Predialysis Period Research Articles

Impacts of Recombinant Human Erythropoietin Treatment During Predialysis Periods on the Progression of Chronic Kidney Disease in a Large‐Scale Cohort Study (Co‐JET study)

The effect of recombinant human erythropoietin (rHuEPO) treatment on the progression of chronic kidney disease (CKD) has not been fully evaluated in Japan. We therefore retrospectively evaluated this in a sub-cohort of a prospective multicenter study to investigate optimal hemoglobin (Hb) level of CKD patients on hemodialysis (HD) treated with rHuEPO; Japan Erythropoietin Treatment Study for Target Hb and Survival (JET study). Effect of rHuEPO treatment during predialysis period to delay initiation of HD was retrospectively assessed in 2434 patients from the JET study comparing groups with and without rHuEPO treatment. The assessment was done by Cox proportional hazards regression analysis and inverse probability-weighted (IPW) analysis to adjust for time-dependent confounders. The weights used in the IPW analysis were calculated using a logistic model that included baseline confounders and time-dependent variables. During the predialysis period, 71.7% (1746 patients) were treated with rHuEPO (mean Hb level of 8.7 g/dL at initiation of rHuEPO treatment). Covariates significantly associated with initiation of rHuEPO treatment were Hb level, serum creatinine level, age, diabetes, cardiac insufficiency, and hypertension. The adjusted hazard ratio for time until HD initiation under rHuEPO treatment was 0.272 (95% CI, 0.223-0.331; P < 0.001) in the Cox analysis and 0.63 (95% CI, 0.53-0.76; P < 0.0001) in the IPW analysis. This retrospective study suggests that rHuEPO treatment during the predialysis period has preventive effects on the progression of CKD although further prospective investigation on the efficacy is needed.

English

BACKGROUND: Mortality risk among haemodialysis (HD) patients may be highest soon after initiation of HD. Studies from different geographical areas have been published regarding the predictors of early mortality among incident haemodialysis patients. With this background we started our study to asses early mortality causes among incident haemodialysis patients in our institute in Central India so that group of patients with risk factors can be educated and can be intervened early. MATERIALS & METHODS: 215 patients eligible for the evaluation of mortality in the first 120 days of dialysis were reviewed for their clinical and biochemical data. Univariate statistical tests using chi-square for binary variables and t-test for continuous variables were performed. RESULTS: The overall incident mortality within 120 days was 39 (18.1%) patients of which cardiovascular causes accounted for 51% of all the causes. Early mortality rate was not significantly increased in the comparison of gender groups but increased in patients with diabetes mellitus (29.4% vs.14.6%), those with reduced dialysis frequency (27.9% vs. 11.6%), the presence of low serum albumin (34.2% vs. 9.3%), the presence of a central venous catheter (26.7% vs. 10.1%) and the lack of Pre-ESRD nephrology care (23.6% vs. 11.6%) and in old age. The low serum albumin below 35 g/l was the strongest predictor of early mortality, the survival rates in patients with serum albumin less than 35 g/l and those with serum albumin equal to or greater than 35 g/l were 65.8% and 90.7%, respectively (p< 0.001). CONCLUSION: T he present study suggest that the important predictors of early mortality in the first 120 days of starting HD include the presence of diabetes mellitus, decreased frequency of dialysis sessions, the presence of low serum albumin, the presence of a central venous catheter, presence of urinary tract infection and the lack of Pre- ESRD nephrology care. These results also support the importance of arterio-venous fistula placement in the predialysis period with avoidance of temporary or permanent catheter placement and adequate predialysis nephrology care with a nephrologist at least 1 month before HD.

Providing nutrition support in pre-dialysis chronic kidney disease

Nutrition support in chronic kidney disease (CKD) is a cornerstone treatment for end-stage kidney disease (ESKD) and there is growing awareness this is also essential in the pre-dialysis or pre-dialysis period. Current treatment strategies and practice guidelines are based on either evidence from dialysis populations or from a limited range of studies in pre-dialysis. This paper will review the literature regarding the nutritional management in chronic kidney disease, to identify effectiveness of nutrition support and supplementation in pre-dialysis.

