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Fiona Karet

Renal tubular homeostasis in health and disease

My group's work began in the area of renal tubular function and its associated diseases, many of which are inherited and most of which are rare but confer a major health burden on both patients and providers.

Our laboratory research has more recently been focused on three areas:

1. Characterization of the human urinary exosome as potential functional player in renal homeostasis (the first being maintenance of urinary sterility) and source of biomarkers;

2. The natural history of a variety of rare tubulopathies

3. Development of a hand-held sensor for point-of-care potassium testing, which has resulted in the recent creation of a small spin-out company, Kalium Health Ltd

Having previously demonstrated a role for urinary exosomes in maintenance of urinary sterility, our current characterization of human and animal urinary exosomes focuses on biomarker development in tubular disorders, function in recurrent urinary tract infections (UTIs), assessment of RNA species and developing better methods for quantitative assessments.

Our laboratory work is complemented by clinic-based studies emanating from the Cambridge Renal Genetic and Tubular Disorders service that I lead, where patients with a variety of such disorders are investigated and managed. Current clinical studies focus upon patient cohorts with Polycystic Kidney Disease, Gitelman Syndrome and recurrent renal stone disease.

 

Karet lab

Key papers

ND Palmer, FE Karet Frankl, E Kruzel-Davila & BI Freedman. Genetics and Chronic Kidney Disease. in: Chronic Renal Disease (2nd Edition). Ed. PL Kimmel & MD Rosenberg, Elsevier, ISBN 978-0-12-815876-0, 2020

R El-Damanawi, M Lee, T Harris, LB Cowley, S Bond, H Pavey, RN Sandford, IB Wilkinson, FE Karet Frankl & TF Hiemstra. High Water versus Ad libitum Water Intake for Autosomal Dominant Polycystic Kidney Disease: A Randomised Controlled Feasibility Trial. QJM doi: 10.1093/qjmed/hcz326, 2020

TL Williams, C Bastos, N Faria & FE Karet Frankl. Making urinary extracellular vesicles a clinically tractable source of biomarkers for inherited tubulopathies using a small volume precipitation method: proof of concept. J Nephrol. doi: 10.1007/s40620-019-00653-8, 2019

Day C, Søpstad S, Ma H, Jiang C, Nathan A, Elliott SR, Karet Frankl FE & Hutter TF. Impedance-based sensor for potassium ions. Analytica Chimica Acta 1034:39-45, 2018

El-Damanawi R, Lee M, Harris T, Mader L, Bond S, Pavey H, Sandford RN, Wilkinson IB, Woznowski P, Ben-Shlomo Y, Karet Frankl FE & Hiemstra TF.A Randomised Controlled Trial of High versus Ad Libitum Water Intake in Patients with Autosomal Dominant Polycystic Kidney Disease: Rationale and Design of the DRINK Feasibility Trial. BMJ Open 8:e022859. doi:10.1136/ bmjopen-2018-022859, 2018

Gracia TR, Wang X, Su Y, Norgett EE, Williams TL, Moreno P, Micklem G & Karet Frankl FE. Urinary exosomes contain microRNAs capable of paracrine modulation of tubular transporters. Sci. Rep. 7:40601, 2017

Su Y, Hiemstra TF, Yan Y, Li J, Karet HI, Rosen L, Moreno P and Karet Frankl FE. PDLIM5 links kidney anion exchanger 1 (AE1) to ILK and is required for membrane targeting of kAE1. Sci. Rep. 7:39701, 2017

A Blanchard, D Bockenhauer, D Bolignano,LA Calò, E Cosyns, O Devuyst, DH Ellison, FE Karet Frankl, NVAM Knoers, M Konrad, S-H Lin, R Vargas-Poussou (all joint, listed alphabetically). Gitelman syndrome: Consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int  91:24-33, 2017

C Robinson and FE Karet Frankl. Magnesium Lactate in the Treatment of Gitelman Syndrome – Patient Reported Outcomes. Nephrol. Dialysis Transplant 32:508-512, 2017

FE Karet Frankl. The importance of being rare. Lancet 388:632, 2016

Fiona Karet

Professor Fiona Karet

Professor of Nephrology; Honorary Consultant in Renal Medicine;
Director of Organisational Affairs, School of Clinical Medicine

Department: Medical Genetics

Contact: fek1000@cam.ac.uk

 

 

Plain English

Our kidneys are responsible for keeping many substances in the body in balance (such as salt, potassium, calcium and acid) and, when any of these goes wrong, disorders including Gitelman syndrome, hypertension or recurrent kidney stones can result. We have previously characterized the genes that are mutated in these diseases, and looked to understand their underlying function in the kidney. A related aim focuses on small packages termed 'exosomes' that are released by kidney cells into urine that we have discovered kill bacteria, and may also have potential for diagnosis of kidney malfunction. We also study common inherited kidney disorders such as polycystic kidney disease, and are developing a handheld kit that will enable anyone, anywhere to measure blood potassium levels, which is crucial to management of almost all forms of kidney disease.

Group members

Tim Williams and Jenni Karttunen (University of Cambridge), Susana Borja-Boluda (NHS), Liz Norgett and Greg Orlowski (Kalium Health Ltd)

Funding

Kidney Research UK

NIHR Cambridge Biomedical Research Centre