RENAL MINERAL DELIVERY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent work has shown that calcium kidney stone formers have deposits of calcium phosphate (apatite) in their renal papillae, which serve as anchor points for stones. In patients calcium oxalate stones, mineral deposits are found in the interstitium, and the initial site of formation is the basement membrane of the thin limbs of Henle. In others, usually calcium phosphate stone formers, crystal deposits are located in the terminal collecting ducts. The mechanisms by which high urine calcium promotes mineral deposition at specific sites are not known. The objective of the project is to understand the driving forces for the formation of apatite plaque in the kidneys of patients with calcium kidney stones and the forces driving collecting duct.crystal formation in in brushite stone formers. For this purpose, we studied a group of hypercalciuric stone formers and comparable non-stone formers. All subjects were admitted to the GCRC for 14 hours, where they were fed 3 defined meals designed by the CRC dietician to vary with respect to protein and carbohydrate content, but to have equivalent amounts of calcium, phosphate and sodium. One hour urine samples were collected and blood samples were draw at the end of each urine and at the mid-points of the first 2 hours after each meal. Serum and urine mineral levels were determined, as well as PTH, calcitriol and insulin levels. We have also measured all urine factors needed to calculate urine supersaturation with respect to calcium oxalate and calcium phosphate, and as well the ability of each urine to inhibit crystal formation, an indicator of the level of urinary inhibitors of crystallization. Results were analyzed with appropriate adjustment for sex, age, creatinine clearance, height and weight.