Clinical Investigation

Kidney International (1981) 19, 716–727; doi:10.1038/ki.1981.72

Mineralocorticoid-resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): Role of increased renal chloride reabsorption

Morris Schambelan1, Anthony Sebastian1 and Floyd C Rector Jr1

1Medical Service and Clinical Study Center, San Francisco General Hospital Medical Center, and the Department of Medicine, Cardiovascular Research Institute, and the General Clinical Research Center, University of California, San Francisco, California

Correspondence: Dr M Schambelan, Room 310, Building 100, San Francisco General Hospital Medical Center, 1001 Potrero Avenue, San Francisco, California 94110, USA

Received 16 June 1980; Revised 17 September 1980.

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Abstract

Mineralocorticoid-resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): Role of increased renal chloride reabsorption. A rare syndrome has been described in which mineralocorticoid-resistant hyperkalemia of renal origin occurs in the absence of glomerular insufficiency and renal sodium wasting and in which hyperchloremic acidosis, hypertension, and hyporeninemia coexist. The primary abnormality has been postulated to be a defect of the potassium secretory mechanism of the distal nephron. The present studies were carried out to investigate the mechanism of impaired renal potassium secretion in a patient with this syndrome. When dietary intake of sodium chloride was normal, renal clearance of potassium was subnormal (CK/GFR = 3.6 plusminus 0.2%; normal subjects, 9.0 plusminus 0.9%, N = 4) despite high normal or supernormal levels of plasma and urinary aldosterone. The fractional clearance of potassium remained subnormal (CK/GFR = 5.1 plusminus 0.2%) during superimposed chronic administration of superphysiologic doses of mineralocorticoid hormone. Little increase in renal potassium clearance occurred when the delivery of sodium to distal nephron segments was increased further by the i.v. infusion of sodium chloride, despite experimentally sustained hypermineralocorticoidism. But potassium clearance increased greatly when delivery of sodium to the distal nephron was increased by infusion of nonchloride anions: sulfate (sodium sulfate infusion, low sodium chloride diet; CK/GFR = 63.7 plusminus 0.4%) or bicarbonate (sodium bicarbonate plus acetazolamide infusion; CK/GFR = 81.7 plusminus 1.7%). These findings indicate that mineralocorticoid-resistant renal hyperkalemia in this patient cannot be attributed to the absence of a renal potassium secretory capability or to diminished delivery of sodium to distal nephron segments; instead it may be dependent on chloride delivery to the distal nephron. We suggest that the primary abnormality in this syndrome increases the reabsorptive avidity of the distal nephron for chloride, which (1) limits the sodium and mineralocorticoid-dependent voltage driving force for potassium and hydrogen ion secretion, resulting in hyperkalemia and acidosis and (2) augments distal sodium chloride reabsorption resulting in hyperchloremia, volume expansion, hyporeninemia, and hypertension.

Hyperkaliémie rénale résistant aux minéralocorticoïdes sans perte de sel (pseudohypoaldostéronisme de type II): Rôle de l'augmentation de la réabsorption de chlore. Un syndrome rare a été décrit dans lequel une hyperkaliémie d'origine rénale résistant aux minéralocorticoïdes survient en l'absence de diminution du débit de filtration glomérulaire et de perte rénale de sodium et dans lequel une acidose hyperchlorémique, une hypertension et une hyporéninémie coexistent. L'anomalie primaire qui a été postulée est un déficit du mécanisme de sécrétion de potassium du néphron distal. Ce travail a été entrepris pour étudier le mécanisme de la modification de la sécrétion rénale de potassium chez un malade atteint de ce syndrome. Quand l'apport alimentaire de chlorure de sodium était normal, la clearance rénale du potassium était inférieure à la normale (CK/GFR = 3,6 plusminus 0,2%; sujets normaux 9,0 plusminus 0,9%, N = 4) malgré des niveaux á la limite supérieure ou franchement élevés d'aldostérone plasmatique et urinaire. La clearance fractionnelle du potassium était inférieur à la normale (CK/GFR = 5,1 plusminus 0,2%) au cours de l'administration de doses supra-physiologiques de minéralocorticoïdes. Une augmentation faible de la clearance du potassium a été observée quand le débit de sodium aux segments distaux du néphron a été encore augmenté, par l'administration intraveineuse de chlorure de sodium, malgré l'hyerminéralocorticisme expérimentalement maintenu. La clearance du potassium, cependant, a considérablement augmenté quand le débit de sodium au néphron distal a été augmenté par la perfusion d'anions différents du chlore: sulfate (perfusion de sulfate de sodium, régime pauvre en chlorure de sodium: CK/GFR = 63,7 + 0,4%) ou en bicarbonate (perfusion de bicarbonate de sodium et perfusion d'acetazolamide: CK/GFR = 81,7 plusminus 1,7%). Ces constatations indiquent que l'hyperkaliémie rénale résistant aux minéralocorticoïdes chez ce malade ne peut être attribuée à l'absence de capacité sécréter le potassium ou à une diminution du débit de sodium aux segments distaux. Par contre elle peut dépendre du débit de chlore au néphron distal. Nous suggérons que l'anomalie initiale dans ce syndrome est une augmentation de la capacité réabsorption du chlore par le néphron distal qui (1) limite la force électro-motrice, dépendant du sodium et des minéralocorticoïdes, de sécrétion des ions hydrogène et potassium, ce qui a pour résultat l'hyperkaliémie et l'acidose et (2) augmente la réabsorption distale de chlorure de sodium ce qui a pour résultat l'hypercholorémie, l'expansion volémique, l'hyporéninémie et l'hypertension.

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