Zusammenfassung
Die Entstehung von Nierensteinen ist ein multifaktorieller Prozess. Während für Harnsäure‑, Zystin- und Xanthinsteine ätiopathogenetisch die Übersättigung und Kristallisation ausschlaggebend sind, wird die Formation calciumbasierter Steine, die die Mehrheit aller Steinarten darstellen, durch dieses physikochemische Konzept nicht ausreichend erklärt. Aktuelle Konzepte gehen von einer nidusassoziierten Steinbildung der calciumbasierten Nephrolithiasis an Randall-Plaques oder an Ductus-Bellini-Plugs aus. Während Randall-Plaques infolge eines nicht vollständig geklärten Zusammenspiels aus interstitieller Calciumübersättigung in der Papille, vaskulären und interstitiellen Inflammationsprozessen und mineralischen Ablagerungen von „calcifying nanoparticles“ an der Basalmembran des dünnen aufsteigenden Asts der Henle-Schleife entstehen, sind Ductus-Bellini-Plugs auf mineralische Ablagerungen am Rand des Sammelrohrlumens zurückzuführen. Für das weitere Steinwachstum im Kelchurin ist die Interaktion von Matrixproteinen mit calciumübersättigtem Urin unter ungünstigem Verhältnis von Promotoren gegenüber Inhibitoren der Lithogenese verantwortlich, wobei diese Vorgänge ebenfalls noch nicht abschließend ergründet sind. Obwohl die bisherige Forschung mit der Aufklärung über die Physiologie von Nephron und Papille, der Analyse medullärer vaskulärer, inflammatorischer und kalzifizierender Prozesse und der Untersuchung des Proteoms, des Mikrobioms, der Promotoren und Inhibitoren der Steinbildung im Urin sowie erste genomweite Assoziationsstudien viele Faktoren der Steinbildung aufgedeckt haben, sind weitere Forschungsbemühungen erforderlich, um die Lücken im Verständnis der komplexen Zusammenhänge schließen zu können und über den aktuellen Wissensstand hinausgehende prophylaktische, therapeutische oder metaphylaktische Werkzeuge zu erhalten.
Abstract
The process of kidney stone formation is complex and still not completely understood. Supersaturation and crystallization are the main drivers for the etiopathogenesis of uric acid, xanthine and cystine stones but this physicochemical concept fails to adequately explain the formation of calcium-based nephrolithiasis, which represents the majority of kidney stones. Contemporary concepts of the pathogenesis of calcium-based nephrolithiasis focus on a nidus-associated stone formation of calcium-based nephrolithiasis on Randall’s plaques or on plugs of Bellini’s duct. Randall’s plaques originate from the interaction of interstitial calcium supersaturation in the renal papilla, vascular and interstitial inflammatory processes and mineral deposits of calcifying nanoparticles on the basal membrane of the thin ascending branch of the loop of Henle; however, plugs of Bellini’s duct are assumed to be caused by mineral deposits on the wall of the collecting ducts. Aggregation and overgrowth are influenced by the interaction of matrix proteins with calcium supersaturated urine, by an imbalance between promoters and inhibitors of stone formation in the calyceal urine. Current research has elucidated many factors contributing to stone formation by revealing novel insights into the physiology of nephron and papilla, by analyzing vascular, inflammatory and calcifying processes in the renal medulla, by examining the proteome, the microbiome, promoters and inhibitors of stone formation in the urine and by conducting the first genome-wide association studies; however, more future research is mandatory to fill the gap of knowledge and hopefully, to obtain novel prophylactic, therapeutic and metaphylactic tools beyond the current state of knowledge.
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Mager, R., Neisius, A. Aktuelle Konzepte zur Pathogenese von Harnsteinen. Urologe 58, 1272–1280 (2019). https://doi.org/10.1007/s00120-019-1017-z
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DOI: https://doi.org/10.1007/s00120-019-1017-z
Schlüsselwörter
- Nephrolithiasis
- Randall-Plaques
- Idiopathische Hyperkalziurie
- Kalzifizierung
- Kalzifizierende Nanopartikel