An inheritable anomaly of red-cell oxalate transport in "primary" calcium nephrolithiasis correctable with diuretics

N Engl J Med. 1986 Mar 6;314(10):599-604. doi: 10.1056/NEJM198603063141002.

Abstract

We measured the rate of oxalate flux across the red-cell membrane in the steady state in 114 patients with a history of calcium oxalate kidney stones and in 25 controls. Of the patients, 98 had recurrent, "idiopathic" kidney stones, 8 had primary hyperparathyroidism, 7 had renal or urinary tract malformations, and 1 had primary hyperoxaluria. Oxalate exchange was significantly higher in the 98 patients with idiopathic stone formation than in the controls (-1.10 +/- 0.95 [SD] X 10(-2) min-1 vs. -0.31 +/- 0.12 X 10(-2); P less than 0.001); it was above the upper limits of normal in 78 of these patients. All 8 patients with hyperparathyroidism and the patient with primary hyperoxaluria had values in the normal range; 2 of the patients with renal or urinary tract malformation had values at the upper normal limit. A study of five families indicated that the abnormality is an autosomal monogenic dominant trait with complete penetrance and variable expressivity. Oxalate-tolerance tests were carried out in five pairs of brothers. One brother in each pair had the abnormality in oxalate flux, and had a significantly higher percentage of oxalate excretion at two hours after oxalate loading (18.09 +/- 3.07 [SD] vs. 10.37 +/- 3.08 percent; t = 3.97; P less than 0.005) and four hours (14.87 +/- 2.91 vs. 9.89 +/- 2.93 percent; t = 2.70; P less than 0.05). Treatment with oral hydrochlorothiazide (50 mg per day) or amiloride (5 mg per day) or both restored normal or nearly normal red-cell oxalate exchange in all of 33 patients who initially had increased rates. We conclude that an inherited cellular defect in oxalate transport may be a factor in "primary" calcium oxalate stone formation and that this defect may be corrected with diuretics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amiloride / therapeutic use
  • Biological Transport
  • Calcium Oxalate / metabolism*
  • Child
  • Child, Preschool
  • Diuretics / therapeutic use*
  • Drug Tolerance
  • Erythrocytes / metabolism*
  • Female
  • Humans
  • Hydrochlorothiazide / therapeutic use
  • Kidney Calculi / drug therapy
  • Kidney Calculi / etiology*
  • Kidney Calculi / genetics
  • Male
  • Middle Aged
  • Models, Biological
  • Oxalates / blood*
  • Oxalates / urine
  • Pedigree

Substances

  • Diuretics
  • Oxalates
  • Hydrochlorothiazide
  • Calcium Oxalate
  • Amiloride