Drugs linked to plasma homoarginine in chronic kidney disease patients-a cross-sectional analysis of the German Chronic Kidney Disease cohort.

Autor:	Maas R; Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Mieth M; Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Titze SI; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Hübner S; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Fromm MF; Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Kielstein JT; Divison of Nephrology, Medical School Hannover, Hannover, Germany.; Medical Clinic V Nephrology Rheumatology Blood Purification, Klinikum Braunschweig, Braunschweig, Germany., Schmid M; Department of Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany., Köttgen A; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Centre, University of Freiburg, Freiburg, Germany., Kronenberg F; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria., Krane V; Department of Medicine I, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany., Hausknecht B; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Eckardt KU; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany., Schneider MP; Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Jazyk:	angličtina
Zdroj:	Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2020 Jul 01; Vol. 35 (7), pp. 1187-1195.
DOI:	10.1093/ndt/gfy342
Abstrakt:	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. (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
Databáze:	MEDLINE
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