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Potassium and Magnesium-Sparing Diuretics

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Potassium and Magnesium-Sparing Diuretics Originalia Potassium and Magnesium-Sparing Diuretics M. P. Ryan Summary chez i) des rats non anesthesies avec une gebnis entspricht der unterschiedlichen Be­ charge saline ii) la clearance renale chez les handlung von Kalium und Magnesium im The renal handling of potassium and mag­ animaux anesthesies iii) des patients avec distalen Tubulus und im Sammelrohr. nesium and the effects of diuretics on these insuffisance cardiaque congestive chroni­ Auch bei Triamteren wurden magnesium­ processes are reviewed. Loop-blocking que. Dans des etudes sur I'animal, une rela­ sparende Eigenschaften nachgewiesen. Die diuretics cause major losses of both potas­ tion dose-reponse a ete etablie pour les ac­ Wirkungen von Aldosteron-Antagonisten sium and magnesium. Thiazide diuretics tions de I'amiloride dans la reduction de sind allerdings noch nicht so eingehend cause major losses of potassium while their !'excretion fractionnee du Mg et du K au nachgewiesen. effects on magnesium excretion are less well cours de la diurese induite par le furose­ established. Evidence has accumulated in mide. Les effets de l'amiloride sur !'excre­ recent years that the potassium-sparing tion du Mg sont moindres que ceux sur diuretics also exert magnesium-sparing !'excretion du K qui est compatible avec un Introduction properties. Experiments from our own traitement different de K et de Mg dans le laboratories and from other investigators tubule distal et le canal collecteur. L'triam­ Congestive heart failure is a disease are reviewed. Amiloride has been demons­ terene est I'diuretique peuvent avoir aussi trated to exert magnesium-sparing proper­ proprietes d'epargne du Mg. Lcs effets des which may be associated with dis­ ties in i) conscious saline-loaded rats ii) re­ antagonistes de I' aldosterone sur l'excretion turbances in the four main cations nal clearance studies in rats iii) congestive du Mg sont mains bien etablis que ceux de namely sodium, potassium, calcium heart failure patients. In animal studies, a l'amiloride. and magnesium. The electrolyte dose-response relationship has been estab­ lished for the actions of amiloride in reduc­ disturbances may be due to i) dis­ ing fractional excretion of magnesium and Zusammenfassung ease-related processes such as hy­ potassium during furosemide-induced Die Behandlung von Kalium und Magne­ poperfusion, tissue anoxia, malab­ diuresis. The effects of amiloride on mag­ sium in den Nieren sowie die Wirkung von sorption, alterations in the renin­ nesium excretion are much less than those Diuretika auf diese Prozesse werden unter­ on potassium excretion and this is compat­ angiotensin-aldosterone system sucht. Schleifendiuretika verursachen be­ and atrial natiuretic peptides or ible with the different handling of potassium triichtliche Verluste sowohl von Kalium als and magnesium in the distal tubule and col­ auch von Magnesium. Thiazid·Diuretika may be related to ii) drug treatment lecting duct. Triamterene has also been verursachen ebenfalls groBe Kaliumverlu­ including treatment with diuretics, shown to have magnesium-sparing proper­ ste, die Auswirkungen auf die Ausscheidung inotropic agents and inhibitors of ties. The effects of aldosterone antagonists von Magnesium sind jedoch noch nicht so on magnesium excretion are less well estab­ the renin-angiotensin-aldosterone gut belegt. In den letzten Jahren hat sich system. lished. herausgestellt, daB kaliumsparende Diure­ tika auch magnesiumsparende Eigenschaf­ In this article, I will review the Resume ten aufweisen. In unserem Labor durchge­ effects of diuretics on the renal ftihrte Versuche sowie Versuche anderer handling of potassium and mag­ L'excretion renale du K et Mg, et les effets Wissenschaftler wurden iiberpriift. Es nesium with particular emphasis on de diuretiques sur I'excretion renale du K et konnte nachgewiesen werden, daB Amilorid Mg seront passees en revue. Lcs diun!tiques eine magnesiumsparende Wirkung hatte i) recent findings which indicate that bloquant l'anse provoquent cependent des bei mit Kochsalzlosung behandelten, nicht some potassium-sparing diuretics pertes urinairs majeurs de K et Mg. Lcs betiiubten Ratten, ii) bei Studien zur Nie­ also exert magnesium-sparing diuretiques thiazidiques provoquent cepen­ renclearance bei ratten, und iii) bei Patien­ properties. Diuretics are used clini­ dent des pertes urinairs majeurs de K mais ten mit kongestiver Herzinssuffizienz. In cally for the mobilization of excess les effects des diuretiques thiazidiques sur Tierversuchen wurde eine von der Dosis l'excretion du Mg sont mains bien etablis. abhangige Wechselbeziehung der Wirkung body fluid in states of oedema in­ Un ensemble de donnees dans ces dernieres von Amilorid