Antioxidant status and dialysis: Plasma and saliva antioxidant activity in patients with fluctuating urate levels

The present study is concerned with the influence of processes occurring during dialysis on the antioxidant capacity of plasma and saliva. The biological fluids were also tested for uric acid and total protein content. Before hemodialysis, plasma antioxidant status of hemodialyzed patients appears slightly higher than the corresponding status in normal subjects; after hemodialysis it is found unchanged. The result can be explained by a balance between a reduction in uric acid plasma content, due to the dialytic procedure, and an increase in protein content, possibly due to a dialysis-related hemoconcentration. Moreover, pre-dialysis total antioxidant capacity of whole saliva samples is higher than in healthy individuals and drastically decreases towards normal values following dialytic procedure. Our data indicate a certain concentration of the uric acid in the saliva of hemodialyzed patients and evidence that both total protein concentration and uric acid level show a good correlation with saliva total antioxidant capacity, suggesting that proteins are major antioxidants of this fluid. Further observations are needed to assess whether this improved saliva antioxidant ability has any consequence on the periodontal conditions of hemodialyzed subjects.     

高通量血液透析对糖尿病肾病血液透析患者心脏功能及结构的影响及预后的影响因素分析

摘要 目的：探讨高通量血液透析对糖尿病肾病（DN）血液透析患者心脏功能及结构的影响,并分析预后的影响因素。方法：选取2017年5月~2018年11月期间我院收治的DN血液透析患者（n=172）,上述DN血液透析患者中普通透析治疗者60例（普通透析组）、高通量血液透析治疗者112例（高通量透析组）。普通透析组采用低通量透析治疗,高通量透析组采用高通量透析治疗,比较两组患者心脏功能及结构以及预后情况,采用单因素、多因素Logistic回归分析预后的影响因素。结果：高通量透析组治疗6个月后左心房内径（LAD）、左心室舒张末内径（LVDd）、左心室心肌重量指数（LVMI）低于治疗前和普通透析组（P<0.05）,高通量透析组治疗6个月后左心室射血分数( LVEF )高于治疗前和普通透析组（P<0.05）。高通量透析组的生存率高于普通透析组（P<0.05）。存活组年龄、上机前舒张压、上机前收缩压、血磷、全段甲状旁腺激素（iPTH）均低于死亡组（P<0.05）,存活组透析频率、白蛋白、血红蛋白均高于死亡组（P<0.05）,两组性别、血钙比较无差异（P>0.05）。多因素Logistic回归分析结果显示,上机前舒张压高、上机前收缩压高、血磷高、iPTH高、透析频率少、白蛋白低、血红蛋白低均是DN血液透析患者死亡的危险因素（P<0.05）。结论：高通量血液透析能减轻DN患者血液透析所引起的心脏功能及结构损伤,改善患者预后。影响DN血液透析患者预后的因素较多,其中上机前舒张压、上机前收缩压、血磷、iPTH越高,白蛋白、血红蛋白越低,透析频率越少,患者的死亡风险越大。     

Antioxidant status and dialysis: Plasma and saliva antioxidant activity in patients with fluctuating urate levels

The present study is concerned with the influence of processes occurring during dialysis on the antioxidant capacity of plasma and saliva. The biological fluids were also tested for uric acid and total protein content. Before hemodialysis, plasma antioxidant status of hemodialyzed patients appears slightly higher than the corresponding status in normal subjects; after hemodialysis it is found unchanged. The result can be explained by a balance between a reduction in uric acid plasma content, due to the dialytic procedure, and an increase in protein content, possibly due to a dialysis-related hemoconcentration. Moreover, pre-dialysis total antioxidant capacity of whole saliva samples is higher than in healthy individuals and drastically decreases towards normal values following dialytic procedure. Our data indicate a certain concentration of the uric acid in the saliva of hemodialyzed patients and evidence that both total protein concentration and uric acid level show a good correlation with saliva total antioxidant capacity, suggesting that proteins are major antioxidants of this fluid. Further observations are needed to assess whether this improved saliva antioxidant ability has any consequence on the periodontal conditions of hemodialyzed subjects.     

