Defect In Renal Calcium Reabsorption Research Articles

Male hypercalciuric stone formers with low renal calcium reabsorption

AimsHypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for...

Genetic hypercalciuric stone-forming rats

We will describe the pathophysiology of hypercalciuria and the mechanism of the resultant stone formation in a rat model and draw parallels to human hypercalciuria and stone formation. Through inbreeding we have established a strain of rats that excrete 8-10 times more urinary calcium than control rats. These genetic hypercalciuric rats absorb more dietary calcium at lower 1,25-dihydroxyvitamin D3 levels. Elevated urinary calcium excretion on a low-calcium diet indicated a defect in renal calcium reabsorption and/or an increase in bone resorption. Bone from hypercalciuric rats released more calcium when exposed to 1,25-dihydroxyvitamin D3. Bisphosphonate significantly reduced urinary calcium excretion in rats fed a low-calcium diet. Clearance studies showed a primary defect in renal calcium reabsorption. The intestine, bone and kidneys of the hypercalciuric rats had increased numbers of vitamin D receptors. When hydroxyproline is added to their diet they form calcium oxalate stones, the most common stone type in humans. Increased numbers of vitamin D receptors may cause hypercalciuria in these rats and humans. Understanding the mechanism of hypercalciuria and stone formation in this animal model will help clinicians devise effective treatment strategies for preventing recurrent stone formation in humans.

Renal Function and Urinary Excretion of Electrolytes in Patients Receiving Cyclic Parenteral Nutrition

Long-term parenteral nutrition (LTPN) has been shown to induce renal impairment and bone demineralization. However, the mechanism of both injuries has not been clarified. This prospective study was performed in 16 patients with short bowel syndrome, aged 28 to 63 years, who had received LTPN for 31 +/- 7 months. Urinary excretion of electrolytes were measured before (diurnal, 12 hours) and during (nocturnal, 12 hours) parenteral nutrition. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in the morning after the nutritional bag supply. Mean GFR was 86 +/- 7 mL/min/1.73 m2 and ERPF was 412 +/- 31 mL/min/1.73 m2. Decreased GFR was present in 9 patients. There was no relation between renal function and age or the duration of LTPN. Urine volume and excretion of urea, creatinine, sodium, magnesium, and phosphate but not potassium increased significantly in nocturnal urine compared with diurnal urine. On the basis on 24-hour calciuria, 7 patients were normocalciuric (NCa) whereas 9 were hypercalciuric (HCa). Both had excessive nocturnal calciuria, but only the HCa group had diurnal hypercalciuria, the calcium supply being identical. Bone mineral density (BMD) was slightly, although not significantly, higher in NCa group, but in all patients BMD correlated significantly with calciuria. Serum parathyroid hormone and vitamin D were not different in the two groups. In patients receiving LTPN, renal function is frequently impaired, by a mechanism which remains unclear. In nocturnal cyclic mode of nutrition, urinary volume and electrolyte excretion occurred predominantly during the infusion, but some patients have diurnal hypercalciuria. In these patients a defect in renal calcium reabsorption or more likely the inability of bone to retain the infused calcium may be responsible for bone demineralization.