An open-label study of darbepoetin alfa administered once monthly for the maintenance of haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis.

OBJECTIVE: To demonstrate the efficacy and safety of once-monthly (QM) darbepoetin alfa administration in maintaining haemoglobin (Hb) 11.0-13.0 g dL(-1) in subjects with chronic kidney disease (CKD) not receiving dialysis and previously treated with darbepoetin alfa every other week (Q2W). SUBJECTS: This open-label study enrolled subjects > or =18 years of age who had glomerular filtration rate > or =15 and < or =60 mL min(-1)/1.73 m(2), had Hb 11.0-13.0 g dL(-1), and were receiving Q2W darbepoetin alfa. DESIGN: Subjects were switched to QM darbepoetin alfa therapy for 28 weeks; the QM dose was titrated to maintain Hb levels. Primary end-point: proportion of subjects maintaining Hb > or =11.0 g dL(-1) during the final 8 weeks of the study (evaluation phase). Secondary end-points: Hb concentration during evaluation, darbepoetin alfa dose during the study, adverse events, laboratory parameters, and blood pressure. RESULTS: The study enrolled 152 subjects (female 52%, white 64%). Mean Hb > or =11.0 g dL(-1) during evaluation was achieved by 76% of the 150 subjects who received at least one dose of darbepoetin alfa [95% confidence interval (CI): 68%, 83%]. Mean (SD) Hb during evaluation was 11.71 (0.92) g dL(-1). Eighty-five per cent of 129 subjects who completed the study (95% CI: 78%, 91%) had Hb > or =11.0 g dL(-1) during evaluation. The dose of darbepoetin alfa over the study period was median (95% CI) 124.4 mug (106.2, 140.0). Darbepoetin alpha administered QM was well tolerated in study subjects. CONCLUSION: Darbepoetin alpha administered QM maintained Hb in study subjects with CKD not receiving dialysis.

Use of ACE inhibitors is associated with prolonged survival of arteriovenous grafts.

Vascular access complications are common in hemodialysis patients. To investigate whether the use of angiotensin-converting enzyme (ACE) inhibitors influences the rate of polytetrafluoroethylene (PTFE) graft complications, we compared the rate of intervention-free graft survival among patients treated versus not treated with ACE inhibitors. We retrospectively analyzed the survival of grafts placed at our institution between January 1, 1995, and October 31, 1999. Among 121 grafts, 25 grafts were placed in 19 patients treated with ACE inhibitors and 96 grafts were placed in 68 patients not treated with ACE inhibitors. Follow-up ranged from 1 month to 5 years. Ten of 25 grafts failed in the ACE-inhibitor group and 62 of 95 grafts failed in the non-ACE-inhibitor group. Actuarial intervention-free access survival rates (Kaplan-Meier) were significantly greater in the ACE-inhibitor than non-ACE-inhibitor group (71% versus 53% at 6 months, 58% versus 35% at 12 months, and 44% versus 22% at 24 months; P = 0.04). Using a Cox model adjusting for age, race, sex, and diabetes, the relative risk (RR) for access failure in the ACE-inhibitor group was 53% less than in the non-ACE-inhibitor group (RR, 0.47; p < 0.03). In a more complex Cox model with additional adjustment for comorbid conditions, the RR was even lower (RR, 0.32; P = 0.003) for the ACE-inhibitor compared with non-ACE-inhibitor group (reference = 1.00). The lower RR was observed for patients with and without congestive heart failure. These results suggest that ACE inhibitors offer clinical promise in the prevention of PTFE graft failure. A prospective randomized trial is warranted to confirm the benefit of ACE inhibitors.

Analysis of variable flow Doppler hemodialysis access flow measurements and comparison with ultrasound dilution.

