Iron Metabolism in Patients Undergoing Regular Dialysis Therapy

Thirteen patients with chronic renal failure maintained on regular renal dialysis were studied. Seven proved to have iron deficiency on the basis of marrow iron studies, reticulocyte iron uptake, and saturation of the serum iron-binding capacity. They absorbed iron when given it by mouth and were able to utilize it for haemoglobin formation. Iron-deficient patients given 600 mg of ferrous sulphate daily for three months showed an increase in haemoglobin, but the failure to replace stores of iron is probably related to their relatively limited ability to absorb iron and the variable but sometimes considerable blood loss occurring with each dialysis.The loss may be occult, and prolonged iron therapy may be required. This is most safely achieved by giving iron by mouth.     

White blood count in patients on regular haemodialysis

Total white cell, neutrophil, and lymphocyte counts were compared in patients with chronic renal failure treated successively by conservative means (low-protein diet), regular haemodialysis, and renal allotransplantation. The lowest total white cell and neutrophil counts and the highest lymphocyte counts were found in patients on regular haemodialysis. A rapid fall in neutrophil count during the first half-hour of dialysis and a more gradual fall between the first and sixth hours were observed. Adherence of neutrophils and mononuclear cells to the cuprophane (PT 150) dialysis membrane has been shown.     

腹膜透析病人的预后影响因素

在我国,终末期肾脏病的发病率逐年增加,相应地,腹膜透析病人的数量也在不断增长。明确腹膜透析病人预后的影响因素是临床医师亟待解决的重要课题。尿毒症毒素的积蓄可对腹膜透析病人的心血管系统产生不良作用,影响病人的生活质量。腹膜透析充分性的相关指标对于预测病人的生存率也有一定的指导意义。此外,腹膜炎的发生可使超滤量明显下降,增加病人的死亡率。合并症可能通过加重病人的营养不良状态、促进炎症水平,影响病人的预后。因此,重视病人的尿毒症毒素水平、透析充分性指标与合并症情况,积极防治腹膜炎,将有助于改善腹膜透析病人的预后。     

The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry

Background/Aims

Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD).

Methods

Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008.

Results

Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31–1.81 and HR, 1.44; 95% CI, 1.13–1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79–1.65).

Conclusions

Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients.     

Elevated Levels of Procoagulant Plasma Microvesicles in Dialysis Patients

Cardiovascular (CV) death remains the largest cause of mortality in dialysis patients, unexplained by traditional risk factors. Endothelial microvesicles (EMVs) are elevated in patients with traditional CV risk factors and acute coronary syndromes while platelet MVs (PMVs) are associated with atherosclerotic disease states. This study compared relative concentrations of circulating MVs from endothelial cells and platelets in two groups of dialysis patients and matched controls and investigated their relative thromboembolic risk. MVs were isolated from the blood of 20 haemodialysis (HD), 17 peritoneal dialysis (PD) patients and 20 matched controls. Relative concentrations of EMVs (CD144^{+ ve}) and PMVs (CD42b^{+ ve}) were measured by Western blotting and total MV concentrations were measured using nanoparticle-tracking analysis. The ability to support thrombin generation was measured by reconstituting the MVs in normal plasma, using the Continuous Automated Thrombogram assay triggered with 1µM tissue factor. The total concentration of MVs as well as the measured sub-types was higher in both patient groups compared to controls (p<0.05). MVs from HD and PD patients were able to generate more thrombin than the controls, with higher peak thrombin, and endogenous thrombin potential levels (p<0.02). However there were no differences in either the relative quantity or activity of MVs between the two patient groups (p>0.3). Dialysis patients have higher levels of circulating procoagulant MVs than healthy controls. This may represent a novel and potentially modifiable mediator or predictor of occlusive cardiovascular events in these patients.     

