transplanted have been excluded.

Over the next two years data will be collected from the records of patients in the five participating centres, and this will be entered into their existing clinical computing systems.  The data will therefore be available for direct patient care, by integrating the study data into existing data will allow the dataset to keep up-to-date with changes in the patients record.  An anonymous set of this data will be collated, and used for the purpose of the study, but no patient will be identifiable in the research database.

In parallel to this, patients who fullfill the inclusion criteria will be approached to complete a series of questionnaires relating to their  quality of life and health, and a validated symptom measure.  Patients will be approached regardless of whether their first renal transplant is still functioning, or whether they are back on haemodialysis, peritoneal dialysis or re-transplanted.  The rational for this is that the study aim is to investigate the long-term effects of renal transplantation, many of which will extend beyond the renal transplant failing.

Towards the end of the next two years the study investigators will begin to investigate both the biomedical factors which are associated with long-term transplant outcome (be that patient or graft survival, or developing specific complications).  They will also correlate patient reported measures of life and health with some of these important complications, and outcomes, and also their drug treatments.

References
1      The UNOS Scientific Renal Transplant Registry (2000).  Cecka JM.  Clin Transpl 2000:1-18.  http://www.unos.org/
2      Report of the ANZDATA Registry Chapter 8: transplantation.  Russ GR (2002) http://www.anzdata.org.au/
3      Effect of early graft function on patient survival in renal transplantation.  Fernandez-Frsnedo G., Rodrigo, E., Escallada R. et al.  Trans Proc 35(5): 1653-4, 2003
4      Mortality risk assessment after renal transplantation.  Kaplan B., Meier-Kriesche HU.  Clin Trans 131-6, 2002
5      Development of diabetes mellitus post-renal transplantation is associated with poor short-term clinical outcomes. Saleem TF. Cunningham KE. Hollenbeak CS. Alfrey EJ. Gabbay RA. Transplantation Proceedings. 35(8):2916-8, 2003 Dec
6      The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death.  Meier-Kriesche HU, Arndorfer JA, Kaplan B.  Transplantation 2002;73(1):70-74
7      Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.  ALERT Study Investigators. Lancet. 361(9374):2024-31, 2003 Jun 14.

Last modified: Sun Jan 20 2008