Familial proximal renal tubular acidosis. A distinct clinical entity.

We have studied a family in which nine members present hyperchloremic acidosis with normal plasma creatinine and good ability to acidify urine. Renal functions, other than bicarbonate wasting, are normal, which identifies the condition as a pure form of proximal renal tubular acidosis. The acidosis persists into adult life and appears to be inherited as an autosomal dominant trait. All affected members are asymptomatic and the only peculiar finding is a decrease in stature. No hypercalciuria was detected, and no evidence of rickets or osteomalacia was found by x-ray studies. We consider these findings characteristic of a familial trait different from that in previously reported cases of renal tubular acidosis.

Impaired urinary ammonium excretion in patients with isolated proximal renal tubular acidosis.

During previous studies in patients with isolated proximal renal tubular acidosis (pRTA), the rates of urinary ammonium excretion were considered inappropriately low for their state of chronic metabolic acidosis. These observations were made while the patients were on a normal diet as well as when they were undergoing a short ammonium chloride test. Because these findings suggested an impaired ability to excrete maximal amounts of ammonium, the response to the 3-day acid loading test was evaluated in eight patients with isolated pRTA and in 10 normal control subjects. Plasma creatinine, acid-base, and electrolyte values were analyzed before and after 3 days of ingesting 2 mmol/kg.24 h of ammonium chloride. Twenty-four-hour urine specimens were collected the day before and on the third day of acid loading to determine urine pH, as well as the rate of excretion of NH4+ and titratable acid in milliequivalents per 24 h per 1.73 m2. During the basal state, all patients with pRTA had hyperchloremic metabolic acidosis and they excreted urine of lower pH (5.51 +/- 0.18 versus 6.00 +/- 0.13; P < 0.05) and greater titratable acid (29.1 +/- 4.3 versus 21.8 +/- 1.4; P < 0.05); however, they had rates of NH4+ excretion similar to those of controls. On the third day of acid loading, they excreted urine of lower pH (4.66 +/- 0.03 versus 5.00 +/- 0.03; P < 0.05) and equivalent amounts of titratable acid, whereas their NH4+ excretion was significantly less than that of controls (47.7 +/- 4.4 versus 76.3 +/- 5.7; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid and mineral balances and bone in familial proximal renal tubular acidosis.

BACKGROUND: Metabolic acidosis caused by increased rates of fixed acid production is associated with increased urinary excretion of Ca and negative Ca balances. Metabolic acidosis caused by a reduced capacity of the kidneys to excrete acid contributes to the development of bone disease in the course of chronic renal failure and may be associated with bone disease among some patients with renal tubular acidosis. METHODS: To assess the effects of life-long metabolic acidosis alone in the absence of other physiological disturbances, we measured the net balances of fixed acid and minerals in two brothers in a Costa Rican family with hereditary proximal renal tubular acidosis. Bone radiographs were assessed, and radial bone densities were measured. On a subsequent occasion, transiliac bone biopsies, following double-tetracycline labeling, were obtained from these two patients and an unaffected brother. RESULTS: During the balance studies, serum [HCO3-] concentrations of the two affected patients were stable at 12.5 +/- 0.9 and 19.2 +/- 0.7 mmol/L, respectively. Their rates of net fixed acid production were normal and appropriate for their body weights, averaging 0.90 and 1.02 mEq/kg/day. Because their distal renal tubular function was normal, they were capable of acidifying their urine maximally, allowing sufficient urinary excretion of titratable acid and ammonium to maintain net acid excretion at a level that matched acid production. Thus, their acid balances were near zero, as observed among healthy subjects, at -1.9 +/- 2.3 and -2.2 +/- 2.2 mEq/day, respectively. Their rates of urinary Ca excretion were normal at 1.6 +/- 0.3 and 2.7 +/- 2.4 mmol/day, and the their balances of Ca and other minerals were close to zero so that ongoing bone loss was not occurring despite the acidosis. Nevertheless, their heights, relative to their ages, were shorter than the heights of their unaffected relatives. Their radial bone densities were lower than normal for their age and sex, and their iliac cortices were thinner than that of their unaffected brother. However, they had no histomorphometric evidence of osteomalacia or osteitis fibrosa, and their rates of bone mineralization were normal. CONCLUSIONS: The results indicate that this chronic metabolic acidosis reduces growth, including that of bone. We speculate, without direct supporting evidence, that bone stores of HCO3-/CO3= are reduced, as has been observed in patients with the metabolic acidosis of chronic renal failure and in experimental metabolic acidosis in animals.