Optimum Calcium Concentration of Dialysis Fluid for Maintenance Haemodialysis

To define the minimum and maximum levels for calcium concentration of dialysis fluid a combination of acute and long-term observations was carried outIn acute experiments the external calcium balance during dialysis was dependent on the gradient between plasma ultrafilterable calcium and dialysis fluid calcium concentration. Changes in plasma calcium during dialysis did not correlate with measured external balance.In long-term studies it was found that raising the dialysis fluid calcium concentration from 5.0 to 6.0 mg./ 100 ml. both arrested biochemical and radiological changes of hyperparathyroidism, and, by causing a progressive fall in plasma phosphates, made metastatic calcification less likely. Raising the concentration to 6.5 mg./lOO ml. in an attempt to compensate for negative alimentary calcium balance caused nausea and vomiting in some patients.A concentration of 6.0±0.2 mg./100 ml. is recommended.     

Erythrocyte glutathione transferase: a new biomarker for hemodialysis adequacy,overcoming the Kt/Vurea dogma?

Kt/V_urea ratio is commonly used to assess the delivered dose of dialysis in maintenance hemodialysis (MHD) patients. This parameter only reflects the efficacy of dialytic treatments in removing small toxins, but not middle and protein-bound toxins. Erythrocyte glutathione transferase (e-GST), an enzyme devoted to cell depuration against a lot of large and small toxins, is overexpressed in uremic patients. Aim of the present study is to verify whether e-GST may represent a novel biomarker to assess the adequacy of different dialytic techniques complementary to Kt/V_urea parameter. Furthermore, it will be investigated whether e-GST could reflect the ‘average'' adequacy of multiple dialytic sessions and not of a single one treatment as it occurs for Kt/V_urea. One hundred and three MHD patients and 82 healthy subjects were tested. Fourty four patients were treated with standard bicarbonate hemodialysis (HD) and 59 patients were on online hemodiafiltration (HDF). In all MHD patients e-GST activity was 60% higher than in healthy controls. In HDF, e-GST activity was lower than in HD subgroup (8.2±0.4 versus 10.0±0.4 U/g_Hb, respectively). Single-pool Kt/V_urea and total weekly Kt/V_urea were higher in HDF than in HD, but no correlation was found between e-GST activity and Kt/V_urea data. e-GST, whose level is stable during the erythrocyte life-span, provides information on the long-term depurative efficacy of dialysis treatments.     

血液透析和腹膜透析对终末期肾病患者预后的影响及其安全性比较

目的:分析和比较血液透析和腹膜透析终末期肾病患者预后的影响及其安全性。方法:选取2010年1月至2016年4月本医院收治的透析患者246例作为研究对象,将其分为血液透析组和腹膜透析组,比较两组患者治疗后的生存情况及并发症的发生情况。结果:两组患者死亡原因是心力衰竭、消化道出血、重度感染、脑梗死,两组的病死率及死因构成比较差异均无统计学意义(P0.05)。腹膜透析组患者1年、3年、5年生存率均显著高于血液透析组(P0.05),两组患者7年生存率比较差异无统计学意义(P0.05)。首次透析年龄超过60岁的终末期肾病患者中,腹膜透析组1年、3年、5年、7年生存率均显著低于血液透析组(P0.05)。血液透析组心力衰竭、动静脉内瘘闭塞发生率显著高于腹膜透析组(P0.05),腹膜透析组腹膜炎的发生率显著高于血液透析组(P0.05),血液透析组总并发症发生率明显高于腹膜透析组(P0.05)。结论:血液透析和腹膜透析各有优缺点,对终末期肾病患者应个体化选择透析方式,减少并发症,提高生活质量及生存率。     

Changes in Plasma Copeptin Levels during Hemodialysis: Are the Physiological Stimuli Active in Hemodialysis Patients?

