Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Titel eines Journals oder einer Zeitschrift: | Nephrology Dialysis Transplantation | ||||
Verlag: | Oxford Univ. Press | ||||
Band: | 35 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 7 | ||||
Seitenbereich: | S. 1187-1195 | ||||
Datum: | 2018 | ||||
Institutionen: | Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | ADMA, CKD, homoarginine, risk marker, SDMA | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Zum Teil | ||||
Dokumenten-ID: | 46444 |
Zusammenfassung
Background Elevated plasma concentrations of symmetric and asymmetric dimethylarginine (SDMA and ADMA, respectively) and a lower plasma concentration of the structurally related homoarginine are commonly observed in patients with chronic kidney disease (CKD) and independently predict total mortality as well as progression of renal disease. We aimed to identify drugs that may alter this adverse ...
Zusammenfassung
Background
Elevated plasma concentrations of symmetric and asymmetric dimethylarginine (SDMA and ADMA, respectively) and a lower plasma concentration of the structurally related homoarginine are commonly observed in patients with chronic kidney disease (CKD) and independently predict total mortality as well as progression of renal disease. We aimed to identify drugs that may alter this adverse metabolite pattern in a favourable fashion.
Methods
Plasma ADMA, SDMA, homoarginine and l-arginine were determined by liquid chromatography–tandem mass spectrometry in 4756 CKD patients ages 18–74 years with an estimated glomerular filtration rate (eGFR) of 30–60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 and overt proteinuria who were enrolled in the German Chronic Kidney Disease (GCKD) study. Associations between laboratory, clinical and medication data were assessed.
Results
Intake of several commonly used drugs was independently associated with plasma concentrations of homoarginine and/or related metabolites. Among these, the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate was associated with the most profound differences in ADMA, SDMA and homoarginine plasma concentrations: 66 patients taking fenofibrate had a multivariable adjusted odds ratio (OR) of 5.83 [95% confidence interval (CI) 2.82–12.03, P < 0.001] to have a plasma homoarginine concentration above the median. The median homoarginine plasma concentration in patients taking fenofibrate was 2.30 µmol/L versus 1.55 in patients not taking the drug (P < 0.001). In addition, fibrates were significantly associated with lower plasma SDMA and higher l-arginine concentrations. In contrast, glucocorticoids were associated with lower plasma homoarginine, with adjusted ORs of 0.52 (95% CI 0.40–0.67, P < 0.001) and 0.53 (95% CI 0.31–0.90, P = 0.018) for prednisolone and methylprednisolone, respectively.
Conclusions
In a large cohort of CKD patients, intake of fenofibrate and glucocorticoids were independently associated with higher and lower plasma homoarginine concentrations, respectively. Effects on plasma homoarginine and methylarginines warrant further investigation as potential mechanisms mediating beneficial or adverse drug effects.
Metadaten zuletzt geändert: 29 Sep 2021 07:42