Computer Simulations of Continuous Flow Peritoneal Dialysis Using the 3-Pore Model-A First Experience.

Background:Continuous flow peritoneal dialysis (CFPD) is performed using a continuous flux of dialysis fluid via double or dual-lumen PD catheters, allowing a higher dialysate flow rate (DFR) than conventional treatments. While small clinical studies have revealed greatly improved clearances using CFPD, the inability to predict ultrafiltration (UF) may confer a risk of potentially harmful overfill. Here we performed physiological studies of CFPD in silico using the extended 3-pore model.Method:A 9-h CFPD session was simulated for: slow (dialysate to plasma creatinine [D/P crea] < 0.6), fast (D/P crea > 0.8) and average (0.6 ≤ D/P crea ≤ 0.8) transporters using 1.36%, 2.27%, or 3.86% glucose solutions. To avoid overfill, we applied a practical equation, based on the principle of mass-balance, to predict the UF rate during CFPD treatment.Results:Increasing DFR > 100 mL/min evoked substantial increments in small- and middle-molecule clearances, being 2 - 5 times higher compared with a 4-h continuous ambulatory PD (CAPD) exchange, with improvements typically being smaller for average and slow transporters. Improved UF rates, exceeding 10 mL/min, were achieved for all transport types. The ß2-microglobulin clearance was strongly dependent on the UF rate and increased between 60% and 130% as a function of DFR. Lastly, we tested novel intermittent-continuous regimes as an alternative strategy to prevent overfill, being effective for 1.36% and 2.27%, but not for 3.86% glucose.Conclusion:While we find substantial increments in solute and water clearance with CFPD, previous studies have shown similar improvements using high-volume tidal automated PD (APD). Lastly, the current in silico results need confirmation by studies in vivo.

The secretory response of parathyroid hormone to acute hypocalcemia in vivo is independent of parathyroid glandular sodium/potassium-ATPase activity.

The involvement of sodium/potassium-ATPase in regulating parathyroid hormone (PTH) secretion is inferred from in vitro studies. Recently, the α-klotho-dependent rapid recruitment of this ATPase to the parathyroid cell plasma membrane in response to low extracellular calcium ion was suggested to be linked to increased hormone secretion. In this study, we used an in vivo rat model to determine the importance of sodium/potassium-ATPase in PTH secretion. Glands were exposed and treated in situ with vehicle or ouabain, a specific inhibitor of sodium/potassium-ATPase. PTH secretion was significantly increased in response to ethylene glycol tetraacetic acid-induced acute hypocalcemia and to the same extent in both vehicle and ouabain groups. The glands were removed, and inhibition of the ATPase was measured by (86)rubidium uptake, which was found to be significantly decreased in ouabain-treated parathyroid glands, indicating inhibition of the ATPase. As ouabain induced systemic hyperkalemia, the effect of high potassium on hormone secretion was also examined but was found to have no effect. Thus, inhibition of the parathyroid gland sodium/potassium-ATPase activity in vivo had no effect on the secretory response to acute hypocalcemia. Hence, the suggested importance of this ATPase in the regulation of PTH secretion could not be confirmed in this in vivo model.

Increased parathyroid expression of klotho in uremic rats.

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.

[A severe case of interstitial nephritis caused by sodium valproate]. / Valproatinduceret akut interstitiel nefritis med et alvorligt forløb.

A case of acute interstitial nephritis caused by sodium valproate is reported. The sodium valproate treatment was continued after initial diagnosis and the patient developed end-stage renal failure. After transplantation, interstitial nephritis was demonstrated in the renal graft.