Translational research in kidney transplantation and the role of patient engagement

BackgroundTranslational research is an evolving discipline that is intended to bridge the gaps between basic science research, clinical research, and implementation in clinical practice. It is a fluid, multidirectional process that requires strong interdisciplinary collaboration to produce research that is relevant to end-users.Purpose of this reviewThis review summarizes current perspectives on translational research and outlines its relevance and importance to kidney transplantation research.Sources of informationSources of information used for this review include published reports, articles, and research funding websites.FindingsTissue typing is used as an in-depth example of how translational research has been applied in the field of kidney transplant medicine, and how it has resulted in successful implementation of diagnostic and management options for sensitized individuals undergoing kidney transplantation. The value of actively involving kidney transplant stakeholders (patients, caregivers, and clinicians) in setting research priorities and determining relevant outcomes for future investigation is also discussed.LimitationsThis is a narrative review of the literature which has been partly influenced by the perspectives and experiences of its authors.ImplicationsTranslational and patient-oriented research practices should be incorporated into future research endeavours in the field of kidney transplantation in order to create beneficial change in clinical practice and improve patient outcomes.What was known beforeTranslational research which engages patients in the investigative process can enhance the likelihood that medical discoveries will have a meaningful impact at the bedside.What this addsThis article applies current perspectives on translational research and patient engagement to the field of kidney transplantation, illustrating how these approaches have led to significant advancements in the field. It provides further justification for deliberate, targeted efforts to cross-collaborate and incorporate the patient voice into kidney transplant research.AbrégéContexteLa recherche translationnelle est une discipline évolutive qui a pour but de faire le pont entre la recherche fondamentale, la recherche clinique et la mise en œuvre de pratiques cliniques dans le domaine des transplantations rénales. Il s’agit d’un processus multidirectionnel et fluide qui demande la collaboration étroite de toutes les disciplines impliquées afin que la recherche qui en résulte soit pertinente et touche directement les usagers.Objectifs de la revueCette revue fait la synthèse des éléments actuels de la recherche translationnelle, et décrit sa pertinence et son importance dans le domaine de la recherche sur la transplantation rénale.SourcesLa réalisation de cette revue a été possible suite à la consultation de recueils et d’articles publiés ainsi que de sites web dédiés au financement de la recherche.ConstatationsL’étude de la compatibilité immunologique est utilisée à titre d’exemple pour démontrer en détail la façon dont la recherche translationnelle a été appliquée dans le domaine des greffes du rein jusqu’à maintenant, et comment elle a permis la mise en œuvre de solutions efficaces pour le diagnostic et l’organisation des soins aux patients subissant une greffe de rein. On a également discuté de l’importance d’impliquer toutes les parties prenantes d’une procédure de transplantation rénale, soit les patients eux-mêmes et le personnel soignant et le personnel clinique, afin d’établir les priorités de recherche et de définir les résultats pertinents en vue d’études ultérieures.Limites de l’étudeIl s’agit d’une revue non systématique de la littérature influencée en partie par la perspective et les connaissances des auteurs sur le sujet.ConséquencesIl apparait important d’intégrer les pratiques courantes en recherche translationnelle de même qu’en recherche axée sur le patient lors de futures études sur les greffes de reins. Ceci afin d’instaurer un changement bénéfique dans la pratique clinique et par conséquent, d’améliorer les résultats chez les patients.Données connuesUne approche de recherche translationnelle favorisant l’implication des patients dans le processus d’analyse peut augmenter les chances de voir les découvertes médicales avoir des répercussions directes et plus significatives pour le patient.Ce que cette étude ajouteCette revue expose les différents points de vue sur la recherche translationnelle et la collaboration des patients au processus, dans le domaine de la transplantation rénale. Elle illustre également la façon dont ces approches ont mené à des progrès marqués dans le domaine et plaide pour une collaboration volontaire et ciblée entre les différents intervenants ainsi que pour une plus grande implication des patients dans la recherche.

[1]  L. Czer,et al.  Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. , 1994, Transplantation.

[2]  S. Greenstein,et al.  Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study. , 1998, Transplantation.

[3]  J M Smith,et al.  OPTN/SRTR 2012 Annual Data Report: Kidney , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  A. Bingaman,et al.  Histocompatibility considerations for kidney paired donor exchange programs , 2012, Current opinion in organ transplantation.

[5]  P. Stratta,et al.  Quality of life in renal transplant patients over 60 years of age. , 2008, Transplantation proceedings.

[6]  G. Forrest Inpatient rehabilitation of patients requiring hemodialysis. , 2004, Archives of physical medicine and rehabilitation.

