Risk factors for high erythropoiesis stimulating agent resistance index in pre-dialysis chronic kidney disease patients, stages 4 and 5.

BACKGROUND/AIMS: Anemia is common in patients with chronic kidney disease (CKD). Recently, the erythropoiesis-stimulating agent/hemoglobin level (ESA/Hb) index emerged as a new factor associated with increased morbidity and mortality in this population. In this study, we evaluated the factors that influence the ESA/Hb index in a pre-dialysis CKD population. METHODS: Ninety-five patients were evaluated for clinical and laboratory parameters, nutritional status and ESA/Hb index. For comparison, we divided our population into 3 groups: G I--no ESA treatment, G II--patients with ESA/index below 50th percentile and G III--patients with ESA/Hb index above 50th percentile. We performed single and multiple regression models and logistic regression analysis. RESULTS: In a multiple regression model, age (t = -3.456, P = 0.001), SGA (t = 2.059, P = 0.047), ferritin (t = 2.386, P = 0.027), Ca × P (t = 2.066, P = 0.043), TNF-α (t = 2.673, P = 0.009) and IL-6 (t = 2.939, P = 0.004) independently influenced the ESA/Hb index. At logistic regression analysis, gender, cardiovascular disease and TNF-α were independently associated with ESA/Hb higher than 50th percentile compared to the other patients (R(2) = 0.457). CONCLUSION: In a pre-dialysis population, female gender, cardiovascular disease, malnutrition and inflammation are associated with a higher ESA/Hb index.

Statins and vitamin D: a friendly association in pre-dialysis patients.

The increased mortality rate observed in patients with chronic kidney disease is related to the high prevalence of cardiovascular disease in this population. Recently, it has been shown that interventional therapy with statins and/or vitamin D could improve the outcomes of these patients. The aim of this study was to identify the risk factors for mortality in a group of patients with chronic kidney disease (stages 4 and 5--pre-dialysis) and verify whether vitamin D and statins could change the outcome. We included 95 patients (mean age--69.4) with stages 4 and 5 (pre-dialysis) of our "low-clearance" outpatient clinic, with an average eGFR of 16.9 ml/min and a mean follow-up of 24.1 months. Several biological, nutritional, laboratory and inflammatory parameters were analysed at baseline. Our population was divided into three groups: G-I, patients not medicated with either vitamin D or statins; G-II, patients medicated with either vitamin D or statins; and G-III, patients medicated with vitamin D and statins. We found (ANOVA) that the serum levels of pre-albumin (P = 0.018) and PTH (P = 0.03) were lower in G-I. Concerning the inflammatory parameters, G-I showed higher levels of hsCRP (P = 0.014) and a trend to higher IL-6 levels (P = 0.077). We found the actuarial survival at 30 months (Kaplan-Meier), to be 56.4% in G-I, 82.3% in G-II and 100% in G-III (log rank = 13.08 P = 0.0014). Using the Cox proportional hazards model, we found that the existence of coronary artery disease (P = 0.0001) and the absence of medication with vitamin D and/or statins (P = 0.005) independently influenced the mortality of our patients. In conclusion, we found, in our study, that patients under vitamin D and statins (with a synergistic effect) were less inflamed and showed a lower mortality rate.

Inflammation, homocysteine and carotid intima-media thickness.

INTRODUCTION: Cardiovascular disease is the main cause of morbidity and mortality in chronic renal patients. Carotid intima-media thickness (CIMT) is one of the most accurate markers of atherosclerosis risk. In this study, the authors set out to evaluate a population of chronic renal patients to determine which factors are associated with an increase in intima-media thickness. METHODS: We included 56 patients (F=22, M=34), with a mean age of 68.6 years, and an estimated glomerular filtration rate of 15.8 ml/min (calculated by the MDRD equation). Various laboratory and inflammatory parameters (hsCRP, IL-6 and TNF-alpha) were evaluated. All subjects underwent measurement of internal carotid artery intima-media thickness by high-resolution real-time B-mode ultrasonography using a 10 MHz linear transducer. RESULTS: Intima-media thickness was used as a dependent variable in a simple linear regression model, with the various laboratory parameters as independent variables. Only parameters showing a significant correlation with CIMT were evaluated in a multiple regression model: age (p=0.001), hemoglobin (p=00.3), logCRP (p=0.042), logIL-6 (p=0.004) and homocysteine (p=0.002). In the multiple regression model we found that age (p=0.001) and homocysteine (p=0.027) were independently correlated with CIMT. LogIL-6 did not reach statistical significance (p=0.057), probably due to the small population size. CONCLUSION: The authors conclude that age and homocysteine correlate with carotid intima-media thickness, and thus can be considered as markers/risk factors in chronic renal patients.

Anaemia correction in predialysis elderly patients: influence of the antihypertensive therapy on darbepoietin dose.

Anaemia and hypertension are common in patients with chronic renal insufficiency. The correction of anaemia with erythropoiesis stimulating agents (ESA) can improve survival and decrease the decline of renal function. Angiotensin converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (AIIRA) can also slow the progression of renal failure, but the blockade of the renin-angiotensin system can worsen anaemia. The aim of our study was to assess the impact of antihypertensive therapy (ACEI plus AIIRA) in the requirements of darbepoietin in a group of elderly predialysis patients. We included 71 patients (m = 39, f = 32), mean age of 76.3 years with a mean creatinine clearance of 17.5 ml/min. Patients were divided in two groups according to their antihypertensive therapy: G-I patients under ACEI or AIIRA therapy and G-II normotensive patients or hypertensive patients under antihypertensive drugs other than ACEI or AIIRA. The groups were compared regarding demographic, nutritional, biochemical and inflammatory parameters. We also compared the mean darbepoietin dose. In GI the mean dose of darbepoietin was higher than in GII (0.543 vs. 0.325 microg/kg/week, P = 0.032). We did not find any difference regarding other parameters analysed. We conclude that ACEI and AIIRA can increase the needs of darbepoietin in predialysis elderly patients. However, when formally indicated to treat hypertension in a specific patient, they should not be switched to another antihypertensive agent. Instead, in such cases, higher doses of ESA should be used, if necessary.