Impact of prior CKD management in a renal care network on early outcomes in incident dialysis patients: a prospective observational study

BackgroundEffective therapeutic strategies are available to prevent adverse outcomes in patients with chronic kidney disease (CKD) but their clinical results are hindered by unplanned implementation. Coordination of care emerges as a suitable way to improve patient outcomes. In this study, we evaluated the effect of planned and coordinated patient management within a dedicated renal care network comparatively to standard renal care delivered in nephrology departments of teaching hospitals.MethodsThis observational matched cohort study included 40 patients with CKD stage 4–5 in the network group as compared with a control group of 120 patients matched for age, sex and diabetic status. Main outcome was a composite endpoint of death from cardiovascular cause and cardiovascular events during the first year after dialysis initiation.ResultsThere was no difference between the two groups neither for the primary outcome (40% vs 41%) nor for the occurrence of death from cardiovascular cause or cardiovascular events. Whereas the proportion of patients requiring at least one hospitalization was identical (83.3% vs 75%), network patients experienced less individual hospitalizations than control patients (2.3±2.0 vs 1.6±1.7) during the year before dialysis start. Patients of the network group had a slower renal function decline (7.7±2.5 vs 4.9±1.1 ml/min/1,73m2 per year; p=0.04).ConclusionsIn this limited series of patients, we were unable to demonstrate a significant impact of the coordinated renal care provided in the network on early cardiovascular events in incident dialysis patients. However, during the predialysis period, there were less hospitalizations and a slower slope of renal function decrease.

RETRACTED ARTICLE: Risk factors for increased left ventricular hypertrophy in patients with chronic kidney disease

BackgroundAlthough left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the predialysis period has not been fully examined.MethodsWe measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study in order to identify factors that are associated with increased LVMI in patients with stage 3–5 CKD. LVH was defined as LVMI > 125 g/m2 in male patients and >110 g/m2 in female patients.ResultsWe analyzed baseline characteristics in 1185 participants (male 63.7 %, female 36.3 %). Diabetes mellitus was the underlying disease in 41.3 % of patients, and mean age was 61.8 ± 11.1 years. LVH was detected in 21.7 % of patients at baseline. By multivariate logistic analysis, independent risk factors for LVH were past history of cardiovascular disease (odds ratio [OR] 0.574; 95 % confidence interval [CI] 0.360–0.916; P = 0.020), systolic blood pressure (OR 1.179; 95 % CI 1.021–1.360; P = 0.025), body mass index (OR 1.135; 95 % CI 1.074–1.200; P < 0.001), and serum calcium level (OR 0.589; 95 % CI 0.396–0.876; P = 0.009).ConclusionCross-sectional baseline data from the CKD-JAC study shed light on the association between LVH and risk factors in patients with decreased renal function. Further longitudinal analyses of the CKD-JAC cohort are needed to evaluate the prognostic value of LVH in CKD patients.

Ultrasound-guided angioplasty of dialysis fistula – technique description

SummaryEndovascular procedures are commonly used for treatment of vascular pathologies. These interventions are routinely performed under angiographic control. Angioplasty is increasingly more often used for correction of dialysis fistula – especially dilatation of stenosis. We describe the technique of dialysis fistula angioplasty under ultrasound control. Benefits of this procedure include lack of nephrotoxic contrast, what is especially important in chronic kidney disease patients in pre-dialysis period. Advantages of ultrasound guidance during dialysis fistula angioplasty lead to cause more and more frequent employment of this technique.

