Timing of nephrology referral and initiation of dialysis as predictors for survival in hemodialysis patients: 5-year follow-up analysis.

BACKGROUND: A consensus about the optimal timing of dialysis initiation is still controversial. Thus, the goal of this analysis was to compare outcomes in patients with early and late referral with early and late initiation of hemodialysis (HD). METHODS: We studied 190 patients (mean age 52.03±14.22) who were initiated on HD between 1994 and 2004. Patients who received regular nephrology care during 12 months before HD initiation were categorized as early referrals (ER) and those without nephrology care were late referrals (LR). The early start (E-start) was defined by the estimated GFR (eGFR) at start of HD≥7.5 mL/min/1.73 m2, and the late start (L-start) by eGFR of <7.5 mL/min/1.73 m2. The four groups of patients (ER with E-start and L-start; LR with E-start and L-start) were prospectively followed in the next 60 months after HD initiation. RESULTS: During the follow-up, 43.3% of E-start and 43.2% of L-start patients died, without significant difference in survival between the groups [HR for L-start vs. E-start=1.06 (95% CI 0.69-1.62); p=0.797]. When survival between ER and LR groups was compared (28.1% patients in the ER and 53.2% in the LR died), there was significant difference in survival [HR for LR vs. ER=2.16 (95% CI 1.28-3.65); p=0.004]. Compared with patients with ER and L-start, higher mortality was observed among those with LR and L-start [HR 3.51 (95% CI 1.48-8.35); p=0.004] and LR with E-start [HR 2.79 (95% CI 1.16-6.7); p=0.022]. There was no significant difference between patients in ER with L-start and ER with E-start. CONCLUSIONS: Our study showed that ER above 12 months before HD initiation and L-start of dialysis was associated with a reduced mortality risk in HD patients.

Long-term follow up of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients.

PURPOSE: The aim of this study was to evaluate the persistence of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients. METHODS: 14 hemodialysis patients with chronic hepatitis C were treated with pegylated interferon alpha-2a for a period of 48 weeks. Achieved sustained viral response rate was 35.7% (5/14 patients) at week 72, i.e. 24 weeks after the treatment ended. All treated patients were then prospectively followed until week 144. Follow-up viral data, such as HCV antibodies, serum HCV RNA, and HCV RNA genotype, were determined at week 96 and week 144. HCV antibodies were determined by a 3rd-generation ELISA assay. The presence of HCV RNA was determined using reverse transcriptase polymerase chain reaction (AMPLICOR Hepatitis C Virus Test). HCV genotype was analyzed by reverse transcriptase polymerase chain reaction followed by hybridization of amplified products. The biochemical data were recorded every 24 weeks during the follow-up period. RESULTS: The 5 patients (35.7%), who achieved sustained viral response (SVR), remained HCV RNA negative at week 96. At week 144, 4 hemodialysis patients (28.6%) remained HCV RNA negative. There was a relapse of HCV infection in 1 patient after week 96 of the study. The patients who remained HCV RNA negative also maintained the achieved biochemical response throughout the follow-up period. CONCLUSION: Long-term follow-up of treated hemodialysis patients with pegylated interferon alpha-2a showed persistence of the sustained viral and biochemical response.

Vascular calcification and atherosclerosis in hemodialysis patients: what can we learn from the routine clinical practice?

BACKGROUND: Hemodialysis (HD) patients are at increased risk for arterial intimal (AIC) and medial calcification (AMC). METHODS: In a cross-sectional study on 153 HD patients we evaluated the presence of AIC and AMC using plain radiography of the pelvis and the presence of atherosclerotic lesions using high-resolution B-mode ultrasonography of the common carotid arteries (CCA). RESULTS: The radiography of the pelvis confirmed the frequent presence of AIC (35.3%) and AMC (35.9%) in our HD patients. Arterial calcification was absent (non calcified-NC) in a minority of patients (28.8%). Patients with AIC had significantly higher prevalence of atherosclerotic plaques on CCA (78.6%) compared with both other groups and a higher number of documented atherosclerotic complications, such as cardiovascular (85.2%), cerebrovascular (33.3%) and peripheral arterial disease (38.9%) in comparison with the NC patients. According to the 1-year calculated data from patient records, there were no significant differences in the specific HD risks, such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of calcium, phosphate, calcium-phosphate product and intact parathyroid hormone. All four bone metabolism markers within the range proposed by K/DOQI guidelines were achieved in 9.3%, 14.5% and 20.4% in the AIC, AMC and NC group, respectively. CONCLUSIONS: Patients with AIC and AMC are frequently found in the HD population. Screening for arterial calcifications in chronic kidney disease patients is suggested even in the early pre-dialysis period. The highest proportion of patients within the guidelines proposed range for bone and mineral metabolism markers was observed in the NC group. A longer period of data analysis is required in order to evaluate the possible role of some traditional and HD-specific risk factors for the development of arterial calcifications. The achievement of the K/DOQI guidelines is an important issue in the prevention of those conditions.

Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium.

BACKGROUND: The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients. METHODS: 52 out of 60 patients with predialysis intact PTH<100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals. RESULTS: There were no differences in predialysis mean phosphate or calcium x phosphorus product (Ca x P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59+/-0.18 vs. 2.44+/-0.19 mmol/l; p<0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08+/-0.05 vs. 1.04+/-0.06 mmol/l; p=0.02) and at the end of dialysis (1.18+/-0.04 vs. 1.48+/-0.04 mmol/l; p<0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [2.40+/-0.21 vs. 2.59+/-0.18 mmol/l (p<0.01); 1.08+/-0.05 vs. 1.18+/-0.04 mmol/l (p<0.01)]. Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [(38.6+/-22.9 vs. 63.3+/-46.0 vs. 78.6+/-44.7 pg/ml); (59.5+/-18.7 vs. 75.9+/-26.7 vs. 84.0+/-35.4 U/l)], respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4+/-7.3 U/l vs. 35.6+/-22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group. CONCLUSION: There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients.

Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up.

BACKGROUND: Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma. METHODS: Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years). RESULTS: After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 +/- 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 +/- 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 +/- 0.03 to 2.3 +/- 1.6 microg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 +/- 1.6 microg/g (P < 0.05). CONCLUSIONS: Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 microg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.