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1.  Improving Hepatitis B Vaccine Efficacy in End-Stage Renal Diseases Patients and Role of Adjuvants 
ISRN Gastroenterology  2012;2012:960413.
Hepatitis B virus (HBV) infection is a serious global health problem.The prevalence of viral hepatitis is higher in dialysis patients than in the general population because of the opportunity for exposure during the dialysis procedure. Immunization is the most effective way to prevent transmission of hepatitis B virus (HBV) and hence the development of acute or chronic hepatitis B. It is well established that patients with end-stage renal disease including dialysis-dependent patients, have an impaired immune response to hepatitis B vaccine. End stage renal diseases (ESRD) patients have lower seroconversion rates compared with the subjects with intact renal function. Moreover, even after the completion of vaccination schedule anti-hepatitis B (anti-HBs) titers of responder dialysis, patients are low and decline logarithmically with time. The impaired efficacy of HBV vaccine in patients with ESRD has been attributed to numerous factors such as immune compromise because of uremia and some other factors. One approach to improve the immunogenicity of existing HBV vaccines is adjuvantation, and it's very important to find more effective adjutants for improving HBV vaccine efficacy. In this paper we have a brief review on recently known new ways for improving HBV vaccine efficacy.
PMCID: PMC3458294  PMID: 23029621
2.  Levamisole Usage as an Adjuvant to Hepatitis B Vaccine in Hemodialysis Patients, Yes or No? 
Nephro-urology monthly  2012;5(1):673-678.
Hepatitis B virus (HBV) infection is much more common in hemodialysis patients than the general population. These patients have an impaired immune response to HBV vaccination; to that end there are certain studies that have evaluated levamisole as an immunomodulator agent improving HBV vaccination response rate in hemodialysis patients.
In the current review, we have assembled all of the results to determine whether lavamisole is of value as an adjuvant to HBV vaccination in hemodialysis patients.
Materials and Methods
Science Direct (Elsevier), ProQuest, Springer, MD Consult, BMJ Journals, Pubmed and Wiley were searched for levamisole application to HBV vaccination in hemodialysis patients. All studies revealed a seroconversion response level between levamisole plus HBV vaccine versus HBV vaccine alone.
From 10 relevant studies, 5 studies fulfilled our inclusion criteria. Three of them suggested the significant benefit of adding levamisole to the HBV vaccine to increase augment seroprotection level in hemodialysis patients. Another study reported a decrease in seroprotection level and another study showed no significant difference caused by levamisole administration.
Due to the limited number of studies evaluated, it is challenging to perform a definite decision about routinely administering levamisole in addition to the HBV vaccine for all hemodialysis patients. However, it does seem reasonable to recommend administration of levamisole for impaired immune response patients.
PMCID: PMC3614321  PMID: 23577329
Hepatitis B; Vaccination; Hemodialysis Units, Hospital
3.  Racial disparities in renal replacement therapy. 
Renal replacement therapy (RRT)--encompassing hemodialysis, peritoneal dialysis, and kidney transplantation--provides life-sustaining treatment for the expanding end-stage renal disease (ESRD) population. There is an excess burden of ESRD in African-American, Hispanic, Native Americans, and Asian/Pacific Islanders. Moreover, there is mounting evidence to suggest that significant racial and ethnic disparities exist in RRT--including referral and initiation of dialysis, adequacy of dialysis, and anemia management--with non-white patients usually at a disadvantage. In addition, there are cultural and sociodemographic differences that lead to racial variation in the choice of ESRD modality. Lastly, in certain ethnic ESRD populations, there are a series of complex issues, from biologic to socioeconomic, which limit kidney transplantation--the treatment of choice. Despite these inequalities, which are often associated with negative outcomes, these non-white groups have better hemodialysis survival rates than white patients. It is essential to develop strategies to address the disparities in ESRD treatment among minority groups in order to minimize the differences in RRT provision and identify the factors that confer improved dialysis survival-thus improving care for all Americans with kidney disease.
PMCID: PMC2594174  PMID: 12152912
4.  Immune Exhaustion and Immune Senescence – Two Distinct Pathways for HBV Vaccine Failure during HCV and/or HIV Infection 
Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared to the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.
