Predialysis Patients Research Articles

Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study

BackgroundChronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation.MethodsThe subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PS-matched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis.ResultsThere were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group (p < 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160–2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events.ConclusionHistory of CHD at dialysis initiation was associated with a higher incidence of heart disease events and mortality and all-cause mortality.Trial registrationUMIN 000007096. Registered 18 January 2012.

Arteriovenous fistula maturation in patients with permanent access created prior to or after hemodialysis initiation.

Multiple factors and comorbidities have been implicated in the ability of arteriovenous fistulas (AVF) to mature, including vessel anatomy, advanced age, and the presence of coronary artery disease or peripheral vascular disease. However, little is known about the role of uremia on AVF primary failure. In this study, we attempt to evaluate the effect of uremia on AVF maturation by comparing AVF outcomes between pre-dialysis chronic kidney disease (CKD) stage five patients and those who had their AVF created after hemodialysis (HD) initiation. We included 612 patients who underwent AVF creation between 2003 and 2015 at the University of Miami Hospital and Jackson Memorial Hospital. Effects of uremia on primary failure were evaluated using univariate statistical comparisons and multivariate logistic regression analyses. Primary failure occurred in 28.1% and 26.3% of patients with an AVF created prior to or after HD initiation, respectively (p = 0.73). The time of HD initiation was not associated with AVF maturation in multivariate logistic regression analysis (p = 0.57). In addition, pre-operative blood urea nitrogen (p = 0.78), estimated glomerular filtration rate (p = 0.66), and serum creatinine levels (p = 0.14) were not associated with AVF primary failure in pre-dialysis patients. Our results show that clearance of uremia with regular HD treatments prior to AVF creation does not improve the frequency of vascular access maturation.

Long-Term Safety and Efficacy of Bixalomer in Hyperphosphatemic Patients With Chronic Kidney Disease Not on Dialysis.

Bixalomer, a metal-free, nonabsorbable phosphate binder, is approved in Japan to treat hyperphosphatemia in dialysis patients. Bixalomer is effective and has a favorable safety profile in predialysis patients with hyperphosphatemia. This study examined the long-term effectiveness and safety of bixalomer in predialysis patients with hyperphosphatemia. This was a 48-week, multicenter, open-label, phase 3 study in Japanese predialysis patients with hyperphosphatemia. Patients received bixalomer at an initial dose of 1500 mg/day, which was titrated to a maximum of 7500 mg/day depending on patients' serum phosphorus responses to bixalomer. A total of 105 patients received bixalomer treatment, and 39 completed the study. The most common reason for discontinuation was initiation of dialysis. Mean serum phosphorus concentrations decreased from 5.15 mg/dL at baseline to 4.67 mg/dL at Week 12 and then fluctuated slightly around this level until it reached 4.58 mg/dL at Week 48. The proportion of total patients achieving the target serum phosphorus concentration (≥2.5 to <4.6 mg/dL) increased after treatment to a maximum of 66.2% at Week 20 and subsequently decreased to 51.3% by Week 48. Most adverse events (AEs) occurred in the first 12 weeks of treatment. The incidence of AEs did not increase with long-term treatment. Common AEs reported included nasopharyngitis (29.5%), constipation (19%), and upper respiratory tract inflammation (12.4%). These findings suggest that long-term treatment with bixalomer is effective, well tolerated, and has no new safety concerns. Bixalomer may be an alternative treatment option for the long-term management of hyperphosphatemia in patients with chronic kidney diseases.

