Klotho is a protein of significant importance for mineral homeostasis. It helps to increase parathyroid hormone (PTH) secretion and in the trafficking of Na+/K+-ATPase to the cell membrane; however, it is also a cofactor for fibroblast growth factor (FGF)-23 to interact with its receptor, FGFR1 IIIC, resulting in decreased PTH secretion. Studies on the regulation of parathyroid klotho expression in uremia have provided varying results. To help resolve this, we measured klotho expression in the parathyroid and its response to severe uremia, hyperphosphatemia, and calcitriol treatment in the 5/6 nephrectomy rat model of secondary hyperparathyroidism. Parathyroid klotho gene expression and protein were significantly increased in severely uremic hyperphosphatemic rats, but not affected by moderate uremia and normal serum phosphorus. Calcitriol suppressed klotho gene and protein expression in severe secondary hyperparathyroidism, despite a further increase in plasma phosphate. Both FGFR1 IIIC and Na+/K+-ATPase gene expression were significantly elevated in severe secondary hyperparathyroidism. Parathyroid gland klotho expression and the plasma calcium ion concentration were inversely correlated. Thus, our study suggests that klotho may act as a positive regulator of PTH expression and secretion in secondary hyperparathyroidism.

Introduction: Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways. Methods: We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.5% glucose fluid or 4.25% glucose fluid for 120 min dwell time to evaluate the effects of SGLT2 inhibition by empagliflozin on peritoneal water and solute transport. To assess the diffusion capacity of glucose, we developed a modified equation to measure small solute diffusion capacity, taking convective- and free water transport into account. Results: SGLT2 inhibition markedly increased the urinary excretion of glucose and lowered plasma glucose after PD compared to sham groups. Glucose absorption for 1.5% glucose was 165 mg 95% CI (145–178) in sham animals and 157 mg 95% CI (137–172) for empagliflozin-treated animals. For 4.25% glucose, absorption of glucose was 474 mg 95% CI (425–494) and 472 mg 95% CI (420–506) for sham and empagliflozin groups, respectively. No significant changes in the transport of sodium or water across the peritoneal barrier could be detected. Conclusion: We could not confirm recent findings that SGLT2 inhibition reduced glucose absorption and increased osmotic water transport during experimental PD.

Introduction: Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD. Methods: A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with ( n = 6) or without ( n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment. Results: Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower ( p < 0.05) being 196 µL/min (IQR 178–213) for phlorizin-treated animals compared to 238 µL/min (IQR 233–268) in controls. Median fractional dialysate glucose concentration at 60 min ( D/ D 0) was significantly higher ( p < 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63–0.67) compared to 0.61 (IQR 0.60–0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane. Conclusion: Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells.