Prevalence, clinical correlates and therapy cost of mineral abnormalities among haemodialysis patients: a cross-sectional multicentre study.

BACKGROUND: This study evaluated the proportion of patients who met National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guidelines for mineral status, and assessed the cost of therapy for mineral management of patients under haemodialysis treatment in Spain. METHODS: Demographic and biochemical data were collected for 1312 patients undergoing standard three-times weekly maintenance haemodialysis at six Spanish centres during December 2003. Age, gender, diabetic nephropathy, haemodialysis duration, serum calcium, phosphorus, calcium-phosphorus product (Ca x P), and intact parathyroid hormone (iPTH) levels were monitored. Exploratory analyses of associations between demographic and biochemical parameters, were undertaken using bivariate and multivariate regression techniques. RESULTS: Mean age of patients was 62 years. 97% were Caucasian, 23% were diabetic. In total, 51% of patients received calcium binders, 21% sevelamer, 16% aluminium hydroxide, and 29% received no binders; 33% of patients received calcitriol. Prevalence of patients outside K/DOQI targets was: calcium 50%, phosphorus 46%; Ca x P 33%; iPTH 77%. Elevated phosphorus (>5.5 mg/dl) was independently associated with younger age [OR 0.972 (95% CI 0.963-0.980), P<0.001] and higher iPTH [OR 1.0005 (95% CI 1.0002-1.0008), P<0.001]. Elevated Ca x P (>or=55 mg(2) x dl(2)) showed a similar relationship. High iPTH levels (>300 pmol/l) were associated with female gender [OR 1.574 (95% CI 1.213-2.041), P<0.001], high serum phosphorus [OR 1.230 (95% CI 1.130-1.338), P<0.001], and longer duration of dialysis [OR 1.003 (95% CI 1.001-1.005), P<0.01]. Poorly controlled serum phosphorus, Ca x P and iPTH were associated with more expensive therapy for mineral management. CONCLUSIONS: One in three haemodialysis patients in Spain remains above the upper target range defined in current mineral metabolism guidelines. This abnormal profile is more common in younger patients and females and therapy is more expensive in younger patients.     

Determinants of progressive vascular calcification in haemodialysis patients.

BACKGROUND: We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups. METHODS: We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52). RESULTS: Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated. CONCLUSION: Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.     

A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients.

BACKGROUND: Cardiovascular morbidity and mortality are highly prevalent in haemodialysis (HD) patients and have been recently associated with vascular calcifications. The objective of our study was to assess the value of a simple vascular calcification score for the prediction of cardiovascular death, cardiovascular hospitalizations and fatal and non-fatal cardiovascular events in HD patients, and to correlate this score with cardiovascular disease and with other known predictors of vascular disease. METHODS: In this observational, prospective study 123 chronic HD patients (75 males and 48 females; 20% diabetic) were included, who were on low-flux HD treatment for 46.6+/-52 months (mean+/-SD). We set up a simple vascular calcification score based on plain radiographic films of pelvis and hands. Brachial pulse pressure and mean arterial pressure (MAP) were measured and cardiovascular events and hospitalization episodes were assessed. RESULTS: During an observational period of 37 months there were 17 cardiovascular deaths; 28 patients needed cardiovascular hospitalizations and 32 patients suffered fatal and non-fatal cardiovascular events. Coronary artery disease was diagnosed in 43 patients (35%), peripheral arterial disease in 33 patients (26.8%), cerebrovascular disease in 16 patients (13%) and vascular disease (coronary artery disease or peripheral arterial disease or cerebral vascular disease) in 61 patients (49.6%). By binary logistic regression, diabetes (P = 0.01), male sex (P<0.001), age (P = 0.02), HD duration (P = 0.02) and MAP (P = 0.03) were independently associated with a vascular score > or =3. This score > or =3 was independently associated with coronary artery disease (P = 0.008), peripheral arterial disease (P<0.001) and vascular disease (P = 0.001). Patients with a vascular calcification score > or =3 had a 3.9-fold higher risk of cardiovascular mortality (P = 0.03), a 2.8-fold higher risk of cardiovascular hospitalizations (P = 0.02) and a 2.3-fold higher risk of fatal or non-fatal cardiovascular events (P = 0.04). CONCLUSIONS: The present vascular calcification scoring represents a simple tool for the assessment of cardiovascular risk related with vascular calcifications in chronic HD patients.     

Short-term effects of nocturnal haemodialysis on carnitine metabolism.

BACKGROUND: Functional carnitine deficiency [as indicated by an abnormal acyl-carnitine/free-carnitine (AC:FC) ratio] is commonly seen in patients with end-stage renal disease (ESRD), resulting in significant clinical detriments including anaemia, cardiomyopathy and muscle weakness. Nocturnal haemodialysis (NHD) (5-6 sessions per week, 8 h per treatment) has been reported to reverse several surrogate markers of uraemia. Conversely, as a consequence of increased dialysis dose, NHD may have the potential to aggravate plasma nutrient deficiencies. Our objective was to determine the effects of NHD on plasma free-carnitine levels and carnitine metabolism. METHODS: We conducted an observational cohort study with a before and after design. Nine ESRD patients (age: 47 +/- 3; mean +/- SEM) were studied. Routine biochemical, haemodynamic and carnitine metabolic products were analysed at baseline while on conventional haemodialysis and 2 months post-conversion to NHD. Free-carnitine and total-carnitine levels were generated by colorimetric assays. The difference between total- and free-carnitine concentrations was estimated to be the acyl-carnitine level. Paired t-test was used to ascertain statistical significance. RESULTS: After conversion to NHD, there was a significant increase in urea clearance in all patients. Plasma free-carnitine levels fell from 26.54 +/- 2.99 to 15.6 +/- 2.34 micromol/l (P < 000.1). A similar reduction in plasma acyl-carnitine levels was observed (from 13.22 +/- 1.34 to 6.24 +/- 1.20 micromol/l (P < 0.001)). The AC:FC ratio improved from 0.51 +/- 0.03 to 0.39 +/- 0.03 (P < 0.005) (Normal < 0.25). CONCLUSION: NHD is associated with an improvement in AC:FC ratio. Further research is needed to examine the longitudinal clinical impact of this metabolic correction and to examine whether this effect is sustained.     

Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis.

BACKGROUND: Coronary artery calcification (CAC) is an extensive and common complication in patients with end-stage renal disease (ESRD). The aim of this study was to assess prospectively the change in CAC over a 2-year period and to identify the factors that may be associated with CAC progression in ESRD patients. METHODS: The final analysis was performed on 40 of 43 stable haemodialysis patients who initially entered into the study. The study population underwent multirow spiral computed tomography to derive CAC scores at baseline and after a minimum of 12 months (24 months in 30 patients, 18 months in four, and 12 months in the remaining six patients). To provide a stable estimate that was unbiased with respect to the baseline CAC, square root-transformed CAC scores were used for the analyses of the changes in CAC. RESULTS: The median CAC score was 191 (range, 0-2403) mm3 at baseline and increased to 253 (range, 0-2745) mm3 at follow-up (P < 0.001) and the median annualized change in square root-transformed CAC score was 1.48 (range, -0.95-8.64) mm3/year. The annualized change of the square root-transformed CAC score positively correlated with the time-integrated levels of C-reactive protein (R = 0.521, P = 0.001), phosphorus (R = 0.433, P = 0.005) and calcium x phosphorus product (R = 0.394, P = 0.012), but did not correlate with the levels of fetuin-A or lipid parameters. Even after adjusting for age, gender and baseline CAC score, C-reactive protein levels were independently associated with CAC progression. CONCLUSION: These data suggest that chronic inflammation as well as altered mineral metabolism contributes to a rapid progression of CAC in ESRD patients. Additional, larger scale studies are required to confirm our findings.     

Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis

Aim: Uraemia is associated with hyperprolactinaemia, low total (TT) and free (FT) serum testosterone, high luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) and, in women, anovulatory cycles and premature menopause. We hypothesize that extended hours haemodialysis may improve these derangements. Methods: This is an observational cohort study of 30 men (age 54 ± 13 years, body mass index (BMI) 28.1 ± 5.8 kg/m²) and seven women (age 41 ± 11 years, BMI 32.2 ± 11.2 kg/m²) established on chronic home haemodialysis (3–5 h, 3.5–5 sessions weekly) who were converted to nocturnal home haemodialysis (6–9 h, 3.5–5 sessions weekly). Serum was collected at baseline and 6 months for measurement of TT, sex hormone binding globulin (SHBG), LH, FSH, prolactin, thyroid‐stimulating hormone and thyroxine. Results: In the male patients (n = 25), serum prolactin significantly fell (281 (209.5–520) vs 243 (187–359) mU/L, P = 0.001) and TT (12.6 ± 5.8 vs 15.2 ± 8.1 nmol/L, P = 0.06) and FT (281 ± 118 vs 359 ± 221 pmol/L, P = 0.01) increased. SHBG, LH and FSH were unchanged. At 6 months, two of the three women under 40 years of age had return of regular menses after being amenorrhoeic or having prolonged and irregular menses at baseline. There were insufficient women in this study to further analyse changes in sex hormone levels. Thyroid function tests remained stable. Conclusion: Alternate nightly nocturnal haemodialysis significantly improves hyperprolactinaemia and hypotestosteronaemia in men. Menstrual cycling may be re‐established in young women. The effect of these changes on fertility has not been established. Patients should be counselled about the possibility of increased fertility before conversion to extended hours haemodialysis regimens.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Aim:   Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO₄) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO₄ product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.
Methods:   This was a single centre randomized open label study. Patients with serum intact iPTH of 50 pmol/L or more were randomized to receive either i.v. calcitriol (0.01 ug/kg) or i.v. paricalcitol (0.04 ug/kg) during every haemodialysis treatment. Serum iPTH, calcium, phosphorus and alkaline phosphatase were measured at the beginning of the study and every 3 weeks for 12 weeks.
Results:   Twenty-five patients were enrolled into the study – 12 were randomized into the calcitriol group and 13 into the paricalcitol group. There were no differences in the baseline study parameters between both groups. Serum iPTH levels were significantly reduced ( P  = 0.003) only in the paricalcitol group but not in the calcitriol group ( P  = 0.101). On the other hand, serum calcium levels were significantly increased only in the calcitriol group ( P  = 0.004 vs P  = 0.242). Serum phosphorus, alkaline phosphatase and Ca X PO₄ product were not different.
Conclusion:   Intravenous paricalcitol may be superior to i.v. calcitriol for the treatment of severe SHPT in our chronic haemodialysis population. A larger randomized controlled trial is indicated to confirm these initial findings.     

Aortic calcification in haemodialysis patients with diabetes mellitus.

BACKGROUND: Certain metabolic disorders, such as hyperphosphatemia induce vascular calcification in haemodialysis patients; it is unclear, however, whether these disorders contribute to aortic calcification in diabetic haemodialysis patients. This study examined the risk factors of aortic calcification in a large number of haemodialysis patients, and compared risk factors between diabetic and non-diabetic patients. METHODS: The subjects were 667 patients on maintenance haemodialysis: 184 with type 2 diabetes and 483 without. Aortic calcification was measured semi-quantitatively using a plain computed tomography image of the abdominal aorta, and an aortic calcification index (ACI) was calculated. RESULTS: The ACI of the diabetic subjects was significantly higher than that of those without diabetes (57.3+/-22.1 vs 44.8+/-28.3%, P < 0.0001), although the dialysis vintage of the former was significantly shorter (P < 0.001). Multiple regression analyses showed that diabetes was a significant independent risk factor for increased ACI. Multiple regression analyses, performed separately in diabetics and non-diabetics, revealed that advanced age, higher systolic blood pressure, smoking and longer haemodialysis vintage were common independent risk factors significantly associated with increased ACI in both patient groups (R2 = 0.296, P < 0.0001 for non-diabetics; R2 = 0.193, P < 0.0001 for diabetics). Higher serum phosphate concentration was not significantly associated with increased ACI in diabetic patients (P = 0.429), although it was a significant independent factor in non-diabetic patients (beta = 0.150, P < 0.0005). CONCLUSION: Aortic calcification in diabetic haemodialysis patients is more advanced, compared with non-diabetic patients, even with short haemodialysis vintage. Since disorders of mineral metabolism are not significantly associated with aortic calcification in diabetic haemodialysis patients, aortic calcification in these patients could be affected by metabolic abnormalities associated with the diabetic state per se, independent of other confounding factors; and aortic calcification may be advanced even before haemodialysis induction.     

