NDT Advance Access published online on July 5, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm386
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Effect of fludrocortisone acetate on reducing serum potassium levels in patients with end-stage renal disease undergoing haemodialysis
Department of Internal Medicine, Chosun University College of Medicine, Gwangju, Republic of Korea
Correspondence and offprint requests to: Hyun Lee Kim, MD. Assistant professor, Department of Internal Medicine, Chosun University College of Medicine, 588 Susuk-dong, Dong-gu, Gwangju, 501-717, Korea. Email: hyunkim{at}chosun.ac.kr
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Abstract |
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Background. Hyperkalaemia is a commonly encountered problem in dialysis patients with end-stage renal disease (ESRD). The aim of the present study was to assess the effect of fludrocortisone acetate (FCA) on reducing serum potassium levels in haemodialysis (HD) patients with hyperkalaemia.
Methods. Prospectively, 21 HD patients with hyperkalaemia were enrolled in this study. Patients were divided into two groups, including FCA (0.1 mg/d, n = 13) administration or no treatment (control, n = 8) for 10 months. No changes in dialysis or drug regimens were made during this period.
Result. There were no significant differences in the baseline characteristics and biochemical parameters between the two groups (FCA therapy and control). At 10-months after FCA therapy, serum potassium levels were not significantly different between the treatment and control groups [median value (range): 5.2 (4.4–6.0) vs 5.8 (4.8–6.3) mEq/l, P = 0.121]. However, using the Wilcoxon signed ranks test, serum potassium levels were significantly lower at the end of the 10 month time period after FCA therapy compared with serum potassium levels of the pre-treatment period [5.2 (4.4–6.0) vs 6.1 (5.3–6.8), P = 0.01]. The biochemical values, including sodium, chloride, protein, albumin, blood nitrogen, creatinine, interdialytic weight change and blood pressure, did not show significant difference in comparisons between the two groups and pre-and post-FCA therapy period.
Conclusions. FCA therapy appears to slightly decrease serum potassium value in hyperkalaemic HD patients. However, these results are insufficient to explain the effectiveness of FCA. Therefore, potentially large-scale studies with increased dose concentrations are needed to minimize the positive potassium balance in hyperkalaemic HD patients.
Keywords: dialysis; fludrocortisone acetate; hyperkalaemia
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Introduction |
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Hyperkalaemia is a relatively common finding in patients with end-stage renal disease (ESRD). Indeed, serious hyperkalaemia has been reported to occur in about
10% of haemodialysis (HD) patients [1,2]. Several factors render these patients susceptible to hyperkalaemia including an increase in potassium intake, a decrease in potassium excretion or a shift of potassium from intracellular fluid. Chronic metabolic conditions (e.g. acidosis, progressive nephron loss, mineralocorticoid deficiency, oligoanuria) and medications [e.g. angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, non-steroidal anti-inflammatory drugs (NSAIDs)] may also cause hyperkalaemia [3–6]. Mineralocorticoid is known to regulate renal and extrarenal potassium secretion. Several reports have shown that the potent synthetic mineralocorticoid, fludrocortisone acetate (FCA), decreased serum potassium in patients with renal insufficiency and those on maintenance HD by colonic potassium secretion [7].
The purpose of the present study was to investigate the potassium lowering effect of FCA in HD patients.
Patients and methods
A total of 21 patients with ESRD undergoing haemodialysis were included in this prospective study. The inclusion criteria were 
6 months on HD, 18 years of age and serum potassium >5.0 mEq/l for at least three consecutive months. All patients were non-uric and received 4 h HD sessions three times a week. We divided the patients into two groups according to treatment. Patients were assigned that FCA (Florinet®, 0.1 mg/d) was taken orally every morning or no treatment during a 10-month period of time. During the study period, all patients were allowed to continue their usual diet. No changes in dialysis or drug regimens were made during this period.
The biochemical variables, serum potassium, sodium, chloride, urea, creatinine and total protein/albumin, were measured monthly. Baseline plasma aldosterone (upright position) was also measured in all patients. Pre-dialysis and post-dialysis body weight and pre-dialysis blood pressure were recorded at every dialysis session. The primary end points of this study were comparison of serum potassium levels between pre-treatment and post-treatment period. This study was approved by the Chosun University Hospital, Gwangju, Korea. Also, prior to the study, we obtained signed consent from each patient.
Statistical analysis
For statistical analysis, we used the Statistical Package for Social Sciences for Windows, version 12.0 (SPSS Inc, Chicago, IL). All values are expressed as median values with ranges. Comparisons of demographic and clinical characteristics were performed by using the Mann–Whitney U-test. The biochemical variables before and after FCA treatment were compared by using Wilcoxon signed ranks test. P-values of <0.05 were considered statistically significant.
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Results |
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The baseline characteristics and the measured biochemical parameters of the treatment and control groups were shown in Table 1. There were no significant differences in gender and age between the two groups. The median age in the study population was 50 (28–72) years and 48% of participants were males. The most prevalent underlying kidney disease was chronic glomerulonephritis (37%). The prevalence of other kidney disease was diabetic nephropathy 33%, hypertensive nephropathy 10%, obstructive uropathy 5%, autosomal dominant polycystic kidney disease 5% and other or unknown underlying kidney disease accounted for 10% of cases.