PMCID: PMC3792483  PMID: 23400275
Immune exhaustion; immune senescence; HCV; HIV; HBV vaccine response
5.  A Modified Method in Laparoscopic Peritoneal Catheter Implantation: The Combination of Preperitoneal Tunneling and Pelvic Fixation 
ISRN Surgery  2013;2013:248126.
Introduction. Continuous ambulatory peritoneal dialysis (CAPD) is widely accepted for the management of end-stage renal disease (ESRD). Although not as widely used as hemodialysis, CAPD has clear advantages, especially those related to patient satisfaction and simplicity. Peritoneal dialysis (PD) catheter insertion can be accomplished by several different techniques. In this study, we aimed to evaluate our results obtained with peritoneal dialysis catheter placement by combination of pelvic fixation plus preperitoneal tunneling. Material and Methods. Laparoscopic peritoneal catheter implantation by combining preperitoneal tunneling and pelvic fixation methods was performed in 82 consecutive patients with end-stage renal disease. Sex, age, primary disease etiology, complications, mean duration of surgery, mean duration of hospital stay, morbidity, mortality, and catheter survival rates and surgical technique used were assessed. Analysis of catheter survival was performed using the Kaplan-Meier method. Results. Mean follow-up period was 28.35 ± 14.5 months (range of 13–44 months). Mean operative time was 28 ± 6 minutes, and mean duration of hospital stay was 3 ± 1 days. There were no conversions from laparoscopy to other insertion methods. None of the patients developed serious complications during surgery or the postoperative period. No infections of the exit site or subcutaneous tunnel, hemorrhagic complications, abdominal wall hernias, or extrusion of the superficial catheter cuff was detected. No mortality occurred in this series of patients. Catheter survival was found to be 92% at 3 years followup. Conclusions. During one-year followup, we had seven patients of migrated catheters due to separation of pelvic fixation suture from peritoneal surface, but they were reimplanted and fixated again laparoscopically with success. Over a three-year followup period, catheter survival was found to be 92%. In the literature, similar catheter survival rates without combination of the two techniques are reported. As a conclusion, although laparoscopic placement of PD catheters avoids many perioperative and early complications, as well as increasing catheter free survival period and quality of life, our results comparing to other studies in the literature indicate that different laparoscopic placement methods are still in debate, and further studies are necessary to make a more accurate decision.
PMCID: PMC3671265  PMID: 23762625
6.  Protective Status of End-Stage Renal Disease Children Against Tetanus and Diphtheria Vaccination 
Vaccination against fatal viral and bacterial diseases is still the best protective way to lower morbidity and mortality rate in end-stage renal disease (ESRD) patients. It has been reported that there is high incidence of low protective levels of IgG after vaccination in ESRD adult patients. The aim of this study was to evaluate the protective status of vaccination against diphtheria and tetanus in ESRD children after completing routine vaccination.
This cross-sectional study was carried on 83 participants less than 18 years including 27 patients on hemodialysis or peritoneal dialysis and 56 normal populations from February 2008 until December 2008 at St. Alzahra hospital, Isfahan, Iran. To determine anti-tetanus and anti-diphtheria antibodies level, Tetanus IgG ELISA kit (IBL International, Germany, RE56901) and Diphtheria IgG ELISA kit (IBL International, Germany, RE56191) were used. The participants must not received immunoglobulin, blood products or immunosuppressive medication in the current 6 months.
The mean age of case and control group were 12.5 ± 2.7 years and 11.7 ± 3.3 years, respectively, P > 0.05. According to IgG levels, 93% of hemodialysis patients and approximately 87% of peritoneal dialysis children needed booster doses of diphtheria vaccination. The results for IgG titer against tetanus revealed that in 91% of hemodialysis patients and 83% of peritoneal dialysis children booster doses of tetanus were recommended.
Booster doses of vaccines may be required in ESRD children. Measuring serum IgG levels against vaccines to define protective levels are recommended.
