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Article ; Online: Urinary extracellular vesicles as a source of protein-based biomarkers in feline chronic kidney disease and hypertension.

Lawson, J S / Syme, H M / Antrobus, P R / Karttunen, J M / Stewart, S E / Karet Frankl, F E / Williams, T L

2022 Volume 64, Issue 1, Page(s) 3–11

Abstract: Objectives: To validate a methodology for isolating feline urinary extracellular vesicles and characterise the urinary extracellular vesicle population and proteome in cats with normal renal function and cats with normotensive or hypertensive chronic ... ...

Abstract	Objectives: To validate a methodology for isolating feline urinary extracellular vesicles and characterise the urinary extracellular vesicle population and proteome in cats with normal renal function and cats with normotensive or hypertensive chronic kidney disease. Methods: Feline urinary extracellular vesicles were isolated using three different methods (precipitation alone, precipitation followed by size exclusion chromatography and ultrafiltration followed by size exclusion chromatography, which were compared via transmission electron microscopy and nanoparticle tracking analysis. Cats with normal renal function (n=9), normotensive chronic kidney disease (n=10) and hypertensive chronic kidney disease (n=9) were identified and urinary extracellular vesicles isolated from patient urine samples via ultrafiltration followed by size exclusion chromatography. Extracellular vesicle size and concentration were determined using nanoparticle tracking analysis, and subsequently underwent proteomic analysis using liquid chromatography with tandem mass spectrometry to identify differences in protein expression between categories. Results: Urinary extracellular vesicle preparations contained particles of the expected size and morphology, and those obtained by ultrafiltration + size exclusion chromatography had a significantly higher purity (highest particle: protein ratio). The urinary extracellular vesicle proteomes contained extracellular vesicle markers and proteins originating from all nephron segments. Urinary extracellular vesicle concentration and size were unaffected by renal disease or hypertension. There were no differentially expressed proteins detected when comparing urinary extracellular vesicles derived from cats in the healthy category with the combined chronic kidney disease category, but five differentially expressed proteins were identified between the normotensive chronic kidney disease and hypertensive chronic kidney disease categories. Clinical significance: Feline urinary extracellular vesicles can be successfully isolated from stored urine samples. Differentially expressed urinary extracellular vesicle proteins were discovered in cats with hypertensive chronic kidney disease, and warrant further investigation into their utility as biomarkers or therapeutic targets.
MeSH term(s)	Cats ; Animals ; Proteomics/methods ; Biomarkers/analysis ; Biomarkers/metabolism ; Extracellular Vesicles/chemistry ; Extracellular Vesicles/metabolism ; Proteome/analysis ; Proteome/metabolism ; Hypertension, Renal/metabolism ; Hypertension, Renal/veterinary ; Renal Insufficiency, Chronic/veterinary ; Cat Diseases
Chemical Substances	Biomarkers ; Proteome
Language	English
Publishing date	2022-07-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	410743-3
ISSN	1748-5827 ; 0022-4510 ; 1748-5827
ISSN (online)	1748-5827
ISSN	0022-4510 ; 1748-5827
DOI	10.1111/jsap.13536
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Article ; Online: Urinary extracellular vesicles as a source of protein‐based biomarkers in feline chronic kidney disease and hypertension

Lawson, J. S. / Syme, H. M. / Antrobus, P. R. / Karttunen, J. M. / Stewart, S. E. / Karet Frankl, F. E. / Williams, T. L.

Journal of Small Animal Practice. 2023 Jan., v. 64, no. 1 p.3-11

2023

Abstract: OBJECTIVES: To validate a methodology for isolating feline urinary extracellular vesicles and characterise the urinary extracellular vesicle population and proteome in cats with normal renal function and cats with normotensive or hypertensive chronic ... ...

