Renal reabsorption of magnesium and calcium by cattle with renal tubular dysplasia

Abstract

The concentrations of magnesium and calcium in the serum and urine and their rates of clearance were determined in cattle with renal tubular dysplasia, an autosomal recessive hereditary disease associated with a deletion of the paracellin-1 gene in Japanese Black cattle. There were no significant differences in the serum or urine magnesium concentrations between normal cattle and cattle which were heterozygous or homozygous for the condition. Serum calcium concentrations tended to be lower in the homozygous cattle, and the serum creatinine and urea nitrogen concentrations were significantly higher in the homozygous cattle. The ratio of magnesium:creatinine and the fractional excretion of magnesium were higher in cattle with the disease than in normal cattle. There were no significant differences in urine calcium concentration, the calcium:creatinine ratio, and fractional excretion of calcium between normal cattle and cattle which were homozygous or heterozygous for the condition. The creatinine clearance was significantly lower in the homozygous cattle than in normal cattle. The clearance, excretion rate, reabsorption rate and reabsorption rate:clearance ratio of magnesium in cattle with renal tubular dysplasia were significantly lower than in normal cattle. The clearance rate and reabsorption rate of calcium were also significantly lower in the affected cattle, but the excretion rate and reabsorption rate:clearance of calcium were not different between the normal cattle and the cattle homozygous for the condition. In cattle with the condition the rate of reabsorption of magnesium by the kidneys was low, but the rate of reabsorption of calcium was normal.

Restricted Localization of Claudin-16 at the Tight Junction in the Thick Ascending Limb of Henle's Loop Together with Claudins 3, 4, and 10 in Bovine Nephrons

“…Moreover, even under physiological conditions, the presence of claudin-4 seems to affect the function of claudin-16 in generating the lumenpositive potential in the TAL segments of bovine nephrons, suggesting that reabsorption of divalent cations in TAL regions is less fundamental in cattle. This may partly explain why the affected animals do not have aberrant phenotypes in Mg 2+ and Ca 2+ metabolisms [21]. However, the physiological role and the regulatory mechanism for functional interaction of claudin-16 and claudin-4 in cattle remain to be clarified.…”

“…Although the significance of claudin-16 function in Mg 2+ and Ca 2+ metabolism remains uncertain in cattle [21], the affected animals [24] and FHHNC patients [35] share several histopathological findings, including tubular atrophy, immature tubules, and interstitial fibrosis. These renal lesions are observed in affected animals with claudin-16 deficiency at 1 to 2 months of age, and appear to progressively lead to decreases in the number of glomeruli [24].…”

“…These histological findings suggest that the primary lesion of bovine renal dysplasia is an anomalous defect in differentiation of renal tubular epithelial cells and that claudin-16 therefore has some pivotal roles in differentiation and formation of renal tubule segment(s) in addition to the function in paracelluar transport. Interestingly, in contrast to FHHNC, decreases in serum Mg 2+ and Ca 2+ concentrations are not apparent in cattle with claudin-16 deficiency, while a reduction in renal reabsorption rate has been suggested for Mg 2+ [21]. This suggests that there is a compensatory system(s) for metabolism of these divalent cations in the absence of claudin-16 or that bovine claudin-16 may have functions in paracellular transport of Mg 2+ and Ca 2+ distinct from those of the human counterpart despite their high homology in amino acid sequences [9,20].…”

Abnormal Development of Nephrons in <i>Claudin-16</i>- Defective Japanese Black Cattle

“…It is also known as "renal tubular dysplasia in Japanese Black cattle" [13][14][15][16][17] or "bovine chronic interstitial nephritis with diffuse zonal fibrosis" [5,8]. This disease is caused by a homozygous deletion of gene and is transmitted by autosomal recessive inheritance [8,14].…”

“…It is thought that Paracellin-1 protein forms a component of magnesium channel [20,21]. Although the amino acid has more than 90% homology with Paracelline-1 [5,13], the CL-16 defect in cattle exhibits no hypomagnesemia [17] which is a common finding in humans.…”