auf die Reduzierung der teil­ cluding congestive heart failure. In annees indiquent que les diuretiques epar­ weisen Ausscheidung von Kalium und Ma­ addition to the excretion of gnant le K peuvent avoir aussi certaines gnesium bei Furosemid-induzierter Diurese sodium, chloride and water, diure­ proprietes d'epargne du Mg. Les recherches nachgewiesen. Die Wirkungen von Amilo­ de notre propre laboratoire et celles d'autres rid auf die Magnesiumausscheidung sind tics may also alter the renal han­ chercheurs seront passees en revue. L'ami­ doch wesentlich geringer als die Auswirkun­ dling of other electrolytes including loride ont reduit !'excretion urinaire du Mg gen auf die Kaliumausscheidung, dieses Er· potassium and magnesium. One of 210 Mag.-Bull. 8 (1986) Potassium and Magnesium-Spring Diuretics the most common and potentially the remaining (10%) of the filtered for potassium the existence of sec­ serious side-effects of diuretic potassium is reabsorbed and the retory mechanisms for magnesium therapy is an increased urinary loss reabsorption at this site may be re­ in the distal tubule and collecting of potassium which may lead to lated to chloride reabsorption [25]. duct is not well established. While hypokalemia and possibly reduced The thick ascending limb of the some workers [4, 20, 37, 51, 59] cellular and total body potassium loop of Henle appears to be the have produced evidence for mag­ concentrations [23, 34, 72]. These major site for reabsorption of mag­ nesium secretion under certain ex­ losses of potassium can be espe­ nesium where approximately perimental circumstances, other cially serious in patients being 50-60% of the filtered magnesium workers [ 1, 9, 41] have failed to treated with cardiac glycosides. is reabsorbed [67]. The distal demonstrate magnesium secretion Although loss of potassium caused tubule and collecting duct are be­ at these sites. The processes and by diuretic agents has received ma­ lieved to be the major regulatory sites involved in the renal handling jor attention, the magnesium losses sites for renal modification of of potassium and magnesium are associated with diuretic treatment potassium homeostasis [25]. Potas­ summarized in tab. 1. have not, to date, received the sium secretory processes are in­ The kidneys can vary excretion same attention. Treatment with volved and potassium secretion is rates of magnesium under different modern diuretics can indeed result subject to control by factors such as conditions. During periods of mag­ in enhanced urinary losses of mag­ sodium delivery, flow rate, acid­ nesium deprivation, the kidneys nesium leading to hypomagnesemia base balance, intracellular potas­ play a major role in reducing uri­ and possibly reduced cellular and sium concentrations, hormonal fac­ nary excretion of magnesium to total body concentrations of mag­ tors including aldosterone [25]. The very low levels. This has been de­ nesium [16, 43, 50, 56, 67]. Diure­ role of the distal tubule and collect­ monstrated in experimental mag­ tic-induced magnesium deficiency ing in the renal handling of mag­ nesium deficiency in animals [72] can itself give rise to serious clinical nesium is less well established com­ and also most elegantly by Shils consequences and furthermore pared to the situation for potas­ [62] in a study of magnesium depri­ magnesium deficiency can interact sium. vation in human subjects. How­ with potassium deficiency and con­ The distal tubule normally reab­ ever, the homeostatic role of the tribute to further losses of potas­ sorbs about 5% of filtered mag­ kidney in maintaining magnesium sium including reductions in in­ nesium [67]. However, the reab­ balance can be interfered with by a tracellular potassium [56]. Impor­ sorption of magnesium in the distal number of drugs currently in tant interactions of magnesium and tubule has been shown to be load­ therapeutic use. A number of drugs potassium will be discussed by a dependent. Accordingly, in the interfere with the renal handling of number of other contributors to presence of diuretics acting at sites magnesium and produce renal this meeting. proximal to the distal tubule, mag­ wasting of magnesium. It is highly nesium transport in the distal probable that magnesium defi­ tubule may be highly significant in ciency will become a more frequent Renal Handling of terms of overall renal handling of and serious clinical problem with Potassium and magnesium. Unlike the situation the increasing usage of drugs which Magnesium interfere with the renal handling of Tab. 1: Renal handling of magnesium. A number of the drugs The kidneys play major roles in potassium and magnesium such as aminoglycoside antibiotics both potassium and magnesium [5, 31, 70], the anticancer drug cis­ Processes and homeostasis. Potassium and mag­ Potassium [Magnesium platin [7, 60] and the immunosup­
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