Abstract	OBJECTIVES: To validate a methodology for isolating feline urinary extracellular vesicles and characterise the urinary extracellular vesicle population and proteome in cats with normal renal function and cats with normotensive or hypertensive chronic kidney disease. METHODS: Feline urinary extracellular vesicles were isolated using three different methods (precipitation alone, precipitation followed by size exclusion chromatography and ultrafiltration followed by size exclusion chromatography, which were compared via transmission electron microscopy and nanoparticle tracking analysis. Cats with normal renal function (n=9), normotensive chronic kidney disease (n=10) and hypertensive chronic kidney disease (n=9) were identified and urinary extracellular vesicles isolated from patient urine samples via ultrafiltration followed by size exclusion chromatography. Extracellular vesicle size and concentration were determined using nanoparticle tracking analysis, and subsequently underwent proteomic analysis using liquid chromatography with tandem mass spectrometry to identify differences in protein expression between categories. RESULTS: Urinary extracellular vesicle preparations contained particles of the expected size and morphology, and those obtained by ultrafiltration + size exclusion chromatography had a significantly higher purity (highest particle: protein ratio). The urinary extracellular vesicle proteomes contained extracellular vesicle markers and proteins originating from all nephron segments. Urinary extracellular vesicle concentration and size were unaffected by renal disease or hypertension. There were no differentially expressed proteins detected when comparing urinary extracellular vesicles derived from cats in the healthy category with the combined chronic kidney disease category, but five differentially expressed proteins were identified between the normotensive chronic kidney disease and hypertensive chronic kidney disease categories. CLINICAL SIGNIFICANCE: Feline urinary extracellular vesicles can be successfully isolated from stored urine samples. Differentially expressed urinary extracellular vesicle proteins were discovered in cats with hypertensive chronic kidney disease, and warrant further investigation into their utility as biomarkers or therapeutic targets.
Keywords	biomarkers ; cats ; gel chromatography ; gene expression regulation ; hypertension ; kidney diseases ; nanoparticles ; patients ; protein synthesis ; proteome ; proteomics ; renal function ; small animal practice ; tandem mass spectrometry ; therapeutics ; transmission electron microscopy ; ultrafiltration ; urine
Language	English
Dates of publication	2023-01
Size	p. 3-11.
Publishing place	Blackwell Publishing Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	410743-3
ISSN	1748-5827 ; 0022-4510 ; 1748-5827
ISSN (online)	1748-5827
ISSN	0022-4510 ; 1748-5827
DOI	10.1111/jsap.13536
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: PDLIM5 links kidney anion exchanger 1 (kAE1) to ILK and is required for membrane targeting of kAE1.

Su, Ya / Hiemstra, Thomas F / Yan, Yahui / Li, Juan / Karet, Hannah I / Rosen, Lawrence / Moreno, Pablo / Karet Frankl, Fiona E

Scientific reports

2017 Volume 7, Page(s) 39701

Abstract: Anion exchanger 1 (AE1) mediates ... ...

Abstract	Anion exchanger 1 (AE1) mediates Cl
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Anion Exchange Protein 1, Erythrocyte/genetics ; Anion Exchange Protein 1, Erythrocyte/metabolism ; Cell Membrane/metabolism ; Cell Polarity ; Chlorides/metabolism ; Cytoskeleton/metabolism ; HEK293 Cells ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Kidney/metabolism ; LIM Domain Proteins/metabolism ; Multiprotein Complexes/metabolism ; Protein Binding ; Protein Serine-Threonine Kinases/metabolism ; Protein Sorting Signals/genetics ; Protein Transport ; RNA, Small Interfering/genetics ; Sodium Bicarbonate/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Anion Exchange Protein 1, Erythrocyte ; Chlorides ; LIM Domain Proteins ; Multiprotein Complexes ; PDLIM5 protein, human ; Protein Sorting Signals ; RNA, Small Interfering ; Sodium Bicarbonate (8MDF5V39QO) ; integrin-linked kinase (EC 2.7.1.-) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2017-01-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep39701
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Article: Developing a patient-centred tool for pain measurement and evaluation in autosomal dominant polycystic kidney disease.

El-Damanawi, Ragada / Lee, Michael / Harris, Tess / Cowley, Laura B / Scholtes, Ingrid / Bond, Simon / Sandford, Richard N / Wilkinson, Ian B / Casteleijn, Niek F / Hogan, Marie C / Karet Frankl, Fiona E / Hiemstra, Thomas F

Clinical kidney journal

2021 Volume 14, Issue 11, Page(s) 2338–2348

Abstract: Background: Pain affects 60% of the autosomal dominant polycystic kidney disease (ADPKD) population. Despite being an early and debilitating symptom, it is poorly characterized and management is suboptimal. This study aimed to develop an ADPKD-specific ... ...

