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Free and total 1,25-dihydroxy vitamin D levels in subjects with renal disease. Patients with nephrotic syndrome and varying degrees of renal failure, including those on chronic hemo- and peritoneal dialysis, may have low serum concentrations of total 1,25-dihydroxyvitamin D [1,25(OH)2D]. However, it is unknown whether the true activity of 1,25(OH)2D is better reflected by the free 1,25(OH)2D fraction. We measured total 1,25(OH)2D, free 1,25(OH)2D, and vitamin-D-binding protein (DBP) in normal subjects (group A), subjects with moderate renal failure (group B), subjects on hemodialysis (group C), subjects on peritoneal dialysis (group D), and subjects with nephrotic syndrome (group E). The serum concentrations of total and free l,25(OH)2D decreased with worsening renal function in groups A through C, with a high degree of correlation (r = 0.974, P < 0.0001). Levels of DBP and the percent free 1,25(OH)2D remained constant in these groups. Patients on peritoneal dialysis and nephrotic patients had lower levels of DBP (203 ± 14 µg/ml and 371 ±46 µg/ml, respectively) than normal subjects (436 ± 33 µg/ml) and had significantly higher percent free 1,25(OH)2D (0.98 ± 0.13% and 1.27 ± 0.14%, respectively) compared to 0.63 ± 0.03% (P < 0.05). Thus, the loss of DBP in these patients correlated with a rise in the percent free 1,25(OH)2D. We conclude that levels of total 1,25(OH)2D are an accurate representation of 1,25(OH)2D status in normal subjects, subjects with renal insufficiency without nephrotic syndrome, and hemodialysis patients. In peritoneal dialysis and nephrotic patients, who lose DBP, measurements of free 1,25(OH)2D may be necessary in order to accurately assess 1,25(OH)2D status.

Delivered dose of hemodialysis (HD) in large patients with end-stage renal disease is often less than adequate. Fourteen chronic HD patients with weights greater than 80 kg participated in a prospective, cross-over study comparing urea reduction ratio (URR +/- SEM) and the fractional clearance index for urea (eKt/V(urea) +/- SEM) on a single polysulfone dialyzer for a control (HDC) period of 4 weeks versus clearances obtained with two dialyzers in parallel during an intervention (HDP) period of 4 weeks. Clearance of the surrogate middle molecule iohexol (C(Io)) was also measured. Health status was assessed with the SF-36. Blood and dialysate flow rates and duration of HD sessions were constant. URR increased from 0.67 +/- 0.006 during HDC to 0.72 +/- 0.006 with HDP (P < 0.0001). eKt/V(urea) increased from 1.16 +/- 0.021 to 1.34 +/- 0.021 (P < 0.0001). Increased URR and eKt/V(urea) occurred in all 14 during HDP (P < 0.05). C(Io) during HDP averaged 182 +/- 7.7 mL/min compared with 131 +/- 5.4 mL/min in HDC sessions (P < 0.00001). Health status improved in six of eight categories. Expense increased approximately $14.27 per dialysis with HDP. In 11 of 14 patients continued on two dialyzers in parallel for 1 year, monthly eKt/V averaged 1.46 +/- 0.066, and health status further improved in five of eight categories. In large patients, two dialyzers in parallel increased urea and iohexol clearance. Increased urea clearance was maintained for 1 year, and health status improved.