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Published on: August 21, 2012
Renal citrate metabolism and urinary citrate excretion in the infant rat
J Z Melnick1, P A Preisig, R J Alpern
1Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA. j-melnick@nwu.edu
Insights
Infant rats exhibit higher urinary citrate excretion than adults, despite similar tissue citrate levels. This difference is linked to developmental changes in the kidney
Area of Science:
- Nephrology
- Pediatric Nephrology
- Biochemistry
Background:
- Hypercalciuria is common in both children and adults.
- Children rarely develop kidney stones despite similar hypercalciuria prevalence.
- Infants may have higher urinary citrate excretion than adults, potentially explaining reduced stone formation.
Purpose of the Study:
- To investigate renal citrate excretion in infant versus adult rats.
- To examine renal cortical citrate metabolism differences between infant and adult rats.
Main Methods:
- Adult and infant male rats were housed in metabolic cages and fed synthetic diets.
- Urine was collected, and renal cortical citrate metabolism was assayed.
- Key enzyme activities and transporter functions related to citrate metabolism were assessed.
Main Results:
- Infant rats showed significantly higher urinary citrate excretion (fourfold higher citrate:creatinine ratio and twofold higher concentration).
- Plasma bicarbonate was lower and plasma potassium was higher in infant rats.
- Despite higher urinary citrate, renal cortical citrate concentrations were comparable, and mitochondrial aconitase activity was lower in infants.
Conclusions:
- Infant rats excrete more citrate in urine than adults, but this doesn't correlate with tissue citrate levels.
- The increased urinary citrate in infants is likely due to developmental differences in proximal tubule citrate transport, independent of Na/citrate cotransport.
- Further research into maturational changes in renal citrate handling is warranted.
Background:
Although hypercalciuria has the same prevalence in children as adults, children rarely develop renal stones. This may be explained by a greater urinary citrate excretion in infants compared with adults. The present study examines the renal excretion of citrate and renal cortical citrate metabolism in infant and adult rats.
Methods:
Adult male and newly weaned infant rats were acclimated to metabolic cages and fed synthetic diets. Urine was collected after two days, and renal cortical citrate metabolism was assayed.
Results:
Infant rats had a lower plasma [HCO3-] and higher plasma [K+] and had a fourfold higher urinary citrate:creatinine ratio and a twofold higher concentration of citrate in their urine compared with adult rats. This higher urinary citrate excretion was not due to a difference in renal proximal tubular Na/citrate cotransporter activity, nor renal cortical citrate synthase or ATP citrate lyase activities in infants as compared with adults. However, infant rat kidneys had significantly lower mitochondrial aconitase (m-aconitase) activity. Renal cortical citrate concentrations were comparable in infant and adult rats. Manipulation of plasma [K+] to adult levels did not affect the higher urinary citrate excretion in infant rats.
Conclusions:
Urinary citrate excretion in infant rats is greater than in adults but does not parallel tissue [citrate]. Thus, this higher urinary citrate is likely due to maturational differences in the proximal tubule, other than Na/citrate cotransport, that directly affect citrate transport.
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