ObjectivesPlasma levels of copeptin, a surrogate marker for the vasoconstrictor hormone arginine vasopressin (AVP), are increased in hemodialysis patients. Presently, it is unknown what drives copeptin levels in hemodialysis patients. We investigated whether the established physiological stimuli for copeptin release, i.e. plasma osmolality, blood volume and mean arterial pressure (MAP), are operational in hemodialysis patients.MethodsOne hundred and eight prevalent, stable hemodialysis patients on a thrice-weekly dialysis schedule were studied during hemodialysis with constant ultrafiltration rate and dialysate conductivity in this observational study. Plasma levels of copeptin, sodium, MAP, and blood volume were measured before, during and after hemodialysis. Multivariate analysis was used to determine the association between copeptin (dependent variable) and the physiological stimuli plasma sodium, MAP, excess weight as well as NT-pro-BNP immediately prior to dialysis and between copeptin and changes of plasma sodium, MAP and blood volume with correction for age, sex and diabetes during dialysis treatment.ResultsPatients were 63±15.6 years old and 65% were male. Median dialysis vintage was 1.6 years (IQR 0.7–4.0). Twenty-three percent of the patients had diabetes and 82% had hypertension. Median predialysis copeptin levels were 141.5 pmol/L (IQR 91.0–244.8 pmol/L). Neither predialysis plasma sodium levels, nor NT-proBNP levels, nor MAP were associated with predialysis copeptin levels. During hemodialysis, copeptin levels rose significantly (p<0.01) to 163.0 pmol/L (96.0–296.0 pmol/L). Decreases in blood volume and MAP were associated with increases in copeptin levels during dialysis, whereas there was no significant association between the change in plasma sodium levels and the change in copeptin levels.ConclusionsPlasma copeptin levels are elevated predialysis and increase further during hemodialysis. Volume stimuli, i.e. decreases in MAP and blood volume, rather than osmotic stimuli, are associated with change in copeptin levels during hemodialysis.     

Clinical course of uremic neuropathy in long-term hemodialysis

One hundred and thirty-one patients on long-term hemodialysis were examined for the presence of clinical symptoms and signs, and for the effects of dialytic age, age and sex on uremic neuropathy. According to dialysis age, the patients were divided into three subgroups: low dialysis age, < 5 years of dialysis (n = 58); intermediate dialysis age, 5-10 years of hemodialysis (n = 39); and high dialysis age, > 10 years of dialysis (n = 34). Two patient subgroups were differentiated according to mean age of 53.2 years: younger (n = 57) and older (n = 74). Clinical grading of uremic neuropathy was based on Nielsen's criteria. The most common symptoms were restless legs syndrome (47%) and cramps (51%). Sensory symptoms were less common in patients on long-term hemodialysis, most common of them being paresthesia (29%) and burning feet syndrome (28%). Abnormal Achilles reflex (53%) and impaired vibration sense (59%) were the most common clinical signs. Clinically manifested uremic neuropathy was present in more than 80% of all study patients, i.e. mild in 41%, and moderate to severe forms of uremic neuropathy according to Nielsen's criteria in 39%. There was no evident effect of dialytic age and sex on the clinical course of uremic neuropathy, however, there was a clear impact of age. It is concluded that long-term hemodialysis does not influence the clinical course of uremic neuropathy unlike evident deterioration of electroneurophysiologic findings.     

Beta2-microglobulin removal by extracorporeal renal replacement therapies

There is increasing evidence that end-stage renal disease patients with lower beta₂-microglobulin plasma levels and patients on convective renal replacement therapy are at lower mortality risk. Therefore, an enhanced beta₂-microglobulin removal by renal replacement procedures has to be regarded as a contribution to a more adequate dialysis therapy. In contrast to high-flux dialysis, low-flux hemodialysis is not qualified to eliminate substantial amounts of beta₂-microglobulin. In hemodialysis using modern high-flux dialysis membranes, a beta₂-microglobulin removal similar to that obtained in hemofiltration or hemodiafiltration can be achieved. Several of these high-flux membranes are protein-leaking, making them suitable only for hemodialysis due to a high albumin loss when used in more convective therapy procedures. On-line hemodiafiltration infusing large substitution fluid volumes represents the most efficient and innovative renal replacement therapy form. To maximize beta₂-microglobulin removal, modifications of this procedure have been proposed. These modifications ensure safer operating conditions, such as mixed hemodiafiltration, or control albumin loss at maximum purification from beta₂-microglobulin, such as mid-dilution hemodiafiltration, push/pull hemodiafiltration or programmed filtration. Whether these innovative hemodiafiltration options will become accepted in clinical routine use needs to be proven in future.     