PRE DIALYSIS PATIENTS;

Introduction: Chronic kidney disease (CKD) is an alarmingly increasingcondition from day to day andit is assumed that malnutrition is co-existent in patients withchronic renal failure (CRF). Malnutrition also occurs in pre-dialysis patients. Such patientshave reduced body weight, depleted fat (energy) stores, loss of somatic protein (low musclemass) and low levels of different plasma proteins like pre-albumin albumin, transferrin, andothers. Objective: To ascertain the frequency of malnutrition in dialysis independent patientsof chronic kidney disease. Setting: Department of nephrology, Jinnah Postgraduate MedicalCentre Karachi. Duration of study: 6 month from 1 June 2013 – 1 December 2013. Studydesign: cross sectional study. Subjects and methods: Patients with chronic kidney disease(GFR &lt;60ml/min/1.73m2) on conservative management irrespective of cause and sex werestudied. All Patients with CKD stage 3 and onwards i. ecreatinine clearance less than 60ml/min/1.73m2for more than 6 months were considered. Descriptive analysis of these patientswas done by: Calculating mean ± SD for age and duration of disease. Male to female ratiowas calculated. Frequency of malnutrition in undialysed patients was calculated. The effectmodifier of age, gender, duration of disease was controlled through stratification. Chi squaretest was applied and p value ≤0.05 was taken as significant. Result: Out of 137 patients, 80were males and 57 were females and the mean age of patients was 58 ±5.8. Mean duration ofdisease was 5.2 ±1.05. Moderate malnutrition cases were 58(42.3%) while severe malnutritionwas observed in 32(23.35%) cases. Conclusion: Patients of chronic kidney disease were foundto be at risk of malnutrition.

The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071–1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123–1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016–1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996–1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Erythropoiesis stimulating agents and reno-protection: a meta-analysis

BackgroundErythropoiesis stimulating agents (ESAs) were proposed to enhance survival of renal tissues through direct effects via activation of EPO receptors on renal cells resulting in reduced cell apoptosis, or indirect effects via increased oxygen delivery due to increased numbers of Hb containing red blood cells. Thus through several mechanisms there may be benefit of ESA administration on kidney disease progression and kidney function in renal patients. However conflicting ESA reno-protection outcomes have been reported in both pre-clinical animal studies and human clinical trials. To better understand the potential beneficial effects of ESAs on renal-patients, meta-analyses of clinical trials is needed.MethodsLiterature searches and manual searches of references lists from published studies were performed. Controlled trials that included ESA treatment on renal patients with relevant renal endpoints were selected.ResultsThirty two ESA controlled trials in 3 categories of intervention were identified. These included 7 trials with patients who had a high likelihood of AKI, 7 trials with kidney transplant patients and 18 anemia correction trials with chronic kidney disease (predialysis) patients. There was a trend toward improvement in renal outcomes in the ESA treated arm of AKI and transplant trials, but none reached statistical significance. In 12 of the anemia correction trials, meta-analyses showed no difference in renal outcomes with the anemia correction but both arms received some ESA treatment making it difficult to assess effects of ESA treatment alone. However, in 6 trials the low Hb arm received no ESAs and meta-analysis also showed no difference in renal outcomes, consistent with no benefit of ESA/ Hb increase.ConclusionsMost ESA trials were small with modest event rates. While trends tended to favor the ESA treatment arm, these meta-analyses showed no reduction of incidence of AKI, no reduction in DGF or improvement in 1-year graft survival after renal transplantation and no significant delay in progression of CKD. These results do not support significant clinical reno-protection by ESAs.

Short-acting erythropoiesis-stimulating agents for anaemia in predialysis patients.

