N-Acetylcystein in der Prophylaxe der Kontrastmittel-induzierten Nephropathie

Zusammenfassung

Einleitung: Die zunehmende Zahl endovaskulärer Prozeduren bei gefäßchirurgischen Patienten führt zur vermehrten Kontrastmittelexposition, womit diese Patienten einem erhöhten Risiko für eine Kontrastmittel-induzierte Nephropathie (KIN) ausgesetzt sind. Diese KIN ist mit einer Mortalität bis zu 20 % gekennzeichnet. Bei der Implementierung von standardisierten Behandlungspfaden zur Prozessoptimierung in medizinischen Versorgungssystemen stellt sich die Frage, inwieweit der Einsatz von N-Acetylcystein (NAC) zur Prophylaxe einer KIN Evidenz-basiert begründbar ist. Methodik: Bibliografie-Studium und Analyse 1990 bis 10 / 2005. Die Schlüsselwörter „N-acetylcysteine OR acetylcysteine AND contrast-induced nephropathy OR contrast induced nephropathy OR nephropathy” wurden in die Suchmaske der PubMed-Medline eingegeben. Die Suche erfolgte ohne Sprachbeschränkung, es wurden nur Artikel mit Abstract akzeptiert. Ergebnisse: Nach Ausschluss von redundanten Veröffentlichungen, tierexperimentellen Untersuchungen oder retrospektiven Analysen, Editorials, Reviews und Metaanalysen verblieben von 115 gefundenen Referenzen 28 Arbeiten mit einem prospektiven Studiendesign. Diese umfassten 3 604 Patienten, die überwiegend koronaren Angiografie ± Interventionen unterzogen wurden, Extremitätenangiografien oder CT-Untersuchungen bildeten eine Minderheit. Die applizierten Kontrastmittel variierten in Zusammensetzung und Menge. Verwendeten die meisten Studien eine orale Medikation von NAC, so erfolgte bei drei eine intravenöse Gabe. Die gepoolten Daten zeigten eine relative Risikoreduktion (RR = 0,69, 95 % CI = 0,57-0,82) für die Anwendung von NAC in der Prophylaxe der KIN. In einer Einzelbetrachtung wiesen 20 Studien fehlende prophylaktische Wirkung der NAC-Gabe nach. Zusammenfassung und Schlussfolgerungen: Die statistische Heterogenität lässt die einfache Ergebniszusammenführung der Studien und Wiedergabe in Form von Odds-Ratios von geringem, wenn nicht sogar ohne klinischen Wert erscheinen. Eine zukünftige multizentrische Studie sollte bei ausreichender Kollektivgröße neben der glomerulären Filtrationsrate andere Parameter der Nierenfunktion (z. B. Serum-Cystatin C) messen und „harte” Endpunkte, wie Hospitalmorbidität, Mortalität, sowie die Notwendigkeit der Dialyse ins Studienprotokoll integrieren.

Abstract

Purpose: Clinical trials evaluating N-acetylcysteine (NAC) for the prevention of radiocontrast-induced nephropathy (RCN) have reported mixed results. Despite formerly published meta-analyses and due to currently published RCTs, time has come to re-evaluate the current evidence of preventing RCN by administering NAC. Methods: We performed a computerized search without restricted to a language to identify relevant published randomized clinical trials that evaluated N-acetylcysteine for the prevention of radiocontrast-induced nephropathy. Abstracted data from each trial included assessments of clinical outcomes, trial quality, and additional characteristics. The primary outcome of interest was the incidence of nephropathy after contrast administration. Data were combined using random effects models with the performance of standard tests to assess for heterogeneity and publication bias. Subgroup analyses were also performed. Results: Twenty-eight trials involving 3 604 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-related nephropathy was 0.69 (95 % confidence interval: 0.57 to 0.82; P = 0.02), a statistically significant trend towards benefit in patients treated with N-acetylcysteine. This effect varied, however, across the 28 trials, and only eight of the 28 trials demonstrated significant results although higher-quality trials demonstrated a stronger benefit for N-acetylcysteine in general, few reported important elements of study design, such as concealment of allocation, placebo-controls, or double-blinding. Heterogenity was unexplained by subgroup analyses. Summary and Conclusions: N-acetylcysteine (NAC) may reduce the incidence of contrast-related nephropathy, but this finding is reported inconsistently across currently available trials. Large high-quality, clinical trials are needed before the application of N-acetylcysteine can be recommended in general for this indication.

Schlüsselwörter

N-Acetylcystein - Kontrastmittel-induzierte Nephropathie - Prophylaxe

Key words

N-acetylcysteine - contrast-induced nephropathy - prophylaxis

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