[7]  D. Hathaway,et al.  The first report from the patient outcomes registry for transplant effects on life (PORTEL): differences in side‐effects and quality of life by organ type, time since transplant and immunosuppressive regimens , 2003, Clinical transplantation.

[8]  R. Colvin,et al.  Humoral rejection in kidney transplantation: new concepts in diagnosis and treatment , 2002, Current opinion in nephrology and hypertension.

[9]  S. De Geest,et al.  Supporting medication adherence in renal transplantation (SMART): a pilot RCT to improve adherence to immunosuppressive regimens , 2006, Clinical transplantation.

[10]  Alexander A Kon,et al.  The Clinical and Translational Science Award (CTSA) Consortium and the Translational Research Model , 2008, The American journal of bioethics : AJOB.

[11]  P. Reese,et al.  Deceased-donor kidney perfusate and urine biomarkers for kidney allograft outcomes: a systematic review. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[12]  M. Schnitzler,et al.  Transplant Outcomes and Economic Costs Associated with Patient Noncompliance to Immunosuppression , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  D. Wishart,et al.  Urinary Metabolomics for Noninvasive Detection of Borderline and Acute T Cell–Mediated Rejection in Children After Kidney Transplantation , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  D. Segev,et al.  Kidney paired donation and optimizing the use of live donor organs. , 2005, JAMA.

[15]  R. Montgomery,et al.  Defining unacceptable HLA antigens. , 2008, Current opinion in organ transplantation.

[16]  K. Tinckam Histocompatibility methods. , 2009, Transplantation reviews.

[17]  R. Kowalewski,et al.  Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study. , 2009, Transplantation proceedings.

[18]  L. Kucirka,et al.  Desensitization in HLA-incompatible kidney recipients and survival. , 2011, The New England journal of medicine.

[19]  Susan Martin,et al.  Tools for human leukocyte antigen antibody detection and their application to transplanting sensitized patients. , 2008, Transplantation.

[20]  S. Knechtle,et al.  Urine proteomics in kidney transplantation. , 2014, Transplantation reviews.

[21]  J. Westfall,et al.  Practice-based research--"Blue Highways" on the NIH roadmap. , 2007, JAMA.

[22]  D. Rubio,et al.  Defining Translational Research: Implications for Training , 2010, Academic medicine : journal of the Association of American Medical Colleges.

[23]  M. Fiatarone Singh,et al.  Exercise Training in Patients Receiving Maintenance Hemodialysis: A Systematic Review of Clinical Trials , 2005, American Journal of Nephrology.

[24]  S. Mulgaonkar,et al.  Renal Transplantation in Patients With Pre‐Transplant Donor‐Specific Antibodies and Negative Flow Cytometry Crossmatches , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[25]  A. Matas,et al.  Graft and quality of life outcomes in older recipients of a kidney transplant. , 2003, Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation.

[26]  R. Montgomery,et al.  Transplanting the highly sensitized patient: trials and tribulations , 2013, Current opinion in nephrology and hypertension.

[27]  J. Kanellis,et al.  Understanding crossmatch testing in organ transplantation: A case‐based guide for the general nephrologist , 2011, Nephrology.

[28]  R. Montgomery,et al.  PLASMAPHERESIS AND INTRAVENOUS IMMUNE GLOBULIN PROVIDES EFFECTIVE RESCUE THERAPY FOR REFRACTORY HUMORAL REJECTION AND ALLOWS KIDNEYS TO BE SUCCESSFULLY TRANSPLANTED INTO CROSS-MATCH-POSITIVE RECIPIENTS , 2000, Transplantation.

[29]  S. Reis,et al.  Crossing the Research Valleys of Death: The University of Pittsburgh Approach , 2008, Clinical and Translational Science.

[30]  M. Fernandez-Vina,et al.  A HIGH PANEL-REACTIVE ANTIBODY RESCUE PROTOCOL FOR CROSS-MATCH-POSITIVE LIVE DONOR KIDNEY TRANSPLANTS1 , 2000, Transplantation.

[31]  P. Terasaki,et al.  Predicting Kidney Graft Failure by HLA Antibodies: a Prospective Trial , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[32]  Michele Tarsilla Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[33]  P. Archdeacon,et al.  Summary of FDA Antibody‐Mediated Rejection Workshop , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[34]  Michael Hoerger,et al.  Educating the Psychology Workforce in the Age of the Affordable Care Act: A Graduate Course Modeled after the Priorities of the Patient-Centered Outcomes Research Institute (PCORI). , 2015, Training and education in professional psychology.

[35]  I. Doxiadis,et al.  The acceptable mismatch program as a fast tool for highly sensitized patients awaiting a cadaveric kidney transplantation: short waiting time and excellent graft outcome. , 2004, Transplantation.