The benefits of erythropoiesis-stimulating agents (ESA) for chronic kidney disease (CKD) patients have been previously demonstrated. However, the efficacy and safety of short-acting epoetins administered at larger doses and reduced frequency as well as of new epoetins and biosimilars remains uncertain. This review aimed to evaluate the benefits and harms of different routes, frequencies and doses of epoetins (epoetin alpha, epoetin beta and other short-acting epoetins) for anaemia in adults and children with CKD not receiving dialysis. We searched the Cochrane Kidney and Transplant Specialised Register to 12 September 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised control trials (RCTs) comparing different frequencies, routes, doses and types of short-acting ESAs in CKD patients. Two authors independently assessed study eligibility and four authors assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model. We identified 14 RCTs (2616 participants); nine studies were multi-centre and two studies involved children. The risk of bias was high in most studies; only three studies demonstrated adequate random sequence generation and only two studies were at low risk of bias for allocation concealment. Blinding of participants and personnel was at low risk of bias in one study. Blinding of outcome assessment was judged at low risk in 13 studies as the outcome measures were reported as laboratory results and therefore unlikely to be influenced by blinding. Attrition bias was at low risk of bias in eight studies while selective reporting was at low risk in six included studies.Four interventions were compared: epoetin alpha or beta at different frequencies using the same total dose (six studies); epoetin alpha at the same frequency and different total doses (two studies); epoetin alpha administered intravenously versus subcutaneous administration (one study); epoetin alpha or beta versus other epoetins or biosimilars (five studies). One study compared both different frequencies of epoetin alpha at the same total dose and at the same frequency using different total doses.Data from only 7/14 studies could be included in our meta-analyses. There were no significant differences in final haemoglobin (Hb) levels when dosing every two weeks was compared with weekly dosing (4 studies, 785 participants: MD -0.20 g/dL, 95% CI -0.33 to -0.07), when four weekly dosing was compared with two weekly dosing (three studies, 671 participants: MD -0.16 g/dL, 95% CI -0.43 to 0.10) or when different total doses were administered at the same frequency (four weekly administration: one study, 144 participants: MD 0.17 g/dL 95% CI -0.19 to 0.53).Five studies evaluated different interventions. One study compared epoetin theta with epoetin alpha and found no significant differences in Hb levels (288 participants: MD -0.02 g/dL, 95% CI -0.25 to 0.21). One study found significantly higher pain scores with subcutaneous epoetin alpha compared with epoetin beta. Two studies (165 participants) compared epoetin delta with epoetin alpha, with no results available since the pharmaceutical company withdrew epoetin delta for commercial reasons. The fifth study comparing the biosimilar HX575 with epoetin alpha was stopped after patients receiving HX575 subcutaneously developed anti-epoetin antibodies and no results were available.Adverse events were poorly reported in all studies and did not differ significantly within comparisons. Mortality was only detailed adequately in four studies and only one study included quality of life data. Epoetin alpha given at higher doses for extended intervals (two or four weekly) is non-inferior to more frequent dosing intervals in maintaining final Hb levels with no significant differences in adverse effects in non-dialysed CKD patients. However the data are of low methodological quality so that differences in efficacy and safety cannot be excluded. Further large, well designed, RCTs with patient-centred outcomes are required to assess the safety and efficacy of large doses of the shorter acting ESAs, including biosimilars of epoetin alpha, administered less frequently compared with more frequent administration of smaller doses in children and adults with CKD not on dialysis.

GAMBARAN KADAR UREUM DAN KREATININ SERUM PADA PASIEN GAGAL GINJAL KRONIS (GGK) YANG MENJALANI TERAPI HEMODIALISIS DI RSUD SANJIWANI GIANYAR

The kidneys are responsible for filtering waste from the body such as urea, uric acid, and creatinine. When these organs stop functioning properly, waste builds up to high levels in the blood. In patients with kidney failure are usually equipped with a blood chemistry that urea and serum creatinine as an amplifier diagnosis of the patient's illness. CKD is the progressive loss of function of kidney and patient requires a long treatment in the form of renal replacement therapy. Hemodialysis is one of the renal replacement therapy, during waste products of the body are removed. Patients with kidney failure are associated with increased levels of some biochemical parameters. In several studies, urea and creatinine serum of CKD patients pre-dialysis revealed abnormal levels and indicated hyperuremic. &#x0D; Therefore, this study was aimed to analyzed urea and creatinine serum in CKD patient undergoing hemodialysis in Sanjiwani Hospital. A description study, used purposive sampling methods, involving 30 patients with CKD undergoing hemodialysis. Blood samples were analyzed for urea and creatinin level. Data are presented as table. &#x0D; Results of this study showed that all samples (100%) had serum urea and creatinine levels high or exceed the normal limits. While of urea/creatinine levels as many as 20 patients (66,7%) had low ratio, 7 patients (23,3%) had a normal ratio, and 3 patients (10%) have a high ratio, so that it can be concluded that all patients had hyperuremic. &#x0D; &#x0D; Key words: Urea, Creatinine, Hemodialysis

