Glucose modulation of the disposal of an acute potassium load in patients with end-stage renal disease

  • Michael Allon
    Requests for reprints should be addressed to Michael Allon, M.D., Division of Nephrology, 668 LHR, UAB Station, Birmingham, Alabama 35294.
    From the Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama, USA

    From the Veterans Administration Medical Center, Birmingham, Alabama, USA
    Search for articles by this author
  • Linda Dansby
    From the Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama, USA

    From the Veterans Administration Medical Center, Birmingham, Alabama, USA
    Search for articles by this author
  • Nancy Shanklin
    From the Veterans Administration Medical Center, Birmingham, Alabama, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      purpose: Extrarenal potassium disposal plays an important role in the tolerance of an acute potassium load and is particularly critical in patients with renal failure. Insulin is known to stimulate this disposal by enhancing potassium uptake into the cells. Since dietary potassium is generally ingested in combination with carbohydrates, the predictable stimulation of endogenous insulin release may blunt the expected increase in plasma potassium. The goal of the current study was to evaluate the effect of oral glucose on the disposition of an acute oral potassium load in hemodialysis patients and in normal controls.
      patients and methods: Eight hemodialysis patients and eight normal control subjects were studied after an overnight fast. Each subject received an oral load of potassium chloride elixir (0.25 mmol/kg). Plasma potassium was measured at baseline and at 30-minute intervals for 3 hours. On a separate study day, the subjects underwent the identical protocol, with the addition of 50 g of oral glucose to the potassium load to stimulate endogenous insulin release. The identical two experimental protocols were repeated in each subject during concomitant β blockade with propranolol.
      results: The maximal increase in plasma potassium after the potassium load was significantly greater in the hemodialysis patients than in the controls (0.93 ± 0.08 versus 0.52 ± 0.04 mmol/L, p < 0.001). Concomitant oral glucose markedly blunted the maximal rise in potassium levels in both experimental groups (0.40 ± 0.09 and 0.22 ± 0.07 mmol/L, respectively, p < 0.005 versus potassium alone). With concomitant β blockade, the maximal increase in plasma potassium after the potassium load was significantly greater in the hemodialysis patients than in the controls (1.11 ± 0.12 versus 0.72 ± 0.09 mmol/L, p = 0.02). Concomitant oral glucose again markedly blunted the maximal increase in potassium in both experimental groups (0.72 ± 0.09 and 0.39 ± 0.06 mmol/L, respectively, p < 0.01 versus potassium alone). The potassium load in the absence of glucose did not produce changes in plasma insulin concentration in either experimental group. The potassium load in combination with oral glucose load produced more sustained hyperinsulinemia in the dialysis patients than in the control subjects.
      conclusions: Exogenous glucose, by stimulating endogenous secretion of insulin, enhances extrarenal disposal of a potassium load. This protective effect of exogenous glucose against hyperkalemia is independent of adrenergic stimulation. The beneficial effect of exogenous glucose defends against the development of severe hyperkalemia after dietary potassium ingestion, and is critically important in hemodialysis patients, due to their negligible renal potassium excretion.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Brown RS
        Extrarenal potassium homeostasis.
        Kidney Int. 1986; 30: 116-127
        • DeFronzo RA
        • Felig P
        • Ferrannini E
        • Wahren J
        Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man.
        Am J Physiol. 1980; 238: E421-E427
        • Minaker KL
        • Rowe JW
        Potassium homeostasis during hyperinsulinemia: effect of insulin level, β-blockade, and age.
        Am J Physiol. 1982; 242: E373-E377
        • Alvestrand A
        • Wahren J
        • Smith D
        • DeFronzo RA
        Insulin-mediated potassium uptake is normal in uremic and healthy subjects.
        Am J Physiol. 1984; 246: E174-E180
        • Allon M
        • Copkney C
        Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients.
        Kidney Int. 1990; 38: 869-872
        • Blumberg A
        • Weidmann P
        • Shaw S
        • Gnadinger M
        Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure.
        Am J Med. 1988; 85: 507-512
        • Lens XM
        • Montoliu J
        • Cases A
        • Campistol JM
        • Revert L
        Treatment of hyperkalemia in renal failure: salbutamol v insulin.
        Nephrol Dial Transplant. 1989; 4: 228-232
        • DeFronzo RA
        • Sherwin RS
        • Dillingham M
        Influence of basal insulin and glucagon secretion on potassium and sodium metabolism: studies with somatostatin in normal dogs and in normal and diabetic human beings.
