Type of Referral, Dialysis Start and Choice of Renal Replacement Therapy Modality in an International Integrated Care Setting.

INTRODUCTION: Integrated Care Settings (ICS) provide a holistic approach to the transition from chronic kidney disease into renal replacement therapy (RRT), offering at least both types of dialysis. OBJECTIVES: To analyze which factors determine type of referral, modality provision and dialysis start on final RRT in ICS clinics. METHODS: Retrospective analysis of 626 patients starting dialysis in 25 ICS clinics in Poland, Hungary and Romania during 2012. Scheduled initiation of dialysis with a permanent access was considered as planned RRT start. RESULTS: Modality information (80% of patients) and renal education (87%) were more frequent (p<0.001) in Planned (P) than in Non-Planned (NP) start. Median time from information to dialysis start was 2 months. 89% of patients started on hemodialysis, 49% were referred late to ICS (<3 months from referral to RRT) and 58% were NP start. Late referral, non-vascular renal etiology, worse clinical status, shorter time from information to RRT and less peritoneal dialysis (PD) were associated with NP start (p<0.05). In multivariate logistic regression analysis, P start (p≤0.05) was associated with early referral, eGFR >8.2 ml/min, >2 months between information and RRT initiation and with vascular etiology after adjustment for age and gender. "Optimal care," defined as ICS follow-up >12 months plus modality information and P start, occurred in 23%. CONCLUSIONS: Despite the high rate of late referrals, information and education were widely provided. However, NP start was high and related to late referral and may explain the low frequency of PD.

Pharmacovigilance as a tool for safety and monitoring: a review of general issues and the specific challenges with end-stage renal failure patients.

Pharmacovigilance is instrumental in helping to ensure patient safety for both newly released drugs and those that are well established in the market. However, while pharmacovigilance procedures are strictly regulated in the clinical trial setting, post-marketing adverse event reporting is not well implemented or enforced. As such, the underreporting of adverse events, in relation to drugs that are on the market, is estimated to be in the region of 90%. The identification of drug safety issues in patients with complex diseases and extensive comorbidities is therefore particularly challenging. Dialysis patients - those with end-stage renal disease and often other comorbidities such as diabetes, hypertension, and cardiovascular disease - are a population with significant treatment challenges. Patients receive dialysis using complex medical devices (eg, a peritoneal dialysis home cycler) and also receive a range of pharmaceutical agents as part of dialysis itself (eg, peritoneal dialysis solutions). Many of the pharmaceutical agents used to treat these patients have been developed in populations without these complications and, therefore, an extensive knowledge of potential problems and contraindications in the dialysis population is lacking. It is important that the nephrology community understands the concept of pharmacovigilance - the pharmacologic science relating to the detection, assessment, understanding, and prevention of adverse effects, particularly long-term and short-term side effects, of medicines. Health care professionals (HCPs) and providers, pharmaceutical companies, global regulatory agencies, and the patients themselves all play unique and critical roles in this process. This review defines the science of pharmacovigilance and the process of adverse event reporting, highlights the new directions that pharmacovigilance has taken, and provides insight for HCPs managing dialysis patients into the important role that they play in helping to shape the understanding of a drug's safety profile in order to continually enhance patient safety.

Effect of self-administered intraperitoneal bemiparin on peritoneal transport and ultrafiltration capacity in peritoneal dialysis patients with membrane dysfunction. A randomized, multi-centre open clinical trial.

BACKGROUND: Progressive peritoneal membrane injury and dysfunction are feared repercussions of peritoneal dialysis (PD), and may compromise the long-term feasibility of this therapy. Different strategies have been attempted to prevent or reverse this complication with limited success. METHODS: We performed a randomized, open multi-centre trial, aimed at scrutinizing the efficacy of self-administered intraperitoneal (i.p.) bemiparin (BM) to modulate peritoneal membrane dysfunction. The main outcome variables were peritoneal creatinine transport and the ultrafiltration (UF) capacity, estimated during consecutive peritoneal equilibration tests. The trial included a control group who did not undergo intervention. The treatment phase lasted 16 weeks with a post-study follow-up of 8 weeks. RESULTS: Intraperitoneal BM did not significantly improve creatinine transport or the UF capacity, when the whole group was considered. However, we observed a time-limited improvement in the UF capacity for the subgroup of patients with overt UF failure, which was not observed in the control group. Intraperitoneal injection of BM did not carry an increased risk of peritoneal infection or major haemorrhagic complications. CONCLUSIONS: Our data do not support the systematic use of BM for management of peritoneal membrane dysfunction in PD patients. Further studies on the usefulness of this approach in patients with overt UF failure are warranted. Intraperitoneal administration of BM is safe in PD patients, provided regulated procedures are respected.

'Reality and desire' in the care of advanced chronic kidney disease.

There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process.

