Predialysis CKD Research Articles

Arterial Hypertension Induced by Erythropoietin and Erythropoiesis-Stimulating Agents (ESA)

This review summarizes the evidence for a hypertensinogenic effect of Erythropoietin (Epo) in normal human subjects and predialysis, hemodialysis, and continuous ambulatory peritoneal dialysis (CAPD) patients. The possible mechanisms of Epo-induced hypertension are examined with in vivo animal and in vitro data, as well as pathophysiological human studies in both normal subjects and CKD patients. The evidence for a hypertensinogenic effect of erythropoiesis-stimulating agents (ESAs) in normal subjects, predialysis CKD, hemodialysis, and CAPD patients is compelling. Epo increases BP directly and notably independently of its erythropoietic effect and its effect on blood rheology. The potential for the development of future agents that might act as specific stimulators of erythropoiesis, devoid of direct hemodynamic side effects is underscored.

Efficacy of hyperphosphatemia control in the progression of chronic renal failure and the prevalence of cardiovascular calcification

Chronic kidney disease mineral- and bone disorder (CKD-MBD) has been studied more often in dialysis than in predialysis CKD patients. The association between efficacy of hyperphosphatemia control and chronic renal failure (CRF) progression, prevalence of bone disease and cardiovascular calcification was the objective of the present investigation. 42 patients with CKD in Stage 5, regularly monitored for 5 years, were divided into Group 1 of 20 patients with normal serum phosphate (sPO4) levels and Group 2 of 22 patients with hyperphosphatemia registered at the majority of checks. Serum urea, creatinine, calcium (sCa) and sPO4 levels were regularly determined in the retrospective 5-year period. At the end of this period iPTH, bone alkaline phosphatase-BAP and inflammation markers (CRP, fetuin-A) were measured, valvular and arterial calcifications were detected by B mode echocardiogram and soft-tissue native radiograms of the pelvis and the wrist. Progression of CRF (1/sCr over time) was faster in Group 2 than in Group 1 (b = -0.0577 vs. -0.0288, p = 0.003) during the study period. Average BAP and iPTH values were similar in both groups and 23/42 patients had PTH > 300 pg/ml. Arterial and valvular calcifications were found in 5/23 patients from Group 1 and 14/22 patients from Group 2 (p = 0.011). Linear regression analysis revealed sPO4 as a predictor for total calcification number, inflammatory diseases as a predictor for valvular calcifications, while sPO4 and iPTH were predictors for arterial calcifications. More than half the patients with Stage 5 CKD not yet on dialysis exhibited elevated PTH. Faster CRF progression and frequent arterial and valvular calcifications were seen in patients with poor phosphate control and sPO4 was selected as an independent predictor of total calcification score.

Serum 25-hydroxyvitamin D as an independent determinant of 1-84 PTH and bone mineral density in non-diabetic predialysis CKD patients

The role of 25-hydroxyvitamin D [25(OH)D] and fibroblast growth factor-23 (FGF-23) in chronic kidney disease–mineral and bone disorder (CKD-MBD) remains elusive in predialysis CKD patients. From the fact that FGF-23 suppresses bone mineralization in vitro and that 1α-hydroxylase is present in parathyroid cells and osteoblasts, they may be associated with bone mass or serum parathyroid hormone (PTH) level. In this cross-sectional observational study, we investigated the potential associations of 25(OH)D or FGF-23 with 1-84 PTH and bone mineral density (BMD) in the femoral neck (FN) and lumbar spine (LS) of 325 non-diabetic patients. All patients had stages 3–5 CKD and had never been treated with bisphosphonate, estrogen, or vitamin D. We measured bone-specific alkaline phosphatase (bone ALP), intact FGF-23 and 1-84 PTH in a third generation assay, and performed a multiple regression analysis for 1-84 PTH and BMD Z-score. In our cohort, 80.1% had 25(OH)D levels less than 30 ng/mL, and 4.1% had levels less than 15 ng/mL. A univariate analysis indicated a negative association for 25(OH)D with 1-84 PTH and bone ALP. A multivariate analysis showed that the significant determinants for 1-84 PTH were 25(OH)D, estimated glomerular filtration rate (eGFR), corrected calcium, serum calcitriol and phosphate. Intriguingly, the three former parameters had negative associations with 1-84 PTH while calcitriol had a positive association. While further adjustment of FGF-23 extinguished the positive association of phosphate and 1-84 PTH, there was absolutely no increase in the R2. With regard to the BMD Z-score, 25(OH)D and the body mass index were the significant common independent positive determinants for both FN and LS, whereas bone ALP was the negative determinant even though there was no correlation noted for 1-84 PTH, calcitriol, or FGF-23 with BMD. In addition, eGFR positively contributed to the Z-score only in FN. Therefore, despite a positive correlation between 25(OH)D and calcitriol, their contribution to the CKD-MBD appears to be different. Since the significant associations for 25(OH)D with 1-84 PTH and BMD were independent of serum calcitriol and bone ALP, this might imply that 25(OH)D has a direct effect on the parathyroid gland and bone.