Evaluation of Mental Disorders Using Proton Magnetic Resonance Spectroscopy in Dialysis and Predialysis Patients

Background/Aims: Psychological complications are prevalent in patients with chronic kidney disease (CKD). This study aimed to investigate mental disorders in stage 4-5 CKD patients, to detect metabolite concentrations in the brain by proton magnetic resonance spectroscopy (¹H-MRS) and to compare the effects of different dialysis therapies on mental disorders in end-stage renal disease (ESRD). Methods: The sample population was made up of predialysis (13), hemodialysis (HD) (13), and peritoneal dialysis (PD) patients (12). We collected the baseline data of patients’ age, sex, hemoglobin (Hb) and parathyroid hormone（PTH） levels. The predialysis patients served as the control group. The psychological status of the three groups was assessed using three psychological scales. ¹H-MRS was used to evaluate the relative metabolite concentrations in the bilateral amygdala, hippocampus and unilateral anterior cingulated cortex (ACC). Results: The psychological status was better in HD patients than in predialysis and PD patients. ¹H-MRS alterations were predominantly found in the ACC. Choline-containing compounds relative to creatine (Cho/Cr), myo-inositol relative to creatine (MI/Cr) and glutamate and glutamine relative to creatine (Glx/Cr) in the ACC were higher in HD patients. ¹H-MRS results were correlated with the baseline data and the scores of psychological scales. Conclusions: CKD patients showed different types of mental disorders as well as metabolite disturbances in the brain. The metabolite concentrations correlated with the psychological status which was better in HD than in predialytic and PD patients.

Predictors of Vitamin D deficiency in predialysis patients with stage 3-5 chronic kidney diseases in Southern China.

Vitamin D status and risk factors of Vitamin D deficiency in chronic kidney disease (CKD) patients in China have been seldom reported before. In this study, we aim to investigate serum 25-hydroxyvitamin D [25(OH)D] status and find the predictors of Vitamin D deficiency in predialysis patients with Stage 3-5 CKDs in Southern China. In this retrospective cross-sectional study, hospitalized predialysis patients who were diagnosed of Stage 3-5 CKD and had taken measurement of serum 25(OH)D in a single center from January 2014 to June 2015 were included. Patients were divided into Vitamin D deficiency group and nondeficiency group depending on the cutoff serum 25(OH)D value of 37 nmol/L. Clinical and biochemical parameters were collected and evaluated for predictors of Vitamin D deficiency by logistic regression. One hundred and fifty-two patients were included in this study, of which 87 (57.2%) were in Vitamin D insufficiency state while 60 (39.5%) were in Vitamin D deficiency state. Serum 25(OH)D levels of patients in Stage 4 and Stage 5 CKD were lower than that of patients in Stage 3 CKD (P = 0.002). It was discovered that female gender (odds ratio [OR] = 3.674; 95% confidence interval [CI], 1.607-8.396; P = 0.002), serum albumin level <30.0 g/L (OR = 6.816; 95% CI, 2.634-17.633; P < 0.001), and estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (OR = 4.761; 95% CI, 1.353-16.754; P = 0.015) were independent predictors of Vitamin D deficiency. Vitamin D insufficiency and deficiency are common in predialysis patients with Stage 3-5 CKD in Southern China. Female gender, hypoalbuminemia with serum albumin level <30.0 g/L, and severe damaged renal function with eGFR <30 ml/min/1.73 m2 are independent predictors of Vitamin D deficiency in predialysis patients with Stage 3-5 CKD.

Evaluation of medication use in Malaysian predialysis patients.

