Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism

Abstract

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 ageand sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calsium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.Primary hyperparathyroidism is a disease charac¬ terized biochemically by hypercalcemia, hypophosphatemia, and elevated level of immunoreactive parathyroid hormone (PTH). The hypercalcemia in primary hyperparathyroidism can be accounted for by the enhancing effect of PTH on flux of cal¬ cium from gut and bone and an increased capacity for renal tubular reabsorption of calcium (1), the latter apparently playing the major role (1,2).Another hypercalcémie disorder which biochem¬ ically have much in common with primary hyper¬ parathyroidism is familial hypocalciuric hypercal¬ cemia (3). However, several studies have estab¬ lished that aspects of the pathophysiology of famil¬ ial hypocalcimic hypercalcemia differ from those of typical primary hyperparathyroidism (4-9).Recently we investigated the nephron site of the enhanced tubular calcium reabsorption in familial hypocalcimic hypercalcemia by means of combined determination of the glomerular filtration rate (GFR) and lithium clearance (10). Compared with normal healthy controls, the results suggested that the increased tubular calcium reabsorption in fa¬ milial hypocalcimic hypercalcemia took place ex¬ clusively in the proximal tubule. Furthermore, the same study revealed a difference in renal handling of sodium between familial hypocalcimic hypercal¬ cemia and controls (11).As an extension of that study we have attempted to elucidate the renal tubular function in primary hyperparathyroidism with special reference to:1. Estimation of the increased capacity for renal tubular reabsorption of calcium.2. Determination of fractional and absolute reabsorptio...

Clinical and laboratory characteristics of calcium stone‐formers with and without primary hyperparathyroidism

“…Others have found that urinary calcium excretion factored by GFR is low in HPT vs NS when plotted against serum calcium or ultrafilterable calcium; this implies a lower FECa in HPT than in NS, and is opposite to what we found. However, serum calcium values of NS did not overlap with HPT, so such a comparison requires either that normal serum calcium values are extrapolated to the high levels in HPT using a regression equation [13], or as we did previously [3], use studies of NS rendered hypercalcaemic by calcium infusion, or be content to calculate FECa from actual values, as in the present study. We think that the last of the three is most useful because it returns a value of FECa that actually applies to the persons under question, whereas the other two relate to conditions that are in fact theoretical.…”

“…Kristiansen et al. [13], using graphical extrapolation, concluded that the FECa of HPT was below that of NS. However, using their data, we conclude otherwise.…”

Chemical evidence for the tradeoff-in-the-nephron hypothesis to explain secondary hyperparathyroidism

“…PTH regulates reabsorption of the 10% of filtered Ca that reaches the DCT by controlling expression of the apical calcium channel transient receptor potential vanilloid 5 (TRPV5), the intracellular transporter calbindin-D 28K , and the basolateral extrusion proteins sodium-calcium exchanger 1 (NCX1) and plasma membrane calcium ATPase 1b (PMCA1b) [ 10 , 11 , 30 ]. In primary hyperparathyroidism (PHPT), elevated [PTH] causes hypercalcemia by increasing TR Ca /C cr [ 12 , 49 ]; in SHPT, comparable or higher [PTH] is associated with and presumably required to achieve normal TR Ca /C cr and normocalcemia [ 12 ]. This presumption is consistent with the observation that cinacalcet, a calcimimetic that suppresses synthesis and secretion of PTH, reduced tubular Ca reabsorption and caused hypocalcemia as it lowered [PTH] in CKD stages G 3 and G 4 [ 50 ].…”