Elevated concentrations of cardiac troponins are associated with severe coronary artery calcification in asymptomatic haemodialysis patients.

BACKGROUND: Elevated concentrations of cardiac biomarkers, such as troponins and natriuretic peptides, have been shown to be predictive of poorer long-term cardiovascular outcomes in stable patients with end-stage renal disease (ESRD). However, little is known about the relationship between elevated concentrations of these cardiac markers and underlying coronary artery pathology in these patients. The aim of the present study was to investigate associations between coronary artery calcification (CAC) and the concentrations of cardiac biomarkers in ESRD patients. METHODS: We conducted a cross-sectional study of 38 asymptomatic patients (median age, 54 years; 26 males, 12 females; diabetic, 39%) who were undergoing chronic haemodialysis. In these patients, pre-dialysis circulating concentrations of cardiac troponin T (cTnT), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were measured. We quantified the level of CAC by multirow spiral computed tomography to obtain a CAC score. CAC scores > or = 400 were defined as being indicative of severe CAC. RESULTS: Severe CAC was detected in 17 patients (45%). The degree of CAC severity was positively associated (P < 0.05) with cTnT concentrations. Thus, 15% of patients had severe CAC in the lowest tertile of cTnT, 50% had severe CAC in the middle third, and 69% in the highest third. Similarly, the degree of severity of CAC was positively associated (P < 0.01) with cTnI concentrations across concentration categories. In contrast, there was no association between the degree of CAC severity and the concentrations of either BNP or CK-MB. A logistic regression analysis revealed that elevated concentrations of cTnT (> or = median vs or = 0.1 ng/ml vs 相似文献   

Risk factors of the progression of abdominal aortic calcification in patients on chronic haemodialysis

Background. Vascular calcification is an independent determinantof cardiovascular events in maintenance haemodialysis (HD) patients.It is not known whether acute changes of the serum calcium concentrationbefore and after HD (Ca) are associated with the developmentof aortic calcification. Methods. We enrolled 71 patients dialysed with a dialysate with3.0 mEq/l calcium and determined their aortic calcificationindex (ACI) by abdominal computed tomography twice at an intervalof 3 years. To identify the factors contributing to the rateof progression of aortic calcification, we analysed the averagevalues for clinical and laboratory data obtained between thefirst and second evaluations of ACI. Results. The second ACI (mean ± SD: 80.2 ± 63.9)was significantly greater than the first ACI (61.0 ±61.0) after an interval of 35.8 ± 4.2 months. The annualizedchange of ACI (ACI/year) was significantly and directly associatedwith the Ca and C-reactive protein (CRP) (both P < 0.001,P for trend). Stepwise multivariate regression analysis revealedthat ACI/year was positively and independently associated withCRP, presence of diabetes mellitus and Ca, but negatively associatedwith a premenopausal status in women. Similarly, Ca was positivelyand independently associated with ACI/year and the ultrafiltrationrate, but was negatively associated with pre-HD Ca. Conclusion. The increase of serum calcium after HD was relatedto the rate of progression of aortic calcification. Excess calciumis transferred into patients on HD when using a dialysate of3.0 mEq/l calcium. This may be a risk factor for the developmentof vascular calcification.     

