Nephron overload as a therapeutic target to maximize kidney lifespan.

[en] Kidney lifespan is a patient-oriented outcome that provides much needed context for understanding chronic kidney disease (CKD). Nephron endowment, age-associated decline in nephron number, kidney injury history and the intrinsic capacity of nephrons to adapt to haemodynamic and metabolic overload vary widely within the population. Defining percentiles of kidney function might therefore help to predict individual kidney lifespan and distinguish healthy ageing from progressive forms of CKD. In response to nephron loss, the remaining nephrons undergo functional and structural adaptations to meet the ongoing haemodynamic and metabolic demands of the organism. When these changes are no longer sufficient to maintain kidney cell homeostasis, remnant nephron demise occurs and CKD progression ensues. An individual's trajectory of glomerular filtration rate and albuminuria reflects the extent of nephron loss and adaptation of the remaining nephrons. Nephron overload represents the final common pathway of CKD progression and is largely independent of upstream disease mechanisms. Thus, interventions that efficiently attenuate nephron overload in early disease stages can protect remnant kidney cells and nephrons, and delay CKD progression. This Review provides a conceptual framework for individualized diagnosis, monitoring and treatment of CKD with the goal of maximizing kidney lifespan.

Disciplines :

Urology & nephrology

Author, co-author :

Luyckx, Valerie A ; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa ; Department of Nephrology, University Children's Hospital, Zurich, Switzerland

Rule, Andrew D ; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA ; Division of Epidemiology, Mayo Clinic, Rochester, MN, USA

Tuttle, Katherine R ; Providence Medical Research Center, Providence Health Care, Spokane, WA, USA ; Institute of Translational Health Sciences, Kidney Research Institute and Nephrology Division, University of Washington, Seattle, WA, USA

DELANAYE, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de néphrologie ; Department of Nephrology-Dialysis-Apheresis, Hopital Universitaire Caremeau, Nimes, France

Liapis, Helen; Renal Division, Department of Medicine IV, University Hospital of the Ludwig Maximilian University, Munich, Germany

Gandjour, Afschin ; Frankfurt School of Finance and Management, Frankfurt am Main, Germany

Romagnani, Paola ; Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy ; Nephrology Unit, Anna Meyer Children's Hospital, Florence, Italy

Anders, Hans-Joachim ; Renal Division, Department of Medicine IV, University Hospital of the Ludwig Maximilian University, Munich, Germany. hjanders@med.uni-muenchen.de

Language :

English

Title :

Nephron overload as a therapeutic target to maximize kidney lifespan.

Publication date :

08 December 2021

Journal title :

Nature Reviews Nephrology

ISSN :

1759-5061

eISSN :

1759-507X

Publisher :

Nature Research, England

Volume :

Issue :

Pages :

171-183

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.nature.com/articles/s41581-021-00510-7.pdf

Funding text :

K.R.T. is supported by four NIDDK/NIH grants, one NCATS/ NIH grant, one NIMHD/NIH grant, and a CDC contract all from the US Government, as well as research grants from Goldfinch Bio, Bayer and Travere. A.D.R. is supported by funding from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK090358). H.-J.A. is supported by the Deutsche Forschungsgemeinschaft (AN372/30-1).

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