RESUMEN
BACKGROUND: Bartter syndrome (BS) is a salt-wasting tubulopathy with induced expression of cyclooxygenase-2 in the macula densa, leading to increased prostaglandin production and hyperreninemia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in BS; however, there is limited information on the impact of NSAIDs at treatment initiation or the potential utility of plasma renin level to guide therapy in patients with BS. METHODS: We included 19 patients with BS treated with NSAIDs between 1994 and 2016. We assessed serum levels of renin, aldosterone, electrolytes, calcium, phosphorus, vitamin D, and intact parathyroid hormone (iPTH) before and after treatment initiation. We also recorded modifications in sodium and potassium supplements and changes in urine calcium. RESULTS: Median age at diagnosis was 0.9 months [IQR 0-6.9]. Seven patients had BS types 1 or 2, 12 had BS type 3 and two had no mutation identified. There was a trend towards a decrease in sodium chloride supplementation after initiation of NSAIDs. When defining response to treatment based on the normalization of plasma renin level, responders had a greater reduction in their electrolytes supplementation. NSAIDs treatment was associated with a reduction in urine calcium. Before treatment, half of the patients had elevated iPTH, but iPTH normalized following initiation of NSAIDs in all but one patient. CONCLUSIONS: This study confirms that NSAIDs reduce urine wasting of sodium and calcium in patients with BS. Monitoring serum renin levels may be useful to identify the lowest effective dose of NSAIDs that optimizes reduction of urine electrolyte losses.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Síndrome de Bartter/tratamiento farmacológico , Ciclooxigenasa 2/metabolismo , Indometacina/uso terapéutico , Túbulos Renales/efectos de los fármacos , Antiinflamatorios no Esteroideos/efectos adversos , Síndrome de Bartter/sangre , Síndrome de Bartter/enzimología , Síndrome de Bartter/orina , Biomarcadores/sangre , Biomarcadores/orina , Calcio/orina , Femenino , Humanos , Indometacina/efectos adversos , Lactante , Recién Nacido , Túbulos Renales/enzimología , Masculino , Renina/sangre , Estudios Retrospectivos , Sodio/orina , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
Asunto(s)
Síndrome de Bartter/diagnóstico , Condrocalcinosis/etiología , Suplementos Dietéticos , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Síndrome de Bartter/sangre , Síndrome de Bartter/genética , Síndrome de Bartter/orina , Calcio/orina , Canales de Cloruro/genética , Condrocalcinosis/prevención & control , Conferencias de Consenso como Asunto , Diagnóstico Diferencial , Pruebas Genéticas , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/genética , Humanos , Hipopotasemia/sangre , Hipopotasemia/genética , Magnesio/administración & dosificación , Magnesio/sangre , Magnesio/uso terapéutico , Mutación , Fenotipo , Potasio/administración & dosificación , Potasio/sangre , Potasio/uso terapéutico , Guías de Práctica Clínica como Asunto , Calidad de Vida , Enfermedades Raras/genética , Cloruro de Sodio Dietético/uso terapéutico , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , UltrasonografíaRESUMEN
Bartter's and Gitelman's syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter's syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman's syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.
Asunto(s)
Síndrome de Bartter/congénito , Síndrome de Gitelman/congénito , Hipopotasemia/etiología , Potasio/sangre , Síndrome de Bartter/sangre , Síndrome de Bartter/diagnóstico , Niño , Diagnóstico Diferencial , Femenino , Síndrome de Gitelman/sangre , Síndrome de Gitelman/diagnóstico , Humanos , Hipopotasemia/sangre , Hipopotasemia/diagnóstico , Masculino , Adulto JovenRESUMEN
The metabolism of potassium and magnesium are closely linked (in situations where potassium and magnesium depletion coexist, magnesium restoration alone is sufficient to correct hypokalemia). Moreover, magnesium deficiency blunts the interplay between circulating calcium and the calciotropic hormones. Renal magnesium wasting, hypokalemia, alkalosis, hypocalciuria, and a tendency towards hypocalcemia characterize Gitelman syndrome. Plasma or intracellular potassium, circulating calcium, and calciotropic hormones were therefore investigated in eight patients (4 females, 4 males, aged 9-20 years) with Gitelman syndrome before and during oral supplementation with magnesium pyrrolidone carboxylate 30 mmol daily for 4 weeks. Magnesium supplementation significantly increased plasma and intracellular magnesium and plasma calcium, but failed to completely restore magnesium deficiency. In contrast, blood levels of parathyroid hormone and calcitriol and plasma and intracellular potassium were not modified following magnesium administration.
