Pediatr Nephrol (2005) 20:818–820 DOI 10.1007/s00467-005-1833-9
BRIEF REPORT
Nilzete Liberato Bresolin · EugÞnio Grillo · Vera Regina Fernandes · Francisca Lgia Cirilo Carvalho · Jos Eduardo Coutinho Goes · Ronaldo Jos Melo da Silva
A case report and review of hypokalemic paralysis secondary to renal tubular acidosis Received: 11 May 2004 / Revised: 8 December 2004 / Accepted: 14 December 2004 / Published online: 17 March 2005 IPNA 2005
Abstract A 5-year-old girl with distal renal tubular acidosis (RTA) and hypokalemic muscle paralysis is reported. RTA is a known cause of hypokalemia, but in spite of the presence of persistent hypokalemia muscular paralysis is uncommon, rarely described in children, and the onset of paralysis may initially be misinterpreted particularly if the patient is attended by a physician who is not a pediatric nephrologist. Therefore parents must be informed about this possibility. Still, as the clinical appearance of hypokalemic paralysis is quite similar to familial hypokalemic periodic paralysis, and because the emergent and prophylactic treatment of the two disorders are quite different, we discuss the diagnostic evaluation and the treatment for both of them. Keywords Paralysis · Acidosis · Hypokalemia · Acidosis renal tubular · Hypokalemic periodic paralysis · Children
Introduction Renal tubular acidosis (RTA) is a syndrome of disordered renal acidification that is recognized in two major forms, i.e., distal and proximal, which may occur in overt and latent forms [1, 2]. Proximal RTA is due to disordered bicarbonate reabsortion in proximal nephrons, and the distal type is due to impaired renal acid secretion in distal nephrons resulting in metabolic acidosis [1, 3]. The final site of titration of the urinary buffers is the collecting tubule. When this process fails urinary acid excretion is unable to match the 1.5 mEq/kg body weight of nonvolatile acid generated daily as a consequence of the high N. L. Bresolin ()) · E. Grillo · V. R. Fernandes · F. L. C. Carvalho · J. E. C. Goes · R. J. Melo da Silva Hospital Infantil Joana de Gusm¼o, Rua Rui Barbosa 152, Florianpolis Santa Catarina, Brazil e-mail:
[email protected] Tel.: +55-48-99824148 Fax: +55-48-2280215
protein diet consumed by most persons, and the clinical expression is distal RTA [4]. Although hypokalemia is common in RTA, muscular paralysis is uncommon and rarely described in children [1, 5, 6, 7]. The proximal type of RTA is far less frequently complicated by hypokalemic paralysis than the distal type. Currently diagnosing distal RTA is based on inhibition of hydrogen-potassium adenosine triphosphatase in renal principal cells and a intercalated cells [1, 4]. There is good evidence that hydrogen production is not impaired, and it seems likely that the abnormal acidification process represents an impairment of hydrogen transport. With the decrease in hydrogen secretion the excretion of others cations, such as sodium, potassium, and calcium, increases, as does bicarbonate excretion [5]. Hypokalemia is thought to result from this compensatory responses and also from bicarbonaturia (nonreabsorbable anion), which enhances luminal eletronegativity, and potassium secretion [8]. Calcium salts are continuously mobilized from bones for buffering, which results in nephrocalcinosis and renal rickets. If administered before 4 years of age, prophylactic long-term treatment with bicarbonate can prevent paralytic attacks and nephrocalcinosis [1, 6]. In isolated distal RTA the growth failure is the main clinical manifestation, and there is no aminoaciduria, glicosuria, or hyperphosphaturia, as is reported in Fanconi syndrome [1]. Distal overt RTA is characterized by hyperchloremic metabolic acidosis and urinary pH of 6.0 and higher [2]. In distal RTA renal potassium wasting can result in sudden lifethreatening hypokalemic muscle paralysis, periodic paralytic attacks, and chronic persistent muscle weakness [2, 5, 9, 10, 11]. The clinical presentation of hypokalemic paralysis secondary to RTA is quite similar to that of familial hypokalemic periodic paralysis (FPP), which is a rare hereditary disorder, usually autosomal dominant, with onset in middle to late childhood with intermittent episodes of profound muscle weakness precipitated by high-carbohydrate low-potassium diet, exercise, infection, stress, or alcohol ingestion [12, 13]. Initially the attacks are infre-
819
Fig. 1 Medullary nephrocalcinosis at renal ultrasound
quent, but daily attacks may occur during early adulthood. The episodes decrease in frequency in late adulthood, but older patients may have a fixed limb weakness. Attacks are accompanied by a modest and sudden fall in serum potassium concentration and in urinary retention of sodium, potassium, chloride, and water [14]. Glucose-insulin infusion may provoke an attack, and oral potassium salts attenuate the episode. These findings are diagnostic of the condition [14]. Hypokalemia in FPP is not due to loss of potassium as observed in distal RTA, but to abnormalities in its redistribution between intra- and extracellular compartments. Mutations in two genes encoding subunits of skeletal muscle voltage-gated calcium or sodium channels (CACNL1A3 and SCN4A) have been identified in hypokalemic FPP [15]. Differential diagnosis is emphasized in this case of distal RTA, which developed acute hypokalemic muscle paralysis, because the emergency, as well as the prophylactic treatment of these two disorders, are different [2].