PMCID: PMC3650593  PMID: 23671773
Children; diphtheria; end-stage renal disease; prevention; tetanus; vaccination
7.  Comparing Survival between Peritoneal Dialysis and Hemodialysis Patients with Subclinical Peripheral Artery Disease: a 6-Year Follow-Up 
Peripheral artery disease (PAD) is known to be an increased mortality risk in patients with end-stage renal disease (ESRD). The aim of this study was to compare patient survival between patients with subclinical PAD undergoing peritoneal dialysis (PD) and hemodialysis (HD). Subclinical peripheral artery was defined as an ankle-brachial index of less than 0.9. This study was conducted from April 2005, and the observation period ended on 30 June 2011. At the end of the follow-up, the status of all patients was assessed and data on mortality were obtained for the entire cohort. A total of 91 patients (61 HD and 30 PD) were included for analyses in this study. Mortality rate was 60.0% (18/30) for PD and 52.5% (32/61) for HD. Kaplan-Meier estimate demonstrate that PD patients had a higher mortality rate than those underwent HD (log-rank p = 0.0039). Cox regression model demonstrated that PD was an independent predictor for further mortality in ESRD patients with subclinical peripheral artery disease.(p = 0.012, HR: 1.776, 95% CI: 1.136-2.775). In multivariate analysis, the HD group still had a greater survival than PD group (p = 0.005, HR:1.916, 95% CI: 1.218-3.015). In patients with subclinical peripheral artery disease, the patient survival is better in HD patients as compared with PD patients.
PMCID: PMC3590604  PMID: 23471522
Survival; hemodialysis; peritoneal dialysis; peripheral artery disease.
8.  The Relationship Between Erythropoietin Resistance and Antibody Response to Hepatitis B Vaccine in Hemodialysis Patients 
Nephro-urology Monthly  2013;5(3):806-812.
Seroconversion following Hepatitis B virus (HBV) vaccine in hemodialysis (HD) patients has been shown to be suboptimal. Nutritional and immunological factors were shown to influence the seroconversion related to HBV vaccination in HD patients. Resistance to erythropoiesis stimulating agents (ESA) for correction of anemia has also been shown to be associated with nutrition and inflammation in these patients.
The aim of the current study was to analyze the relationship between anti-HBs response and erythropoietin (EPO) resistance in HD patients.
Patients and Methods
Demographics, clinical characteristics, laboratory parameters and the data about vaccination status were obtained from dialysis charts and vaccination registries retrospectively. To calculate the EPO resistance ESA hypo responsiveness index (EHRI) was used. The EHRI was calculated through deviding the weekly dose of EPO by per kilogram of body weight divided by the hemoglobin level. Patients were divided into non-seroconversion (anti-HBs titers were < 10 IU/L) and seroconversion groups (anti-HBs titers were ≥ 10 IU/L) after completion of the four-dose vaccination schedule.
In total 97 patients were enrolled. For the entire group, stepwise linear regression analysis revealed that square root transformed anti-HBs levels were independently associated with age (P = 0.016), blood urea nitrogen (P = 0.019), high sensitive C-Reactive Protein (P = 0.009), and square root transformed EHRI (P = 0.019). Logistic regression analysis have also demonstrated that blood urea nitrogen (P = 0.002), creatinine (P = 0.046), albumin (P = 0.01) and square root transformed EHRI (P = 0.011) were independently related to seroconversion.
EPO resistance was negatively associated with anti-HBs levels and seroconversion. More studies are needed to highlight the underlying mechanisms regarding EPO resistance and response to HBV vaccination in HD patients.
PMCID: PMC3830906  PMID: 24282790
Erythropoietin; Hepatitis B; Renal Dialysis; Vaccines
9.  Pathogenesis and Treatment of Dyskalemia in Maintenance Hemodialysis and CAPD 
In end-stage renal disease (ESRD) patients regardless of dialysis modes, i.e. maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), potassium (K) homeostasis is regulated primarily via dialysis and extrarenal K regulation in the diverse daily K intake. However, K metabolism has been known to differ greatly between the two main methods of dialysis. Hyperkalemia is a common complication (10-24%) and the most common cause of the death (3-5%) among electrolyte disorders in patients on maintenance HD. On the contrary, hypokalemia (10-36%) is responsible for a rather common complication and independent prognostic factor on CAPD. Although excessive K intake or inadequate dialysis on maintenance HD and poor nutritional K intake on CAPD are accused without doubts upto 50% of ESRD patients as a primary cause of the K-imbalance, i.e. hyperkalemia on HD and hypokalemia on CAPD, other contributory factors including certain medications and unknown causes remain still to be resolved. Accordingly, the effects of medications as another source of K-imbalance on HD with RAS blockades and beta blockers as well as those of conventional and glucose-free dialysates (Icodextrin) for internal K-redistribution on CAPD were evaluated with reviewing the literatures and our data. Furthermore, new developments in the clinical managements of hyperkalemia on HD following the exclusion of pseudohyperkalemia before the initiation of dialysis were suggested, especially, by the comparison of the effects between mono- and dual-therapy with medications for transcellular K shifting in the emergent situation. Also, the intraperitoneal K administration via conventional glucose-containing (2.5%) and glucose-free dialysates (Icodextrin) as a specific route of K-supplementation for hypokalemia on CAPD was examined for its efficiency and the degree of intracellular K shift between these two different types of dialysates.