A study of hydrogenated carbon fibers by scanning electron microscopy and confocal laser scanning microscopy.

The hydrogen absorption process is studied in carbonaceous fibers produced from a mixture of methane and hydrogen. The absorption of the hydrogen was examined in two types of fibers, in "as-grown" state and after a process of desorption during an annealing to 1.473 K under vacuum. Later to its production process, the fibers withstand an oxidation in air to 973 K. The fibers were examined by means of scanning electron microscopy (SEM) and confocal microscopy by reflection. Differences in the behavior during the oxidation were observed between the fibers in as-grown state and those subjected to a further annealing. It could be verified that the fibers were really constituted by two different phases. In one of the phases, the storage of the hydrogen absorbed took place, whereas in the other phase there was no alteration. The process of annealing prior to the absorption of the hydrogen has an appreciable effect on the desorption rate of the hydrogen.

Additive effects of soluble TWEAK and inflammation on mortality in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD. DESIGN, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied. RESULTS: sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients. CONCLUSIONS: The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study.

BACKGROUND: Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. METHODS: The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. RESULTS: There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. CONCLUSION: Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates.

[Systemic and renal effects of preventing contrast nephrotoxicity with isotonic (0.9%) and hypotonic (0.45%) saline]. / Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0,9%) e hiposalino (0,45%).

INTRODUCTION AND OBJECTIVES: Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. METHODS: Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). RESULTS: The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. CONCLUSIONS: During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function.

Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0.9%) e hiposalino (0.45%) / Systemic and renal effects of preventing contrast nephrotoxicity with isotonic (0.9%) and hypotonic (0.45%) saline

Introducción y objetivos. En la prevención de nefrotoxicidad por contraste se han empleado indistintamente suero salino fisiológico o hiposalino, sin analizarse las posibles diferencias de efecto en el medio interno y la distribución compartimental de volumen. Se estudiaron los efectos renales y sistémicos de dos tipos de suero salino, empleados según pauta de prevención de nefrotoxicidad por contraste en coronariografía. Métodos. Se estudiaron aspectos hidroelectrolíticos y de distribución de volumen en 71 individuos, aleatorizados a recibir suero salino isotónico al 0,9% (n = 36) o suero hiposalino al 0,45% (n = 35), durante las 12 h previas y las 12 h tras el contraste (2.000 ml en cada período). Resultados. La incidencia de elevación de creatinina en el grupo salino fue igual que en el hiposalino. El suero salino causó reducción en los valores de hemoglobina, hematocrito y albúmina plasmática, y un incremento del volumen plasmático (el 12,3 y el 10,4%, a las 24 y a las 48 h); estos cambios fueron significativos con respecto al estado basal y al grupo con suero hiposalino. Sin embargo, los sueros administrados no produjeron elevación del péptido natriurético auricular. Las osmolalidades plasmática y urinaria descendieron sólo con el suero hiposalino. Las elevaciones de creatinina plasmática fueron similares con el suero salino y con el hiposalino. Conclusiones. En una pauta preventiva estándar de la nefrotoxicidad por contraste: a) el suero salino, pero no el hiposalino, aumenta el volumen plasmático; b) este aumento no incrementa la concentración de péptido natriurético auricular, y c) no se ha detectado diferencias entre los sueros en la elevación de creatinina sérica. Estos resultados aportan evidencia de que el suero hiposalino, a la dosis preventiva de nefrotoxicidad por contraste, implica menos riesgo de expansión. Este dato es relevante en pacientes con función ventricular críticamente afectada (AU)

Introduction and objectives. Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. Methods. Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). Results. The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. Conclusions. During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function (AU)

Peritoneal defence--lessons learned which apply to diabetes complications.

Peritoneal dialysis (PD) and diabetes mellitus share the high glucose concentration in the cell microenvironment. This has led to the suggestion that they may also share pathogenic pathways of cell and tissue injury. Hypotheses have been formulated on the pathogenesis of peritoneal injury in the course of PD that take into account knowledge of the mechanisms of tissue injury in diabetes patients. More recently, research on the pathways of PD complications has uncovered potentially novel mediators of diabetes complications. Accelerated leucocyte apoptosis has been identified as a cause of impaired peritoneal antibacterial defence in PD, which may lead to new therapeutic interventions. In this regard, interference with leucocyte apoptosis by the use of caspase inhibitors may accelerate the clearance of bacteria such as Staphylococcus aureus, which cause significant morbidity in both PD and diabetes patients. Evidence suggests that glucose degradation products in PD solutions accelerate leucocyte apoptosis. In particular, 3,4-di-deoxyglucosone-3-ene (3,4-DGE) accounted for most, if not all, the cytotoxicity of PD fluids against neutrophils and lymphocytes. Interestingly, 3,4-DGE also induces apoptosis in cells, such as renal epithelium, from organs that are targets of diabetes complications. This raises the possibility that apoptosis induction by glucose metabolites that are the key participants in PD complications may underlie the pathogenesis of some features of diabetic tissue injury.