The New Comorbidity Index for Predicting Survival in Elderly Dialysis Patients: A Long-Term Population-Based Study

Background

The worldwide elderly (≥65 years old) dialysis population has grown significantly. This population is expected to have more comorbid conditions and shorter life expectancies than the general elderly population. Predicting outcomes for this population is important for decision-making. Recently, a new comorbidity index (nCI) with good predictive value for patient outcomes was developed and validated in chronic dialysis patients regardless of age. Our study examined the nCI outcome predictability in elderly dialysis patients.

Methods and Findings

For this population-based cohort study, we used Taiwan''s National Health Insurance Research Database of enrolled elderly patients, who began maintenance dialysis between January 1999 and December 2005. A total of 21,043 incident dialysis patients were divided into 4 groups by nCI score (intervals ≤3, 4–6, 7–9, ≥10) and followed nearly for 10 years. All-cause mortality and life expectancy were analyzed. During the follow-up period, 11272 (53.55%) patients died. Kaplan-Meier curves showed significant group difference in survival (log-rank: P<0.001). After stratification by age, life expectancy was found to be significantly longer in groups with lower nCI scores.

Conclusion

The nCI, even without the age component, is a strong predictor of mortality in elderly dialysis patients. Because patients with lower nCI scores may predict better survival, more attention should paid to adequate dialysis rather than palliative care, especially in those without obvious functional impairments.     

Changes in Skeletal Mineral in Patients on Prolonged Maintenance Dialysis

The measurement of bone loss in patients undergoing maintenance dialysis over a period of two and a half years is reported. The tendency to lose bone is a likely event in renal failure, but depends more on the individual patient than on the type of dialysis used, provided that steps are taken to prevent avoidable calcium loss during dialysis. Vitamin D therapy was an important factor in preventing bone loss in some cases. The tendency to lose bone more readily when both kidneys were absent may have reflected a deficiency of 1-25 dihydrocholecalciferol. On the other hand, bone loss was also observed in transplanted patients. The need to measure bone loss at regular intervals once renal failure has been diagnosed is stressed.     

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.     

Pediatric Chronic Dialysis in Brazil: Epidemiology and Regional Inequalities

Introduction

There are few reports in the literature estimating the epidemiologic characteristics of pediatric chronic dialysis. These patients have impaired physical growth, high number of comorbidities and great need for continuous attention of specialized services with high demand for complex and costly procedures.

Objective

The aim of this study was to estimate the incidence and prevalence rates and describe the characteristics of children and adolescents undergoing chronic dialysis treatment in a Brazilian demographic health survey.

Materials and Methods

A cross-sectional study was performed in a representative sample of dialysis centers (n^c = 239) that was established from the 2011 Brazilian Nephrology Society Census (N^c = 708). We collected data encompassing the five Brazilian macro-regions. We analyzed the data from all patients under 19 years of age. The sample population consisted of 643 children and adolescents who were on chronic dialysis program anytime in 2012. Data collection was carried out in the dialysis services by means of patients'' records reviews and personal interviews with the centers’ leaders.

Results

We estimated that there were a total of 1,283 pediatric patients on chronic dialysis treatment in Brazil, resulting in a prevalence of 20.0 cases per million age-related population (pmarp) (95% CI: 14.8–25.3) and an incidence of 6.6 cases pmarp in 2012 (95% CI: 4.8–8.4). The South region had the highest prevalence and incidence rates of patients under dialysis therapy, 27.7 (95% CI: 7.3–48.1) and 11.0 (95% CI: 2.8–19.3) cases pmarp, respectively; the lowest prevalence and incidence rates were found in the North-Midwest region, 13.8 (95% CI: 6.2–21.4), and in the Northeast region, 3.8 (95% CI: 1.4–6.3) cases pmarp, respectively.

Conclusion

Brazil has an overall low prevalence of children on chronic dialysis treatment, figuring near the rates from others countries with same socioeconomic profile. There are substantial differences among regions related to pediatric chronic dialysis treatment. Joint strategies aiming to reduce inequities and improving access to treatment and adequacy of services across the Brazilian regions are necessary to provide an appropriate care setting for this population group.     