PMCID: PMC3894544  PMID: 24459485
Hyperkalemia; Hypokalemia; Hemodialysis; Continuous ambulatory peritoneal dialysis
10.  Incidence, management, and outcomes of end-stage renal disease in the elderly 
Purpose of review
The elderly constitute a substantial and growing fraction of the end-stage renal disease (ESRD) population. We review recent studies on ESRD incidence, management, and outcomes in the elderly.
Recent findings
Rates of treated ESRD among the elderly (>80 years) have risen by more than 50% in the last decade. In studies with a large number of elderly patients, median survival after dialysis initiation is modest, and although a majority have reasonable life expectancy, a substantial minority of elderly patients experience very high early mortality rates after dialysis initiation. Quality of life results are mixed – compared with younger ESRD patients or non-ESRD elderly, mental well being is similar and physical well being is reduced in elderly patients with ESRD. In several studies, elderly patients with ESRD initiating peritoneal dialysis had higher mortality rates than elderly patients with ESRD initiating hemodialysis. Strategies such as nondialytic management of ESRD or dietary protein restriction and delayed dialysis initiation may be alternatives for elderly patients wishing to avoid dialysis initiation, but further studies are needed to determine the patients best suited for these approaches. Quality improvement initiatives in geriatric ESRD care have been successfully implemented in some centers and may ultimately improve care for elderly patients with ESRD.
These findings should help to clarify some of the risks and benefits of dialysis in the elderly and may be useful in dialysis decision-making and management.
PMCID: PMC2738843  PMID: 19374012
dialysis; elderly; end-stage renal disease
11.  Hepatitis B Precore Protein: Pathogenic Potential and Therapeutic Promise 
Yonsei Medical Journal  2012;53(5):875-885.
Hepatitis B virus (HBV), a small and economically packaged double-stranded DNA virus, represents an enormous global health care burden. In spite of an effective vaccine, HBV is endemic in many countries. Chronic hepatitis B (CHB) results in the development of significant clinical outcomes such as liver disease and hepatocellular carcinoma (HCC), which are associated with high mortality rates. HBV is a non-cytopathic virus, with the host's immune response responsible for the associated liver damage. Indeed, HBV appears to be a master of manipulating and modulating the immune response to achieve persistent and chronic infection. The HBV precore protein or hepatitis B e antigen (HBeAg) is a key viral protein involved in these processes, for instance though the down-regulation of the innate immune response. The development of new therapies that target viral proteins, such as HBeAg, which regulates of the immune system, may offer a new wave of potential therapeutics to circumvent progression to CHB and liver disease.
PMCID: PMC3423855  PMID: 22869468
Hepatitis B e antigen; precore protein; chronic hepatitis B; intrabody
12.  A cost-effectiveness analysis of hepatitis B vaccine in predialysis patients. 
Health Services Research  1993;28(1):97-121.