Case report A 5-year-old girl was admitted to our hospital because of weakness and pain in her extremities. A pediatric nephrologist had been following her since she was 2 months of age, with a diagnosis of typical distal RTA with hypercloremic acidosis, alkaline urine, hypokalemia, and hypercalciuria. Bilateral medullary nephrocalcinosis had been previously documented by ultrasound (Fig. 1). Creatinine was normal. There was no family history of paralysis or consanguinity. Five days before admission she had been showing difficulty in walking. Her mother had observed unusual gait with frequent falls soon after awaking. These complaints were occurring every morning, with gradual improvement throughout the day. A neurological examination was carried out in the afternoon of the fourth day and revealed very discrete gait abnormalities, suggesting a proximal deficit, with normal deep tendon reflexes. On the fifth morning, as soon as she awoke, and while she was still in bed, it was observed that motor disturbances had abruptly worsened, and that she could not stand, sit, or even control her head. She was admitted to the hospital, and this time she was treated with spironolactone (1.5 mg/kg per day), potassium chloride 6% 10 ml (1.3 mEq/kg per day), and sodium bicarbonate 7 ml (1.2 mEq/kg per day).
Physical examination on admission showed weight and height on the 50th percentile, with a severe flaccid quadriparesis, involving predominantly the proximal muscles. The deep tendon reflexes were present but had decreased. Consciousness, cranial nerves, respiratory muscles, and pain sensation were intact. She was admitted to the pediatric intensive care unit for closer surveillance, but mechanical ventilation was not required, as respiration was intact. Analysis of arterial blood showed mild metabolic acidosis (pH 7.33, PaCO2 34.7 mmHg, PaO2 118 mmHg, bicarbonate 18.6 mEq/l and base excess 7.5 mmol/l). Serum electrolytes revealed severe hypokalemia (2.1 mEq/l), and serum sodium was 137 mEq/l. Sodium bicarbonate (2 mEq/kg per day) was administered, along with oral potassium chloride (2 mEq/kg per day). An infusion was started of 0.4 mEq/kg potassium hourly administered for 6 h. After this the patient’s serum potassium was 2.2 mEq/l, and her muscular weakness had not improved. A new infusion of potassium chloride (0.5 mEq/kg per hour for 6 h) was given under electrocardiographic control and the serum potassium reached normal levels (3.5 mEq/l) with improvement in weakness. The child was walking without assistance. She was discharged from hospital on the fourth day, with normal neurological examination and receiving oral bicarbonate and potassium.
Discussion Potassium deficiency ranges from mild disturbances of the potassium homeostasis to serious and potentially fatal conditions and is widely found in clinical practice [16]. There are a wide variety of conditions giving rise to potassium deficiency as well as a wide variety of effects that such a deficiency might have on many processes related to cellular metabolism [16]. Although the most common form of hypokalemic periodic muscular paralysis is reported to be the FPP variety, some patients with chronic potassium depletion may exhibit episodic weakness [17]. Such paralysis may result from hypopotassemia due to any cause in several different diseases. Hypokalemic paralysis may result from excessive excretion by the kidney or gastrointestinal tract or from redistribution with a shift of the cation into cells [5, 18, 19]. In addition to the diuretic phase of acute tubular acidosis, renal wasting of potassium with paralysis has been noted in a variety of diseases including Fanconi syndrome, nephrotic syndrome, treatment phase of diabetic acidosis, primary aldosteronism, “salt losing nephritis,” RTA, and following bilateral ureterosigmoidostomy [5]. We describe here the clinical features in a patient suffering from hypokalemic paralytic episodes secondary to distal RTA, which was diagnosed and treated since she was 2 months old. As nephrocalcinosis had already been observed at this age, she was receiving prophylactic longterm bicarbonate, but nephrocalcinosis persisted. In isolated distal RTA the growth failure is the main clinical manifestation, but as a consequence of early treatment with bicarbonate and potassium she was at the 50th percentile for weight and height. Her first paralytic attack occurred at 5 years of age. The paralysis onset was insidious with a fluctuating course, worsening soon after she awoke, until the morning of the fourth day, when a severe and generalized flaccid paralysis was observed. The clinical features of patients
820
