Aldosterone and potassium balance in dialysis patients

Sir,

The article by Hussain et al. [1], showing that spironolactone, even at dosages as low as 25 mg/day, may cause dangerous hyperkalaemia in some dialysis patients (two out of 15 patients) reminds us of the importance of aldosterone-driven potassium (K) secretion in extrarenal sites (among others, the colon, salivary and sweat glands) in uraemia [2,3]. Though extrarenal K excretion is <10% of total K excretion in subjects with normal renal function, it increases (at least in the colon) in the course of chronic renal failure, up to 30 mmol/day [2]. Aldosterone exerts in the colon the same effects as in the collecting tubule, by interacting with a specific mineralocorticoid receptor (MR) [3]. Thus, inhibition or stimulation of MRs are expected to result in corresponding changes in faecal K secretion. Stimulation of MRs in anuric patients on chronic haemodialysis with either fludrocortisone [4] or glycyrrhetinic acid (which allows direct activation of MRs by endogenous cortisol in aldosterone-sensitive cells) [5] is associated with significant reductions in plasma K levels. However, there has been little appreciation so far of the clinical relevance of colonic K secretion in dialysis patients. There is a general belief that colonic K secretion does not consistently affect K balance and that in dialysis patients, effective disposal of dietary K load has to rely mostly, if not entirely, on the dialysis procedure itself. In fact, the paper by Hussain et al. [1], and few previous observations [4], indicate that extrarenal K disposal in dialysis patients may be quantitatively relevant enough to result in dangerous hyperkalaemia when aldosterone effects are pharmacologically inhibited, unless parallel changes on dialysate K concentration are also made.

We have been able to asses the relevance of extrarenal aldosterone effects on the control of plasma K levels in dialysis patients in a patient with Addison's disease. This patient, a 73-year-old female with autosomal dominant polycystic kidney disease, had been on dialysis for 3 years. She also had a polyglandular autoimmune hypofunction syndrome, resulting in hypoparathyroidism, hypothyroidism, recurrent pericarditis and global adrenal insufficiency. The latter diagnosis had been made 25 years ago and was supported by very low urine 17-keto and 17-hydroxycorticosteroids unresponsive to exogenous ACTH and increased levels of plasma ACTH, renin and K levels. She was treated with thyroxin, glucocorticoid and mineralocorticoid (fludrocortisone 0.1 mg/day) oral substitution. Her pre-dialysis plasma K usually ranged from 4.5 to 5.7 mmol/l. She was dialysed three times weekly for 4.5 h, by use of a 1.6 m2 polyamide-membrane filter and a custom bicarbonate dialysate with 2 mmol/l K concentration. Her interdialytic weight gain was constant at <2.5 kg and Kt/V values ranged from 1.19 to 1.35. Since fludrocortisone is not available in Italy, and its use was considered non-essential in the context of chronic dialysis treatment, it was stopped in February 2002 (dialysis schedule and all other medications remaining unchanged). Glucocorticoid therapy consisted of methylprednisolone 8 mg in the morning and 2 mg in the evening (this over-substitutive dosage was accounted for by a pericarditis episode 2 months earlier). Last pre-dialysis plasma K was 5.5. Two weeks after fludrocortisone was withdrawn, plasma K was 6.3, the patient began complaining of progressive lassitude and numbness and after an additional 10 days pre-dialysis plasma K was 7.8 mmol/l. No other possible causes of hyperkalaemia could be found and, specifically, intestinal bleeding, fistula malfunction and dietary K load were all excluded. Fludrocortisone (0.1 mg/day) was restarted, with a progressive fall in plasma K levels. Since then, her pre-dialysis K levels have been stable at 4.8–5.3 mmol/l. Urine excretion was 300–500 ml/day, with a K content (on fludrocortisone therapy) of <3 mmol/day, indicating that renal contribution to overall K balance was negligible and that fludrocortisone was likely to affect K excretion through the colon. Even though transcellular K shift cannot be ruled out in an acute setting [6], this mechanism cannot account for chronic changes in plasma K levels, which instead require changes in K balance. In dialysis patients, on a fixed dialysis schedule, balance changes may occur only at the intestinal level.

This observation teaches us that also in anuric patients aldosterone is not a useless hormone and that mineralocorticoid function has to be substituted in the occasional patient with adrenal failure and on regular dialysis treatment. Enhanced extrarenal effects of aldosterone on K balance in uraemia may limit the safety of antialdosterone drugs in patients on chronic dialysis treatment.

Conflict of interest statement. None declared.

Giacomo Colussi and Fiorella Dossi

U. O. Nefrologia A. O. Ospedale di Circolo e Fondazione Macchi Varese Italy Email: giacomo.colussi{at}ospedale.varese.it

References

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