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.     

Dialysis cultures

Dialysis techniques are discussed as a means for effective removal of low-molecular-mass components from fermentation broth to reach high cell density. Reactor systems and process strategies, the relevant properties of membranes and examples for high-density fermentation with dialysis, and problems related to scale-up are addressed. The dialysis technique has turned out to be very efficient and reliable for obtaining high cell densities. As in dialysis processes the membranes are not perfused, membrane clogging is not a problem as it is for micro- and ultrafiltration. By applying a “nutrient-split” feeding strategy, the loss of nutrients can be avoided and the medium is used very efficiently. The potential of dialysis cultures is demonstrated on the laboratory scale in a membrane dialysis reactor with an integrated membrane and in reactor systems with an external dialysis loop. In dialysis cultures with different microorganisms (Staphylococci, Escherichia coli, extremophilic microorganisms, Lactobacilli) the cell densities achieved were up to 30 times higher than those of other fermentation methods. The technique enables high cell densities to be attained without time-consuming medium optimization. For animal cell cultures the concept of a fixed bed coupled with dialysis proved to be very effective. Received: 24 March 1998 / Received revision: 18 June 1998 / Accepted: 19 June 1998     

Statins Improve the Resolution of Established Murine Venous Thrombosis: Reductions in Thrombus Burden and Vein Wall Scarring

Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins—lipid-lowering agents with anti-thrombotic and anti-inflammatory properties—in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.     

Dialysis fermentation. II. Kinetic analysis of salicylic acid production via cell growth and maintenance

A kinetic analysis was made of the relationship between salicylate production from naphthalene and growth of Pseudomonas fluorescens in semicontinuous dialysis culture. The specific rates both of product formation and growth initially were increased by the diffusional withdrawal of salicylate, but subsequently were reduced to low levels despite continued salicylate removal. Productivity and growth were correlated by the Luedeking-Piret equation in an initial nondialysis period and in the early stages of dialysis fermentation, when specific growth rates exceeded. 005 hr^?1. Below this level of growth at later stages of dialysis fermentation, the specific production rate was correlated only with total cell mass by a proportionality constant of .035 hr^?1, which was attributed to maintenance metabolism. Maintenance accounted for about 84% of the total salicylate produced, while growth-associated metabolism accounted for the remainder.     

乳清蛋白质制剂改善慢性肾功能衰竭透析患者营养状况的效果观察

目的用乳清蛋白质制剂作为蛋白质补充营养制剂,观察其对慢性肾功能衰竭透析患者营养改善的效果。方法 60例接受透析治疗的慢性肾功能衰竭患者,平均年龄(59.3±6.7)岁,随机分为试验组和对照组,每组30例。试验组每天除常规饮食外,按0.6g/kg补充乳清蛋白质制剂,共15 d,对照组为正常治疗饮食。在干预前、后分别检测营养相关的指标。结果根据身高和体重进行营养评价,干预开始前试验组、对照组的患者均有不同程度营养不良,15 d后体重与干预前相比,虽有所改善,但无显著性差异(P>0.05)。体重、上臂肌围、三头肌皮褶厚度在干预后变化均不明显,无显著性差异(P>0.05)。血红蛋白有所升高,但无统计学意义(P>0.05)。干预前后,试验组血清白蛋白、前白蛋白均有升高,前白蛋白与对照组相比有显著性差异(P<0.05)。干预后试验组血清磷与对照组比较无显著性差异(P>0.05)。试验组和对照组血清尿素氮、肌酐在干预后,均降低非常显著(P<0.05)。干预前患者血清氨基酸,特别是必需氨基酸和组氨酸含量降低明显(P<0.05),用乳清蛋白质制剂后血清氨基酸谱有所变化,支链氨基酸-亮氨酸、异亮氨酸和缬氨酸含量明显增高,苏氨酸、酪氨酸、组氨酸也有所升高,其余氨基酸血清含量无明显改变。结论乳清蛋白质制剂对慢性肾功能衰竭透析患者有明显的改善蛋白质营养状况的效果。     

