Elevated plasma levels of endostatin are associated with chronic kidney disease.

BACKGROUND/AIMS: Angiogenesis may play an important role in the renal repair process after injury. We investigated the association between plasma endostatin, an endothelial-specific antiangiogenic factor, and chronic kidney disease (CKD). METHODS: We compared plasma endostatin levels in 201 CKD patients and 201 controls. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) or presence of albuminuria (≥30 mg/24 h). RESULTS: After adjustment for established CKD risk factors, the median (interquartile range) of plasma endostatin was 276.7 ng/dl (199.3-357.5) in patients with CKD and 119.4 ng/dl (103.7-134.6) in controls without CKD (p < 0.0001 for group difference). log-transformed plasma endostatin was significantly and inversely correlated with eGFR (r = -0.83, p < 0.0001) and positively correlated with log-transformed urine albumin (r = 0.66, p < 0.0001) in the study participants. In addition, one standard deviation increase in log-transformed plasma endostatin (0.55 ng/dl) was associated with a decline in eGFR of -26.2 ml/min and an increase in urine albumin of 3.26 mg/ 24 h after adjusting for multiple covariables. Furthermore, the multivariable-adjusted odds ratio for CKD comparing the highest tertile (≥131.4 ng/dl) to the two lower tertiles of plasma endostatin was 21.6 (95% CI: 10.2-45.5; p < 0.0001). CONCLUSION: These data indicate that elevated plasma endostatin is strongly and independently associated with CKD. Prospective cohort studies and clinical trials are warranted to further examine the causal relationship between endostatin and risk of CKD and to develop novel interventions targeting circulating endostatin aimed at reducing CKD risk.

Simultaneous control of PTH and CaxP Is sustained over three years of treatment with cinacalcet HCl.

BACKGROUND & OBJECTIVES: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENT: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. RESULTS: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were < or =300 pg/ml (weeks 16 through 180) and median CaxP values were < or =55 mg(2)/dl(2) (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. CONCLUSIONS: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk.

Impact of multidisciplinary, early renal education on vascular access placement.

BACKGROUND: The Ochsner Clinic Foundation initiated the Healthy Start Clinic to identify, educate, and refer chronic kidney disease patients to nephrologists earlier in the course of their disease. This study investigated the impact of a structured educational session on the type and timing of permanent vascular access placement in patients receiving hemodialysis. METHODS: Before initiating dialysis, the HSC patient group received a general overview of the kidney and kidney disease, plus one-on-one instruction from a registered nurse, a dietitian, and a social worker. The HSC group was compared with a concurrent, conventionally prepared group of CKD patients who initiated dialysis during the same study period. RESULTS: Of the 147 patients initiating hemodialysis at OCF between April 1997 and December 2000, 61 had received structured HSC education, and 86 had received conventional care. In HSC-educated patients, the incidence of PVAs placed before hemodialysis initiation was twofold greater than in patients who received conventional care (77% HSC; 36% non-HSC, p < 0.001), and more HSC-educated patients initiated hemodialysis using their PVA (49% HSC; 23% non-HSC, p < 0.01). In addition, five times more patients who received HSC education received arteriovenous fistulas (52% HSC; 10% non-HSC, p < 0.001). Finally, significantly fewer HSC-educated patients initiated dialysis on a temporary catheter (51% HSC; 77% non-HSC, p < 0.001). CONCLUSIONS: Education programs for CKD patients help increase the number of patients receiving early PVA placement, as well as the proportion of patients receiving AVFs as opposed to grafts or temporary catheters.

Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.

Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH > or =300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of < or =250 pg/ml. During a 10-wk efficacy assessment phase, cinacalcet was more effective than control for PTH reduction outcomes, including proportion of patients with mean iPTH levels < or =300 pg/ml (46 versus 9%), proportion of patients with > or =30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with > or =20, > or =40, or > or =50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH < or =300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.