New Treatment Approaches for the Anemia of CKD Bonomini, Mario, MD; Del Vecchio, Lucia, MD; Sirolli, Vittorio, MD ...
American journal of kidney diseases,
01/2016, Letnik:
67, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Normocytic normochromic anemia is a common complication in chronic kidney disease and is associated with many adverse clinical consequences. Erythropoiesis-stimulating agents (ESAs) and adjuvant iron ...therapy represent the primary treatment for anemia in chronic kidney disease. The introduction of ESAs into clinical practice was a success story, mediating an increase in hemoglobin concentrations without the risk for recurrent blood transfusions and improving quality of life substantially. However, recombinant ESAs are still expensive and require a parenteral route of administration. Moreover, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm. This, together with changes in ESA reimbursement policy in some countries, has resulted in a significant reduction in ESA prescribing and the hemoglobin level targeted during therapy. Several attempts are being made to develop new drugs with improved characteristics and/or easier manufacturing processes compared with currently available ESAs, including new treatment approaches that may indirectly improve erythropoiesis. We give an update on the new investigational strategies for increasing erythropoiesis, examining in depth their characteristics and possible advantages in the clinical setting and the caveats to be aware of at the present stage of development.
Background In peritoneal dialysis, the high glucose load absorbed from dialysis fluid contributes to several metabolic abnormalities, including insulin resistance. We evaluate the efficacy of a ...peritoneal dialysis solution containing l -carnitine as an additive to improve insulin sensitivity. Study Design Multicenter parallel randomized controlled trial. Setting & Participants Nondiabetic uremic patients on continuous ambulatory peritoneal dialysis enrolled in 8 peritoneal dialysis centers. Intervention Patients were randomly assigned to receive peritoneal dialysis diurnal exchanges with either a standard glucose-based solution (1.5% or 2.5% according to the patient's need) or a glucose-based solution (identical glucose amount) enriched with l -carnitine (0.1%, weight/volume; 2 g/bag) for 4 months, the nocturnal exchange with icodextrin being unmodified. Outcomes & Measurements The primary outcome was insulin sensitivity, measured by the magnitude of change from baseline in glucose infusion rate (in milligrams per kilogram of body weight per minute) during a euglycemic hyperinsulinemic clamp. Secondary outcomes were safety and tolerability, body fluid management, peritoneal dialysis efficiency parameters, and biochemistry tests. Results 35 patients were randomly assigned, whereas 27 patients (standard solution, n=12; experimental solution, n = 15) were analyzed. Adverse events were not attributable to treatment. Glucose infusion rates in the l -carnitine–treated group increased from 3.8 ± 2.0 (SD) mg/kg/min at baseline to 5.0 ± 2.2 mg/kg/min at day 120 ( P = 0.03) compared with 4.8 ± 2.4 mg/kg/min at baseline and 4.7 ± 2.4 mg/kg/min at day 120 observed in the control group ( P = 0.8). The difference in glucose infusion rates between groups was 1.3 (95% CI, 0.0-2.6) mg/kg/min. In patients treated with l -carnitine–containing solution, urine volume did not change significantly ( P = 0.1) compared to a significant diuresis reduction found in the other group ( P = 0.02). For peritoneal function, no differences were observed during the observation period. Limitations Small sample size. Conclusions The use of l -carnitine in dialysis solutions may represent a new approach to improving insulin sensitivity in nondiabetic peritoneal dialysis patients.
Background Fetuin A, a circulating inhibitor of ectopic calcification, is downregulated in hemodialysis and has been shown to predict cardiovascular mortality in this setting. The association of ...altered calcium-phosphorus with serum fetuin A levels is still a matter of debate. Although carotid intima-media thickness (cIMT) is a strong predictor of major cardiovascular events, its association with serum fetuin A levels is poorly defined. Study Design Cohort study. Participants & Settings 174 uremic patients on long-term hemodialysis therapy enrolled in 4 university hospitals. Predictors Serum fetuin A levels at the beginning of the study (T0) and after 12 months (T12). Outcomes Progression of atherosclerosis assessed by means of cIMT measurements at 24 months (T24); cardiovascular morbidity and mortality at 36 months. Results Serum fetuin A concentrations at T0 and T12 were 282.3 ± 79.4 and 290.0 ± 92.2 μg/mL, respectively. Mean T0 and T24 cIMT values were 1.02 ± 0.2 and 1.06 ± 0.2 mm, respectively ( P < 0.001). Fatal and nonfatal cardiovascular disease occurred in 36 and 86 patients by 36 months, respectively. In multivariate logistic regression, higher calcium-phosphorus product was associated with lower serum fetuin A level (odds ratio, 0.96; 95% confidence interval CI, 0.93 to 1.00; P = 0.02). Multiple regression analysis showed that T0 serum fetuin A level was associated with T24 cIMT ( P = 0.01) after adjustments for age, cholesterol level, high-sensitivity C-reactive protein level, previous cardiovascular events, and T0 cIMT. In a multivariate Cox regression analysis, cardiovascular mortality was independently associated with a 1-tertile lower T0 serum fetuin A level, and a 1-tertile higher T0 cIMT value was independently associated with greater cardiovascular mortality (hazard ratio, 0.45; 95% CI, 0.15 to 0.65; P = 0.007 and hazard ratio, 10.00; 95% CI, 3.16 to 31.73; P < 0.001, respectively) after adjustment for age and previous cardiovascular events. Limitation Length of follow-up. Conclusion Calcium-phosphorus product in hemodialysis patients inversely correlated with serum fetuin A level, which, in turn, was associated inversely with progression of atherosclerotic lesions and cardiovascular mortality in this study population.
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