BACKGROUND: Progressive renal failure in patients with classic Bartter's 
syndrome (cBS) due to inactivating mutations in CLCNKB gene is extraordinarily 
rare.
DISCUSSION: We describe a 17-year-old Chinese boy who presented with progressive 
muscle weakness and renal failure. He was diagnosed as BS of unknown type at the 
age of 9 months and treated with indomethacin (2 mg/kg/day) and potassium 
chloride (KCl) supplementation (1.5 mEq/kg/day) for hypokalemia (2.5 mmol/l). At 
the age of 12 years, serum K+ was 3.0 mmol/l and creatinine reached 2.0 mg/dl. 
On admission, his blood pressure was normal but volume status was depleted. 
Urinalysis was essentially normal. Biochemical studies showed hypokalemia (K+ 
2.4 mmol/l) with a high transtubular K+ gradient (TTKG) 9.6, metabolic alkalosis 
(HCO3- 28.4 mmol/l), normomagnesemia (2.0 mg/dl), severe renal failure (BUN 94 
mg/dl, Cr 6.3 mg/dl), and hypocalciuria (urine calcium/creatinine ratio 0.02 
mg/mg). Abdominal sonography revealed bilateral small size kidneys without 
nephrocalcinosis or renal stones. After the withdrawal of indomethacin with 
regular KCl and adequate fluid supplementation for 1 year, serum creatinine and 
K+ levels have been maintained at 4.0 mg/dl and 3.3 mmol/l, respectively. Direct 
sequencing of NKCC2, ROMK, ClC-Kb, and NCCT in this patient disclosed a novel 
homozygous missense mutation (GGG to GAG, G470E) in CLCNKB. This G470E mutation 
was not identified in 100 healthy Chinese subjects. Long-term therapy of 
non-steroidal anti-inflammatory drugs (NSAIDs), prolonged hypokalemia, chronic 
volume depletion, and underlying genetic variety may contribute to the 
deterioration of his renal function. The cautious use of NSAIDs, aggressive 
correction of hypokalemia, and avoidance of severe volume depletion may prevent 
the irreversible renal damage in patients with BS due to a Cl- channel defect.