Miguel C. Riella

Reimbursement and economic factors influencing dialysis modality choice around the world

The worldwide incidence of kidney failure is on the rise and treatment is costly; thus, the global burden of illness is growing. Kidney failure patients require either a kidney transplant or dialysis to maintain life. This review focuses on the economics of dialysis. Alternative dialysis modalities are haemodialysis (HD) and peritoneal dialysis (PD). Important economic factors influencing dialysis modality selection include financing, reimbursement and resource availability. In general, where there is little or no facility or physician reimbursement or payment for PD, the share of PD is very low. Regarding resource availability, when centre HD capacity is high, there is an incentive to use that capacity rather than place patients on home dialysis. In certain countries, there is interest in revising the reimbursement structure to favour home-based therapies, including PD and home HD. Modality selection is influenced by employment status, with an association between being employed and PD as the modality choice. Cost drivers differ for PD and HD. PD is driven mainly by variable costs such as solutions and tubing, while HD is driven mainly by fixed costs of facility space and staff. Many cost comparisons of dialysis modalities have been conducted. A key factor to consider in reviewing cost comparisons is the perspective of the analysis because different costs are relevant for different perspectives. In developed countries, HD is generally more expensive than PD to the payer. Additional research is needed in the developing world before conclusive statements may be made regarding the relative costs of HD and PD.

Economic evaluations of dialysis treatment modalities

OBJECTIVES The purpose of this paper is to review published economic evaluations of dialysis treatment modalities, including hemodialysis (HD) and peritoneal dialysis (PD). METHODS A systematic literature review was conducted in both PubMed and EMBASE for the years 1996-2006. Articles were included if they were original research articles comparing PD and HD or comparing subtypes of PD and HD. RESULTS Twenty-five articles were included in the formal literature review. The majority of articles were cost evaluations, rather than full economic evaluations of both costs and outcomes. The results show that, in developed nations, HD is generally more expensive than PD to the payer. In developing and emerging economies, mainly due to inexpensive labor and high imported equipment and solution costs, PD is not infrequently perceived to be more expensive than HD. However, the costs of dialysis differ by region and additional research is needed particularly in developing economies. CONCLUSIONS HD is a more expensive dialysis modality in developed regions of the world. Research in the developing world is too limited to draw definitive conclusions.

EFFECT OF ORAL N-ACETYLCYSTEINE TREATMENT ON PLASMA INFLAMMATORY AND OXIDATIVE STRESS MARKERS IN PERITONEAL DIALYSIS PATIENTS: A PLACEBO-CONTROLLED STUDY

♦ Background: Inflammation and oxidative stress (OS) are cardiovascular risk factors in patients with chronic kidney disease. N-acetylcysteine (NAC) is a thiol-containing antioxidant with anti-inflammatory properties and has been shown to reduce the number of cardiovascular events in hemodialysis patients. ♦ Methods: The current study aimed to determine the effect of oral NAC (2 × 600 mg/daily) on plasma levels of inflammatory and OS markers in peritoneal dialysis (PD) patients. We performed a placebo-controlled study over 8 weeks in 30 patients (40% males, age 52 ± 13 years) on regular PD. Before the study was started, the patients were divided into 2 groups of 15 patients matched for age and gender. 22 patients completed the study (12 on NAC, 10 on placebo). Proinflammatory cytokines [high-sensitivity C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha, and pentraxin 3] and markers of OS (pentosidine, advanced oxidation protein products, homocysteine, glutathione, asymmetric dimethylarginine, and free sulfhydryls) were measured before and after treatment with NAC. ♦ Results: Treatment with NAC for 8 weeks increased mean baseline plasma NAC levels from 2.6 to 24.8 μmol/L (p = 0.007). This intervention, which caused no side effects, significantly diminished IL-6 levels, from 9.4 (4.5 – 31) to 7.6 (4.9 – 13.5) pg/mL (p = 0.006), whereas no such changes were observed in the placebo group. NAC treatment did not significantly affect the other inflammatory and OS markers. ♦ Conclusion: Short-term oral NAC treatment resulted in reduction of circulating IL-6, suggesting that such treatment could be a useful strategy in blunting the inflammatory response in PD patients.