OBJECTIVE. Our objective was to assess the cost effectiveness of hepatitis B vaccine in predialysis patients. DATA SOURCES. Costs were calculated from estimated rates of health services use and unit costs of resource use. Efficacy data were based on probability estimates from the medical literature and included vaccination response rates, anticipated hepatitis B virus (HBV) infection rates, and outcomes from HBV. STUDY DESIGN. Costs and effectiveness of HBV vaccination was modeled with a decision tree constructed to analyze three vaccination strategies for patients with renal insufficiency: vaccine given prior to dialysis, vaccine given at time of dialysis, and no vaccine. Sensitivity analyses were performed to assess the effect of varying important clinical and cost variables. DATA COLLECTION/EXTRACTION METHODS. All analyses were based on efficacy and cost estimates derived from the medical literature. Analyses were conducted with the aid of SMLTREE software. PRINCIPAL FINDINGS. The number of patients requiring vaccination per case of HBV prevented was higher for dialysis patients (625 vaccinees/case prevented) than for predialysis patients (434 vaccinees/case prevented). The cost-effectiveness ratios were $25,313/case of HBV prevented for vaccination at the time of dialysis and $31,111 for the predialysis vaccine. When a higher HBV infection rate (based on clinical trial data) was substituted in the analysis, the cost effectiveness of a predialysis vaccination strategy improved to $856 per case prevented. Results were sensitive to the cost of the vaccine and the incidence of HBV infection in dialysis patients. For the predialysis strategy to become cost saving, the price of the vaccine would have to decrease from $114 to $1.50, or the incidence of infection would have to increase from 0.6 percent to 38 percent, holding all other variables constant. CONCLUSIONS. Additional HBV infection can be prevented by immunizing predialysis patients, but the cost is high. Decisions concerning vaccination policy should be influenced by local prevalence of HBV infection.
PMCID: PMC1069923  PMID: 8463111
13.  Survival of patients treated for end-stage renal disease by dialysis and transplantation. 
The results of treatment in 213 patients with end-stage renal disease who underwent hemodialysis, peritoneal dialysis or transplantation, or a combination, between 1962 and 1975 were analysed. Comparison by censored survival analysis showed significantly better (P less than 0.01) patient survival with the integrated therapy of dialysis and transplantation than with either form of dialysis alone. There was no significant difference in survival of males and females but survival at the extremes of age was poorer. Analysis of survival by major cause of renal failure indicated best survival in patients with congenital renal disease. Graft and patient survival rates at 1 year after the first transplantation were 42% and 69%. The major cause of death in this series was vascular disease but infection was responsible for 50% of deaths after transplantation. While integration of dialysis with transplantation produces best patient survival, this course is possible only when sufficient cadaver kidneys are available.
PMCID: PMC1880114  PMID: 334354
14.  Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection 
Molecular Biology Reports  2013;40:6899-6911.
Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (anti-HBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre >10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre >10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs >10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0–2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6–24.9, P < 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1–0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03–0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection.
PMCID: PMC3835950  PMID: 24158609
Anti-HBs; Gene polymorphism; Hemodialysis; Infection; Interleukin-12; Vaccination
15.  End-Stage Renal Disease and Renal Replacement Therapy in older Patients 
Nephro-urology monthly  2012;4(2):425-430.
As the world’s population continues to age, practitioners encounter increasing numbers of older patients with end-stage renal disease (ESRD) who require renal replacement therapy (RRT). Conservative management may be considered in older patients and has been shown to offer comparable survival rates and hospital-free days to RRT patients. At present, for those who choose RRT, hemodialysis is the most commonly used modality. Many practitioners believe that peritoneal dialysis (PD), including assisted peritoneal dialysis, can be used safely in this population. Age is not a contra-indication to peritoneal dialysis, and a choice of modality should be offered to older patients. Assisted peritoneal dialysis has been used successfully in multiple regions without an increase in complication rates. Quality of life is an important issue for older patients with ESRD, and studies such as Broadening options for long-term Dialysis in the Elderly support the use of PD in older patients as it is associated with fewer fluctuations in symptoms of ESRD and less intrusion into people’s lives. This review discusses the appropriateness of initiating RRT in older patients, choices of modality, underutilization of PD in older patients, use of assisted PD, complication rates, and quality of life in these patients. overall, PD seems to be a safe and effective modality of RRT in older patients, and assisted PD can be used in patients with limited functional impairment.
PMCID: PMC3614263  PMID: 23573460
Chronic Kidney Disease; Peritoneal Dialysis; Aging
16.  Long-term survival and predictors for mortality among dialysis patients in an endemic area for chronic liver disease: a national cohort study in Taiwan 
BMC Nephrology  2012;13:43.