Involvement of parathyroid hormone-related protein in vascular calcification of chronic haemodialysis patients

Aims: To investigate the role of parathyroid hormone‐related protein (PTHrP) in vascular calcification of patients with chronic hemodialysis. Methods: The inferior epigastric arteries were obtained from 23 patients on chronic haemodialysis and 16 patients with renal carcinoma as control. Haematoxylin‐eosin staining, elastic fibre staining, Alizarin Red calcium staining and immunohistochemical staining of PTHrP, bone morphogenetic protein‐2 (BMP‐2), Cbfa1/Runx2 were performed. Real‐time polymerase chain reaction (PCR) was used to examine mRNA expressions of PTHrP, BMP‐2 and Cbfa1/Runx2. Western blot and real‐time PCR were used to detect the effects of PTHrP‐siRNA and rh‐PTHrP‐1–34 on the expressions of PTHrP, BMP‐2 and Cbfa1/Runx2 in human aortic smooth muscle cells (HASMC). Alkaline phosphatase (ALP) activities and intracellular calcium content in HASMCs were assessed after treatment with 10 mmol/L β‐glycerol phosphoric acid for 48 h. Results: Vascular calcification was confirmed in 78.2% of patients on chronic haemodialysis, and the expressions of PTHrP, BMP‐2 and Cbfa1 in the arteries were significantly upregulated. PTHrP‐siRNA could downregulate the expression of PTHrP by 60%, BMP‐2 by 25% and Cbfa1 by 25% at 24 h (P < 0.05). Exogenous rh‐PTHrP‐1–34 could upregulate the expressions of BMP‐2 and Cbfa1 by 1.37‐fold and 1.46‐fold, respectively, at 24 h in a time‐independent manner (P < 0.05), which were attenuated by PTHrP‐siRNA. Moreover, it could promote intracellular calcium deposition and increase ALP activities, which were partially blocked by PTHrP‐siRNA (P < 0.05). Conclusions: Vascular calcification was common in patients with chronic haemodialysis, to which PTHrP might contribute by activating BMP‐2/ Cbfa1 signalling pathway.     

Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders.

BACKGROUND: Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. METHODS: We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. RESULTS: During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). CONCLUSIONS: The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.     

Mineral metabolism, bone histomorphometry and vascular calcification in alternate night nocturnal haemodialysis

BACKGROUND: Poor control of bone mineral metabolism (BMM) is associated with renal osteodystrophy and mortality in dialysis-dependent patients. The authors explored the efficacy of alternate nightly home haemodialysis (ANHHD) in controlling BMM parameters and its effects on bone mineral density and histomorphometry. METHODS: In this prospective observational study, 26 patients on home haemodialysis (3-5 h, 3.5-4 sessions weekly) were converted to ANHHD (6-9 h, 3.5-4 sessions weekly). Biochemical parameters of BMM at baseline, 6 and 12 months, radiological parameters at baseline and 12 months and bone histomorphometry at 12 months are described. RESULTS: Pre-dialysis serum phosphate fell from 2.13+/-0.65 to 1.38+/-0.35 mmol/L; P<0.0001. No binders were required in 77.2% compared with 7.7% at baseline. Calcium-phosphate product fell from 5.28+/-1.64 to 3.42+/-0.88 mmol2/L2; P<0.0001 and parathyroid hormone (PTH) from 301 (110-471) to 127 (47-240) ng/L; P=0.01. Bone mineral density remained stable. Vascular and ectopic calcification improved or stabilized in 87.5%. Bone histomorphometry at 12 months showed high, normal and low bone turnover in 10, 3 and 4 patients, respectively, with 6/17 patients having abnormal mineralization. CONCLUSION: Alternate nightly home haemodialysis effectively manages biochemical parameters of BMM. Patients with very high PTH at baseline (>1000 ng/L) did not significantly improve parathyroid hormone status. Abnormal bone turnover and mineralization were present in a significant proportion of patients at 12 months but low turnover was uncommon. Vascular calcification was stabilized or improved in the majority. ANHHD compares favourably with every night and short daily therapy in relation to BMM management and may offer lifestyle advantages for patients.     

Carotid atherosclerosis is a predictor of coronary calcification in chronic haemodialysis patients.