Inflammation, malnutrition and atherosclerosis in end-stage renal disease: A global perspective

End-stage renal disease (ESRD) is characterized by an exceptional cardiovascular mortality rate. Although traditional risk factors are common in ESRD patients, they alone may not be sufficient to account for the high prevalence of cardiovascular disease (CVD). Recent evidence demonstrated that chronic inflammation, a non-traditional risk factor which is commonly observed in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. Although both malnutrition and inflammation have been shown to be strong predictors of cardiovascular mortality in ESRD patients, it must be remembered that the majority of studies describing the presence of inflammation and malnutrition have been performed in Western and Asian industrialized countries. As it is evident that the prevalence of malnutrition and inflammation may differ markedly between different regions of the world and developing countries face a much higher prevalence of chronic infectious diseases, comparative inter-regional studies focusing on the etiology and prevalence of the malnutrition, inflammation and atherosclerosis syndrome are warranted.

Increased plasma and endothelial cell expression of chemokines and adhesion molecules in chronic kidney disease.

Chemokines and adhesion molecules are involved in early events of atherogenesis. In the present study, we investigated the effects of the uremic milieu on the expression of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) and their relationship to cardiovascular status. Plasma samples were obtained from patients in different stages of chronic kidney disease (CKD). Cardiovascular status was evaluated by intima-media thickness and endothelial dysfunction by flow mediation dilatation and proteinuria. In vitro studies were performed using human umbilical endothelial cells exposed to uremic plasma or plasma from healthy subjects. MCP-1, IL-8, sVCAM-1 and sICAM-1 levels in plasma and in supernatant were analyzed by enzyme-linked immunosorbent assay. The population consisted of 73 (mean age 57 years; 48% males) CKD patients with glomerular filtration rate (GFR) of 37 ± 2 ml/min. MCP-1 and sVCAM-1 plasma levels were negatively correlated with GFR (ρ = –0.40, p < 0.0005 and ρ = –0.42, p < 0.0005, respectively). Fibrinogen was positively correlated with MCP-1, sICAM-1 and sVCAM-1 (ρ = 0.33, p < 0.005, ρ = 0.32, p < 0.05 and ρ = 0.25, p < 0.05, respectively) and ultra-high-sensitivity C-reactive protein was positively correlated with sICAM-1 (ρ = 0.25, p < 0.0005). Plasma IL-8 had a significant positive correlation with proteinuria (ρ = 0.31, p < 0.01). There was a time- and CKD-stage-dependent MCP-1, IL-8 and sVCAM-1 endothelial expression (p < 0.05). In summary, plasma levels of markers of endothelial cell activation (MCP-1 and sVCAM-1) are increased in more advanced CKD. Exposure of endothelial cells to uremic plasma results in a time- and CKD-stage-dependent increased expression of MCP-1, IL-8 and sVCAM-1, suggesting a link between vascular activation, systemic inflammation and uremic toxicity. Future studies are necessary to investigate whether these biomarkers add predictive value in comparison to the previously described ones. Also, endothelial response to uremic toxicity should be viewed as a potential target for intervention in order to reduce morbidity and mortality in CKD-related cardiovascular disease.