Patients with end-stage renal disease (ESRD) are at a higher risk for chronic hepatitis, liver cirrhosis (LC) and mortality than the general population. Optimal modalities of renal replacement therapy for ESRD patients with concomitant end-stage liver disease remain controversial. We investigated the long-term outcome for chronic liver disease among dialysis patients in an endemic area.
Using Taiwan’s National Health Insurance claim data (NHRI-NHIRD-99182), We performed a longitudinal cohort study to investigate the impact of comorbidities on mortality in dialysis patients. We followed up 11293 incident hemodialysis (HD) and 761 peritoneal dialysis (PD) patients from the start of dialysis until the date of death or the end of database period (December 31, 2008). A Cox proportional hazards model was used to identify the risk factors for all-cause mortality.
Patients receiving PD tended to be younger and less likely to have comorbidities than those receiving HD. At the beginning of dialysis, a high prevalence rate (6.16 %) of LC was found. Other than well-known risk factors, LC (hazard ratio [HR] 1.473, 95 % CI: 1.329-1.634) and dementia (HR 1.376, 95 % CI: 1.083-1.750) were also independent predictors of mortality. Hypertension and mortality were inversely associated. Dialysis modality and three individual comorbidities (diabetes mellitus, chronic lung disease, and dementia) interacted significantly on mortality risk.
LC is an important predictor of mortality; however, the effect on mortality was not different between HD and PD patients.
PMCID: PMC3422197  PMID: 22709415
Hemodialysis; Peritoneal dialysis; Mortality; Liver cirrhosis
17.  Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients 
BMC Nephrology  2014;15:12.
The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients.
Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier.
GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype.
Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.
PMCID: PMC3909531  PMID: 24423050
Cardiovascular disease; ESRD; Polymorphism; Mortality risk; Oxidative stress
18.  Antibody response following Hepatitis B vaccination in peritoneal dialysis patients: does normalized urea clearance matter? 
Clinics  2011;66(9):1559-1562.
Data on the factors that contribute to the antibody response to hepatitis B virus vaccination in peritoneal dialysis patients are scarce. The current study was conducted on a group of peritoneal dialysis patients to learn how the response to hepatitis B virus vaccination varies according to the patient's clearance of urea normalized to total body water (Kt/V).
A convenience sample of 33 peritoneal dialysis patients (13 women and 20 men, with a mean age of 49±12 years) was administered double doses (20 µg IM in each deltoid muscle) of recombinant hepatitis B vaccine at 0, 1, 2, and 6 months. Response to immunization was measured at one to three months after the final dose of vaccine. The subjects were divided into groups according to the level of antibodies to hepatitis B surface antigen (anti-HBs), including non-responders (<10 IU/L), weak responders (10-100 IU/L), and good responders (>100 IU/L).
Among non-responders, weak responders, and good responders, significant differences were found in age (54±12 vs. 56±9 vs. 45±12 years, respectively; p = 0.049) and recombinant human erythropoietin use (20 vs. 29 vs. 76%, respectively; p = 0.016). No significant differences in weekly total Kt/V (p = 0.704), weekly peritoneal Kt/V (p = 0.064) and residual glomerular filtration rate (p = 0.355) were found across the three groups.
Delivered clearance measured by weekly peritoneal Kt/V and total clearance measured by weekly total Kt/V did not predict the response to hepatitis B virus vaccination in patients on peritoneal dialysis.
PMCID: PMC3164404  PMID: 22179159
Continuous ambulatory peritoneal dialysis; Hepatitis B virus; Vaccination; Dialysis adequacy; Kt/V
19.  Substance P and intensity of pruritus in hemodialysis and peritoneal dialysis patients 
Uremic pruritus is a common complication in patients undergoing dialysis. The pathophysiological mechanisms of pruritus in patients with end-stage renal disease remain unknown. Neuropeptides, including substance P, are postulated to play an important role in the pathogenesis of pruritus. The aim of this study was to evaluate the role of substance P in uremic pruritus in patients on hemodialysis and peritoneal dialysis.
We included 197 patients with end-stage renal disease: 54 on continuous ambulatory peritoneal dialysis and 143 on hemodialysis. Substance P, calcium, phosphorus, iron, ferritin, CRP, albumin, hemoglobin, Ca × P product, and iPTH level were determined in all participants. The correlation between these parameters and self-reported itching was evaluated in patients on hemodialysis in comparison with peritoneal dialysis patients.
