Effects of sevelamer hydrochloride on mortality, lipid abnormality and arterial stiffness in hemodialyzed patients: a propensity-matched observational study.

BACKGROUND: Cause-and-effect associations between sevelamer hydrochloride (HCl) and mortality have yet to be clarified. The effects of sevelamer HCl on mortality, lipid abnormality and arterial stiffness were examined in patients with chronic kidney disease stage 5D. METHODS: The effects of sevelamer HCl were studied by a single-center cohort study that was conducted from January 1, 2005 to December 31, 2008 (n = 483). By the end of the study, 172 patients (Sevelamer group) had succeeded in continuing sevelamer HCl for >6 months (median 37 months), and 300 patients (Control group) had received calcium carbonate (n = 264) or no phosphate binder (n = 36). The mortality and other outcomes were compared between these two groups after matching by a propensity score calculated using age, gender, diabetes prevalence, and dialysis vintage. RESULTS: All-cause [hazard ratio (HR) 0.4, P = 0.02] and cardiovascular (CV)-cause [HR 0.29, P = 0.03] cumulative mortality were significantly lower in the matched Sevelamer group than in the matched Control group. The matched Sevelamer group showed increased high-density lipoprotein cholesterol (P = 0.003) and no change in pulse wave velocity (PWV) and ankle-brachial index (ABI), whereas the matched Control group showed increased serum low-density lipoprotein (LDL) cholesterol (P = 0.003), increased PWV (P = 0.03), and decreased ABI (P = 0.0009). Change in serum LDL cholesterol level correlated inversely with sevelamer HCl dosage (P = 0.02). CONCLUSIONS: Reduced mortality in patients with sevelamer HCl may, at least in part, be explained by an improvement in dyslipidemia and arterial stiffness by sevelamer HCl.

Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients--a single-center cohort study.

BACKGROUND: In chronic kidney disease stage 5D, diagnostic usefulness of bone mineral density (BMD) in predicting fracture has not been established because of variable results in previous studies. The reason for this may be the heterogeneity of underlying pathogenesis of the fracture. METHODS: BMD was measured annually and serum biochemistry monthly for 485 hemodialyzed patients from April 2003 to March 2008, and all fractures were recorded. RESULTS: Forty-six new episodes of any type of fracture and 29 cases of prevalent spine fracture were recorded. Serum bone-specific alkaline phosphatase (b-AP) was a very useful surrogate marker for any type of incident fracture risk [area under curve (AUC) = 0.766, P < 0.0001]. A significantly greater risk of any type of incident fracture was associated with parathyroid hormone (PTH) levels either <150 pg/mL [hazard ratio (HR) = 3.47, P < 0.01] or >300 pg/mL (HR = 5.88, P < 0.0001) compared with 150-300 pg/mL. Receiver-operating characteristic analysis demonstrated a significant predictive power for incident of any type of fracture by BMD at the total hip (AUC = 0.760, P < 0.0001) and other hip regions in females in the lower PTH group (PTH < 204 pg/mL). BMDs at every site but whole body or lumbar spine had significant power to discriminate prevalent spine fracture regardless of gender or PTH. CONCLUSIONS: Hemodialyzed patients with low or high PTH or increased b-AP had a high fracture risk. BMD by Dual Energy X-ray Absorptiometry (DEXA), especially at the total hip region, was useful to predict any type of incident of fracture for females with low PTH or to discriminate prevalent spine fracture for every patient.

[Case of immune complex crescentic glomerulonephritis with consistently high titers of MPO-ANCA for 6 years].

A male patient, now 65 years old, experienced fever, hemoptysis, and respiratory failure about six years ago. Soon thereafter, he developed rapid progressive renal dysfunction with pulmonary hemorrhage and positive findings for MPO-ANCA. We commenced methylprednisolone pulse (MP) therapy followed by oral prednisolone (PSL) and intravenous cyclophosphamide (CY) for the treatment of ANCA-associated microscopic polyangiitis (MPA). Therapeutic efficacy was obtained comparatively rapidly. Light microscopic findings of a percutaneous renal biopsy demonstrated focal necrotizing and crescentic glomerulonephritis. Immunofluorescent microscopy indicated diffuse deposition of IgG and C3 along the periphery of the tufts and in the mesangium. On the basis of these findings, the condition was diagnosed as immune complex crescentic glomerulonephritis associated with MPO-ANCA. MPO-ANCA titers were high (714 EU) at onset and remained high (250-450 EU) over the ensuing 6 years with oral administration of PSL 5 mg. Though his condition remitted completely, his MPO-ANCA titers recently increased to above 600 EU once more. We conducted a follow-up renal biopsy to ascertain if the fluctuation of MPO-ANCA titers reflected an early stage of relapse. Light microscopic findings of the biopsied tissue revealed no signs of necrosis or crescentic formation of the glomeruli. Immunofluorescent microscopic findings were negative. The elevated MPO-ANCA titers were not valuable for the early prediction of relapse in our case, and the immune complex may have played an important role. When judging relapse and remission in ANCA-associated glomerulonephritis, it is important to evaluate the overall clinical findings and histopathological findings in addition to the serial ANCA titers.