Accuracy of Physical Examination and Intra‐Access Pressure in the Detection of Stenosis in Hemodialysis Arteriovenous Fistula

Both physical examination (PE) and intra‐access pressure (IAP) measurements have been used in the identification of stenosis in an arteriovenous access. The aim of this study was to evaluate the accuracy of PE and IAP in the diagnosis of arteriovenous fistula (AVF) stenosis. A total of 84 patients were enrolled in the study (54% men, mean age of 50.7 ± 12.7 years and mean AVF patency of 24.9 ± 7.8 months, 52% radiocephalic). Abnormalities of pulse and thrill were used as the diagnostic tools for the detection of stenosis using the physical examination. For IAP, stenosis was suspected when the ratio between IAP at the arterial puncture site and the mean blood pressure was <0.13 or >0.43. The diagnosis of stenosis was confirmed by Doppler ultrasound (DU). Sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (PNV), and accuracy were calculated for the two early detection tests. According to DU, 50 (59%) AVF were considered positive for the presence of stenosis. Fifty‐six (66%) AVF were considered positive for the presence of stenosis by PE and 34 (40%) by IAP. S, SP, PPV, and NPV for PE and IAP were 96%, 76%, 86%, and 93% and 60%, 88%, 88%, and 60%, respectively. The accuracy for PE and IAP was 88% and 71%, respectively. PE proved to be an accurate method for the diagnosis of stenosis and should be part of all surveillance protocols of stenosis detection in AVF.

The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD): Characterization of the cohort

The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD) was launched in December 2004 aiming to collect data monthly and continuously from a representative cohort, allowing for a continuous snapshot of the peritoneal dialysis (PD) reality in the country. This is an observational study of PD patients comprising follow-up from December 2004 to February 2007 (mean follow-up of 13.6 months-ranging from 1 to 26 months) in 114 Brazilian centers. All centers report data through a central web-based database. After an initial baseline retrospective data collection, all patients are followed prospectively every month until they drop out from the PD program. Total number of patients recruited until February 2007 was 3226 (2094 incident patients). Mean age was 54+/-19 years (37% above 65 years old), with 55% females and 64% Caucasians. The more frequent causes of renal failure were diabetic nephropathy (34%), renal vascular disease associated with hypertension (26%), and glomerulopathies (13%). The most common comorbidities were hypertension (76%), diabetes (36%), and ischemic heart disease (23%). Automated PD (APD) was the modality utilized in 53%. The estimated overall peritonitis rate was 1 episode per 30 patient-months (most frequently due to Staphylococcus aureus). The total dropout rate was 33%, mainly due to deaths, whereas 20% of dropouts were due to renal transplant. The gross mortality was 17.6% and the main causes of mortality were cardiovascular diseases (40%) and infections (15%). The initial results of this first Brazilian PD registry provide a unique opportunity to develop future clinical studies addressing specific PD questions in the Brazilian reality and context.

Minocycline-EDTA Lock Solution Prevents Catheter-Related Bacteremia in Hemodialysis

There is growing concern about the development of antibacterial resistance with the use of antibiotics in catheter lock solutions. The use of an antibiotic that is not usually used to treat other serious infections may be an alternative that may reduce the clinical impact should resistance develop. We conducted a randomized controlled trial to compare a solution of minocycline and EDTA with the conventional unfractionated heparin for the prevention of catheter-related bacteremia in hemodialysis patients during a period of 90 d. The study included 204 incident catheters (27.8% tunneled); 14 catheters were excluded because of early dysfunction and 3 because of protocol violations. We observed catheter-related bacteremia in 19 patients in the heparin group (4.3 per 1000 catheter-days) and in 5 patients in the minocycline-EDTA group (1.1 per 1000 catheter-days; P = 0.005). We did not detect a significant difference in the rate of catheter removal for dysfunction. Catheter-related bacteremia-free survival was significantly higher in the minocycline-EDTA group than in the heparin group (P = 0.005). In conclusion, a minocycline-EDTA catheter lock solution is effective in the prevention of catheter-related bacteremia in hemodialysis patients.