New markers of apoptosis in children on chronic dialysis

Enhanced apoptosis is characteristic for chronic kidney disease (CKD). A specific type of apoptosis, anoikis, is connected with the extracellular matrix turnover and cell detachment. Although E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP)-8 may play an important role in this process, they have not been analyzed in any nephrological aspect, either in CKD. The aim of study was to evaluate the serum concentrations of E-cadherin, EMMPRIN and their potential regulators (MMP-8, MMP-7, TIMP-1, TIMP-2), with relevance to apoptosis/cell damage markers (sFas, sFasL, Hsp27), in children with CKD. 39 CKD children stages 3–4, 26 CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 30 controls were examined. Serum concentrations of those parameters were assessed by ELISA. Median E-cadherin, EMMPRIN and MMP-8 values were significantly increased in patients on dialysis versus those in pre-dialysis period and versus controls. The highest values were noticed in the HD subjects. Regression analysis revealed that EMMPRIN and MMP-8 predicted various apoptosis markers, whereas E-cadherin turned out the best predictor of both apoptosis (Hsp27, sFas, sFasL) and matrix turnover (MMP-7, TIMP-1, TIMP-2) indexes in dialyzed patients. Children with CKD are prone to E-cadherin, EMMPRIN and MMP-8 elevation, aggravated by the dialysis commencement and most evident on hemodialysis. Correlations between parameters suggest their role as indexes of apoptosis in children on dialysis. E-cadherin seems the most accurate marker of anoikis in this population.

Effect of erythropoietin-stimulating agent on uremic inflammation

BackgroundThe goal of the present study was to explore the effect of medications that are commonly prescribed for CKD patients on uremic state.MethodsThis was a cross-sectional study. From January 2006 to October 2009, 1,623 patients with end-stage kidney disease (ESKD) commenced hemodialysis (HD) at the 9 participating hospitals. The criteria for exclusion from the database were 1) serum C-reactive protein (CRP) > 3 mg/dL, 2) WBC count > 9,000/mm3 or <4,000/mm3, and 3) patients with cancer, immune complex disease, or vasculitis. A total of 900 patients were entered into the final database. We explored the association of serum CRP just before the first HD session with clinical characteristics, laboratory data, and medications for CKD in the predialysis period.ResultsOn univariate analysis, age, CTR, eGFR, and WBC were significantly correlated with CRP. Systolic and diastolic blood pressure, serum albumin, LDL-C, HDL-C, Hb, Cr, and Ca were inversely associated with CRP. Use of erythropoietin-stimulating agents (ESA) using (r = −0.111, p = 0.0015), renin-angiotensin-aldosterone system inhibitors (r = −0.083, p = 0.0154), and calcium channel blockers (r = −0.1, p = 0.0039) was also negatively correlated with CRP. However, only use of ESA showed a significant negative correlation with CRP that was independent of other clinical factors and CKD medications on multiple regression analysis.ConclusionESA may strongly reduce uremic inflammation in addition to improving anemia. To confirm this potential effect, a large-scale longitudinal study would be required.

Hsp27 as a marker of cell damage in children on chronic dialysis

Intracellular heat shock protein (Hsp) 27 is a potent anti-apoptotic factor that, among other activities, prevents the binding of membrane receptor Fas to its ligand FasL. However, the potential role of extracellular Hsp27 and possibilities to control it have not been clarified. Moreover, there are no data on relations between Hsp27, sFas/sFasL system, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in patients with chronic kidney disease (CKD)—neither children nor adults. The aim of this study was to evaluate serum concentrations of Hsp27 and their potential regulators (sFas, sFasL, MMP-7, TIMP-1) in children with CKD and on chronic dialysis. Twenty-six CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD), and 30 controls were examined. Serum concentrations of Hsp27, sFas, sFasL, MMP-7, and TIMP-1 were assessed by ELISA. Median values of Hsp27 were significantly elevated in all dialyzed patients vs. those in pre-dialysis period and vs. controls, the highest values being observed in subjects on HD. Regression analysis revealed that MMP-7, TIMP-1, sFas, and sFasL were the best predictors of Hsp27 concentrations in dialyzed patients. Children with CKD are prone to Hsp27 dysfunction, aggravated by the dialysis commencement, and more pronounced in patients on hemodialysis. Correlations between Hsp27 and examined parameters suggest the potential role for Hsp27 as a marker of cell damage in the pediatric population on chronic dialysis.