BACKGROUND: Coronary artery calcification scores (CACS) calculated by electron beam computed tomography (EBCT) have been correlated with atherosclerotic burden in the non-uraemic population. However, the validity of this test in chronic haemodialysis patients (HD) is currently uncertain. In the present cross-sectional study, associations between carotid atherosclerosis and coronary calcification in HD patients are investigated. METHODS: We studied 79 chronic HD patients (39 male, 40 female; mean age, 45+/-12 years). The mean time on HD was 68+/-54 months (range, 6-187 months). In these patients, we measured serum calcium, phosphorus, total cholesterol, cholesterol subgroups and iPTH levels. EBCT, echocardiography, and high-resolution B-mode carotid Doppler ultrasonography were also performed. RESULTS: Plaque-positive HD patients had significantly higher CACS than plaque-negative patients (851+/-199 vs 428+/-185, mean+/-SE, P = 0.006). Coronary calcification scores were correlated with serum phosphorus (r = 0.37; P = 0.001). Only 8 of the 24 HD patients without coronary calcification had carotid plaques (33%), whereas 34 of the 53 patients with coronary calcification had carotid plaques (64%) (P = 0.015). Carotid plaque scores were correlated with CACS (r = 0.40; P = 0.001). A stepwise linear regression (model r = 0.72; P<0.001) revealed that CACS (log-transformed data of CACS) was associated with age (P<0.001), time on dialysis (P = 0.004), serum phosphorus level (P = 0.016) and carotid plaque scores (P = 0.037). CONCLUSIONS: Atherosclerosis is independently associated with coronary artery calcification and with hyperphosphataemia in chronic HD patients. CACS appeared to be predictive of both coronary atherosclerosis and carotid atherosclerosis.     

Effect of calcitriol treatment and withdrawal on hyperparathyroidism in haemodialysis patients with hypocalcaemia.

BACKGROUND: Calcitriol is used to treat secondary hyperparathyroidism in dialysis patients. For similarly elevated parathyroid hormone (PTH) levels, the PTH response to calcitriol treatment is believed to be better in hypocalcaemic dialysis patients than in dialysis patients with higher serum calcium values. Furthermore, few studies have evaluated the rapidity of the rebound in serum PTH values after prolonged treatment with calcitriol. Our goal was to evaluate (i) the PTH response to calcitriol treatment in hypocalcaemic haemodialysis patients, (ii) the rapidity of rebound in PTH after calcitriol treatment was stopped, and (iii) whether the effect of calcitriol treatment on PTH levels could be separated from those produced by changes in serum calcium and phosphate values. METHODS: Eight haemodialysis patients (29+/-3 years) with hypocalcaemia and hyperparathyroidism were treated thrice weekly with 2 microg of intravenous calcitriol and were dialysed with a 3.5 mEq/l calcium dialysate. Parathyroid function (PTH-calcium curve) was determined before and after 30 weeks of calcitriol treatment and 15 weeks after calcitriol treatment was stopped. RESULTS: Pretreatment PTH and ionized calcium values were 907+/-127 pg/ml and 3.89+/-0.12 mg/dl (normal, 4.52+/-0.07 mg/dl). During calcitriol treatment, one patient did not respond, but basal (predialysis) PTH values in the other seven patients decreased from 846+/-129 to 72+/-12 pg/ml, P<0.001 and in all seven patients, the decrease exceeded 85%. During the 15 weeks after calcitriol treatment was stopped, a slow rebound in basal PTH values in the seven patients was observed, 72+/-12 to 375+/-44 pg/ml. Covariance analysis was used to evaluate the three tests of parathyroid function (0, 30, and 45 weeks), and showed that calcitriol treatment was associated with reductions in maximal PTH values while reductions in basal PTH were affected by ionized calcium and serum phosphate. The basal/maximal PTH ratio and the set point of calcium were associated with changes in ionized calcium. CONCLUSIONS: In haemodialysis patients with hypocalcaemia, (i) moderate to severe hyperparathyroidism responded well to treatment with calcitriol, (ii) reductions in maximal PTH were calcitriol dependent while reductions in basal PTH were affected by the ionized calcium and serum phosphate concentrations, (iii) changes in the basal/maximal PTH ratio and the set point of calcium were calcium dependent, and (iv) the delayed rebound in basal PTH levels after withdrawal of calcitriol treatment may have been due to the long duration of treatment and the marked PTH suppression during treatment.     

Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation.

BACKGROUND: Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associated with improved blood pressure control when compared to conventional haemodialysis (CHD). Current studies suggest that NHD lowers blood pressure through a decrease in peripheral resistance. The graft and blood pressure outcomes of NHD patients who undergo renal transplantation are unknown. METHODS: We reviewed the renal allograft and blood pressure outcomes of 15 NHD patients who underwent renal transplantation. An age and vintage matched cohort of 29 CHD patients was used as controls. RESULTS: The rate of delayed graft function (DGF) tended to be higher in the NHD group compared to the CHD group (64 vs 41%, P = 0.15), however the 1-year graft function (53+/-6 vs 59+/-5 ml/min, P = 0.426) and graft survival (92 vs 95%, P = 0.751) were similar. Intra-operatively, NHD patients had lower minimum systolic (92+/-5 vs 109+/-4, P = 0.03) and diastolic (48+/-3 vs 64+/-2, P = 0.02) blood pressures in comparison to the CHD cohort. Pathologically, acute tubular necrosis accounted for 100% of DGF in the NHD group in contrast to 75% in the CHD population (P = 0.01). Pre-transplant mean systolic BP (sBP) was significantly lower in the NHD group compared to the CHD group (113+/-6 vs 145+/-10 mmHg, P<0.001). At 12 months post-transplant, mean sBP increased from baseline in the NHD group ( triangle up sBP 22+/-7 mmHg, P = 0.009) while in the CHD group mean sBP fell (Delta sBP -14+/-5 mmHg, P = 0.014). Mean arterial and diastolic BP exhibited similar changes. These trends persisted after 24 months of post-transplant follow-up. CONCLUSIONS: One-year graft outcomes and blood pressures are similar for NHD and CHD patients who undergo renal transplantation. Unlike CHD patients, NHD patients experienced a significant fall in their intra-operative blood pressures, which likely contributed towards the delayed graft function in this cohort of patients. Further prospective studies are needed to examine the underlying differences in haemodynamics and long-term graft survival between the two renal replacement modalities.     

Development of a cardiovascular calcification index using simple imaging tools in haemodialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is highly prevalent in haemodialysis patients and is associated with cardiovascular outcomes. Though cardiac computed tomography (CCT) is accurate, it is not widely available. METHODS: We developed a cardiovascular calcification index (CCI) to predict the presence of CAC for haemodialysis patients using simple in-office techniques. Prevalent haemodialysis patients (n = 140) underwent CCT imaging for CAC, a lateral abdominal X-ray for calcification of the abdominal aorta, an echocardiogram for valvular calcification, and pulse pressure measurement. A CCI was derived by weighting the prevalence rate ratios of CAC > or =1000. Using bootstrap techniques, validation was performed using receiver operator characteristic curves and likelihood ratios. RESULTS: Points were assigned for patients' age (60-69 and > or =70 years, 1 and 2 points, respectively), dialysis vintage > or =2 years (1 point), aortic and mitral valve calcification (3 and 1 points, respectively), and abdominal aorta X-ray scores of 1-6 and > or =7 (2 and 4 points, respectively). Race, sex and pulse pressure did not contribute to the CCI. The CCI ranged from 0 to 11 points. The likelihood ratio of CAC > or =1000 associated with CCI scores of 2-4, 5, 6-8 and 9-11 were 1.28, 2.03, 2.94 and 3.83, respectively. Given the prevalence of CAC > or =1000 of 21% in the current study, the probability of having CAC > or =1000 was 26%, 38%, 43% and 50% for participants with CCI scores of 2-4, 5, 6-8, and > or =9, respectively. CONCLUSIONS: Although refinement is needed, the CCI developed in the current study provides an alternative for predicting CAC when CCT is not available.