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Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD), but the reasons for this are incompletely understood. CKD associates with a decrease in liver cytochrome P450 (CYP450) enzymes, and specific CYP450 isoforms mediate vitamin D 3 C-25-hydroxylation, which forms calcidiol. Abnormal levels of parathyroid hormone (PTH), which also modulates liver CYP450, could also contribute to the decrease in liver CYP450 associated with CKD. Here, we evaluated the effects of PTH and uremia on liver CYP450 isoforms involved in calcidiol synthesis in rats. Uremic rats had 52% lower concentrations of serum calcidiol than control rats (P Ͻ 0.002). Compared with controls, uremic rats produced 71% less calcidiol and 48% less calcitriol after the administration of vitamin D 3 or 1␣-hydroxyvitamin D 3 , respectively, suggesting impaired C-25-hydroxylation of vitamin D 3 . Furthermore, uremia associated with a reduction of liver CYP2C11, 2J3, 3A2, and 27A1. Parathyroidectomy prevented the uremia-associated decreases in calcidiol and liver CYP450 isoforms. In conclusion, these data suggest that uremia decreases calcidiol synthesis secondary to a PTH-mediated reduction in liver CYP450 isoforms. ] deficiency has also been demonstrated in patients with stages 3 and 4 chronic kidney disease (CKD) and in patients who are on dialysis. [1][2][3][4][5][6][7][8] In fact, low serum 25(OH)D 3 is so intimately associated with CRF that in one study, only 29 and 17% of patients with stages 3 and 4 CKD, respectively, had sufficient levels [defined as a serum 25(OH)D 3 concentrations Ͼ75 nmol/L or 30 ng/ml]. 2 A more recent study showed a prevalence of calcidiol insufficiency and deficiency as high as 98% in predialysis patients with a mean GFR of 18.3 ml/min. 4 Prevalence of low serum 25(OH)D 3 was 78 and 89% in two large cohorts of hemodialysis patients 9,10 and 87% in a large cohort of peritoneal dialysis patients. 11 The metabolic consequences of calcidiol defi-

SummaryBackground and objectives Peritonitis is a well known complication of peritoneal dialysis (PD), whereas in hemodialysis (HD), bacteremia can be life threatening. Whether patients undergoing PD have higher risk than HD patients for infection-related hospitalizations (IRH) remains unknown.Design, setting, participants, & measurements A propensity score-matched retrospective cohort of patients undergoing long-term dialysis between January 2001 and December 2007 was assembled. Propensity scores were calculated using multivariable (demographic characteristics, smoking, body mass index, comorbid conditions, and laboratory data) logistic regression to estimate probability of receiving PD versus HD. A comparison of IRH risk by dialysis modality was estimated using a counting-process survival model.Results A total of 910 pairs of patients were matched by propensity scores. During a median follow-up of 2.1 years (interquartile range, 1.1-3.5 years), 341 patients were hospitalized once for an infection, 123 twice, and 106 at least three times. PD was associated with an increased risk for IRH compared with HD (propensity-matched hazard ratio [HR], 1.52). PD was associated with a reduced risk for septicemia (HR, 0.31) and pneumonia (HR, 0.58) but also an increased risk for dialysis-related infectious hospitalizations (HR, 3.44), defined as all cases of peritonitis and vascular access-related bacteremia, but not all septicemia cases.Conclusions PD patients are at higher risk for IRH than are HD patients. This risk is mostly explained by dialysisrelated infections. However, further studies are needed to evaluate whether the severity of those hospitalizations is similar and whether this increased risk for IRH is associated with worse outcomes.