ESRD patients using permanent vascular access report greater physical activity compared with catheter users

Low levels of physical activity among end-stage renal disease (ESRD) patients are associated with increased risk of hospitalization and mortality, and contributors to low activity levels are important to identify. Among hemodialysis (HD) patients, use of a central venous catheter (CVC) might impede physical activity due to factors such as infection or patient fear of catheter dislodgement. This Comprehensive Dialysis Study surveyed patients who had recently started regular dialysis. Physical activity level was ascertained using responses to the Human Activity Profile (HAP) provided by 1,458 HD participants. We examined the association of vascular access type with patients' scores on HAP subscales measuring self-care and leg effort, two dimensions that are especially important for daily living. 32.6% of patients used an arteriovenous fistula (AVF), 11.5% used an arteriovenous graft, 51.8% used a CVC, and 4.1% used a CVC with another maturing access. Patients' self-care and leg effort scores differed by vascular access type and receipt of early nephrology care, and the mean self-care score of AVF users who received early care was similar to the mean score reported for healthy adults. Reported levels of self-care and leg effort activity were higher among incident HD patients using an AVF compared to those using a CVC. Future research should examine whether reinforcing the importance of regular physical activity in the pre-dialysis period, as well as wider early use of AVF in the HD population, may improve physical activity levels among ESRD patients.

Association of Conicity Index and Renal Progression in Pre-dialysis Chronic Kidney Disease

Background/objectives: Abdominal fat deposition is represented by means of the conicity index (CI), an anthropometric estimate that models the relative accumulation of abdominal fat. We examined the influence of markers of cardiovascular disease in terms of inflammation and lipid profile and body fat distribution on the progression of renal disease in patients with stable chronic kidney disease (CKD) stages 3–5. Material and methods: We studied 104 pre-dialysis CKD patients (64 males, 62%; age 64.6 ± 14.7 years). Glomerular filtration rate (GFR) was estimated (44.62 ± 14.38 mL/min/1.73 m2) by modification of diet in renal disease formula. GFR values were estimated at baseline and at the end of the 12-month follow-up. Patients were stratified into three groups: group 1 had a loss of GFR ≥20%; group 2 had a loss of GFR 10–20%; and group 3 patients had stable renal functions or GFR change <10% at the end of 12 months. Body mass index (BMI), waist/hip ratio (WHR), and CI were subsequently computed. Renal resistive index (RRI) was measured using Doppler ultrasonography. Results: CI was strongly correlated with total cholesterol (r = 0.37, p < 0.01), low-density lipoprotein (LDL) (r = 0.53, p < 0.01), C-reactive protein (r = 0.21, p < 0.05), and serum potassium (r = 0.216, p < 0.02), whereas BMI and WHR were not associated with these parameters. The values of CI, serum cholesterol, LDL, alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase activity, the degree of proteinuria and microalbuminuria, and RRI were significantly lower in group 3. In linear regression model, LDL (r2 = 0.17, p = 0.02), uric acid (r2 = 0.19, p < 0.01), and RRI (r2 = 0.64, p < 0.01) were independently associated with CI for all groups. Conclusion: CI is an independent predictor of systemic inflammation, cardiovascular risk, and GFR in patients during the pre-dialysis period.

Hyperphosphatemia in Chronic Kidney Disease: Patient Characteristics and Dialysis Mortality during the First Year of Dialysis

Aims: To describe the characteristics of chronic kidney disease patients with hyperphosphatemia before dialysis. To assess the impact of pre-dialysis hyperphosphatemia on dialysis mortality. Methods: All patients beginning a dialysis treatment in 2005-2006 in all the nephrology units operating in the Lorraine region of northeastern France were considered. Among them, those who were referred to a nephrologist more than 1 month before dialysis and had atleast one pre-dialysis phosphatemia measurement were included. All-cause mortality during the first year of dialysis was the outcome of interest and phosphatemia level the parameter of interest. Results: Of 406 patients included (mean age, 68.2 ± 14.8 years), 53% had pre-dialysis hyperphosphatemia, defined by a mean serum phosphate > 1.45 mmol/L during an average pre-dialysis nephrology follow-up period of 10 months. Patients with hyperphosphatemia were younger than those with normophosphatemia, and more often women. They were more likely to have diabetic nephropathy, less likely to have hypertensive nephropathy and cardiovascular comorbidity, and had fewer comorbidities. We found no association between hyperphosphatemia and mortality. Conclusions: This study shows that patients with pre-dialysis hyperphosphatemia differ from those with normophosphatemia. Larger studies are warranted to confirm or refute the absence of a relationship between predialysis hyperphosphatemia and dialysis mortality.