Chronic kidney disease (CKD) patients suffer from multiple comorbidities and complications as a cause or consequence of kidney disease. Information regarding medication- prescribing patterns in predialysis patients is sparse. We conducted a retrospective study to evaluate the medication prescription patterns among predialysis patients. Medical records (both paper based and computerized) of patients at CKD Resource Centre, Hospital Universiti Sains Malaysia, were reviewed. A total of 615 eligible cases were included in the study. The mean number of medications prescribed per patient was 8.22 ± 2.81, and medication use was correlated to the renal function (stage 3a < stage 3b < stage 4 < stage 5; P <0.001). The top three prescribed medication groups were found to be lipid-lowering agents, calcium channel blockers, and antiplatelet agents. Some medication classes such as nonaluminum/noncalcium phosphate binders, erythropoietin-stimulating agents, and renin-angiotensin-aldosterone system blockers, particularly in advanced stage, were found to be underutilized. In conclusion, predialysis patients are prescribed a large number of medications. Our findings highlight the need for assessing the impact of current medication-prescribing patterns on morbidity and mortality rates in Malaysian predialysis population.

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus.

This study investigated the risk of non-melanoma skin cancer (NMSC) in pre-dialysis patients with chronic kidney disease (CKD) and explored associated risk factors. A population-based cohort of 1,515,858 Taiwanese CKD patients was included. The standardized incidence ratio (SIR) for incident NMSC was determined. Compared with the general population, a 1.14-fold risk of NMSC was found in the CKD cohort. NMSC risk was significant in patients with pre-dialysis stage 5 CKD and anaemia (1.48-fold), and in those with uraemic pruritus after long-term antihistamine treatment (1.38-fold). A higher SIR for NMSC was found in younger patients with CKD (age < 70 years, 1.34-fold; age 20-39 years, 1.63-fold), stage 5 CKD with anaemia (age < 70 years, 2.09-fold), and uraemic pruritus (age <70 years, 2.22-fold). Pre-dialysis patients with CKD are at higher risk of NMSC, especially those with advanced-stage CKD, and those with uraemic pruritus.

A comparison of anxiety and depression between pre-dialysis chronic kidney disease patients and hemodialysis patients using hospital anxiety and depression scale.

Objective:Tocompare frequency of anxiety and depression between pre-dialysis chronic kidney disease (CKD) and hemodialysis patients (ESRD) in Pakistan.Methods:This study was conducted in an out-patient department and hemodialysis unit of Sharif Medical City Hospital. Inclusion criteria included age above 18 years and a diagnosis of CKD including both pre-dialysis CKD and ESRD patients. Patients were screened for anxiety and depression using hospital anxiety and depression scale (HADS).Results:A total of 156 patients were included in the study. Out of these patients, 81 (51.9%) had ESRD and 75 (48.1%) had pre-dialysis CKD. Mean age of all patient was 47.3±18.3 years, 96 (61.5%) were males and 60 (38.5%) were females. Median duration of renal disease was 16 months (IQR 8-36 months). Anxiety and depression were present in 111 (71.2%) and 113 (72.4%) of all patients respectively. Moderate to severe anxiety and depression were present in 54 (34.6%) and 60 (38.5%) patients respectively. In multiple logistic regression model, after adjusting for other variables, ESRD vs. pre-dialysis CKD was significantly associated with moderate to severe depression (AOR 2.26 (1.1-5.1).Conclusion:Both anxiety and depression are common in pre-dialysis CKD and ESRD patients. Patients with ESRD have higher frequency of depression compared to pre-dialysis CKD patients.

Relationship of insulin resistance to vitamin d status in children with nondiabetic chronic kidney disease.