80例血液透析患者上尿路结石患病率及危险因素分析

摘要 目的：分析血液透析患者上尿路结石的患病率及其危险因素,为早期干预提供依据。方法：回顾性分析2017年1月至2018年12月我院肾内科收治的CKD 5期持续性血液透析患者（血液透析组）上尿路结石的患病情况,并与健康体检者80名（对照组,n=80）、CKD1~3期患者（非血液透析组,n=80）进行比较。比较血液透析患者中结石和非结石者人口学资料、血清白蛋白、血糖、血脂、肾功能等生化指标,并记录二者透析时间及24 h尿量。采用多因素logistic回归分析上尿路结石的患病情况的危险因素。结果：血液透析组上尿路结石患病率为25.0%,显著高于非血液透析组13.8%、对照组10.0%(P<0.05);非血液透析组、对照组上尿路结石患病率比较,差异无统计学意义(P>0.05)。结石与非结石患者在性别、透析时间、TG、TC、UA、ALB、24 h尿量方面比较,差异均有统计学意义（P<0.05）。多因素logistic回归分析显示,透析时间、UA、TC是血液透析患者发生上尿路结石的独立危险因素,而ALB则是保护性因素（P<0.05）。结论：血液透析患者上尿路结石的患病率较高,对血脂代谢异常、高血UA、低血清ALB及长期透析者应早期筛查,并纠正脂代谢紊乱和低蛋白血症。     

Protein-Bound Uremic Toxin Profiling as a Tool to Optimize Hemodialysis

Aim

We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage.

Methods

This study included 10 patients on standard (3x4h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V₁), total distribution volume (V_tot) and intercompartment clearance (K₂₁). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies.

Results

Dialyzer clearance K, V₁ and V_tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K₂₁was 2.7–5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3x4h dialysis at 300mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated.

Conclusion

When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal.     

Calcium Acetate or Calcium Carbonate for Hyperphosphatemia of Hemodialysis Patients: A Meta-Analysis

Background

High levels of serum phosphorus both at baseline and during follow-up are associated with increased mortality in dialysis patients, and administration of phosphate binders was independently associated with improved survival among hemodialysis population. Calcium-based phosphate binders are the most commonly used phosphate binders in developing countries for their relatively low costs.

Objectives

To compare the efficacy and safety between calcium carbonate and calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.

Methods

PubMed, EMBASE, Cochrane Library, Google scholar and Chinese databases (Wanfang, Weipu, National Knowledge Infrastructure of China) were searched for relevant studies published before March 2014. Reference lists of nephrology textbooks and review articles were checked. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of calcium acetate and calcium carbonate in adult patients with MHD was performed using Review Manager 5.0.

Results

A total of ten studies (625 participants) were included in this meta-analysis. There was insufficient data in all-cause mortality and cardiovascular events for meta-analysis. Compared with calcium carbonate group, the serum phosphorus was significantly lower in calcium acetate group after4 weeks’ administration (MD -0.15 mmol/L, 95% CI -0.28 to -0.01) and after 8 weeks’ administration (MD -0.25 mmol/L, 95% CI -0.40 to -0.11). There was no difference in serum calcium levels or the incidence of hypercalcemia between two groups at 4 weeks and 8 weeks. No statistical difference was found in parathyroid hormone (PTH) levels or serum calcium by phosphorus (Ca x P) product. There was significantly higher risk of intolerance with calcium acetate treatment (RR 3.46, 95% CI 1.48 to 8.26).

Conclusions

For hyperphosphatemia treatment, calcium acetate showed better efficacy and with a higher incidence of intolerance compared with calcium carbonate. There are insufficient data to establish the comparative superiority of the two calcium-based phosphate binders on all-cause mortality and cardiovascular end-points in hemodialysis patients.     

Factors affecting the reaggregation of rat brain microsomes solubilized with octyl glucoside and their relationship with the base-exchange activity of reaggregates

Rat brain microsomal membranes disaggregated by exposure to octyl glucoside were recovered by centrifugation after dialytic removal of the detergent. The composition of the dialysis medium (divalent cations, pH) was important to this effect; indeed, the reaggregation process which occurred during the dialytic step required the presence of either Ca²⁺ or Mg²⁺ and a slightly acidic pH. The lipid protein/ratio and choline and ethanolamine base-exchange of recovered particles depended on the conditions of dialysis although their lipid composition did not. The lipid composition of membranes was also varied by adding PE or PC to octyl glucoside-microsome suspensions. This treatment produced reaggregates possessing a low content of cholesterol and varying PC/PE ratios. Both choline and ethanolamine base-exchange activities were related to this parameter.     

