Ist die Serumkonzentration von Pentosidin ein Prädiktor kardiovaskulärer Ereignisse bei Patienten mit Diabetes mellitus Typ 2 und Nephropathie?

Zusammenfassung

Hintergrund und Fragestellung: „Advanced glycation endproducts” (AGEs) gelten als Mediatoren der Gefäßschädigung bei der Atherosklerose, besonders bei Diabetes und Niereninsuffizienz. Korreliert das AGE Pentosidin, das durch Glykierung und anschließende Oxidation gebildet (Glykoxidationsprodukt) wird, bei Patienten mit Diabetes mellitus Typ 2 und Nephropathie mit kardiovaskulären Ereignissen?

Patienten und Methodik: 218 kardiovaskuläre Hochrisikopatienten der „Irbesartan in Diabetic Nephropathy Trial” (IDNT)-Studienpopulation mit Typ-2-Diabetes und Nephropathie (mittleres Alter 61 ± 6,4 Jahre, 68 weiblich, 150 männlich) sowie einer mittleren GFR von 47,9 ± 16,0 ml/min (nach MDRD Formel) wurden für im Mittel 2,2 Jahre beobachtet. Pentosidin wurde mittels Hochdruck-Flüssigkeitschromatographie bestimmt. Der Zusammenhang zwischen Pentosidin, traditionellen Risikofaktoren sowie kardiovaskulären Ereignissen wurde mit der Cox-Regressionsanalyse geprüft.

Ergebnisse: Die Pentosidin-Serumkonzentration betrug zu Beginn der Studie 148 ± 113 pmol/ml, die von HbA_1c 8,6 ± 1,7 %. Insgesamt traten 93 kardiovaskuläre Ereignisse auf; 50 Patienten starben, davon 39 an kardiovaskulären Ursachen. Low-density-lipoprotein (LDL) und Diabetesdauer erwiesen sich in einer multivariaten Analyse als unabhängige Risikofaktoren für ein erstes kardiovaskuläres Ereignis (einschließlich kardiovaskulärer Tod) (relatives Risiko (RR) für das höchste, verglichen mit dem niedrigsten Quartil für LDL: 3,041, Konfidenzintervall 1,616 - 5,724, P = 0,001; für Diabetesdauer: RR 2,629, KI 1,279 - 6,151, P = 0,011).

Folgerung: Die Serumkonzentration von Pentosidin konnte in der untersuchten Studienpopulation nicht als unabhängiger Risikofaktor für kardiovaskuläre Endpunkte identifiziert werden. Dieses Ergebnis legt nahe, dass konventionelle Risikofaktoren eine bedeutendere Rolle für kardiovaskuläre Ereignisse spielen, während AGE-Serumkonzentrationen eher von untergeordnetem prädiktivem Wert sind. Ob AGE-Gewebsspiegel von größerer Relevanz sein könnten, ist derzeit Gegenstand der Diskussion.

Summary

Background and objective: Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular damage of atherosclerosis, especially in diabetes and renal failure. Pentosidine, an AGE, is generated by glycation and oxidation reactions (glycoxidation product).

Methods: 218 patients at high risk of cardiovascular events (from the „Irbesartan in Diabetic Nephropathy Trial” [IDNT] cohort) with type 2 diabetes and nephropathy (mean age 61 ± 6,4 years, 68 female, 150male) were followed for a mean of 2.2 years. The mean GFR at baseline was 47,9 ± 16,0 ml/min (MDRD formula). Serum levels of pentosidine were measured by high-performance liquid chromatography. The relationship between pentosidine, traditional risk factors and cardiovascular events (CVE) was tested in Cox proportional hazards models.

Results: The mean serum level of pentosidine at baseline was 148 ± 113 pmol/ml, that of hemoglobin A_1c (HbA_1c) 8.6 ± 1.7 %. During follow-up, 93 CVE occurred; a total of 50 patients died, 39 of cardiovascular causes. Final multivariate analysis showed low density lipoprotein (LDL) and duration of diabetes to be independent risk factors for a first cardiovascular event (including death from cardiovascular causes) (relative risk [RR] for the highest quartile compared with the lowest: LDL 3,041, confidence interval 1.616 - 5.724, P = 0.001; duration of diabetes: RR 2.629, CI 1.279 - 6.151, P = 0.011).

Conclusion: The serum level of pentosidine was not an independent risk factor for cardiovascular outcomes in the selected cohort. This suggests that traditional risk factors may play a more important role in causing cardiovascular events and that serum levels of AGEs are of low predictive value. Further investigations are necessary to assess whether tissue levels of AGEs are of greater relevance.

Schlüsselwörter

chronische Niereninsuffizienz - kardiovaskuläres Risiko - advanced glycation endproducts - Pentosidin - diabetische Nephropathie

Key words

chronic renal failure - cardiovascular risk - advanced glycation endproducts - pentosidine - diabetic nephropathy

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