Asunto(s)
Síndrome de Bartter/tratamiento farmacológico , Magnesio/administración & dosificación , Adolescente , Adulto , Síndrome de Bartter/sangre , Niño , Femenino , Humanos , Magnesio/sangre , Deficiencia de Magnesio/sangre , Deficiencia de Magnesio/tratamiento farmacológico , Masculino , SíndromeRESUMEN
A woman aged 45 years was presented with hypokalemic metabolic alkalosis and hypomagnesemia associated with renal potassium and magnesium wasting. Her 24-hour urinary calcium excretion was strikingly low despite normocalcemia and normal creatinine clearance, which is one of characteristic findings of Gitelman's syndrome (GS). She was evaluated for the responses following Mg supplementation for 10 days, which showed marked increments in serum potassium and magnesium as well as improvements of the degree of renal potassium wasting and hypocalciuria. This amelioration of abnormal biochemical pictures in this patient after Mg supplementation proposes that the hypokalemia with renal potassium wasting and hypocalciuria may be caused by abnormal Mg metabolism.
Asunto(s)
Síndrome de Bartter/terapia , Calcio/orina , Hipopotasemia/terapia , Magnesio/sangre , Síndrome de Bartter/sangre , Síndrome de Bartter/orina , Femenino , Alimentos Fortificados , Humanos , Persona de Mediana Edad , SíndromeRESUMEN
A woman aged 45 years was presented with hypokalemic metabolic alkalosis and hypomagnesemia associated with renal potassium and magnesium wasting. Her 24-hour urinary calcium excretion was strikingly low despite normocalcemia and normal creatinine clearance, which is one of characteristic findings of Gitelman's syndrome (GS). She was evaluated for the responses following Mg supplementation for 10 days, which showed marked increments in serum potassium and magnesium as well as improvements of the degree of renal potassium wasting and hypocalciuria. This amelioration of abnormal biochemical pictures in this patient after Mg supplementation proposes that the hypokalemia with renal potassium wasting and hypocalciuria may be caused by abnormal Mg metabolism.
Asunto(s)
Femenino , Humanos , Síndrome de Bartter/orina , Síndrome de Bartter/terapia , Síndrome de Bartter/sangre , Calcio/orina , Alimentos Fortificados , Hipopotasemia/terapia , Magnesio/sangre , Persona de Mediana Edad , SíndromeRESUMEN
OBJECTIVE: Familial occurrence of Bartter's syndrome is well known, but the simultaneous occurrence of hypokalemia/hypomagnesemia and chondrocalcinosis in one family has not been described. We present the clinical, laboratory and radiological findings of a family, in which 7 members were affected by disease. METHODS: A total of 43 members of the family could be interviewed concerning their general health, past diseases and joint complaints. Serum potassium and magnesium were determined in all and radiographic studies were performed in those who had hypokalemia and hypomagnesemia or those with merely articular complaints. Urinary excretion of potassium, magnesium and calcium were determined in the affected persons. RESULTS: Seven patients were found with hypokalemia and hypomagnesemia. Urinary potassium and magnesium excretion was inappropriately high when compared to the serum levels of these electrolytes. All patients had hypocalciuria and extensive chondrocalcinosis, mainly in the knees, elbows and shoulders. In one patient, most probably as a result of magnesium supplementation, a striking reduction of chondrocalcinosis was observed during a followup of 10 years. CONCLUSION: A family with familial hypokalemia/hypomagnesemia and chondrocalcinosis is described. The reduction of chondrocalcinosis, after years of magnesium supplementation in one patient, suggests that hypomagnesemia is an important factor in the pathogenesis of chondrocalcinosis in these patients.
