Genetic and dietary factors in urinary citrate excretion.
OBJECTIVE
Hypocitraturia, an important risk factor for calcium oxalate nephrolithiasis, is the result of numerous factors. We studied citrate excretion by patients with and without stones consuming normal and controlled formula diets.


METHODS
Subjects with and without a history of calcium oxalate stones (N = 101 per group) provided two or three 24-hour urine specimens during consumption of self-selected diets. Data also were collected on subsets of subjects consuming formula (Ensure) diets. Citrate was determined using the citrate lyase method of Petrarulo and associates, and values for multiple specimens were averaged. The data were adjusted for creatinine excretion and examined on a per-day basis.


RESULTS
The mean citrate excretion of the non-stone formers was slightly but not significantly higher than that of the stone formers (442 +/- 217 versus 378 +/- 153 mg/g of creatinine). All statistical analyses revealed highly significant differences between, but not within, individuals, a result compatible with a genetic influence. In the normal population, 5% of subjects had a citrate excretion <200 mg/g of creatinine, whereas this result was seen in 34% of the stone-forming subjects. When the subjects consumed a formula diet, women in both groups had much higher citrate excretion than when on a self-selected diet, but little difference was seen in the men. The patterns of citrate recovery suggest low, intermediate, and high excretors. In the normal population, 15% of subjects excreted <340 mg/g of creatinine, whereas this was true of 43% of the stone-forming subjects. Analysis of six families suggested three excretor phenotypes, with a codominant pattern of inheritance.


CONCLUSIONS
These findings imply a genetic influence on citrate excretion, as has already been demonstrated for calcium excretion. Further studies of genetic influences on calcium oxalate stone formation are warranted.
Shah
Ojas
O
Department of Urology, Wake Forest University Health Sciences Center, Winston-Salem, North Carolina 27157, USA. oshah@wfubmc.edu
Assimos
Dean G
DG
Holmes
Ross P
RP
D000328:Adult; D002129:Calcium Oxalate / Q000032:analysis; D016022:Case-Control Studies; D019343:Citric Acid / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004032:Diet; D019422:Dietary Sucrose / Q000008:administration & dosage; D005260:Female; D005526:Food, Formulated; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012737:Sex Factors
D019422:Dietary Sucrose; C082131:Ensure formulated food; D002129:Calcium Oxalate; D019343:Citric Acid; D003404:Creatinine