The incidence of itching was similar in hemodialysis and peritoneal dialysis patients. No differences in substance P level between the 2 groups were found. There was no correlation between substance P level and the incidence or intensity of pruritus in dialyzed patients.
This study demonstrates that substance P does not play any important role in pruritus in hemodialysed and peritoneal dialyzed patients. However, further studies are necessary to assess the exact role of neuropeptides in uremic pruritus.
PMCID: PMC3767586  PMID: 23995243
substance P; uremic pruritus; end-stage renal disease; hemodialysis; peritoneal dialysis
20.  Hepatitis B Vaccination in Chronic Kidney Disease: Review of Evidence in Non-Dialyzed Patients 
Hepatitis Monthly  2012;12(11):e7359.
Hepatitis B vaccination of hemodialysis patients is performed all over the world. There are also recommendations from world health organizations to vaccinate patients with chronic kidney disease (CKD) prior dialysis commencement, but the implementation of a hepatitis B vaccination program is less common and not well organized.
Evidence Acquisition
This review article summarizes data indicating why, when and how to vaccinate CKD patients before they start renal replacement therapy. Publication for this review was bringing into being from PubMed.
There is an agreement in the nephrological societies and among clinicians and scientists that CKD patients should be vaccinated in early stages of their disease, because a higher glomerular filtration rate is more likely to be associated with the responsiveness to vaccination. Schedules of vaccination and optimal vaccine doses are still being investigated. Differences in data with respect to these problems may result from comparisons of various vaccine doses and vaccination schedules without reference to one gold standard, variations in patients` clinical status and glomerular filtration rate, and also the small groups of the affected patients make statistical analysis non-conclusive. A titer of antibodies to surface antigen of hepatitis B virus (anti-HBs) > 10 IU/L or ≥ 10 IU/L is commonly considered as a marker of seroconversion to anti-HBs positivity after vaccination in both non-dialyzed and dialyzed patients. In advanced CKD, vaccine–induced serconversion rate is seldom observed in more than 90% of vaccinees. Various strategies have been utilized in order to increase vaccine-induced seroconversion rate in patients with advanced CKD. Changing the injection mode, the use of adjuvants and immunostimulants to improve the immunogenicity of existing recombinant hepatitis B vaccines, introduction of mammalian-cell derived pre-S/S HBV vaccines (third-generation vaccines) were tried in order to improve the immunization rate.
There are a substantial number of non-responders to the hepatitis B vaccine among CKD patients. Therefore, successful prevention of hepatitis B virus transmission and spread will only be attained when hepatitis B vaccination is applied together with full implementation of appropriate infection control procedures.
PMCID: PMC3546461  PMID: 23326280
Vaccination; Hepatitis B Virus; Kidney Disease
21.  Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study 
PLoS ONE  2013;8(3):e58317.
Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.
We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.
The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.
ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.
PMCID: PMC3596393  PMID: 23516462
22.  Dialysis and Quality of Dialysate in Southeast Asian Developing Countries 
Nephron Extra  2014;4(1):64-69.
The number of dialysis patients has been increasing in Southeast Asia, but statistical data about these patients and on the quality of dialysates in Southeast Asian dialysis facilities are still imprecise. For this study, dialysis-related statistical data were collected in Southeast Asia.
A survey of the quality of dialysates was carried out at 4 dialysis facilities in Vietnam and Cambodia. The dialysis patient survey included the numbers of dialysis facilities and patients receiving dialysis, a ranking of underlying diseases causing the initiation of dialysis, the number of patients receiving hemodialysis (HD)/on-line hemodiafiltration/continuous ambulatory peritoneal dialysis, the number of HD monitoring devices installed, the cost of each session of dialysis (in USD), the percentage of out-of-pocket payments, and the 1-year survival rates of the dialysis patients (in percent). The dialysate survey covered the endotoxin (ET) level and bacterial count in tap water, in water filtered through a reverse osmosis system and in dialysate.
In each of the countries, the most frequent reason for the initiation of dialysis is diabetes mellitus. HD is usually carried out according to the ‘reuse’ principle. The 1-year survival rates are 70% in Myanmar and about 90% in the Philippines and Malaysia. The ET levels in standard dialysates were satisfactory at 2 facilities. The bacterial counts in dialysates were not acceptable at any of the facilities investigated.
