Vitamin d and stage 5 chronic kidney disease: a new paradigm?

Vitamin D receptor agonists (VDRA) are currently recommended for the treatment of secondary hyperparathyroidism in stage 5 CKD. They are considered to be contraindicated in the presence of low or normal (for a dialysis patient) levels of PTH due to the risk of developing adynamic bone disease, with consequent vascular calcification. However, these recommendations are increasingly at odds with the epidemiological evidence, which consistently shows a large survival advantage for patients treated with low-dose VDRAs, regardless of plasma calcium, phosphate, or PTH. A large number of pleiotropic effects of vitamin D have been described, including inhibition of renin activity, anti-inflammation, and suppression of vascular calcification stimulators and stimulation of vascular calcification inhibitors present in the uremic milieu. Laboratory studies suggest that a normal cellular vitamin D level is necessary for normal cardiomyocyte and vascular smooth muscle function. While pharmacological doses of VDRA can be harmful, the present evidence suggests that the level of 1,25-dihydroxycholecalciferol should also be more physiological in stage 5 CKD, and that widespread use of low-dose VDRA would be beneficial. A randomized controlled trial to test this hypothesis is warranted.

Clinical implications of converting stable haemodialysis patients from subcutaneous to intravenous administration of darbepoetin alfa.

BACKGROUND: The erythropoiesis-stimulating protein darbepoetin alfa (Aranesp) can be given intravenously (i.v.) or subcutaneously (s.c.). Despite a s.c. bioavailability of only 37%, darbepoetin alfa i.v. or s.c. dose requirements were comparable in previous studies designed to evaluate other aspects of anaemia treatment. The present study was designed to compare i.v. vs s.c. dose requirements. METHODS: A single-centre open-label, prospective and randomized crossover study was undertaken in 71 stable haemodialysis patients. After a run-in period randomized to a 20 week study treatment with either s.c. or i.v. darbepoetin alfa, the patients were crossed over to the other treatment modality for another 20 week study period. The unit dose of weekly darbepoetin alfa was adjusted to maintain each patient's haemoglobin within a target range of -0.8 to +0.8 mmol/l of the individual baseline haemoglobin and between 6.8 and 8.5 mmol/l throughout the study period. The primary endpoint was the mean dose of darbepoetin alfa necessary to maintain the haemoglobin level in the defined range. RESULTS: Data from 58 patients were available for analysis. Haemoglobin concentrations were maintained effectively in subjects, regardless of whether they received darbepoetin alfa i.v. or s.c.. The overall mean difference in haemoglobin levels during s.c. or i.v. was 0.052 mmol/l (95% confidence interval: -0.132 to 0.236 mmol/l). The difference had no statistical or clinical significance. The population mean darbepoetin alfa dose during i.v. treatment was 32.1 microg/week, compared with a mean value for s.c. treatment of 34.1 microg/week. A paired two-tailed ratio t-test showed that P = 0.036, indicating a 95% probability of a mean dose reduction between 1.2% and 28% by i.v. treatment instead of s.c.. CONCLUSIONS: Renal anaemia of stable haemodialysis patients can be treated with darbepoetin alfa more effectively by the i.v. as compared with the s.c. route.

Personal dialysis capacity (PDC(TM)) test: a multicentre clinical study.

BACKGROUND: The assessment of the peritoneal membrane capacity and physiology of the individual patient is becoming increasingly important. It allows the prescription of an individualized peritoneal dialysis (PD)-regimen, and the monitoring of peritoneal membrane function over time. The PDC(TM) program offers the possibility to evaluate the peritoneal membrane characteristics and to predict solute and water removal by simulation of different treatment regimens. METHODS: This study evaluates the relevance of the PDC(TM) program when routinely used. The PDC(TM) data of 336 patients from nine different centres in Europe were evaluated. RESULTS: The area parameter was 20 985+/-7578 cm/1.73 m(2) (mean+/-SD). The reabsorption of fluid after dissipation of glucose, Jv(AR), was 1.97+/-1.00 ml/min/1.73 m(2). The large pore fluid flux, Jv(L), was 0.11+/-0.07 ml/min/1.73 m(2). A multivariate model for prediction of serum albumin included dialysate protein loss, Jv(L), Jv(AR), nPCR, A(0)/deltaX, BMI and gender (R(2)=0.81, P<0.001). Total clearance fell with increasing PD duration (P<0.001). A negative relation between A(0)/deltaX and ultrafiltration (rho=-0.26, P<0.05), a positive relation between A(0)/deltaX and peritoneal creatinine clearance (rho=0.52, P<0.05) and urea clearance (rho=0.36, P<0.05), and a positive relation between measured peritoneal creatinine and urea clearance (rho=0.64, P<0.01) was observed. CONCLUSIONS: In summary, the present study shows that the PDC(TM) program is a robust, accurate method to describe the peritoneal membrane transport characteristics. Analysis of PDC(TM) data of large groups of patients, especially if followed up over time, can give interesting information on the physiology of the peritoneal membrane and the impact of different parameters on it.