Insulin Resistance is common in patients with mild-to-moderate stage chronic kidney disease (CKD), even when the glomerular filtration rate is within the normal range. This study aimed to investigate the association of IR and 25-hydroxyvitamin D levels. In this study, we evaluated the frequency of IR in predialysis patients and the association with 25-hydroxyvitamin (OH)D levels. A total of 32 non-diabetic patients with predialysis were included in the study. Homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated to show presence of IR. Data were analyzed with the Statistical Package for the Social Sciences (SPSS) program version 13.0 (SPSS Inc, Chicago, Ill, USA) using the Chi-square, Student t-test, and logistic regression analysis. Nineteen of 32 subjects (59.4%) were detected to have IR. There was no consistent relationship was detected between IR and glomerular filtration rate, body mass index, and blood pressure in chronic kidney disease (CKD). However; significant difference was detected in 25(OH)D levels with IR in CKD (P = 0.49). The regression analysis showed that 25(OH)D was an independent predictor of IR with an odds ratio of 1.2. In our study, we demonstrated that IR was high in different stages of CKD. Insulin-resistance in non-diabetic CKD was correlated with 25(OH)D levels. 25(OH) vitamin D levels can play a significant role in the development of IR in pediatric patients with CKD. This is important for the early detection and intervention of vitamin D deficiency thereby preventing potentially future complications related to IR.

Plasma Renin Response to Treadmill Exercise in Secondary Hypertension Kidney Disease Patients

Inhibition of renin activity has long been considered to be the logical step to interrupt the renin angiotensin aldosterone system which becomes the cornerstone to retard the progression of Chronic Kidney Disease. Currently, little is known about the impact of aerobic exercise on the plasma renin in chronic kidney disease patients. Aim of this study was to investigate the influence of aerobic exercise on plasma renin in the chronic kidney disease patients with secondary hypertension. Forty chronic kidney disease patients aged 40-55 years were randomly assigned to study group and control group. Study group performed moderate intensity aerobic exercise on an electronic treadmill for 30 minutes, 3 times per week, for 8 weeks. Control group received their medication only and no changes in their life style during the same trail period. The mean values for patients in groups A and B after the study were as following: For Plasma renin level (0.82 ± 0.214) and (2.09 ± 0.468) respectively, for systolic blood pressure (152.1 ± 4.86) and (155.8 ± 5.16) mmHg respectively, for diastolic blood pressure (95 ± 3.81) and (102.6 ± 6.93) mmHg respectively and for 6-minute walk test speed (1.83 ± 0.07) and (1.68 ± 0.06) m/s respectively. There were significant differences between two groups in their Plasma renin level and blood pressure (systolic and diastolic) and 6-minute walk test speed after the study. It was concluded that moderate aerobic exercise resulted in improved kidney functions with chronic kidney disease in pre-dialysis patients as reducing plasma renin and improving the blood pressure with non-significant negative weak correlation between Plasma renin level and blood pressure and a significant moderate negative correlation between exercise improvement and plasma renin.