The variable flow (VF) Doppler method determines access blood flow from the pump speed-induced change in Doppler signal between the arterial and venous needles. This study evaluated 35 patients in two analyses to assess VF Doppler measurement reproducibility (54 paired measurements) and compared VF Doppler and ultrasound dilution flow measurements (24 paired measurements). VF Doppler measurement variations were 4% for access flow less than 800 mL/min (n = 17), 6% for access flow of 801 to 1,600 mL/min (n = 22), and 11% for access flow greater than 1,600 mL/min (n = 15). The mean measurement coefficient of variation was 7% for VF Doppler compared with 5% for ultrasound dilution. Correlation coefficients (r) between VF Doppler and ultrasound dilution access flow measurements were 0.79 (n = 24; P < 0.0001), 0.84 for access flow less than 2,000 mL/min (n = 20; P < 0.0001), and 0.91 for access flow less than 1,600 mL/min (n = 18, P < 0.0001). VF Doppler measurements using indicated versus measured pump flow rates correlated highly (r = 0.99; P < 0.0001). VF Doppler therefore yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements. The VF Doppler method is dependent on the pump-induced change in access Doppler signal and therefore is inherently most accurate and reproducible at lower access blood flow rates. This method appears capable of determining access flow rates in the clinically useful range.

Type of vascular access and mortality in U.S. hemodialysis patients.

BACKGROUND: Vascular access (VA) complications account for 16 to 25% of hospital admissions. This study tested the hypothesis that the type of VA in use is correlated with overall mortality and cause-specific mortality. METHODS: Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Study Wave 1, a random sample of 5507 patients, prevalent on hemodialysis as of December 31, 1993. The relative mortality risk during a two-year observation was analyzed by Cox-regression methods with adjustments for demographic and comorbid conditions. Using similar methods, cause-specific analyses also were performed for death caused by infection and cardiac causes. RESULTS: In diabetic mellitus (DM) patients with end-stage renal disease, the associated relative mortality risk was higher for those with arteriovenous graft (AVG; RR = 1.41, P < 0.003) and central venous catheter (CVC; RR = 1.54, P < 0.002) as compared with arteriovenous fistula (AVF). In non-DM patients, those with CVC had a higher associated mortality (RR = 1.70, P < 0.001), as did to a lesser degree those with AVG (RR = 1.08, P = 0.35) when compared with AVF. Cause-specific analyses found higher infection-related deaths for CVC (RR = 2.30, P < 0.06) and AVG (RR = 2.47, P < 0.02) compared with AVF in DM; in non-DM, risk was higher also for CVC (RR = 1.83, P < 0.04) and AVG (RR = 1.27, P < 0.33). In contrast to our hypothesis that AV shunting increases cardiac risk, deaths caused by cardiac causes were higher in CVC than AVF for both DM (RR = 1.47, P < 0.05) and non-DM (RR = 1.34, P < 0.05) patients. CONCLUSION: This case-mix adjusted analysis suggests that CVC and AVG are correlated with increased mortality risk when compared with AVF, both overall and by major causes of death.

Posttransplant bone disease: a case illustrating dramatic improvements in bone density with vitamin D replacement therapy.

Although bisphosponates are proposed as first-line treatment for posttransplant bone disease they are not optimal in all situations. A kidney transplant recipient developed hypercalcemia from mobilization of extraskeletal calcium. He had low serum parathyroid hormone and vitamin D; high calcium excretion; and normal calcium intake. Bone biopsy revealed severe osteomalacia. Bisphosphonates, used in the early treatment of acute hypercalcemia, were not indicated to treat osteomalacia. However, over several months serum calcium declined sufficiently to allow treatment of the bone disease with oral calcitriol. Dual-energy radiographic absorptiometry over the next 2 years documented dramatic improvements in bone density (percent of young-normal controls) : from 63 to 85%, at the lumbar spine; from 38 to 67%, at the femoral neck. This response to treatment could not have been achieved with an antiresorptive strategy. Optimal management of posttransplant bone disease requires a diagnostic approach, which considers all plausible contributing factors.

Effects of pneumococcal mucopeptide and capsular polysaccharide on phagocytosis.

Pneumoccal cell wall and capsular products from eight serotypes were tested for their ability to inhibit polymorphonuclear neutrophil killing of the same eight pneumococcal strains. Crude pneumococcal cell wall preparations from all serotypes inhibited phagocytic killing of several pneumococcal serotypes, and were just as effective with heterologous as with homologous strains. Phagocytosis dependent on heat-labile serum factors was inhibited, whereas phagocytosis not dependent on heat-labile factors was not significantly affected. These findings were compatible with inhibition of complement consumption. The inhibitory activity was found in a purified cell wall mucopeptide, whereas purified capsular polysaccharides failed to inhibit phagocytosis.