Association between Vitamin D Receptor Gene Polymorphisms and Susceptibility to Chronic Kidney Disease and Periodontitis

Background/Aims: Chronic kidney disease (CKD) and periodontitis (PD) are serious public-health concerns. Vitamin D is a fat-soluble steroid hormone that interacts with its nuclear receptor (VDR) to regulate a variety of biological processes, such as bone metabolism, immune response modulation and transcription of several genes involved in CKD and PD disease mechanisms. The aim of this work was to investigate the association between polymorphisms in the VDR gene and end-stage renal disease (ESRD) and PD. Methods: 222 subjects with and without ESRD (in hemodialysis) were divided into groups with and without PD. Polymorphisms TaqI and BsmI in the VDR gene were analyzed by PCR restriction fragment length polymorphism. The significance of differences in allele, genotype and haplotype frequencies between groups was assessed by the χ2 test (p value <0.05) and odds ratio (OR). Results: Allele G was associated with protection against ESRD: groups without versus with ESRD (GG) × (GA+AA): OR = 2.5, 95% CI = 1.4–4.6, p = 0.00; (G × A): OR = 1.5, 95% CI = 1.0–2.3, p = 0.02; (TG + CG) × (TA + CA): OR = 1.5, 95% CI = 1.0–2.3, p = 0.02. No association was observed between the study polymorphisms and susceptibility to or protection against PD. Conclusion: Allele G of the VDR BsmI polymorphism was associated with protection against ESRD.

Predictive Value of Malnutrition Markers for Mortality in Peritoneal Dialysis Patients

INTRODUCTION Alterations in nutritional status have been described as important predictors of mortality in patients with chronic kidney disease (CKD). However, the association between multiple markers for nutritional status and the mortality rates of patients with CKD on peritoneal dialysis (PD) has not yet been illustrated in previously published data, particularly by using the new definition of protein energy wasting (PEW). OBJECTIVE To evaluate the predictive value of malnutrition markers for mortality rates, on the basis of the PEW definition, of PD patients. MATERIALS AND METHODS At the start of PD treatment, the nutritional status of 199 patients (mean age, 56 ± 13.3 years; 53% females) was evaluated. Body mass index (BMI), arm circumference, mid-arm muscle circumference, protein and caloric intake (by using a 3-day food record), and serum albumin were all recorded, as well as a subjective global assessment (SGA) and presence of PEW. Cut-off points were defined on the basis of the consensus of the International Society for Renal Nutrition and Metabolism (albumin, <3.8 g/dL; BMI, <23 kg/m(2); mid-arm muscle circumference, >10% in comparison with the 50th percentile for the reference population; protein intake, <0.8 g/kg/daily; caloric intake, <25 kcal/kg/daily). The data were obtained retrospectively between the years 2001 and 2008 on the basis of routine nutritional evaluation. Patients were monitored for fatal events from all possible causes. RESULT The mean BMI for the population was 26.6 ± 5.0 kg/m(2). A median protein intake of 0.94 (0.18 to 4.57) g/kg/daily was reported and 60.3% of the patients reported a protein intake of <0.8 g/kg/daily. With respect to caloric intake, 38.7% of the patients consumed <25 kcal/kg/daily. A median of 3.5 (1.4 to 5.3) g/dL for serum albumin was observed and 29.3% of the patients presented values of <3.8 g/dL. PEW was diagnosed in 17.5% of patients. In the univariate model, being of age >65 years (P = .002), cardiovascular disease (P < .001), diabetes mellitus (P = .02), SGA (P = .02), and albumin (P = .002), were all significant markers for mortality. The presence of patients aged >65 years (P = .02), with diabetes mellitus (P = .057), cardiovascular disease (P = .005), and albumin were considered as independent factors for mortality in this study. CONCLUSION SGA, albumin, and PEW were the only nutritional markers found to be associated with mortality in this cohort of PD patients. In the multivariate analysis, after adjusting for classic mortality risk factors, only patients with hypoalbuminemia were found to be at a high risk for mortality at follow-up. These results may be limited by the number of observations and a necessity for confirmation in larger prospective studies.