新型PHD抑制剂类口服抗贫血药物分子的计算机辅助设计

目的：以目标靶蛋白为研究对象设计一系列可口服的抗贫血类化学药物分子结构。方法：本文针对肾性和肿瘤相关性贫血设计口服小分子治疗药物。贫血，特别是糖尿病性贫血治疗领域是一个非常有前景的市场。HIF-PHD抑制剂作为新型治疗贫血药物，可从注射用促红细胞生成药物, 尤其是透析前慢性肾病患者中获取较大的市场份额。更重要的是，由于这类药物可作为对现有促红细胞生成药物治疗无效或因故不能使用、或因价格太贵而未使用人群的一种新的、有效的替代治疗选择，故也具显著拓展贫血治疗市场规模的潜力。通过对已知有活性的化合物的结构特性以及与靶蛋白的作用机制为基础进行研究，设计合成出治疗效果更好的、副作用更小的潜在治疗贫血的口服药物，在贫血治疗领域必将占有一席之地。采用计算机辅助药物设计将理论计算和实际试验相结合，通过计算机的模拟、计算和预算药物与受体生物大分子之间的关系，设计和优化脯氨酸羟化酶抑制剂类先导化合物。采用体外模拟试验进行理论验证，以期对发现新的具有更大的潜在活性药物提供较大的应用价值。结果：设计出一系列以吲哚为母核结构的化合物分子，通过分子对接从理论上证实其中一些分子化合物为潜在的活性化合物。结论：为新型口服抗贫血化学药物的开发奠定了一定的理论基础。 A series of small molecule compound structures oral administration anti-anemia drugs were de-signed based on target protein. Small molecule drug designed in this project is targeted at renal and cancer related anemia. Anemia treatment field, especially diabetic anemia, is a very promising market. As a new kind of anemia inhibitor, HIF-PHD inhibitors could obtain a larger market share from erythropoietic drugs for injection, especially pre-dialysis patients with chronic kidney diseases. More importantly, this kind of drugs could be used as a new, effective replacement therapy for those patients that could not be treated by the existing erythropoietic drugs for that the drugs are invalid for them, or cannot be used for them for some other reasons, or too expensive for them to afford to. So, the potential drugs with better therapeutic effects, less adverse effects, and oral administration developed on the basis of structural characteristic of known active compound and its mechanism of action with target proteins, are doomed to hold a place in the field of anemia treatment. By com-bining theoretical calculation and practical test together via computer aided drug design, with the computer’s simulation, calculation and estimation on the relationship between drugs and biological receptor molecules, this project starts from designing and optimizing the leading compounds of proline hydroxylase inhibitors, then carrying out In Vitro experiments to verify the theoretical ac-tivity, which is of great application value for discovering greater potential active agents. Result: A series of compounds with indole as the parent nucleus structure were designed and some molecular compounds were theoretically confirmed by molecular docking as potential reactive compounds. Conclusion: It has laid a theoretical foundation for the development of new oral anti-anemia drugs.

SERUM PROCALCITONIN LEVELS IN PATIENTS WITH END-STAGE RENAL DISEASE (ESRD)

Background: Although procalcitonin (PCT) has been described as a new marker of inflammation in dialysis patients, it has not been studied in patients with end-stage renal disease (ERSD) in Viet Nam. The objective of this study was to evaluate: serum PCT levels in patients with ERSD and its association to other inflammation (hs-CRP, IL-6) and nutritional (albumin, prealbumin, BMI) factors and the cardiovascular disease (CVD) events (heart failure, cerebrovascular disease, coronary heart disease, urgence hypertension) after 1-year follow-up. Subjects and methods: A total of 174 patients without infection (include: 57 predialysis patients, 56 continuous ambulatory peritoneal dialysis patients, 61 hemodialysis patients) were enrolled. Inflammatory markers (PCT, hs-CRP, IL-6) and nutritional parameters (albumin, prealbumin, BMI) were determined. CVD events (heart failure, cerebrovascular disease, coronary heart disease, urgence hypertension) were evaluated during 12 months of follow-up. Results: The median baseline serum PCT levels of them were 0.44 ng/ml (0.23 – 0.98). Of them, 79 patients (45.4%) had baseline serum PCT levels of over 0.5 ng/ml, which is the cut-off point suggestive of sepsis in non-dialytic individuals. Hemodialysis patients was associated with significantly higher PCT values than predialysis and peritoneal dialysis patients. The patients with elevated PCT plasma levels had the BMI lower. PCT and IL-6 were positively correlated with each other. Compared to patients with serum PCT levels of under 0.5 ng/ml, patients with serum PCT levels of over 0.5 ng/ml had an increased CVD risk in 12 months of follow-up (HR: 2.09; 95% CI: 1.31-3.33; p=0.002). Conclusion: In the absence of infection, PCT may increase due to reduced renal elimination and increased synthesis. Furthermore, serum PCT could serve as a marker of low-grade inflammation, which substantially increase CVD events risk in patients with ERSD. Keywords: Procalcitonin, end-stage renal disease

Assessment of abdominal aortic calcification in predialysis chronic kidney disease and maintenance hemodialysis patients.