Severe hyperparathyroidism in a pre-dialysis chronic kidney disease patient treated with a very low protein diet

The present report describes a case of a 64-year-old pre-dialysis woman with chronic kidney disease (CKD) stage 5, who developed severe hyperparathyroidism. This patient had been on a very low protein diet (VLPD) to delay the progression of CKD and the need for renal replacement therapy (RRT). Her serum calcium levels were high-normal to slightly high during this time. However, her serum intact parathyroid hormone (PTH) levels increased from 400 to 1160pg/ml rapidly over a period of 3months. Serum 1,25-(OH)2D levels were low, and ultrasound of the neck showed three markedly enlarged parathyroid glands exceeding 2cm. Parathyroidectomy was performed, and all glands showed nodular hyperplasia, which indicated severe secondary hyperparathyroidism leading to tertiary. Severe secondary hyperparathyroidism requiring surgical intervention is usually observed in patients with long-term RRT and is relatively rare in the pre-dialysis patient. In this case, extension of the pre-dialysis period by VLPD may have predisposed this patient to develop severe secondary hyperparathyroidism. Thus, careful monitoring of calcium, phosphorus, and PTH may be necessary in patients treated with VLPD even before renal replacement therapy. Furthermore, initiation of dialysis should not be excessively delayed by strict protein restriction dietary therapy.

Chronic Kidney Disease Japan Cohort study: baseline characteristics and factors associated with causative diseases and renal function

Prevalence of chronic kidney disease (CKD) is estimated to be 13.3 million in Japan, but patient characteristics during the predialysis period (CKD stages 3-5) are not well studied. We established the Chronic Kidney Disease Japan Cohort (CKD-JAC) to study the incidence of cardiovascular disease (CVD), end-stage renal disease (ESRD), and all-cause mortality in predialysis patients treated by nephrologists for 4 years. The inclusion criteria were (1) Japanese and Asian patients living in Japan, (2) age 20-75 years, and (3) estimated glomerular filtration rate (eGFR) 10-59 ml/min/1.73 m(2). We analyzed 2977 participants for baseline characteristics. Mean eGFR was 28.6 ± 11.8 ml/min/1.73 m(2), and mean albuminuria was 976 ± 1340 mg/g Cr. In our study, 91.9% of participants had hypertension, but it was well controlled (131/76 mmHg). Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) were used by most participants. Less than 15% of participants had history of ischemic heart disease, and 11.5% had history of stroke. Heart failure and arteriosclerosis obliterans were present in 3.9% and 3.6% of patients, respectively. Indicators of arteriosclerosis, higher pulse wave velocity (PWV), and high pulse pressure were associated with diabetes and particularly with diabetic nephropathy. Patients included due to glomerulonephritis seemed to be at low risk for atherosclerosis and also to show lower levels of hypertension. The difference between causative diseases is associated with different comorbidity and level of arteriosclerosis. Future analysis of the cohort will clarify whether incidence of ESRD and CVD differs among causative diseases.

The Role of Arterio-Venous Shunt in the Pathogenesis of Pulmonary Hypertention in Patients with End-stage Renal Disease