        J Clin Invest. 1978; 61: 472-479
        • Goecke IA
        • Bonilla S
        • Marusic ET
        • Alvo M
        Enhanced insulin sensitivity in extrarenal potassium handling in uremic rats.
        Kidney Int. 1991; 39: 39-43
        • Tzamaloukas AH
        • Avasthi PS
        Temporal profile of serum potassium concentration in nondiabetic and diabetic outpatients on chronic dialysis.
        Am J Nephrol. 1987; 7: 101-109
        • Young JB
        • Landsberg L
        Suppression of sympathetic nervous system during fasting.
        Science. 1977; 196: 1473-1475
        • Young JB
        • Landsberg L
        Stimulation of the sympathetic nervous system during sucrose feeding.
        Nature. 1977; 269: 615-617
        • Landsberg L
        • Young JB
        Fasting, feeding and regulation of the sympathetic nervous system.
        N Engl J Med. 1978; 298: 1295-1301
        • Brown MJ
        • Brown DC
        • Murphy MB
        Hypokalemia from beta2-receptor stimulation by circulating epinephrine.
        N Engl J Med. 1983; 309: 1414-1419
        • DeFronzo RA
        • Bia M
        • Birkhead G
        Epinephrine and potassium homeostasis.
        Kidney Int. 1981; 20: 83-91
        • Allon M
        • Dunlay R
        • Copkney C
        Nebulized albuterol for acute hyperkalemia in patients on hemodialysis.
        Ann Intern Med. 1989; 110: 426-429
        • Allon M
        • Shanklin N
        Adrenergic modulation of extrarenal potassium disposal in men with end-stage renal disease.
        Kidney Int. 1991; 40: 1103-1109
        • Allon M
        • Takeshian A
        • Shanklin N
        Effect of insulin-plus-glucose infusion with or without epinephrine on fasting hyperkalemia in hemodialysis patients.
        Kidney Int. 1993; 43: 212-227
        • Fernandez J
        • Oster JR
        • Perez GO
        Impaired extrarenal disposal of an acute oral potassium load in patients with endstage renal disease on chronic hemodialysis.
        Miner Electrolyte Metab. 1986; 12: 125-129
        • Alvo M
        • Krsulovic P
        • Fernandez V
        • Espinoza AM
        • Escobar M
        • Marusic ET
        Effect of a simultaneous potassium and carbohydrate load on extrarenal potassium homeostasis in end-stage renal failure.
        Nephron. 1989; 53: 133-137
        • Hiatt N
        • Davidson MB
        • Bonorris G
        The effect of potassium chloride infusion on insulin secretion in vivo.
        Horm Metab Res. 1972; 4: 64-68
        • Pettit GW
        • Vick RL
        • Swander AM
        Plasma K+ and insulin: changes during KCl infusion in normal and nephrectomized dogs.
        Am J Physiol. 1975; 228: 107-109
        • Santeusanio F
        • Faloona GR
        • Knochel JP
        • Unger RH
        Evidence for a role of endogenous insulin and glucagon in the regulation of potassium homeostasis.
        J Lab Clin Med. 1973; 81: 809-817
        • Tuck ML
        • Davidson MB
        • Asp N
        • Schultze RG
        Augmented aldosterone and insulin responses to potassium infusion in dogs with renal failure.
        Kidney Int. 1986; 30: 883-890
        • Rosa RM
        • Silva P
        • Young JB
        • et al.
        Adrenergic modulation of extrarenal potassium disposal.
        N Engl J Med. 1980; 302: 431-434
        • Clive DM
        • Gurwitz JH
        • Rossetti RG
        Potassium homeostasis with indomethacin therapy in normal subjects.
        Am J Kidney Dis. 1992; 19: 16-21
        • Williams ME
        • Rosa RM
        • Silva P
        • Brown RS
        • Epstein FH
        Impairment of extra-renal potassium disposal by alpha-adrenergic stimulation.
        N Engl J Med. 1984; 311: 145-149
        • Dluhy RG
        • Axelrod L
        • Williams GH
        Serum immunoreactive insulin and growth hormone response to potassium infusion in normal man.
        J Appl Physiol. 1972; 33: 22-26
        • Sterns RH
        • Feig PU
        • Pring M
        • Guzzo J
        • Singer I
        Disposition of intravenous potassium in anuric man: a kinetic analysis.
        Kidney Int. 1979; 15: 651-660
        • Gifford JD
        • Rutsky EA
        • Kirk KA
        • McDaniel HG
        Control of serum potassium during fasting in end-stage renal disease.
        Kidney Int. 1989; 35: 90-94
        • Castellino P
        • Bia M
        • DeFronzo RA
        Adrenergic modulation of potassium metabolism in uremia.
        Kidney Int. 1990; 37: 793-798
        • Arrizabalaga P
        • Montoliu J
        • Martinez Vea A
        • Andreu L
        • Lopez Pedret J
        • Revert L
        Increase in serum potassium caused by beta-2 adrenergic blockade in terminal renal failure: absence of mediation by insulin or aldosterone.
        in: 4th ed. Proc Eur Dial Transplant Assoc. 20. 1983: 572-576
        • Hager SR
        Insulin resistance of uremia.
        Am J Kidney Dis. 1989; 14: 272-276