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Serum potassium levels, at 10-months after FCA therapy, were not significantly different between the treatment and control groups [median value (range): 5.2 (4.4–6.0) vs 5.8 (4.8–6.3) mEq/l, P = 0.121]. Using the Wilcoxon signed ranks test, serum potassium levels were significantly lower at the end of the 10-month time period after FCA treatment compared to serum potassium levels of the pre-treatment [5.2 (4.4–6.0) vs 6.1 (5.3–6.8), P = 0.01].
At the end of the FCA treatment, other biochemical values, including serum sodium, chloride, urea, creatinine, interdialytic weight change and pre-dialysis blood pressure, did not show significant difference in comparisons between the two groups. In addition, these biochemical values between pre- and post-FCA treatment were not significantly different (Table 2). None of the patients with FCA treatment complained of side effects such as hypervolaemia or hypertension.
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Discussion |
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In this study, we examined the potassium lowering effect FCA administration in HD patients. When comparing the serum potassium concentration at the end of the treatment period with the pre-treatment serum potassium levels, serum potassium levels were significantly lower after FCA treatment.
Hyperkalaemia is one of the most frequent life threatening electrolyte disorders in patients with advanced renal disease undergoing haemodialysis. In theses patients, the gut has been demonstrated to be an important excretory pathway for potassium homeostasis [8]. Gastrointestinal potassium content is proportional to plasma aldosterone and colon potassium secretion adapts to potassium loads. Gerstein et al. [9] demonstrated that the colon has secretory processes for potassium, and that this activity is up-regulated in response to potassium loads, aldosterone and during renal insufficiency. In addition, several studies have demonstrated that colonic excretion of potassium increases in chronic renal failure and may play an important role in extrarenal potassium regulation for such patients. It has been known that increased potassium secretion from the colon is associated with a rise in transmural potential difference and an increase in the Na-K-ATPase activity [7,10,11].
Fludrocortisone (FCA) is a synthetic glucocorticoid with potent mineralocorticoid activity and moderate glucocorticoid activity. FCA stimulated the Na-K-ATPase activity and increased the potassium secretion from the gastrointestinal tract. The intracellular shift of potassium might also play an important role in the potassium-lowering effect of FCA. When used in the dose range of 0.1–0.3 mg/day, FCA reduced serum potassium in several studies [4,12,13]. Nyman et al. [14] reported that FCA decreased serum potassium levels from 4.7 to 4.0 mEq/l during a 3- to 9-month treatment period in anuric dialysis patients. Similarly, Singhal et al. [1] reported that oral FCA at a dose of 0.1–0.3 mg/day decreased mean serum potassium by 0.7 mEq/l during a 3- to 6-month period in 21 dialysis patients. In the present study, after 0.1 mg/day of FCA, mean serum potassium levels were decreased from 6.01 to 5.20 mEq/l at the end of the 10-month study period.
Recently, Kaisar et al. [15] demonstrated that FCA treatment of hyperkalaemic haemodialysis patients did not achieve a clinically important decrease in serum potassium levels. In this study, between treatment and control groups, serum potassium levels were not significantly different after 3 months of therapy. An FCA dose of 0.1 mg/day used in Kaisar et al.'s and our study was known as the most commonly safe and effective dose in a previous study of potassium lowering effect in dialysis patients. Furuya et al. [2] found that FCA doses as low as 0.05 mg/day were still significantly effective, whereas doses >5 mg/day did not result in a decrease in serum potassium levels. However, in our study, a point differing from Kaisar et al.'s study was the lowering effect of the serum potassium levels by 0.81 mEq/l after the 10-month therapy in the treatment group. Moreover, using Wilcoxon signed ranks test, serum potassium levels were significantly lower at the end of the 10-month FCA treatment period compared with serum potassium levels of the pre-treatment period (P < 0.05). We thought that the duration of the Kaisar et al. study was very short to assess the lowering effect of FCA treatment.
FCA has been used to ameliorate hyperkalaemia in the patients with hyporeninaemic hypoaldosteronism [16,17], and Furuya et al.'s [2] study showed the effect of FCA between low plasma aldosterone concentration (PAC) and high PAC groups. Since hyperkalaemia stimulates aldosterone secretion, one might expect aldosterone levels to be higher in patients with renal insufficiency than in individuals with normal renal function. However, aldosterone levels have shown widely varying patterns [3,7,10–12], and its importance as a factor in maintaining potassium balance in renal insufficiency is uncertain. In the Singhal et al. [1] study, despite hyperkalaemia, serum aldosterone levels were not elevated. They suggested the hypothesis that their patients were not in an optimal state to augment potassium secretion by the colonic mucosa during pre-FCA therapy and pre-dialytic serum aldosterone levels might not be representative of the actual mineralocorticoid status of patients with ESRD. Also, our result showed that baseline serum aldosterone levels were not elevated.