Pulmonary hypertension (PHT) is an overlooked cardiovascular morbidity in patients with end stage renal disease. The pathogenesis of PHT in this group of patients is not explained satisfactorily. The aim of our study to evaluate the prevalence and the role of AV shunt in pathogenesis of pulmonary hypertention. Our study included 58 patients with ESRD without a known cause of PHT who were either in the predialysis period (stage 1V CKD) (14 patients) or maintained on chronic hemodialysis (stage V CKD) (44 patients) in Theodor Bilharz Research Institute (TBRI), Cairo, Egypt. In the chronic hemodialysis group, there were 27 males and 17 females with a mean age of 57.11 ± 12.31 years (range 28–65). In the predialysis group, there were 8 males and 6 females with a mean age 53.45 ± 9.41 years (range 28–66). Pulmonary arterial pressure (PAP) and cardiac output were evaluated by Doppler echocardiography in the 14 pre-dialysis patients without PHT few (4.3 ± 0.8) months after creation of AV fistula and in the 44 hemodialysis patients (33.6 ± 4.2 months) after creation of AV fistula within 1 h of completion of hemodialysis session. Arteriovenous fistula (AVF) flow was measured by Doppler sonography. PHT (systolic PAP ≥35 mm Hg) was observed in 25 (56.8%) patients receiving hemodialysis with a mean systolic PAP of 46.4 ± 13.6 mm Hg. In the predialysis group after creation of AV fistula, PHT was found in 6 (42.9%) patients with a mean systolic PAP of 42.8 ± 12.8 mm Hg. The cardiac output and AV shunt flow were found to be increased in patients with elevated systolic PAP in both groups (p < 0.05). CRF duration and AV fistula duration were positively correlated with systolic PAP in patients receiving hemodialysis (p < 0.05). After compression of AV fistula in 11 hemodialysis patients, the mean value of PHT decreased (from 43.98 ± 15.6 to 33.22 ± 11.7 mm Hg). This study demonstrates a high prevalence of PHT among patients with ESRD in predialysis period after creation of AV fistula and on chronic HD via a surgical A-V fistula. Cardiac output, AV shunt flow and duration, and ESRD duration may be involved in the pathogenesis of PHT. The development of PHT following access formation represents a failure of the pulmonary circulation to accommodate the access-mediated elevated CO. Pre-dialysis patients scheduled for access formation should be screened for the presence of sub-clinical PHT.

Thiol levels, protein carbonylation and anaerobic sulfur metabolism in erythrocytes of peritoneal dialysis and predialysis patients

The goal of the present study was to investigate the changes in sulfur metabolism in erythrocytes of end-stage renal failure patients. The following substances were determined in erythrocytes of chronic kidney disease patients before dialysis, patients treated with continuous ambulatory peritoneal dialysis, and in a group of healthy volunteers: (i) sulfane sulfur level and activity of the enzymes involved in its metabolism and in cyanide detoxification; (ii) concentration of total and non-protein sulfhydryl groups -SH; and (iii) protein carbonylation rate. Erythrocytes of chronic kidney disease patients in predialysis period contained lower levels of sulfane sulfur, non-protein thiols, total thiols and 3-mercaptopyruvate sulfotransferase. On the other hand, in erythrocytes of end-stage renal failure patients treated with continuous ambulatory peritoneal dialysis, sulfane sulfur, non-protein thiols, total thiols and 3-mercaptopyruvate sulfotransferase activity remained at the level observed in healthy controls. These changes indicate a disturbed thiol balance and anaerobic cysteine metabolism in non-dialysis patients, whereas continuous ambulatory peritoneal dialysis patients did not show these disorders. γ-Cystathionase activity was equally elevated in predialysis period and in peritoneal dialysis patients, which means that chronic kidney disease pathology is accompanied by an increased expression of this enzymatic activity in erythrocytes. Erythrocytic rhodanese activity was unchanged and stayed at the control level in both groups. Protein carbonylation rate was equally enhanced in both patient groups, which indicated acceleration of oxidative processes and inability of continuous ambulatory peritoneal dialysis to correct these changes in erythrocytes. The CAPD as a replacement therapy helps to preserve thiol levels and anaerobic sulfur metabolism in erythrocytes.

Analysis of risk factors for mortality of incident patients commencing dialysis in East Yorkshire, UK