There is an urgent need to teach medical workers involved in dialysis how to prepare sterile and ET-free dialysates.
PMCID: PMC4036132  PMID: 24926310
Dialysis status; Southeast Asia; Developing countries; Dialysate quality; Endotoxin; Bacterial count

23.  Residual Renal Function in Children Treated with Chronic Peritoneal Dialysis 
The Scientific World Journal  2013;2013:154537.
Residual renal function (RRF) in patients with end-stage renal disease (ESRD) receiving renal replacement therapy is defined as the ability of native kidneys to eliminate water and uremic toxins. Preserved RRF improves survival and quality of life in adult ESRD patients treated with peritoneal dialysis. In children, RRF was shown not only to help preserve adequacy of renal replacement therapy but also to accelerate growth rate, improve nutrition and blood pressure control, reduce the risk of adverse myocardial changes, facilitate treatment of anemia and calcium-phosphorus balance abnormalities, and result in reduced serum and dialysate fluid levels of advanced glycation end-products. Factors contributing to RRF loss in children treated with peritoneal dialysis include the underlying renal disease such as hemolytic-uremic syndrome and hereditary nephropathy, small urine volume, severe proteinuria at the initiation of renal replacement therapy, and hypertension. Several approaches can be suggested to decrease the rate of RRF loss in pediatric patients treated with chronic peritoneal dialysis: potentially nephrotoxic drugs (e.g., aminoglycosides), episodes of hypotension, and uncontrolled hypertension should be avoided, urinary tract infections should be treated promptly, and loop diuretics may be used to increase salt and water excretion.
PMCID: PMC3859254  PMID: 24376376
24.  Survival Analysis of Korean End-Stage Renal Disease Patients According to Renal Replacement Therapy in a Single Center 
This study was to investigate clinical characteristics and any differential trends in survival among renal replacement therapy (hemodialysis [HD], peritoneal dialysis [PD], and kidney transplantation [KT]) in Korean end-stage renal disease (ESRD) population. We tried to analyze retrospectively the survival rate adjusted by risk factors and the relative risk stratified by key risk factors among 447 ESRD patients who began dialysis or had a kidney transplant at Ajou University Hospital from 1994 to 2004. In adjusted Cox survival curves, the KT patients had the best survival rate, and the HD patients had better survival than PD patients. The consistent trends in different subgroups stratified by age and diabetes were as following: 1) The risk of death for PD and HD was not proportional over time, 2) The relative risk of PD was similar or lower than that of HD for the first 12 months, but it became higher at later period. The significant predictors for mortality were age (over 55 yr), presence of diabetes, cerebrovascular accident at ESRD onset, and more than one time of hospitalization caused by malnutrition. Further large-scaled, multicenter-based comparative study is needed in Korean ESRD patients and more meticulous attention is required in high-risk patients.
PMCID: PMC2693574  PMID: 17297256
Renal Replacement Therapy; Kidney Transplantation; Renal Dialysis; Peritoneal Dialysis; Survival Analysis; Risk
25.  Mycobacterium fortuitum Peritonitis in a Patient on Continuous Ambulatory Peritoneal Dialysis (CAPD): A Case Report 
Mycobacterium fortuitum, an environmental organism, is capable of producing a variety of clinical infections such as cutaneous infections, abscesses and nosocomial infections. Rarely, it has been a documented as a cause of peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD). Continuous Ambulatory Peritoneal dialysis (CAPD) is one of the treatment options which are used for patients with end-stage renal disease (ESRD). Although peritonitis rates have declined in parallel with advances in peritoneal dialysis (PD) technology, peritonitis remains a leading complication of CAPD and it is the major cause for transfer to other methods of dialysis. We are reporting a case of M. fortuitum peritonitis in a patient who was undergoing CAPD, which was successfully treated. This case emphasizes the importance of mycobacterial cultures in patients with CAPD-associated peritonitis, whose routine cultures may yield no organisms.
PMCID: PMC3919311  PMID: 24551685
Acid fast bacilli; Dialysate culture, End-stage renal disease; Mycobacterium fortuitum; Peritonitis

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