[36]  Germaine Wong,et al.  The perspectives of kidney transplant recipients on medicine taking: a systematic review of qualitative studies. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[37]  P. Shekelle,et al.  Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials , 2004, BMJ : British Medical Journal.

[38]  A. Laupacis,et al.  A study of the quality of life and cost-utility of renal transplantation. , 1996, Kidney international.

[39]  R. Montgomery,et al.  A GPS for finding the route to transplantation for the sensitized patient , 2012, Current opinion in organ transplantation.

[40]  P. Glasziou,et al.  Avoidable waste in the production and reporting of research evidence , 2009, The Lancet.

[41]  S. Chadban,et al.  Patients' priorities for health research: focus group study of patients with chronic kidney disease. , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[42]  S. Straus,et al.  Learning in practice The case for knowledge translation : shortening the journey from evidence to effect , 2003 .

[43]  A. Terzic,et al.  Clinical and Translational Science: From Bench‐Bedside to Global Village , 2010, Clinical and translational science.

[44]  Gerhard Opelz,et al.  HLA matching and kidney transplantation: beyond graft survival. , 2013, Clinical transplants.

[45]  E. Gordon,et al.  Medication‐taking among adult renal transplant recipients: barriers and strategies , 2009, Transplant international : official journal of the European Society for Organ Transplantation.

[46]  B. Hemmelgarn,et al.  Research priority setting in kidney disease: a systematic review. , 2015, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[47]  J. Klein,et al.  George Snell's first foray into the unexplored territory of the major histocompatibility complex. , 2001, Genetics.

[48]  Iain Chalmers,et al.  How to increase value and reduce waste when research priorities are set , 2014, The Lancet.

[49]  R. Brook Medical leadership in an increasingly complex world. , 2010, JAMA.

[50]  J. Broerse,et al.  Patient involvement in a scientific advisory process: setting the research agenda for medical products. , 2012, Health policy.

[51]  H. Allore,et al.  A program to prevent functional decline in physically frail, elderly persons who live at home. , 2002, The New England journal of medicine.

[52]  F. Marincola Translational Medicine: A two-way road , 2003, Journal of Translational Medicine.

[53]  J. Cecka,et al.  Current methodologies for detecting sensitization to HLA antigens , 2011, Current opinion in organ transplantation.

[54]  K. Budde,et al.  Identification and Therapeutic Management of Highly Sensitized Patients Undergoing Renal Transplantation , 2012, Drugs.

[55]  J F Burdick,et al.  International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. , 1993, Kidney international.

[56]  S. Staniszewska,et al.  Mapping the impact of patient and public involvement on health and social care research: a systematic review , 2014, Health expectations : an international journal of public participation in health care and health policy.

[57]  J. Haymann,et al.  SUPPRESSION OF HLA‐SPECIFIC ALLOANTIBODIES BY HIGH‐DOSE INTRAVENOUS IMMUNOGLOBULINS (IVIg): A POTENTIAL TOOL FOR TRANSPLANTATION OF IMMUNIZED PATIENTS , 1993, Transplantation.

[58]  R. Shapiro,et al.  Antibody-Mediated Rejection in Kidney Transplantation: A Review , 2012, Journal of transplantation.

[59]  J. Farragher,et al.  A Cross-Sectional Study Examining the Functional Independence of Elderly Individuals With a Functioning Kidney Transplant , 2014, Transplantation.

[60]  A. Halawa The early diagnosis of acute renal graft dysfunction: a challenge we face. The role of novel biomarkers. , 2011, Annals of transplantation.

[61]  A. Michael Borkon,et al.  Successful renal transplantation despite low levels of donor‐specific HLA class I antibody without IVIg or plasmapheresis , 2006, Clinical transplantation.

[62]  L. Lesko,et al.  Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. , 2001, Annual review of pharmacology and toxicology.

[63]  P. Terasaki,et al.  THE SIGNIFICANCE OF A POSITIVE FLOW CYTOMETRY CROSSHATCH TEST IN PRIMARY KIDNEY TRANSPLANTATION , 1993, Transplantation.

[64]  P. Nickerson,et al.  Detection of Subclinical Tubular Injury After Renal Transplantation: Comparison of Urine Protein Analysis With Allograft Histopathology , 2007, Transplantation.

[65]  K. Wade,et al.  Practice-Based Research , 2007, Social work in health care.

[66]  G. Elwyn,et al.  Identifying and prioritizing uncertainties: patient and clinician engagement in the identification of research questions. , 2010, Journal of evaluation in clinical practice.