The change in the demographics and the presence of multiple risk factors and co-morbidities in UK patients starting dialysis may lead to poor survival on dialysis. Many of these risk factors are present in the pre-dialysis period allowing a potential window of opportunity to intervene with risk modification measures. To examine various potential factors that may predict early and overall mortality. We carried out an observational prospective study of a cohort of incident patients starting dialysis in a UK centre. Univariate analysis of factors and co-morbidities potentially affecting survival on dialysis were analysed to potential predictors. Factors affecting 1 year mortality were analysed using the t-test, the Mann-Whitney U-test or the chi-square test as appropriate. Mortality over the 5-year follow-up period was analysed using the Kaplan-Meier method. Ninety-four patients [predominantly Caucasian (98%)], of mean age 63 years (15.6) (56% > 65 years) with a slight male preponderance were studied. Vascular disease (39%) and sepsis (33%) accounted for most of the deaths and a significant proportion of mortality was seen in the first year (56%). Patients with early mortality were older (68 vs. 61 years, P = 0.05) with lower haemoglobin (8.4 vs. 9.4 g/dl, P = 0.01) at the start of dialysis, commenced dialysis with a lower eGFR (5.4 vs. 6.5 ml/min/1.73 m(2), P = 0.06) and had more peripheral vascular disease (PVD) (39% mortality in patients with PVD vs. 18.5% in those without PVD, P = 0.04). Diabetes mellitus, high calcium phosphate product, older age and presence of vascular co-morbidities including ischaemic heart disease and peripheral vascular disease were associated with overall mortality over the 5-year follow-up period. In this study, elevated calcium phosphate product and diabetes mellitus in addition to the presence of vascular disease were associated with poor survival. Patients with low haemoglobin and lower first pre-dialysis eGFR suffered higher early mortality. These potentially modifiable factors that could be identified in the pre-dialysis stage provide a valuable opportunity for intervention.

Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events

Besides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain. We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan-Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25-0.5 microg/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of <24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox's proportional hazards analysis. The mean follow-up period was 55.1 +/- 38.9 months in the alfacalcidol treatment group and 41.9 +/- 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin-angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone. These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.

Increased Aortic Wall Stiffness Associated with Low Circulating Fetuin A and High C-Reactive Protein in Predialysis Patients

Background/Aims: Vascular calcification and arterial stiffening are cardiovascular risk factors among chronic kidney disease (CKD) patients. The aim of the study was to analyze relationships between inflammatory markers, fetuin A and arterial wall stiffness in CKD patients in the predialysis period and on maintenance dialysis. Methods: Serum C-reactive protein (hs-CRP), fetuin A, interleukin 6 (IL-6) and other classical markers of atherosclerosis were measured in a group of 155 CKD patients (77 on hemodialysis, HD, 29 on peritoneal dialysis, 49 in CKD stage 5 in the predialysis period) and in 30 healthy volunteers. The aortic pulse wave velocity (aoPWV) was recorded using a tonometric method. Results: The aoPWV, serum hs-CRP and IL-6 were higher and fetuin A levels were lower in all CKD groups than in controls. In multiple regression analysis, the age appeared as the strongest, independent factor increasing arterial wall stiffness in all investigated groups, including controls, whereas the association of aoPWV with IL-6 and fetuin A remained significant only in HD patients. Conclusions: Aortic wall stiffness is higher in CKD patients than in controls, and it already develops in the predialysis period. Age is the principal determinant of arterial wall stiffness also in CKD patients. The acceleration of arterial wall stiffness in CKD is associated with additional factors, i.e. fetuin A deficiency and higher CRP and IL-6.

A Strict Low Protein Diet during the Predialysis Period Suppresses Peritoneal Permeability at Induction of Peritoneal Dialysis

The factors that predict baseline peritoneal permeability remain largely unknown. We noticed that patients that adhered to a strict low protein diet (LPD) during the predialysis period seldom showed high peritoneal permeability on the peritoneal equilibration test (PET) at the introduction of peritoneal dialysis (PD). Therefore, we investigated whether a strict LPD during the predialysis period affects peritoneal permeability. We retrospectively analyzed 37 patients that started PD in a single Japanese center. Patients were divided into group A and group B by the median amount of daily protein intake (PI) during the predialysis period using urine collected over 24 hours. There were no differences between groups A and B in age, gender, proportion of diabetic nephropathy, blood pressure, body mass index, or body surface area. There were also no differences between the groups in laboratory findings, including hematocrit, serum albumin, and serum creatinine. The PETs showed a significantly lower dialysate-to-plasma ratio of creatinine at 4 hours (Cr D/P) for group A than for group B (p = 0.02). Furthermore, a significant positive correlation between Cr D/P and PI was observed (r = 0.53, p < 0.01). It is suggested that a strict LPD during the predialysis period may suppress peritoneal permeability at induction of PD.