Type 3 antenatal Bartter syndrome presenting with mild polyuria

Discussion

We experienced a preterm infant with type 3 ABS. Polyuria was temporary, and the mean urine output during hospitalisation was within the normal range, which was exceptional for ABS. Type 3 ABS is more likely to have mild polyuria than other types.

The patient developed mild polyuria. The normal urine output of new-borns is 1.25–2.5 mL/kg/hour at day 0, and gradually rises to 2–3 mL/kg/hour.3 In the literature, we could not find any definition of polyuria in neonates, especially for preterm neonates. In the literature on diabetes insipidus, the definition of polyuria was ≥5 mL/kg/hour.4 In another study on diabetes insipidus, polyuria was defined as a urine output of 4 mL/kg/hour in children and 6 mL/kg/hour in neonates.5 In this case, the patient had temporary polyuria of 5.3 mL/kg/hour from 35 to 36 weeks postmenstrual age. The average urine output during hospitalisation was 4.3 mL/kg/hour, which was higher than normal, but did not meet the definition of polyuria. As is evident from the above, polyuria was mild.

Polyuria of type 3 ABS may be milder than in other types. From an investigation of 146 children with all types of ABS, patients with types 3 and 4 ABS had the lowest urine output (5 mL/kg/hour). On the other hand, the urine outputs were 7, 6 and 15 mL/kg/h for types 1, 2 and 5 ABS, respectively.6

Polyuria in ABS can occur during the foetal period, resulting in polyhydramnios, which leads to a high incidence of preterm births.2 The average gestational age at delivery for type 3 ABS was 37 weeks, while the average gestational age at delivery for all other types of ABS was 29–33 weeks.6 7 In a study of 34 children with type 3 ABS, the average gestational age at delivery was reported to be 37 weeks, and amniotic fluid overload was reported to be the main symptom in only 56% of cases.7 In a report on 42 cases of ABS, including six cases of type 3 ABS, only two cases with type 3 ABS did not present polyhydramnios.8 Amniocentesis occurred once for types 3 and 4a ABS, compared with twice for types 1, 2 and 5.6 These findings suggest that type 3 ABS can develop mild polyuria, which leads to a low chance of polyhydramnios and preterm births. This patient had a premature birth due to chorioamnionitis, but the urine output was mild even in the preterm period. There have been few reports of preterm infants with type 3 ABS so far; therefore, our case is valuable for the research of type 3 ABS.

Less urine sodium leakage can lead to mild polyuria of type 3 ABS. Urine sodium of type 3 ABS was as low as 22 mmol/L compared with 60 mmol/L for type 1, 82 mmol/L for type 2 and 82 mmol/L for type 4a.8 The pathogenesis of BS is salt loss on the ureteral side, which results in migration of fluid and increased urine output. Type 3 ABS patients have low sodium leakage into the urine, which results in low urine output. We consider this to be the reason why polyuria is mild in patients with type 3 ABS. In our present case, urine sodium was as high as 39 to 96 mmol/L; however, these samples were obtained after sodium supplementation. Immature sodium reabsorption function of the renal tubule in preterm infants may also affect the high sodium excretion in urine in our case. Nephrotic diabetes insipidus can cause polyuria in the foetal and neonatal periods like ABS but does not cause polyhydramnios at a similar rate to ABS. The urinary and amniotic fluid components of ABS are salt and water, whereas those of nephrotic diabetes insipidus are pure water. Sodium and chloride in the amniotic fluid can lead to the retention of water; therefore, ABS results in polyhydramnios much more than nephrotic diabetes insipidus.9 This suggests that lower urine sodium leakage in the amniotic fluid will less likely lead to polyhydramnios and subsequent preterm delivery. Therefore, among all ABS types, type 3 ABS, with the lowest urinary sodium leakage rate, is less likely to result in the development of polyhydramnios and induce preterm delivery.

The reason why type 3 ABS presents with low sodium excretion is unclear. Type 3 ABS is caused by chloride-channel kb dysfunction, which resides in both the Henle’s loop and distal tubule.10 Based on the results of diuretic studies, it has been reported that type 3 BS is not caused by Henle’s loop, but is caused by distal tubular dysfunction.1 Henle’s loop reabsorbs more sodium than the distal tubule; therefore, type 3 ABS with distal tubular dysfunction may lead to less urinary sodium leakage and mild polyuria than other types.

However, the association between mutations and symptoms of CLCNKB gene remain unclear. In a study of five children with homozygous deletion of the whole CLCNKB gene, two patients had a history of polyhydramnios, which presented at 0.5–12 months of age.11 In this case with two large gene deletions, the patient presented with mild polyuria. Although further studies are required for evidence, large deletions of CLCNKB gene may not necessarily indicate severe symptoms at the antenatal/neonatal period.

Our study had some limitations. First, the patient had intrauterine infection, which could have affected the decreasing renal circulation from the foetal period. Treatment with gentamicin may also have affected the electrolyte leakage from the tubules. In addition, significant postnatal weight loss may have suggested dehydration and reduced polyuria, which could have led to less urinary sodium leakage during the perinatal period.