Hypokalaemia and hypomagnesaemia in an oedematous diabetic patient with advanced renal failure
Chun-Chi Chen,
Chiou-An Chen,
Tom Chau and
Shih-Hua Lin
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Correspondence and offprint requests to: Shih-Hua Lin, MD, Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Number 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. Email: shihhualin{at}yahoo.com
Keywords: cation-exchange resins; hypocalcaemia; hypokaleamia; hypomagnesaemia; hypernatraemia; metabolic alkalosis
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Introduction
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Hyperkalaemia and hypermagnesaemia are common in patients with advanced renal failure because renal potassium (K+) and magnesium (Mg2+) excretion are significantly compromised. Concomitant hypokalaemia and hypomagnesaemia are unusual abnormalities, unless these patients have gastrointestinal disorders, use diuretics or suffer from malnutrition. Herein, we describe findings of hypokalaemia, hypomagnesaemia, hypocalcaemia and metabolic alkalosis in an oedematous diabetic patient with advanced renal failure. By analysing her urinary electrolyte excretion, we discovered that her biochemical abnormalities were caused by surreptitious use of sodium polystyrene sulfonate (NaPS), a cation-exchange resin, for the treatment of self-perceived hyperkalaemia. Despite the common use of cation-exchange resins for hyperkalaemia in clinical practice, their complications in acidbase, electrolyte and fluid imbalance apparently remain less appreciated by physicians.
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Case
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A 65-year-old Chinese female presented to our hospital with progressive peripheral oedema, uncontrolled hypertension, muscle weakness, tetany and weight gain of 5 kg over a 3 week period. She had a past history of hypertension, treated with nifedipine 10 mg tid and atenolol 100 mg qd, and chronic renal failure due to diabetic nephropathy diagnosed 2 years previously. Ten months earlier, she had been admitted to a local hospital because of hyperkalaemia, bradycardia and chest tightness. After discharge, she was given NaPS (Kayexalate®) to control hyperkalaemia. However, she discontinued NaPS by herself because of its unpalatability. She denied vomiting and diarrhoea or any recent use of laxatives, diuretics or herbal medicines.
On physical examination at the current admission, her body weight was 62.5 kg, blood pressure 180/110 mmHg, pulse rate 78 beats/min, respiratory rate 16 breaths/min and body temperature 37.1°C. Other remarkable findings included pale conjunctivae, engorged jugular veins, diminished breath sounds over both lung fields, grade II/VI cardiac systolic murmurs and grade III pitting oedema of both lower extremities. Her haemoglobin was 7.9 g/dl and haematocrit was 23.4%. Urinalysis revealed glucose (++) and protein (+++). Blood biochemical studies are shown in Table 1. She had marked azotaemia (blood urea nitrogen 21.6 mmol/l; creatinine 461.2 µmol/l) accompanied by hypokalaemia (K+ 2.6 mmol/l), hypomagnesaemia (Mg2+ 0.49 mmol/l), hypocalcaemia (ionized Ca2+ 0.90 mmol/l) and mild hypernatraemia (Na+ 146 mmol/l). Arterial blood gas revealed mild respiratory and metabolic alkalosis (pH 7.49; PCO2 36.3 mmHg; PO2 88 mmHg;
27.3 mmol/l). A chest radiograph showed moderate cardiomegaly with pulmonary congestion. Electrocardiographic findings included T wave flattening and left ventricular hypertrophy. Renal ultrasound revealed relatively normal sized kidneys without any hydronephrosis.
To investigate the underlying causes of hypokalaemia, both spot urines and a 24 h urine were collected for analysis. Low urinary excretion of K+ (transtubular K+ concentration gradient 2.5), Ca2+ (fractional excretion of Ca2+ 2.8% and daily Ca2+ excretion 0.40 mmol) and Mg2+ (fractional excretion of Mg2+ 10% and daily Mg2+ excretion 0.5 mmol) were found (Table 1). Of note, her urine Na+ excretion was relatively increased (the ratio of Na+ to creatinine in mmol terms was 20.9, and fractional excretion of Na+ was 6.6%) given her severe renal failure, oedema and low sodium diet. These urine findings suggested an extra-renal cause for hypokalaemia. Upon inquiry, she admitted to taking an over-the-counter K+-lowering powder, NaPS (Resonium-A®), 15 g four times daily over the past 3 weeks because she was trying to avoid another episode of hyperkalaemia. NaPS was discontinued, and water and dietary sodium restriction implemented. No diuretics were prescribed, but supplemental K+, Mg2+ and Ca2+ were given intravenously (60 mmol KCl/day for 4 days; 16 mmol MgSO4/day and 9 mmol CaCl2/day for 2 days). Her body weight had decreased by 4 kg by the 7th hospital day and her blood pressure was maintained below 130/80 mmHg with the antihypertensive agents amlodipine 5 mg and ramipril 2.5 mg daily.