In Vivo Brain Dialysis of Amino Acids and Simultaneous EEG Measurements Following Intrahippocampal Quinolinic Acid Injection: Evidence for a Dissociation Between Neurochemical Changes and Seizures

The extracellular content of taurine, glutamate, glutamine, and glycine was measured by the novel method of brain dialysis in the acute phases following an intrahippocampal injection of the excitotoxic convulsant brain metabolite quinolinic acid (QUIN). Using bilaterally implanted depth electrodes physically combined with hollow fibers for dialysis, it was possible to collect continuously brain perfusates while simultaneously monitoring brain activity in the unanesthetized rat. In separate animals, hippocampal amino acid tissue levels were measured 2 h after an intracerebral injection of a convulsant dose (156 nmol) of QUIN. When compared with those in animals receiving the nonconvulsant decarboxylation product of QUIN, nicotinic acid, no differences in tissue levels were detected. In contrast, the same dose of QUIN caused a selective increase (2.24-fold) in taurine levels in perfusates from the injected hippocampus. These changes were apparent prior to the onset of electrographic seizures and did not occur in the contralateral hippocampus where seizure activity was equally severe. Thus, increases in extracellular taurine, triggered by the presence of QUIN in the hippocampus, may reflect a selective tissue response to the neurotoxic (rather than the convulsant) effects of this excitotoxin.     

A Clinical Evaluation of Peritoneal Dialysis

A total of 18 peritoneal dialyses were performed on 14 patients at the Hamilton Civic Hospital over a period of 11 months. Nine of these patients were in uremia, four had non-nephrotoxic intoxication, and one had hepatic coma. Patients with chronic uremia may present with acute renal failure which may be treated by peritoneal dialysis with resultant significant prolongation of life. A decreased mortality rate might be expected in acute renal failure if dialysis is implemented before the classical picture of uremia develops. Many non-nephrotoxic intoxicating substances are readily dialysable. Considerable benefit to the patient and decreased time in hospital may result from the use of this procedure in cases of intoxication with such substances. Peritoneal dialysis may be of value in treatment of intractable congestive heart failure. This procedure may eventually provide another means of treating hepatic coma.     

Impacto de la modalidad de terapia de reemplazo renal en adultos mayores frágiles

IntroductionEnd-stage renal disease prevalence is increasing in older adults. Frailty is highly prevalent in older adults with end-stage renal disease. However, there are no prospective studies comparing the performance of the different modalities of renal replacement therapy (RRT) in frail older adults.ObjectiveTo compare clinically relevant outcomes (hospital admission, falls, hip fractures, and mortality) in prefrail and frail older adults according to the modality of RRT: peritoneal dialysis or haemodialysis.MethodsA prospective observational study in prefrail and frail older adults (according to FRAIL scale) on peritoneal dialysis and haemodialysis was carried out. An evaluation was made using baseline characteristics (age, Charlson, body mass index, time on RRT, compliance with Kt/V dose, haemoglobin, and albumin). The patients were followed-up over 12 months, recording mortality, days and number of hospital admissions, falls, and hip fractures.ResultsA total of 54/65 (83%) older adults on RRT met criteria for prefrailty or frailty, and signed informed consent (27 in each modality). Baseline characteristics were similar, except for serum albumin and time on RRT, both of which were significantly lower in the peritoneal dialysis group. The FRAIL score was similar in both groups. Baseline FRAIL correlated with higher comorbidity, lower albumin levels, and non-compliance of Kt/V dose, while it was independent of age, body mass index, and time on RRT. Days and number of hospital admissions at 12 months were similar in patients on peritoneal dialysis and haemodialysis. Survival on peritoneal dialysis and haemodialysis was similar. There were no differences in falls or hip fractures.ConclusionsPre-frail and frail older adults on peritoneal dialysis and haemodialysis have similar clinical outcomes.     