Bone and mineral disorders in pre-dialysis CKD

Bone and mineral disorders in pre-dialysis CKD

180: Effect of Pharmacological Suppression of Secondary Hyperparathyroidism on Cardiovascular Hemodynamics in Predialysis CKD Patients - A Preliminary Observation

180: Effect of Pharmacological Suppression of Secondary Hyperparathyroidism on Cardiovascular Hemodynamics in Predialysis CKD Patients - A Preliminary Observation

One year of EPO markedly increases HDL cholesterol levels in predialysis CKD patients

One year of EPO markedly increases HDL cholesterol levels in predialysis CKD patients

Treatment of CKD Anemia in Octogenarians: A Comparison of Epoetin Alfa (EPO) in Elderly (65–79; >/=80) and Non-Elderly (

Background: Anemia in the elderly is associated with significant medical consequences even with mild reductions in hemoglobin (Hb). These include worsening physical disability and heart failure. CKD is a common treatable cause of anemia in the elderly. Given the limited published data on epoetin alfa (EPO) therapy in octogenarians, we evaluated whether responses to QW EPO therapy in patients (pts) with anemia due to CKD were influenced by age.Objective: A subset analysis comparing 2 groups of elderly pts (Group 1: 65–79 years (y), Group 2: >/=80y) vs non-elderly (<65y) pts with anemia of CKD not on dialysis was performed on the dataset of a recently completed multicenter, prospective, open-label study examining response to QW EPO therapy. Efficacy was assessed by changes in Hb and transfusion requirements.Methods: All pts had entry Hb </=10g/dL and received EPO at a starting dosage of 10,000U SC QW for 16 weeks (w) titrated to 20,000U SC QW after 4w if Hb increased by <1g/dL.Results: Of 1338 pts evaluable for efficacy, 531 (40%) were 65–79y (mean age 72.5±4.2y; 55% women), 186 (14%) were >/=80y (mean age 84.8±3.6y; 58% women) and 621 (46%) <65y (mean age 52.0±10.5y; 62% women). Baseline (BL) characteristics between groups revealed those <65y, both 65–79y and >/=80y pts with CKD had significant reductions in calculated CrCL, lower SCr, and lower body weight despite comparable mean BL Hb (table). Mean Hb change from BL to final assessment was similar in all three groups (2.4±1.5g/dL for both <65y and 65–79y and 2.4±1.4g/dL for >/=80y). Responses to EPO were seen by weeks 4 and 8 (65–79y, 47.8% and 80.2%, >/=80y, 49.5% and 79.0% and <65y, 52.3% and 83.3%). The overall number of pts responding to EPO (Hb increase >/=2g/dL at any point from BL) was 471 (88.7%) in 65–79y; 166 (89.3%) in >/=80y and 564 (90.8%) in <65y. The percent of pts transfused at BL (65–79y, 10.0% >/=80y, 14.0% vs. <65, 11.3%; p=0.4794 and p=.3173 respectively) and during study was similar for all age groups assessed. Though mean weekly EPO doses were similar for all groups (65–79y, 11,331±3364U/w >/=80y, 11,251±3401U/w, <65, 11,514±3538 U/w), mean body weight dosing was significantly higher in both the 65–79y and >/=80y groups (150.0±50.7U/kg/w, 172±66.3U/kg/w vs <65, 140.0±56.9U/kg/w, p=.0018 and p<.0001 respectively). QW EPO was well tolerated in all three age groups and adverse events were those as previously reported.Conclusions: Though octogenarians with anemia due to pre-dialysis CKD have worse renal function, more comorbidities and presumably less marrow reserve, their response to doses of QW EPO is similar to younger adults. These data suggest that the “oldest old” have comparable Hb responses to EPO demonstrating that age is not a limiting factor in the administration of EPO therapy for CKD anemia. This response may in part be due to higher body weight dosing of EPO.Table 1BL Characteristic (N ± SD)<65 years (n=621)65–79 years (n=531)>/=80 years (n=186)p-valueCalculated CrCL (mL/min)31.5 ± 15.123.1 ± 9.617.1 ± 6.8p< .0001 for bothScr (mg/dL)3.5 ± 1.13.2 ± 1.03.1 ±1.0p= .0004 (<65 vs 65–79) p= .0003 (<65 vs >/=80)Body weight (kg)88.1 ± 25.978.8 ± 19.368.7 ± 14.7p< .0001 for bothMean Baseline Hb (g/dL)9.1 ± 0.79.2 ± 0.79.2 ± 0.7not significant