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Discussion
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The laboratory findings of hypokalaemia, hypomagnesaemia and metabolic alkalosis are unusual in a patient with chronic renal failure in the absence of vomiting, diarrhoea, gastrointestinal disorders or diuretic therapy. The low urinary excretion of K+, Ca2+ and Mg2+ indicated an appropriate renal response to hypokalaemia, hypomagnesaemia and hypocalcaemia, suggesting pathology elsewhere in the body such as the gastrointestinal tract. Concurrently, the relatively increased urinary Na+ excretion (the ratio of Na+ to creatinine in mmol terms was 20.9, and fractional excretion of Na+ was 6.6%) in the setting of renal failure, hypervolaemia and mild hypernatraemia pointed to a high Na+ intake or absorption from the gastrointestinal tract. These acidbase and electrolyte abnormalities proved to be the result of overzealous use of NaPS for the treatment of self-perceived hyperkalaemia in this patient. Discontinuation of NaPS coupled with K+, Ca2+ and Mg2+ supplementation rapidly normalized these electrolyte and acidbase abnormalities.
Cation-exchange resins, cross-linked polymers with negatively charged structural units, have been well established and widely used in the prophylaxis or treatment of hyperkalaemia since the 1960s [1,2]. Two kinds of cation-exchange resins are commonly used: NaPS (Kayexalate® or Resonium-A®), an Na+-based resin, and calcium polystyrene sulfonate (CaPS; Kalimate®), a Ca2+-based resin. Cation exchange takes place throughout the gastrointestinal tract with release of a cation from the resin and binding of other cations present. Following oral administration, a cation (e.g. Na+ or Ca2+) is released from the resin in exchange for hydrogen (H+) ions in the stomach. As the resin passes down the small and large intestines, H+ ions are exchanged with those cations, such as K+, that are present in greater concentrations in the colon. The binding of a cation to the resin is dependent on three factors: (i) the concentration of the cation to which the resin is exposed; (ii) the duration of the resin's exposure to the cation; and (iii) the affinity of the resin for the cation, depending on its size and valency, with Ca2+>Mg2+>K+ (
NH4+)>Na+>H+ [3].
The hazards of hypokalaemia and sodium overload with NaPS treatment have been well documented. The extra Na+ liberated from NaPS may lead to hypernatraemia, oedema, hypertension and even congestive heart failure in patients with acute or chronic renal failure [4,5]. Because NaPS is not selective for K+, it is not surprising to find hypomagnesaemia and hypocalcaemia with NaPS therapy as shown in this case [6]. Concurrent poor intake or use of diuretics for oedema can aggravate these cationic losses further, potentially leading to life-threatening arrhythmias, especially in patients with cardiovascular diseases. In addition, the combined oral administration of NaPS and non-absorbable antacids/phosphate binders containing magnesium hydroxide, aluminum carbonate or calcium carbonate may produce an unexpected metabolic alkalosis [79]. Besides the electrolyte and acidbase abnormality, nausea, vomiting, constipation, intestinal obstruction and, rarely, intestinal ulceration, necrosis or perforation are well known gastrointestinal complications of NaPS [10].
In quantitative analysis, the total amount of NaPS ingested was 1200 g with a daily intake of 60 g of NaPS (4 x 15 g/day) over close to 20 days in this patient. Since NaPS contains 4 mmol sodium (Na+)/g, the extra Na+ load was 4800 mmol. The exchange efficacy of NaPS in vivo is on average 1 mmol K+/g of resin. Hence 1200 mmol K+ would be removed over the 20 day period while adding an equal amount of Na+ to the body. Because of the low daily intake of divalent Ca2+ and Mg2+ cations and the high likelihood of precipitation of Ca2+ with inorganic phosphate in the colon, it is unlikely that binding of these divalent cations to NaPS added a significant Na+ load. If the entire weight gain (5 kg) were due to an expanded extracellular fluid volume, she would have retained 730 mmol of Na+ (5 l x 146 mmol/l). This value represents more than half of the Na+ released when K+ bound to NaPS in her intestinal tract. One must ask at this point whether any of the electrolyte abnormalities might have provided a stimulus for the renal reabsorption of Na+ and contributed to this large retention of the extra Na+ load. Of note, short-term K+ depletion can provide an additional stimulus for renal Na+ retention with an increase in blood pressure, as demonstrated by the studies of Krishna et al. [11,12]. Therefore, it is possible that the combination of the Na+ load and the hypokalaemia contributed to the very large retention of Na+ in this 3 week period. Support for this speculation concerning hypokalaemia can be found in the prompt excretion of Na+ (4 kg weight loss in 7 days) with a fall in blood pressure when the patient stopped taking NaPS, had a low NaCl intake and was given KCl supplements.
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Teaching points
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- The use of Na+-containing exchange resins may produce a large retention of Na+ in a patient with acute or chronic renal failure who is unable to excrete all of the extra Na+ ingested.
- Hypokalaemia, hypomagnesaemia and metabolic alkalosis are common acidbase and electrolyte abnormalities seen with NaPS, and hypokalaemia may augment the Na+ retention through the increased renal Na+ reabsorption.
- A spot urine analysis to assess electrolyte excretion rates can help to make a rapid diagnosis of an electrolyte abnormality, even in patients with advanced renal failure.
- Close monitoring of blood electrolytes and acidbase balance is recommended in patients on cation-exchange resins, especially those with multiple cardiovascular risk factors.
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Acknowledgments
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We are much indebted to Dr Mitchell L. Halperin for his critique of this manuscript.
Conflict of interest statement. None declared.
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References
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Received for publication: 18. 3.05
Accepted in revised form: 24. 3.05