Evaluation of a phosphate kinetics model in hemodialysis therapy-Assessment of the temporal robustness of model predictions

In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a three-compartment phosphate kinetic model to individual patient data and assess the temporal robustness. Intradialytic phosphate samples were collected from the plasma and dialysate of 12 patients during two treatments (HD1 and HD2). 2-h postdialytic plasma samples were collected in four of the patients. First, the model was fitted to HD1 samples from each patient to estimate the mass transfer coefficients. Second, the best fitted model in each patient case was validated on HD2 samples. The best model fits were determined from the coefficient of determination (R2 ) values. When fitted to intradialytic samples only, the median (interquartile range) R2 values were 0.985 (0.959-0.997) and 0.992 (0.984-0.994) for HD1 and HD2, respectively. When fitted to both intra- and postdialytic samples, the results were 0.882 (0.838-0.929) and 0.963 (0.951-0.976) for HD1 and HD2, respectively. Eight patients demonstrated a higher R2 value for HD2 than for HD1. The model seems promising to predict individual plasma phosphate in hemodialysis patients. The results also show good temporal robustness of the model. Further modifications and validation on a larger sample are needed.</p

Treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol

<p>Abstract</p> <p>Background</p> <p>Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its serious clinical consequences include renal osteodystrophy, calcific uremic arteriolopathy, and vascular calcifications that increase morbidity and mortality.</p> <p>Reduced synthesis of active vitamin D contributes to secondary hyperparathyroidism. Therefore, this condition is managed with activated vitamin D. However, hypercalcemia and hyperphosphatemia limit the use of activated vitamin D.</p> <p>In Denmark alfacalcidol is the primary choice of vitamin D analog.</p> <p>A new vitamin D analog, paricalcitol, may be less prone to induce hypercalcemia and hyperphosphatemia.</p> <p>However, a randomised controlled clinical study comparing alfacalcidol and paricalcitol has never been performed.</p> <p>The primary objective of this study is to compare alfacalcidol and paricalcitol. We evaluate the suppression of the secondary hyperparathyroidism and the tendency towards hyperphosphatemia and hypercalcemia.</p> <p>Methods/Design</p> <p>This is an investigator-initiated cross-over study. Nine Danish haemodialysis units will recruit 117 patients with end stage renal failure on maintenance haemodialysis therapy.</p> <p>Patients are randomised into two treatment arms. After a wash out period of 6 weeks they receive increasing doses of alfacalcidol or paricalcitol for a period of 16 weeks and after a further wash out period of 6 weeks they receive the contrary treatment (paricalcitol or alfacalcidol) for 16 weeks.</p> <p>Discussion</p> <p>Hyperparathyroidism, hypercalcemia and hyperphosphatemia are associated with increased cardiovascular mortality in patients with chronic kidney disease.</p> <p>If there is any difference in the ability of these two vitamin D analogs to decrease the secondary hyperparathyroidism without causing hypercalcemia and hyperphosphatemia, there may also be a difference in the risk of cardiovascular mortality depending on which vitamin D analog that are used. This has potential major importance for this group of patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT004695</p

Oral Magnesium Supplementation in Chronic Kidney Disease Stages 3 and 4:Efficacy, Safety, and Effect on Serum Calcification Propensity-A Prospective Randomized Double-Blinded Placebo-Controlled Clinical Trial

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality. Recent evidence suggests that increases in both serum and intracellular magnesium (Mg) can slow or even prevent the development of vascular calcification seen in CKD. Serum calcification propensity (T50) is a novel functional test, which is associated with all-cause mortality in CKD and measures the ability of serum to delay the formation of crystalline nanoparticles. Theoretically, increasing serum Mg should improve T50 and thereby reduce the propensity towards ectopic calcification. Methods: We conducted a randomized placebo-controlled double-blinded clinical trial to investigate the safety of 2 different doses of oral Mg supplementation in subjects with CKD stages 3 and 4 as well as their effects on intracellular Mg and T50. Thirty-six subjects with CKD stages 3 and 4 were randomized to one of 3 groups (placebo, elemental Mg 15 mmol/d or elemental Mg 30 mmol/d) given as slow-release Mg hydroxide and followed for 8 weeks. Results: Thirty-four subjects completed the trial. Intracellular Mg remained stable throughout the trial despite significant increases in both serum and urine Mg. T50 increased significantly by 40 min from 256 ± 60 (mean ± SD) to 296 ± 64 minutes (95% confidence interval, 11–70, P < 0.05) in the Mg 30 mmol/d group after 8 weeks. No serious adverse events related to the study medication were reported during the study. Discussion: Oral Mg supplementation was safe and well tolerated in CKD stages 3 and 4 and improved T50, but did not increase intracellular Mg. Further studies are needed to investigate the long-term effects of Mg supplementation in CKD stage 3 and 4 and whether improvement in calcification propensity is related to clinical endpoints

Catheter Related <i>Escherichia hermannii</i> Sepsis in a Haemodialysis Patient

Escherichia hermannii is an extremely rare etiological agent of invasive infection, and thus, the bacterium was initially considered non-pathogenic. However, in five previously reported case reports E. hermannii has been implicated as the sole pathogen. Our case report describes blood stream infection with E. hermannii in a haemodialysis patient with persisting symptoms, high fever and inflammatory markers despite appropriate antibiotic treatment until replacement of the dialysis catheter. We suspect biofilm formation to be a crucial pathogenic feature for E. hermannii in the maintenance of an infection, which stresses the necessity of antibiotic treatment along with catheter replacement in bloodstream- and catheter-related infection with E. hermannii