Vascular calcification is associated with increased morbidity and mortality among chronic kidney disease (CKD) patients. The aim of the study was to assess the abdominal aortic calcification (AAC) in predialysis CKD patients and patients on hemodialysis (HD) and to study the risk factors associated with it. In this prospective study, 205 patients were including 104 patients with predialysis CKD and 101 patients were on maintenance hemodialysis. AAC was assessed using lateral lumbar radiography. Blood urea nitrogen, serum creatinine, albumin, calcium, phosphorus, highly sensitive C-reactive protein (hsCRP) and total cholesterol were analyzed. AAC was observed in 26 % of predialysis CKD patients and 34% in HD patients. Using multivariate analysis, the age (P = 0.001) was identified as independent predictor for the presence of AAC in predialysis patients, and for HD, the predictors were age (P = 0.025), time on dialysis (P = 0.001), hsCRP (P = 0.002), and corrected calcium (P = 0.030). In conclusion, the prevalence of AAC varies mainly with age and glomerular filtration rate levels in predialysis CKD patients. Advanced age, time on dialysis, and inflammation may be associated with presence and extent of AAC in HD patients. Further research into the risk factors and outcome for AAC is warranted.

B type natriuretic peptide and troponin T as independent predictors of cardiovascular mortality in predialysis patients with chronic kidney disease

The use of cardiac biomarkers in prognostic purposes has been widely studied in the general population and the population of hemodialysis patients but not in patients with early-stage chronic kidney disease (peptide (BNP), N-terminal fragment of BNP (NTproBNP-a), troponin T (TnT), troponin I (TnI) CKD). The aim of this study was to determine the prognostic value of cardiac biomarkers [B-type natriuretic and highly sensitive C-reactive protein (hsCRP -a)] for cardiovascular mortality in asymptomatic predialysis CKD patients, stage IV and V. The study included 61 CKD patients (34 M, average age 62.6 ± 13.6 years, GFR 15.8±5.7 ml/min). All subjects underwent clinical evaluation, laboratory testing, echocardiographic examination and carotid artery ultrasound examination of the carotid arteries. During the period of follow-up (median 28 months), there were 18 deaths of which 9 were cardiovascular in origin. In a multivariate Cox regression analysis, BNP (p = 0.004), aortic calcification (p = 0.005), the TnT (0.018) and serum urea (p = 0.046) showed the independent predictive value for cardiovascular mortality. The optimal cut-off value of BNP for predicting _ cardiovascular mortality rate was 220.8 pg/ml. with a sensitivity of 85.7% and specificity of 78% (AUC = 0.831; p = 0.005) while the TnT cut off value of 0.05 ng / ml was also found to be significant with a sensitivity of 77.8% and a specificity of 78.8% (AUC = 0.798; p = 0.005). In stratified analysis, Kaplan-Meier curves showed _statistically significant differences in cardiovascular survival in patients with different levels of BNP (p = 0.024), TnT (p = 0.001) and NTproBNP (p = 0.033). As independent predictors of cardiovascular mortality, BNP and TnT can be used to stratify CV risk in asymptomatic patients with advanced HBS who have not started dialysis treatments yet.

Association of Pentraxin-3, Galectin-3 and Matrix Metalloproteinase-9/Timp-1 with Cardiovascular Risk in Renal Disease Patients.

Inflammation, apoptosis and extracellular remodeling play significant roles in cardiovascular disease (CVD) underlying the major causes of mortality in renal patients. In 19 pre-dialysis patients, 21 dialysis patients and 20 control subjects, the concentrations of pentraxin-3, galectin-3, MMP-9 and TIMP-1 were determined by ELISA. CVD risk was calculated according to the Framingham risk score algorithm. Pentraxin-3 was increased in renal patients compared to healthy controls (p<0.001). In contrast, galectin-3 was reduced in hemodialysis patients compared to pre-dialysis patients and controls (p<0.001). In addition, MMP-9 and TIMP-1 were elevated in renal patients compared to controls (p<0.01 and p<0.001, respectively). Logistic regression analyses disclosed associations of galectin-3, MMP-9, pentraxin-3 and glomerular filtration with calculated CVD risk score. Combined testing of pentraxin-3, galectin-3, MMP-9 and glomerular filtration rate can discriminate renal patients with high and low risk of a coronary event.