[67]  D. Butler Translational research: Crossing the valley of death , 2008, Nature.

[68]  Matthias Egger,et al.  Inpatient rehabilitation specifically designed for geriatric patients: systematic review and meta-analysis of randomised controlled trials , 2010, BMJ : British Medical Journal.

[69]  K. Tinckam,et al.  Desensitization Outcomes: Quantifying and Questioning , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[70]  P. Giannoudis,et al.  Translational research: from benchside to bedside. , 2008, Injury.

[71]  G. Guyatt,et al.  The impact of measuring patient-reported outcomes in clinical practice: a systematic review of the literature , 2008, Quality of Life Research.

[72]  R. Marcus,et al.  Antibody-mediated rejection following renal transplantation , 2007, Expert opinion on pharmacotherapy.

[73]  S. Chadban,et al.  The Treatment of Acute Antibody-Mediated Rejection in Kidney Transplant Recipients—A Systematic Review , 2012, Transplantation.

[74]  A Chkhotua,et al.  Paired kidney donation: outcomes, limitations, and future perspectives. , 2012, Transplantation proceedings.

[75]  S. Woolf The meaning of translational research and why it matters. , 2008, JAMA.

[76]  C. Haisch,et al.  Incidence and Impact of De Novo Donor-Specific Alloantibody in Primary Renal Allografts , 2013, Transplantation.

[77]  U. Heemann,et al.  Quality of life in kidney recipients: comparison of tacrolimus and cyclosporine‐microemulsion , 2002, Clinical transplantation.

[78]  P. Sinnott,et al.  Pretransplant Donor-Specific Antibodies in Cytotoxic Negative Crossmatch Kidney Transplants: Are They Relevant? , 2008, Transplantation.

[79]  H. Ishida,et al.  Analysis of Predictive and Preventive Factors for De Novo DSA in Kidney Transplant Recipients , 2014, Transplantation.

[80]  P. Nickerson,et al.  Flow cytometric crossmatching in primary renal transplant recipients with a negative anti-human globulin enhanced cytotoxicity crossmatch. , 2001, Journal of the American Society of Nephrology : JASN.

[81]  R. Montgomery,et al.  Renal Transplantation Across HLA and ABO Antibody Barriers: Integrating Paired Donation into Desensitization Protocols , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[82]  A. Laupacis,et al.  Setting research priorities for patients on or nearing dialysis. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[83]  Mario Plebani,et al.  What's next in translational medicine? , 2007, Clinical science.

[84]  N. Heyne,et al.  Urinary Neutrophil Gelatinase-Associated Lipocalin Accurately Detects Acute Allograft Rejection Among Other Causes of Acute Kidney Injury in Renal Allograft Recipients , 2012, Transplantation.

[85]  Ethan M Balk,et al.  KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. , 2010, Kidney international.

[86]  F. Dobbels,et al.  Prevalence, consequences, and determinants of nonadherence in adult renal transplant patients: a literature review , 2005, Transplant international : official journal of the European Society for Organ Transplantation.

[87]  P. Tugwell,et al.  Prevention and self-management interventions are top priorities for osteoarthritis systematic reviews. , 2013, Journal of clinical epidemiology.

[88]  Stephen B. Johnson,et al.  Central challenges facing the national clinical research enterprise. , 2003, JAMA.

[89]  J. Platt,et al.  A national conference to determine research priorities in pediatric solid organ transplantation , 2008, Pediatric transplantation.

[90]  Cecka Jm Current methodologies for detecting sensitization to HLA antigens. , 2011 .

[91]  R. Colvin,et al.  Banff 2011 Meeting Report: New Concepts in Antibody‐Mediated Rejection , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[92]  M. Christiaans,et al.  Clinical Relevance of Pretransplant Donor-Directed Antibodies Detected by Single Antigen Beads in Highly Sensitized Renal Transplant Patients , 2008, Transplantation.

[93]  R. Walker,et al.  Urinary tubular biomarkers as potential early predictors of renal allograft rejection , 2012, Nephrology.

[94]  J. Dipiro,et al.  Impact of clinical pharmacy services on renal transplant patients’ compliance with immunosuppressive medications , 2001, Clinical transplantation.

[95]  P. Nickerson,et al.  Evolution and Clinical Pathologic Correlations of De Novo Donor‐Specific HLA Antibody Post Kidney Transplant , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[96]  M. Mitsnefes,et al.  Kidney NGAL is a novel early marker of acute injury following transplantation , 2006, Pediatric Nephrology.

[97]  B. Benacerraf Significance and biological function of class II MHC molecules. Rous-Whipple Award lecture 1985. , 1985, The American journal of pathology.