Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2022 May 20:35:10139.
doi: 10.3389/ti.2022.10139. eCollection 2022.

Allograft Function as Endpoint for Clinical Trials in Kidney Transplantation

Luuk Hilbrands  1 , Klemens Budde  2 , Maria Irene Bellini  3 , Fritz Diekmann  4 , Lucrezia Furian  5 , Josep Grinyó  6 , Uwe Heemann  7 , Dennis A Hesselink  8 , Alexandre Loupy  9 , Rainer Oberbauer  10 , Liset Pengel  11 , Marlies Reinders  8 , Stefan Schneeberger  12 , Maarten Naesens  13
Affiliations
Editorial

Allograft Function as Endpoint for Clinical Trials in Kidney Transplantation

Luuk Hilbrands et al. Transpl Int. .

Abstract

Clinical study endpoints that assess the efficacy of interventions in patients with chronic renal insufficiency can be adopted for use in kidney transplantation trials, given the pathophysiological similarities between both conditions. Kidney dysfunction is reflected in the glomerular filtration rate (GFR), and although a predefined (e.g., 50%) reduction in GFR was recommended as an endpoint by the European Medicines Agency (EMA) in 2016, many other endpoints are also included in clinical trials. End-stage renal disease is strongly associated with a change in estimated (e)GFR, and eGFR trajectories or slopes are increasingly used as endpoints in clinical intervention trials in chronic kidney disease (CKD). Similar approaches could be considered for clinical trials in kidney transplantation, although several factors should be taken into account. The present Consensus Report was developed from documentation produced by the European Society for Organ Transplantation (ESOT) as part of a Broad Scientific Advice request that ESOT submitted to the EMA in 2020. This paper provides a contemporary discussion of primary endpoints used in clinical trials involving CKD, including proteinuria and albuminuria, and evaluates the validity of these concepts as endpoints for clinical trials in kidney transplantation.

Keywords: clinical study; endpoints; graft dysfunction; graft function; kidney transplantation.

PubMed Disclaimer

Conflict of interest statement

LH reports speaker fees from Astellas, consultancy and research support from Chiesi, consultancy for Novartis, and research support from Sandoz. KB has received honoraria and/or research funding from Alexion, Astellas, Bristol Myers Squibb, Chiesi, Fresenius, Hansa, Hexal, Merck, Novartis, Otsuka, Pfizer, Roche, Sandoz, Siemens, and Veloxis. LF has received honoraria and/or research funding from Astellas, Chiesi, Hansa, and Novartis. JG consults for Sanofi. UH has received grants/research support from Baxter, Chiesi, and Neovii; speakers' bureaux/honoraria from Chiesi and Hansa; and consulting fees from Astellas, Hansa, Neovii, Novartis, and Teva. DH has received lecture fees and consulting fees from Astellas, Chiesi, MedinCell, Novartis, and Vifor; and grant support (paid to institution) from Astellas, Bristol Myers Squibb, and Chiesi. RO has received grants/research support from Amgen, Astellas, and Chiesi; and speakers' bureaux/honoraria from Amgen, Astellas, Chiesi, Hansa, Neovii, Novartis, and Teva. MR has received lecture fees from Astellas and Chiesi; and research grant support (paid to institution) from Astellas and Chiesi for investigator initiated studies. SS has received grants/research support from Bridge to Life, Chiesi, Neovii, Novartis, Organ Recovery Systems, and Sandoz; speakers' bureaux/honoraria from Astellas, BMS, Chiesi, Novartis, OrganOx, and Sanofi; and consulting fees from Astellas, Atara, Merck, NefroHealth, Novartis, Sandoz, and Teva. The remaining authors declare that the work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Naesens M, Kuypers DRJ, De Vusser K, Evenepoel P, Claes K, Bammens B, et al. The Histology of Kidney Transplant Failure. Transplantation (2014) 98:427–35. 10.1097/tp.0000000000000183 - DOI - PubMed
    1. McCaughan JA, Courtney AE, Maxwell AP. Estimated Glomerular Filtration Rate Decline as a Predictor of Dialysis in Kidney Transplant Recipients. Am J Nephrol (2014) 39:297–305. 10.1159/000360426 - DOI - PubMed
    1. European Medicines Agenc. Guideline on the Clinical Investigation of Medicinal Products to Prevent Development/slow Progression of Chronic Renal Insufficiency (2016). Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-cl... (Accessed December 13, 2021).
    1. Levey A, Inker L. Assessment of Glomerular Filtration Rate in Health and Disease: a State of the Art Review. Clin Pharmacol Ther (2017) 102:405–19. 10.1002/cpt.729 - DOI - PubMed
    1. Risch L, Herklotz R, Blumberg A, Huber AR. Effects of Glucocorticoid Immunosuppression on Serum Cystatin C Concentrations in Renal Transplant Patients. Clin Chem (2001) 47:2055–9. 10.1093/clinchem/47.11.2055 - DOI - PubMed

Publication types