Intraperitoneal Insulin for Control of Blood Sugar in Diabetic Patients during Peritoneal Dialysis

We have added insulin to peritoneal dialysis fluid in three uraemic diabetic patients. The hyperglycaemia and pronounced fluctuations in blood glucose which complicate peritoneal dialysis in diabetic subjects have not occurred with this technique. Studies with ¹³¹I-labelled insulin showed that less than 5% of the intraperitoneally administered insulin was absorbed during a one-hour exchange. While the physiology of the procedure needs further evaluation, this procedure has reduced the morbidity of peritoneal dialysis in diabetic patients and made its management easier.     

Potassium Balance and Acid-Base Changes in Patients Undergoing Regular Haemodialysis Therapy

Serial measurements of total body potassium in 21 patients with chronic renal failure being treated with three 10-hour periods of dialysis per week, against a dialysate fluid containing 1·5 mEq of potassium per litre, showed no evidence of potassium depletion. Mild hyperkalaemia was found in some patients before dialysis, correlated with the pre-dialysis hydrogen ion concentration. Hypokalaemia occurred during dialysis in almost half of the studies made; the plasma potassium concentration, however, rose to normal levels within two to four hours of stopping dialysis. A delay in the movement of potassium from the cells into the extracellular fluid is suggested as a cause for the observed hypokalaemia.In all but one patient the pre-dialysis blood pH was normal, but rose to alkalaemic levels during dialysis. A pronounced degree of hypocapnia was noted before dialysis, and this was not altered by a rising blood pH during dialysis. It is suggested that a stimulus to respiration other than the hydrogen ion gradient between the brain cells and cerebral spinal fluid may produce the observed hypocapnia.     

Intracellular calcium in the cells of the outer mantle epithelium of Anodonta cygnea

• 1.1. The intracellular concentration of ionized calcium was measured with double-barrelled ion-sensitive microelectrodes under short-circuit conditions in the isolated outer mantle epithelium of Anodonta cygnea.
• 2.2. When the outside baths contained 1 mmol/1 Ca²⁺ the average intracellular Ca²⁺ was 5.42 ± 0.64 mmol/1(N = 41) while the equilibrium concentration estimated from the intracellular potential measured in the same cells was 5.51 ± 0.33 mmol/l.
• 3.3. Bilateral removal of calcium from the external baths induced a fast fall in the intracellular concentration of this ion by almost three orders of magnitude. This effect was similar to that obtained by removing calcium from the bath on the basolateral side.
• 4.4. Removal of calcium from the bath in contact with the apical side of the preparation had little effect on intracellular calcium.

     

Urgent-Start Peritoneal Dialysis and Hemodialysis in ESRD Patients: Complications and Outcomes

BackgroundSeveral studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients.MethodsIn this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups.ResultsOur study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate.ConclusionIn an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.     

Determinants of Compliance Behaviours among Patients Undergoing Hemodialysis in Malaysia

Background

Patients with end stage renal disease often fail to follow prescribed dietary and fluid regimen, leading to undesirable outcomes. This study aimed to examine and identify factors influencing dietary, fluid, medication and dialysis compliance behaviours in patients undergoing hemodialysis.

Methods

This was a cross-sectional study which employed purposive sampling design. A total of 188 respondents were recruited from 14 dialysis centres in Malaysia between 2008–2011. Self-reported compliance behaviours and biochemical measurements were used as evaluation tools.

Results

Compliance rates of dietary, fluid, medication and dialysis were 27.7%, 24.5%, 66.5% and 91.0%, respectively. Younger, male, working patients and those with longer duration on hemodialysis were found more likely to be non-compliant. Lacks of adequate knowledge, inadequate self-efficacy skills, forgetfulness and financial constraints were the major perceived barriers towards better compliance to fluid, dietary, medication and dialysis, respectively.

Conclusions

Healthcare professionals should recognise the factors hindering compliance from the patients'' perspective while assisting them with appropriate skills in making necessary changes possible.