Our study has several limitations that should be considered. First, patients took the medications that might affect hyperkalaemia to maintain their same usual lifestyle as before this study. However, it is possible that its protocol can introduce potential biases in data analysis because these medications have influence on potassium metabolism.
Secondly, the FCA dose used in our study was 0.1 mg/day. In previous studies, variable doses (0.1–0.3 mg/day) have been used for potassium lowering effect of dialysis patients. Among these dosages, 0.1 mg/day of FCA is the most commonly reported safe and effective dosage to decrease serum potassium levels. Our results demonstrated this dose was sufficient to significantly decrease serum potassium levels in comparisons between pre-treatment and post-treatment. However, we did not evaluate the dose-range study associated with the effect of FCA therapy and its complications such as hypertension or hypervolaemia.
In conclusion, this study shows that FCA therapy for hyperkalaemia in haemodialysis patients helps promote a slight decline in serum potassium levels. However, our protocol is that only a small proportion of patients agreed to this study. Therefore, additional large-scale and increased dose concentration studies (0.15–0.3 mg/day) are needed to assess the effectiveness of FCA in patients on haemodialysis to achieve a decrease in serum potassium levels and determine the appropriate doses.
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Acknowledgements |
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This study was supported by research funds from Chosun University, 2005.
Conflict of interest statement. None declared.
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References |
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- Singhal PC, Desroches L, Mattana J, Abramovici M, Wagner JD, Maesaka JK. Mineralocorticoid therapy lowers serum potassium, in patients with end-stage renal disease. Am J Nephrol (1993) 13:138–141.[Web of Science][Medline]
- Furuya R, Kumagai H, Sakao T, Maruyama Y, Hishida A. Potassium-lowering effect of mineralocorticoid therapy in patients undergoing hemodialysis. Nephron (2002) 92:576–581.[CrossRef][Web of Science][Medline]
- Perez GO, Pelleya R, Oster JR, Kem DC, Vaamonde CA. Blunted kaliuresis after an acute potassium load in patients with chronic renal failure. Kidney Int (1983) 24:656–662.[CrossRef][Web of Science][Medline]
- Sherman DS, Kass CL, Fish DN. Fludrocortisone for the treatment of heparin-induced hyperkalemia. Ann Pharmacother (2000) 34:606–610.[Abstract]
- Knoll GA, Sahgal A, Nair RC, Graham J, van Walraven C, Burns KD. Renin-angiotensin system blockade and the risk of hyperkalemia in chronic hemodialysis patients. AM J Med (2002) 112:110–114.[CrossRef][Web of Science][Medline]
- Whelton A, Hamilton CW. Nonsteroidal anti-inflammatory drugs: effects on kidney function. J Clin Pharmacol (1991) 31:588–598.[Abstract]
- Imbriano LJ, Durham JH, Maesaka JK. Treating interdialytic Hyperkalemia with Fludrocortisone. Semin Dialysis (2003) 16:5–7.[CrossRef][Web of Science][Medline]
- Gennari FJ, Segal AS. Hyperkalemia: an adaptive response in chronic renal insufficiency. Kidney Int (2002) 62:1–9.[Web of Science][Medline]
- Gerstein AR, Kleeman CR, Gold EM, et al. Aldosterone deficiency in chronic renal failure. Nephron (1968) 5:90–105.[Web of Science][Medline]
- Clark BA, Shannon C, Brown RS, Gervino EV. Extrarenal potassium homeostasis with maximal exercise in end-stage renal disease. J Am Soc Nephrol (1996) 7:1223–1227.[Abstract]
- Ahmed J, Weisberg LS. Hyperkalemia in dialysis patients. Semin Dialysis (2001) 14:348–356.[CrossRef][Web of Science][Medline]
- Sebastian A, Schambelan M, Lindenfeld S, Morris RC Jr. Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteroinism. N Engl J Med (1977) 297:576–582.[Abstract]
- Dreyling KW, Wanner C, Schollmeyer P. Control of hyperkalemia with fludrocortisone in a patient with systemic lupus erythematosus. Clin Nephrol (1990) 33:179–183.[Web of Science][Medline]
- Nyman N, Mulgaonkar S, Walcer R, Viscuso R, Jacobs MG. Effects of a mineralocorticoid on extra-renal potassium (K+) homeostasis in anuric patients. Kidney Int (1983) 23:. 155A.
- Kaisar MO, Wiggins KJ, Sturtevant JM, et al. A randomized controlled trial of fludrocortisone for the treatment of hyperkalemia in hemodialysis patients. Am J Kidney Dis (2006) 47:809–814.[CrossRef][Web of Science][Medline]
- Matsuda O, Nonoguchi H, Tomita K, et al. Primary role hyperkalemia in the acidosis of hyporeninaemic hypoaldosteronism. Nephron (1988) 49:203–209.[Web of Science][Medline]
- Kiley J, Zager P. Hyporeninemic hypoaldosteronism in two patients with systemic lupus erythematosus. Am J Kidney Dis (1984) 4:39–43.[Web of Science][Medline]
Accepted in revised form: 24. 5.07
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