The spectrum of endemic renal tubular acidosis in the northeast of Thailand.

We have previously reported a high prevalence of endemic renal tubular acidosis (EnRTA) in the northeast of Thailand, and our subsequent studies provided evidence that K deficiency exists in the same region. Since tubulointerstitial damage is associated with K deficiency, we postulate that this might be implicated in the pathogenesis of EnRTA and, if so, that a spectrum of tubulointerstitial abnormalities can be anticipated. In this study we evaluated renal acidification ability in 4 patients and in 11 of their relatives. We used a 3-day acid load (NH4Cl 0.1 g/kg/day) followed by 20 mg oral furosemide and monitored the maximal renal concentrating ability using water deprivation and intranasal 1-deamino-D-arginine vasopressin. The results showed that the subjects could be divided into three groups; normal relatives of the patients, those with suspected renal tubular acidosis, and patients with overt EnRTA who had chronic metabolic acidosis and a low rate of excretion of NH4+. The rate of excretion of K was very low (20 +/- 4 mmol/day) in patients with EnRTA and in their relatives with suspected EnRTA. The transtubular K concentration gradient was also very low in their relatives, especially in patients with suspected EnRTA (2.8 +/- 0.2). With a 3-day NH4Cl load, the rate of excretion of NH4+ was very low in patients with EnRTA (32 +/- 9 mmol/day), and the relatives with suspected EnRTA also had a decreased capacity to excrete NH+4 (50 +/- 14 mmol/day). In contrast, the normal relatives excreted 92 +/- 12 mmol of NH+4/day. The patients with EnRTA could lower their urine pH to less than 5.5 after the acid loading (6.2 +/- 0.3). After furosemide (20 mg), the NH4+ excretion in the patients with EnRTA was lower than in the normal relatives. Moreover, the minimum urine pH in patients with EnRTA did not fall (6.1 +/- 0.2), but there was a fall to 4.8 +/- 0.1 in the patients with suspected EnRTA after furosemide treatment. In conclusion, there was a spectrum of tubulointerstitial abnormalities ranging from suspected to overt distal RTA in a geographic area known to have a high prevalence of K deficiency. K deficiency might be the important pathogenetic factor of EnRTA in the northeast of Thailand.

Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis.

Sudden unexplained nocturnal death (SUND), a disorder of unknown cause that occurs in otherwise healthy young adults, mostly male, during their sleep, is prevalent in the north-east region of Thailand, where it has been known for generations as lai tai. It occurs in the same population and area where hypokalaemic periodic paralysis (HPP), endemic distal renal tubular acidosis (EdRTA), and renal stones are also endemic. SUND has occurred in families of patients with EdRTA, and HPP can present as sudden onset of muscle parlysis with potentially lethal cardiac arrhythmias and respiratory failure from severe hypokalaemia occurring in the middle of the night. Surveys in which serum and urinary potassium have been measured indicate a deficiency of the electrolyte in the population. Potassium deficiency is probably the prime factor responsible for SUND and HPP. Low urinary citrate concentrations and the high prevalence of acidification defects in the population indicate that potassium deficiency is also responsible for the prevalence of EdRTA and for renal stones.

Endemic primary distal renal tubular acidosis in Thailand.

Within a period of 3 years, 103 patients with primary type I distal renal tubular acidosis were reported from two hospitals in the northeast of Thailand, with cases peaking in the summer. The patients' age ranged from 18 to 76 with a mean and mode of 39 and 47 years, respectively. The female to male ratio was 3.3:1. All patients presented with generalized muscle weakness and bone pain and nocturia were frequent manifestations. Hypokalaemia and hyperchloraemic metabolic acidosis were constant findings and were more pronounced in patients with roentgenographic evidence of nephrocalcinosis and osteomalacia. Urinary citrate was extremely low in most of the patients. Nephrocalcinosis and/or renal stones were present in 27.2% of the patients and osteomalacia was found in 23.3%. All patients were Lao-Thai. This is the first report of a large group of patients with distal renal tubular acidosis, endemic within a particular geographical region.