Abstract	Background: Pain affects 60% of the autosomal dominant polycystic kidney disease (ADPKD) population. Despite being an early and debilitating symptom, it is poorly characterized and management is suboptimal. This study aimed to develop an ADPKD-specific pain assessment tool (APAT) to facilitate pain research. Methods: Following a systematic review of PATs used in ADPKD studies and against international recommendations for pain trials, our multi-disciplinary team of clinical experts and patients constructed an ADPKD-pain conceptual framework of key pain evaluation themes. We compiled a new APAT covering domains prioritized within our framework using components of questionnaires validated in other chronic pain disorders. The APAT was administered longitudinally within a randomized high-water intake trial (NCT02933268) to ascertain feasibility and provide pilot data on ADPKD pain. Results: Thirty-nine ADPKD participants with chronic kidney disease Stages 1-4 provided 129 APAT responses. Each participant completed a median of 3 (range 1-10) assessments. Respondents' mean ± standard deviation age was 47 ± 13 years; 59% (23) were female; and 69% (27) had enlarged kidneys with median time from diagnosis 14.2 (interquartile range 7.0-25.9) years. Pain (52%) and associated analgesic use (29%) were common. Pain severity was associated with increasing age [odds ratio (OR) = 1.07, P = 0.009], female gender (OR = 4.34, P = 0.018), estimated glomerular filtration rate <60 mL/min/1.73 m Conclusions: The APAT demonstrated good acceptability and reliability, and following further validation in a larger cohort could represent an invaluable tool for future ADPKD pain studies.
Language	English
Publishing date	2021-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfaa259
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Article: Patient Survey of current water Intake practices in autosomal dominant Polycystic kidney disease: the SIPs survey.

El-Damanawi, Ragada / Harris, Tess / Sandford, Richard N / Karet Frankl, Fiona E / Hiemstra, Thomas F

Clinical kidney journal

2017 Volume 10, Issue 3, Page(s) 305–309

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2017-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfw153
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Article: Inherited renal tubular acidosis.

Karet, F E

Advances in nephrology from the Necker Hospital

2000 Volume 30, Page(s) 147–162

MeSH term(s)	Acid-Base Equilibrium ; Acidosis, Renal Tubular/complications ; Acidosis, Renal Tubular/genetics ; Deafness/complications ; Deafness/genetics ; Genes, Dominant ; Genes, Recessive ; Genetic Linkage ; Genome ; Humans ; Kidney/metabolism ; Mutation ; Pedigree
Language	English
Publishing date	2000
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	121702-1
ISSN	0084-5957
ISSN	0084-5957
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Article ; Online: Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

Wong, Katie / Pitcher, David / Braddon, Fiona / Downward, Lewis / Steenkamp, Retha / Annear, Nicholas / Barratt, Jonathan / Bingham, Coralie / Chrysochou, Constantina / Coward, Richard J / Game, David / Griffin, Sian / Hall, Matt / Johnson, Sally / Kanigicherla, Durga / Karet Frankl, Fiona / Kavanagh, David / Kerecuk, Larissa / Maher, Eamonn R /

Moochhala, Shabbir / Pinney, Jenny / Sayer, John A / Simms, Roslyn / Sinha, Smeeta / Srivastava, Shalabh / Tam, Frederick W K / Turner, Andrew Neil / Walsh, Stephen B / Waters, Aoife / Wilson, Patricia / Wong, Edwin / Taylor, Christopher Mark / Nitsch, Dorothea / Saleem, Moin / Bockenhauer, Detlef / Bramham, Kate / Gale, Daniel P

Lancet (London, England)

2024 Volume 403, Issue 10433, Page(s) 1279–1289

Abstract: Background: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers ... ...

Abstract	Background: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.
MeSH term(s)	Humans ; Glomerular Filtration Rate ; Kidney ; Kidney Failure, Chronic/epidemiology ; Kidney Failure, Chronic/therapy ; Kidney Failure, Chronic/etiology ; Radar ; Rare Diseases ; Registries ; Renal Insufficiency/epidemiology ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/therapy ; Renal Insufficiency, Chronic/complications ; United Kingdom/epidemiology ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)02843-X
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Article ; Online: Impedance-based sensor for potassium ions.