Iron Supplementation and Mortality in Incident Dialysis Patients: An Observational Study

Background

Studies on the association between iron supplementation and mortality in dialysis patients are rare and conflicting.

Methods

In our observational single-center cohort study (INVOR study) we prospectively studied 235 incident dialysis patients. Time-dependent Cox proportional hazards models using all measured laboratory values for up to 7.6 years were applied to study the association between iron supplementation and all-cause mortality, cardiovascular and sepsis-related mortality. Furthermore, the time-dependent association of ferritin levels with mortality in patients with normal C-reactive protein (CRP) levels (<0.5 mg/dL) and elevated CRP levels (≧0.5 mg/dL) was evaluated by using non-linear P-splines to allow flexible modeling of the association.

Results

One hundred and ninety-one (81.3%) patients received intravenous iron, 13 (5.5%) patients oral iron, whereas 31 (13.2%) patients were never supplemented with iron throughout the observation period. Eighty-two (35%) patients died during a median follow-up of 34 months, 38 patients due to cardiovascular events and 21 patients from sepsis. Baseline CRP levels were not different between patients with and without iron supplementation. However, baseline serum ferritin levels were lower in patients receiving iron during follow up (median 93 vs 251 ng/mL, p<0.001). Iron supplementation was associated with a significantly reduced all-cause mortality [HR (95%CI): 0.22 (0.08–0.58); p = 0.002] and a reduced cardiovascular and sepsis-related mortality [HR (95%CI): 0.31 (0.09–1.04); p = 0.06]. Increasing ferritin concentrations in patients with normal CRP were associated with a decreasing mortality, whereas in patients with elevated CRP values ferritin levels>800 ng/mL were linked with increased mortality.

Conclusions

Iron supplementation is associated with reduced all-cause mortality in incident dialysis patients. While serum ferritin levels up to 800 ng/mL appear to be safe, higher ferritin levels are associated with increased mortality in the setting of concomitant inflammation.     

Pre-Dialysis Visits to a Nephrology Department and Major Cardiovascular Events in Patients Undergoing Dialysis

Background and Objectives

Pre-dialysis care by a nephrology out-patient department (OPD) may affect the outcomes of patients who ultimately undergo maintenance dialysis. This study examined the effect of pre-dialysis care by a nephrology OPD on the incidence of one-year major cardiovascular events after initiation of dialysis.

Design, Setting Participants, & Measurements

The study consisted of Taiwanese patients with chronic kidney disease (CKD) who commenced dialysis from 2006 to 2008. The number of nephrology OPD visits during the critical care period (within 6 months of initiation of dialysis) and the early care period (6–36 months before initiation of dialysis) were analyzed. The primary outcome measure was one-year major cardiovascular events.

Results

A total of 1191 CKD patients who initiated dialysis from 2006 to 2008 were included. Binary logistic regression showed that patients with ≧3 visits during the critical care period and those with ≧11 visits during the early care period had fewer composite major cardiovascular events than those with 0 visits. Patients with early referral are less likely to experience composite major cardiovascular events than those with late referral, with aOR 0.574 (95% CI = 0.43–0.77, P<0.001). Patients with both ≧3 visits during critical care period and ≧11 visits during early care period were less likely to experience composite major cardiovascular events (aOR = 0.25, 95% CI = 0.16–0.39, P < 0.001).

Conclusions

Patients with adequate pre-dialysis nephrology OPD visits, not just early referral, may had fewer one-year composite major cardiovascular events after initiation of dialysis. This information may be important to medical care providers and public health policy makers in their efforts to improve the well-being of CKD patients.