Impact of end-stage renal disease care in planned dialysis start and type of renal replacement therapy--a Spanish multicentre experience.

BACKGROUND: Timely referral, preparation and initiation of dialysis remain problematic issues. The purpose of this study is to analyse the effect of chronic renal disease care and education on the mode of dialysis start (planned vs non-planned) and on the modality of renal replacement therapy (RRT). METHODS: A total of 1504 patients from 35 hospitals started RRT in 2003. Out-patient, scheduled initiation of dialysis with a permanent vascular or peritoneal access was considered planned. RESULTS: About 46% of the patients started non-planned dialysis. Of all the patients, 75% had > or =3 months of nephrological follow-up, but nearly half were never educated on dialysis options. Haemodialysis (HD) occurred in 82% and peritoneal dialysis (PD) in 18%. Planned starts were associated (all P < 0.001) with many factors: younger age, longer renal and pre-dialysis follow-up, more education on RRT and general care, more medical visits, more PD (27 vs 8%), more follow-up by specific end-stage renal disease (ESRD) units, more permanent access and better biochemical status at the start of dialysis. Some global differences were found between patients: planned vs non-planned with > or =3 months of follow-up, vs non-planned <3 months follow-up or acute non-planned and <3 months of follow-up or acute patients. HD occurred in a similar rate (92%) in patients with non-planned start, no previous follow-up or who were never educated in dialysis modality options. CONCLUSION: Although a high prevalence of nephrologic care and follow-up was provided among incident patients in dialysis, nearly half the patients did not have a planned dialysis start nor dialysis modality education. Planned start was associated with better analytical and multidisciplinary status. PD was more prevalent in planned starts and when education was given. Specific ESRD units were more likely to provide an optimal care.

Analysis of patient flow into dialysis: role of education in choice of dialysis modality.

BACKGROUND: Despite advances in predialysis care, morbidity and mortality remain high. OBJECTIVES: To analyze end-stage renal disease (ESRD) patient demographics and clinical data on education on dialysis treatment options, type of chronic renal replacement therapy (RRT), and effects of planned versus non-planned dialysis start. METHODS: 621 patients, from 24 Spanish hospitals, who started RRT in 2002. Peritoneal or vascular access at dialysis initiation was considered "planned." RESULTS: 304 (49%) patients were non-planned and half of them had prior nephrology follow-up. Of the patients with >3 months nephrology follow-up (76% of all), only half were educated on dialysis modalities. Dialysis education was associated with planned start in 73.4% versus 26% in non-educated patients (p < 0.05), shorter follow-up (55 vs 65 months, p = 0.033), more medical visits in the prior year (6.5 vs 4.4, *p < 0.001), more patients starting peritoneal dialysis (31% vs 8.3%*), and more specific follow-up by ESRD unit versus general nephrology care (63% vs 26%*). Non-planned start was associated with older age (63 vs 60.6 years, p = 0.06), fewer medical visits (4.6 vs 6.4*), less education about modality options, and greater use of hemodialysis (92% vs 75%*). Planned patients had better biochemical parameters at start of dialysis. CONCLUSION: Despite nephrology follow-up, half the patients did not have a planned dialysis start. Planned start was associated with better clinical status. More patients chose peritoneal dialysis when educated about dialysis modality options. ESRD-specific units were more likely to provide patient education.

Peritoneal dialysis retardation of progression of advanced renal failure.

OBJECTIVES: The rate of decline of residual renal function is slower in peritoneal dialysis (PD) than in hemodialysis. However, it is unclear which and whether either of the two techniques modifies the natural course of renal failure. We tested whether PD influences the natural course of the progression of chronic renal failure in humans. DESIGN: Retrospective review of clinical charts. SETTING: Tertiary-care center. PATIENTS: Fourteen patients were selected from the 36 patients that were treated with PD in our center from January 1997 to June 2000, applying the following criteria: predialysis follow-up longer than 12 months, renal creatinine clearance 20 mL/minute or more at the start of predialysis follow-up, follow-up while on PD longer than 6 months, and renal creatinine clearance above 0 mL/minute at the start of PD. MAIN OUTCOME MEASURE: Residual renal function calculated as renal creatinine clearance obtained from 24-hour urine samples. RESULTS: A lower mean rate of decline of residual renal function was observed during PD than during the predialysis period (-0.06 +/- 0.16 vs -0.94 +/- 0.74 mL/min/month, p < 0.0005). The rate of decline in renal creatinine clearance was faster in every patient during the predialysis period than during his or her time on PD. CONCLUSIONS: These preliminary data support the hypothesis that PD may contribute to the slowing of the natural progression of renal disease in humans, as it does in rodents. Prospective studies involving a larger number of patients are needed to settle the question.