Day, C / Søpstad, S / Ma, H / Jiang, C / Nathan, A / Elliott, S R / Karet Frankl, F E / Hutter, T

Analytica chimica acta

2018 Volume 1034, Page(s) 39–45

Abstract: A conductometric sensor for potassium ions in solution is presented. Interdigitated, planar gold electrodes were coated with a potassium-selective polymer membrane composed of a poly(vinyl chloride) matrix with about 65 wt% of plasticiser and 2-5 wt% of ... ...

Abstract	A conductometric sensor for potassium ions in solution is presented. Interdigitated, planar gold electrodes were coated with a potassium-selective polymer membrane composed of a poly(vinyl chloride) matrix with about 65 wt% of plasticiser and 2-5 wt% of a potassium-selective ionophore. The impedance of the membrane was measured, using the electrodes as a transducer, and related to the concentration of potassium in a sample solution in contact with the membrane. Sensitivity was optimised by varying the sensor components, and selectivity for potassium over sodium was also shown. The resulting devices are compact, miniature, robust sensors which, by means of impedance measurements, eliminate the need for a reference electrode. The sensor was tested for potassium concentration changes of 2 mM across the clinically relevant range of 2.7-18.7 mM.
MeSH term(s)	Electric Impedance ; Electrochemical Techniques ; Ions/analysis ; Potassium/analysis
Chemical Substances	Ions ; Potassium (RWP5GA015D)
Language	English
Publishing date	2018-06-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2018.06.044
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Article ; Online: High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

El-Damanawi, R / Lee, M / Harris, T / Cowley, L B / Bond, S / Pavey, H / Sandford, R N / Wilkinson, I B / Karet Frankl, F E / Hiemstra, T F

QJM : monthly journal of the Association of Physicians

2019 Volume 113, Issue 4, Page(s) 306

Language	English
Publishing date	2019-12-28
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	1199985-8
ISSN	1460-2393 ; 0033-5622 ; 1460-2725
ISSN (online)	1460-2393
ISSN	0033-5622 ; 1460-2725
DOI	10.1093/qjmed/hcz326
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Article: Endothelin peptides and receptors in human kidney.

Karet, F E

Clinical science (London, England : 1979)

1996 Volume 91, Issue 3, Page(s) 267–273

Abstract: 1. Animal kidneys are exquisitely sensitive to the vasoconstrictor and antinatriuretic effects of the endogenous vascular peptide endothelin. Animal studies have implicated endothelin in cyclosporin A and ischaemia-mediated renal damage. 2. In man, ... ...

Abstract	1. Animal kidneys are exquisitely sensitive to the vasoconstrictor and antinatriuretic effects of the endogenous vascular peptide endothelin. Animal studies have implicated endothelin in cyclosporin A and ischaemia-mediated renal damage. 2. In man, endothelin levels are raised in various disorders. Orally active endothelin antagonists are now being developed, but little was known of endothelin's role as a renal peptide in humans. These studies therefore aimed to characterize endothelin peptides and receptors ETA and ETB in human kidney, to direct potential therapeutic endeavours. 3. Ligand binding, immunocytochemical, radioimmunoassay and molecular biological studies were used to establish endothelin as a renal peptide in man. 4. The identification of species differences between man and rat directed further development of quantitative molecular biological methodology to permit analysis of endothelin receptors in human renal biopsies, and demonstrated perturbation of the system in the context of cyclosporin A therapy in renal transplantation.
MeSH term(s)	Animals ; Base Sequence ; Cyclosporine/therapeutic use ; Endothelins/antagonists & inhibitors ; Endothelins/genetics ; Endothelins/metabolism ; Humans ; Immunohistochemistry ; Kidney/chemistry ; Kidney/metabolism ; Kidney Transplantation ; Molecular Sequence Data ; Polymerase Chain Reaction/methods ; Receptors, Endothelin/metabolism
Chemical Substances	Endothelins ; Receptors, Endothelin ; Cyclosporine (83HN0GTJ6D)
Language	English
Publishing date	1996-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	760216-9
ISSN	0143-5221 ; 0144-9664
ISSN	0143-5221 ; 0144-9664
DOI	10.1042/cs0910267
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