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Verfasst von:Speer, Timotheus [VerfasserIn]   i
 Schunk, Stefan J [VerfasserIn]   i
 Sarakpi, Tamim [VerfasserIn]   i
 Schmit, David [VerfasserIn]   i
 Wagner, Martina [VerfasserIn]   i
 Arnold, Ludger [VerfasserIn]   i
 Zewinger, Stephen [VerfasserIn]   i
 Azukaitis, Karolis [VerfasserIn]   i
 Bayazit, Aysun [VerfasserIn]   i
 Obrycki, Lukasz [VerfasserIn]   i
 Kaplan Bulut, Ipek [VerfasserIn]   i
 Duzova, Ali [VerfasserIn]   i
 Doyon, Anke [VerfasserIn]   i
 Ranchin, Bruno [VerfasserIn]   i
 Caliskan, Salim [VerfasserIn]   i
 Harambat, Jerome [VerfasserIn]   i
 Yilmaz, Alev [VerfasserIn]   i
 Alpay, Harika [VerfasserIn]   i
 Lugani, Francesca [VerfasserIn]   i
 Balat, Ayse [VerfasserIn]   i
 Arbeiter, Klaus [VerfasserIn]   i
 Longo, Germana [VerfasserIn]   i
 Melk, Anette [VerfasserIn]   i
 Querfeld, Uwe [VerfasserIn]   i
 Wühl, Elke [VerfasserIn]   i
 Mehls, Otto [VerfasserIn]   i
 Fliser, Danilo [VerfasserIn]   i
 Schaefer, Franz [VerfasserIn]   i
Titel:Urinary DKK3 as a biomarker for short-term kidney function decline in children with chronic kidney disease
Titelzusatz:an observational cohort study
Verf.angabe:Thimoteus Speer, Stefan J Schunk, Tamim Sarakpi, David Schmit, Martina Wagner, Ludger Arnold, Stephen Zewinger, Karolis Azukaitis, Aysun Bayazit, Lukasz Obrycki, Ipek Kaplan Bulut, Ali Duzova, Anke Doyon, Bruno Ranchin, Salim Caliskan, Jerome Harambat, Alev Yilmaz, Harika Alpay, Francesca Lugani, Ayse Balat, Klaus Arbeiter, Germana Longo, Anette Melk, Uwe Querfeld, Elke Wühl, Otto Mehls, Danilo Fliser, Franz Schaefer
E-Jahr:2023
Jahr:June 2023
Umfang:10 S.
Fussnoten:Online verfügbar: 26. April 2023, Artikelversion: 17. Mai 2023 ; Gesehen am 07.08.2023
Titel Quelle:Enthalten in: The lancet child & adolescent health
Ort Quelle:Kidlington, Oxford : Elsevier, 2017
Jahr Quelle:2023
Band/Heft Quelle:7(2023), 6 vom: Juni, Seite 405-414
ISSN Quelle:2352-4650
Abstract:Background - Childhood-onset chronic kidney disease is a progressive condition that can have a major effect on life expectancy and quality. We evaluated the usefulness of the kidney tubular cell stress marker urinary Dickkopf-related protein 3 (DKK3) in determining the short-term risk of chronic kidney disease progression in children and identifying those who will benefit from specific nephroprotective interventions. - Methods - In this observational cohort study, we assessed the association between urinary DKK3 and the combined kidney endpoint (ie, the composite of 50% reduction of the estimated glomerular filtration rate [eGFR] or progression to end-stage kidney disease) or the risk of kidney replacement therapy (ie, dialysis or transplantation), and the interaction of the combined kidney endpoint with intensified blood pressure reduction in the randomised controlled ESCAPE trial. Moreover, urinary DKK3 and eGFR were quantified in children aged 3-18 years with chronic kidney disease and urine samples available enrolled in the prospective multicentre ESCAPE (NCT00221845; derivation cohort) and 4C (NCT01046448; validation cohort) studies at baseline and at 6-monthly follow-up visits. Analyses were adjusted for age, sex, hypertension, systolic blood pressure SD score (SDS), BMI SDS, albuminuria, and eGFR. - Findings - 659 children were included in the analysis (231 from ESCAPE and 428 from 4C), with 1173 half-year blocks in ESCAPE and 2762 in 4C. In both cohorts, urinary DKK3 above the median (ie, >1689 pg/mg creatinine) was associated with significantly greater 6-month eGFR decline than with urinary DKK3 at or below the median (-5·6% [95% CI -8·6 to -2·7] vs 1·0% [-1·9 to 3·9], p<0·0001, in ESCAPE; -6·2% [-7·3 to -5·0] vs -1·5% [-2·9 to -0·1], p<0·0001, in 4C), independently of diagnosis, eGFR, and albuminuria. In ESCAPE, the beneficial effect of intensified blood pressure control was limited to children with urinary DKK3 higher than 1689 pg/mg creatinine, in terms of the combined kidney endpoint (HR 0·27 [95% CI 0·14 to 0·55], p=0·0003, number needed to treat 4·0 [95% CI 3·7 to 4·4] vs 250·0 [66·9 to ∞]) and the need for kidney replacement therapy (HR 0·33 [0·13 to 0·85], p=0·021, number needed to treat 6·7 [6·1 to 7·2] vs 31·0 [27·4 to 35·9]). In 4C, inhibition of the renin-angiotensin-aldosterone system resulted in significantly lower urinary DKK3 concentrations (least-squares mean 12 235 pg/mg creatinine [95% CI 10 036 to 14 433] in patients not on angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers vs 6861 pg/mg creatinine [5616 to 8106] in those taking angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers, p<0·0001). - Interpretation - Urinary DKK3 indicates short-term risk of declining kidney function in children with chronic kidney disease and might allow a personalised medicine approach by identifying those who benefit from pharmacological nephroprotection, such as intensified blood pressure lowering. - Funding - None.
DOI:doi:10.1016/S2352-4642(23)00049-4
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/S2352-4642(23)00049-4
 Volltext: https://www.sciencedirect.com/science/article/pii/S2352464223000494
 DOI: https://doi.org/10.1016/S2352-4642(23)00049-4
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1854470000
Verknüpfungen:→ Zeitschrift

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