suffering from hypokalemic muscle paralysis due to distal RTA is undistinguishable from attacks due to FPP [2]. Muscle paralysis can begin insidiously with weakness, evolving gradually over period of 24–48 h to complete flaccid quadriplegia in both disorders [2, 5]. Muscles of speech, swallowing, eyes, and respiration are usually spared in both RTA and FPP [2]. In our patient there was a severe flaccid quadriparesis. The deep tendon reflexes were decreased, which is in accordance with previous reports [17]. Cranial nerves, respiratory muscles, and peripheral sensations were intact. It is important to emphasize that in distal RTA the muscular paralysis may be misinterpreted particularly if the patient is attended by a physician who is not a pediatric nephrologist. Therefore families of RTA children must be advised about this possibility. Hypokalemia in FPP is not due to loss of potassium as observed in distal RTA but to abnormalities in its redistribution between intra- and extracellular compartments. Mutations in two genes encoding subunits of skeletal muscle voltage-gated calcium or sodium channels (CACNL1A3 and SCN4A) have been identified in hypokalemic FPP [15]. The episode of weakness responded to potassium chloride and bicarbonate therapy, recovery occurring in 4 days. The patient was discharged on oral sodium bicarbonate and potassium chloride. Thus pathogenesis of RTA is quite different from that of hypokalemic FPP, and treatment of these two conditions also differs, both in the acute and prophylactic approaches. The clinician must be able to distinguish them. In hypokalemic paralysis caused by distal RTA emergency treatment consists of potassium and bicarbonate administration [2]. Alkali and potassium replacement therapy prevents the recurrent, life-threatening episodic weakness [2, 17]. However, treatment for a severe paralytic attack due to FPP requires intravenous or oral potassium. Bicarbonate is contraindicated because it facilitates intracellular potassium influx, and fatal hypokalemia may result [1, 2]. Although in FPP no available drugs afford constant prophylaxis against muscle paralysis, the combination of acetazolamide and potassium is of benefit in prevention of attacks. On the other hand, acetazolamide is strongly contraindicated in prophylaxis of hypokalemic paralysis caused by distal RTA because the drug itself produces acidosis [2, 14]. Acknowledgements This contribution was revised by Fernando S. Vugman, Ph.D.
References 1. Chang Y-C, Huang C-C, Chiou Y-Y, Yu C-Y (1995) Renal tubular acidosis complicated with hypokalemic periodic paralysis. Pediatr Neurol 13:52–54 2. Christensen KS (1985) Hypokalemic periodic paralysis secondary to renal tubular acidosis. Eur Neurol 24:303–305 3. Ruf R, Rensing C, Topaloglu R, Guay-Woodford L, Klein C, Vollmer M, Otto E, Beekmann F, Haller M, Wiedensohler A, Leumann E, Antignac C, Rizzoni G, Filler G, Brandis M, Weber JL, Hildebrandt (2003) Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosis. Pediatr Nephrol 18:105–109 4. Kurtzman NA (1990) Disorders of distal acidification. Kidney Int 38:720–727 5. Owen EE, Verner JV (1960) Renal tubular disease with muscle paralysis and hypokalemia. Am J Med 28:8–21 6. Rowbottom SJ, Ray DC, Brown DT (1987) Hypokalemic paralysis associated with renal tubular acidosis. Crit Care Med 15:1067–1068 7. Koul PA, Saleem SM (1992) Chronic active hepatitis with renal tubular acidosis presenting as hypokalemic periodic paralysis with respiratory failure. Acta Paediatr 81:568–569 8. Nardone DA, Mcdonald WJ, Girard DE (1978) Mechanisms in hypokalemia: clinical correlation. Medicine (Baltimore) 57: 435–446 9. Narins RG, Goldberg M (1977) Renal tubular acidosis: pathophysiology, diagnosis and treatment. Dis Mon 23:1–66 10. Quintanilla AP (1980) Renal tubular acidosis: mechanisms and management. Postgrad Med 67:60–73 11. Raskin RJ, Tesar JT, Lawless OJ (1981) Hypokalemic periodic paralysis in Sjgren’s syndrome. Arch Intern Med 141:1671– 1673 12. Biemond A, Polak DA (1934) Familial periodic paralysis and its transition into spinal muscular atrophy. Brain 57:91 13. Burume OJS, BotsGth AM, Lodewyk NW (1985) Familial hypokalemia period paralysis: 50-year follow-up of a large family. Arch Neurol 42:28 14. De Vivo DC, DiMauro S (1999) Hereditary and acquired types of myopathy. In: DeAngelis CD, Feigin RD, Warshaw JB (eds) Oski’s pediatrics principles and practice, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, 1971–1987 15. Stemberg D, Maisonobe T, Jurkat-Rott K, Nicole S, Launay E, Chauveau D, Tabti N, Lehmann-Horn F, Hainque B, Fontaine B (2001) Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 124: 1091–1099 16. Steen B (1981) Hypokalemia-Clinical spectrum and etiology. Acta Med Scand Suppl 647:61–66 17. Koul PA, Saleem SM, Bhat D (1993) Sporadic distal renal tubular acidosis and periodic hypokalaemic paralysis in Kashmir. J Intern Med 233:463–466 18. Stephens FI (1949) Paralysis due to reduced serum potassium during treatment of diabetic acidosis. Am Intern Med 30:1272 19. Frenkel M, Groen J, Willebrands AF (1947) Low serum potassium during recovery from diabetic coma. Arch Intern Med 80:728
