title: Acid and mineral balances and bone in familial proximal renal tubular acidosis.
abstract: 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.
authors.affiliation: Nephrology Division, Department of Medicine and Clinical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. dr.jack@lemann.net
authors.forename: J
authors.initials: J
authors.lastname: Lemann
authors.forename: N D
authors.initials: ND
authors.lastname: Adams
authors.forename: D R
authors.initials: DR
authors.lastname: Wilz
authors.forename: L G
authors.initials: LG
authors.lastname: Brenes
mesh_terms: D015502:Absorptiometry, Photon; D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology*; D000141:Acidosis, Renal Tubular / Q000150:complications / Q000378:metabolism*; D000328:Adult; D001639:Bicarbonates / Q000097:blood; D015519:Bone Density; D002118:Calcium / Q000008:administration & dosage / Q000652:urine; D005192:Family Health; D005919:Glomerular Filtration Rate; D006801:Humans; D007085:Ilium / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008274:Magnesium / Q000008:administration & dosage; D008297:Male; D008903:Minerals / Q000008:administration & dosage / Q000378:metabolism*; D009679:Nuclear Family; D010012:Osteogenesis / Q000502:physiology; D010018:Osteomalacia / Q000209:etiology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
chemical_list: D001639:Bicarbonates; D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D017673:Sodium Chloride, Dietary; D008274:Magnesium; D002118:Calcium