Asunto(s)
Síndrome de Bartter/genética , Condrocalcinosis/genética , Hipopotasemia/genética , Magnesio/sangre , Adulto , Síndrome de Bartter/sangre , Síndrome de Bartter/diagnóstico por imagen , Síndrome de Bartter/orina , Condrocalcinosis/sangre , Condrocalcinosis/diagnóstico por imagen , Condrocalcinosis/orina , Electrólitos/sangre , Femenino , Estudios de Seguimiento , Humanos , Hipopotasemia/sangre , Hipopotasemia/orina , Magnesio/orina , Masculino , Persona de Mediana Edad , Linaje , Potasio/orina , RadiografíaRESUMEN
A 22-year-old female with Bartter's syndrome presented at 40 weeks' gestation for elective cesarean section under general anesthesia. Her usual medication was ibuprofen and potassium supplements. Preoperative potassium was 3.3 mmol/L, and in anticipation of difficulties in fluid, electrolyte, and acid-base management, a central line and urinary catheter were inserted and blood gases measured. In the first 20 hours postdelivery she had a brisk diuresis and required 3.5 L of crystalloid to maintain her central venous pressure and 100 mmol of potassium to prevent significant hypokalemia. The main features of Bartter's syndrome are growth retardation, hypertrophy, and hyperplasia of the juxtaglomerular apparatus, increased angiotensin II, hyperaldosteronism, hypokalemic alkalosis, normal blood pressure, and decreased response to pressors. The precise biochemical lesion is unknown, but it is most probably an abnormality of chloride transport in the loop of Henle. Anesthetic management is a major challenge, requiring a thorough understanding of the pathophysiology of the syndrome. The specific aims of the anesthetist are to maintain cardiovascular stability, control serum potassium, and prevent renal damage. Perioperative fluid balance must be meticulously managed, and drugs dependent on renal excretion must be used with caution. Metabolic alkalosis may interfere with the binding of drugs. The patient's short stature, platelet abnormalities, and reduced responsiveness to pressors all make regional anesthesia theoretically hazardous.
Asunto(s)
Anestesia General/métodos , Anestesia Obstétrica/métodos , Síndrome de Bartter/cirugía , Cesárea , Adulto , Síndrome de Bartter/sangre , Síndrome de Bartter/fisiopatología , Femenino , Humanos , Potasio/sangre , EmbarazoRESUMEN
Bartter's syndrome is characterized by chronic hypokalaemia, activation of the renin-angiotensin system and normal blood pressure. To investigate whether a generalized disturbance of sodium-potassium pump function might be of pathogenetic importance, lymphocytic sodium-potassium homeostasis was examined in 5 patients suffering from Bartter's syndrome. Two of the patients were treated with potassium chloride supplementation, the others were without medical treatment when studied. All were severely hypokalemic (serum potassium 2.8 +/- 0.24 mmol/l, mean +/- SEM). Lymphocyte sodium and potassium concentration (14.4 +/- 0.37 and 94.4 +/- 7.7 mmol/l, respectively), ouabain sensitive 22Na-efflux rate constant (2.68 +/- 0.25 h), and absolute ouabain sensitive efflux rate (38.16 +/- 4.2 mmol l-1 h) did not differ from matched controls. Ouabain binding capacity was 126 900 +/- 23 500 sites/cell in patients vs 50 400 +/- 17 900 in controls (p less than 0.05). In conclusion, patients with Bartter's syndrome may have an intrinsic abnormal pump function, characterized by an increased pump density and a low cation turn-over rate per pump unit.
Asunto(s)
Síndrome de Bartter/sangre , Hiperaldosteronismo/sangre , Linfocitos/metabolismo , Potasio/sangre , ATPasa Intercambiadora de Sodio-Potasio , Sodio/sangre , Adulto , Síndrome de Bartter/fisiopatología , Femenino , Humanos , Masculino , Receptores de Droga/metabolismoRESUMEN
Discussed here is a patient with normotension, hypokalemic alkalosis, hyperreninemia, hyperaldosteronism, juxtaglomerular cell hyperplasia and insensitivity to the pressor effects of angiotensin (Bartter's syndrome). The hyperreninemia and hyperaldosteronism were both suppressible with volume expansion. Hypokalemia was correctible both short-term with potassium chloride infusions and long-term with spironolactone. Nevertheless, the abnormal pressor response to infused angiotensin could not be corrected by these maeuvers, suggesting that this defect is likely to be of primary pathophysiologic significance. We found that potassium loading markedly stimulated aldosterone excretion. This may explain the inadequacy of potassium supplementation alone to correct the hypokalemia and the observed "escape" from the potassium conserving effects of spironolactone seen in patients with Bartter's syndrome. The administration of propranolol in large doses only partially suppressed the marked hyperreniemia of our patient and failed to prevent a subsequent rise in the renin level which was associated with spironolactone therapy. In contrast, suppression of the renin level to normal was demonstrated by sodium loading. It is suggested that patients with Bartter's syndrome be treated simultaneously with large doses of spironolactone and a high sodium intake.