Journal of Renal Nutrition

Nephrology and Nutrition Leaders Coming to Hawaii for the World Renal Nutrition Week: Why is the 16th Congress in Renal Nutrition and Metabolism in Honolulu, Hawai’i, June 2012, Worth Attending?

2012-01-01

RECENT ADVANCES IN our understanding of, and approach to, caring for patients with kidney disease and their nutritional and dietary management are expected to have unprecedented impact on the current and future status of nephrology and nutrition practice throughout the world. To this end, the International Society of Renal Nutrition and Metabolism (ISRNM, www.RenalNutrition.com) and the Council of Renal Nutrition (CRN) of the National Kidney Foundation (NKF), in collaboration with several professional societies in different countries, have joined together to expand the 16th International Congress in Renal Nutrition and Metabolism into the 1st World Renal Nutrition Week during June 26 to 30, 2012. The beautiful Hawaiian main island is the location of the World Renal Nutrition Week upon gracious agreement of the NKF of Hawaii to serve as the local host of the congress. The Congress’ website, www.RenalNutritionWeek.com, has been updated on a weekly or more frequent basis, posts relevant announcements and provides a convenient venue for all communications including abstract submission (December 1, 2011 to February 29, 2012).

Risk Factors for Hypovitaminosis D in Nondialyzed Chronic Kidney Disease Patients

2011-06-09

Background: Hypovitaminosis D is highly prevalent among patients with chronic kidney disease and has been associated with worse outcome even in the earlier stages of the disease.Objective: This study aimed to investigate the risk factors for hypovitaminosis D in nondialyzed patients with chronic kidney disease.Design: This cross-sectional study included 120 patients with chronic kidney disease at stages 2 to 5 (62% male, age: 55.4 ± 11.3 year, estimated glomerular filtration rate: 35.1 ± 15 mL/minute, body mass index [BMI]: 27.1 ± 5.2 kg/m2, 31% diabetics). Serum 25-hydroxivitamin D [25(OH)D] was measured by chemiluminescence. Subjective global assessment, total body fat (dual-energy X-ray absorptiometry), visceral and subcutaneous abdominal fat (computed tomography), and several laboratory parameters were assessed.Results: Insufficiency of 25(OH)D (15 to 30 ng/mL) was observed in 55% and deficiency (<15 ng/mL) in 20% of the patients. Patients with diabetes, BMI ≥30 kg/m2, and who had the blood collection during the winter or spring had lower levels of 25(OH)D. Serum 25(OH)D correlated inversely with parathyroid hormone, proteinuria, insulin resistance, leptin, and subcutaneous abdominal fat. The risk factors for hypovitaminosis D were diabetes (odds ratio: 3.8; 95% CI: 1.2 to 11.7; P = .022) and BMI ≥30 kg/m2 (odds ratio: 4.3; 95% CI: 1.2 to 15.3; P = .018). In the logistic regression analysis adjusting for gender, skin color, and season of the year, diabetes and BMI ≥30 kg/m2 were independently associated with hypovitaminosis D.Conclusions: Diabetes and obesity were the risk factors for hypovitaminosis D in nondialyzed patients with chronic kidney disease. Effective interventional protocols of vitamin D supplementation taking into account these risk factors are warranted for this population.

Persistent Homocysteine Metabolism Abnormality Accelerates Cardiovascular Disease in Hemodialyzed Patients—the Nishinomiya Study

2011-07-13

Objective: Homocysteine (Hcy) is an intermediate in sulfur amino acid metabolism and may induce oxidative stress. Several studies have reported that elevated Hcy in end-stage renal failure may contribute to cardiovascular disease (CVD). The purpose of this study is to investigate whether the changes in Hcy levels correlate better with the CVD outcomes than baseline Hcy level.Methods: A total of 187 patients on dialysis participated in the present prospective observational study and were followed up for 107 months. Baseline cross-sectional analysis of the relationship between Hcy and several factors related to its metabolism was performed, along with survival analysis for the occurrence of CVD. All subjects were divided into the Increase or Decrease of Hcy group on the basis of changes in Hcy from baseline to year 3.Results: The occurrence of CVD was higher in the Increase (30.1%) than in the Decrease group (9.0%). Greater change of Hcy was associated with risk of CVD (hazard ratio: 3.658) after adjusting basic factors and nutritional status. In stepwise multiple analyses, serum folate, vitamin B12, cysteine, creatinine, and body mass index were considered to be independent predictors of Hcy.Conclusions: These data show that increase in Hcy is a powerful predictor of the occurrence of CVD in patients on dialysis.

Daily Magnesium Intake and Hypermagnesemia in Hemodialysis Patients With Chronic Kidney Disease

Katarzyna Wyskida, Joanna Witkowicz, Jerzy Chudek, Andrzej Więcek — 2011-05-27

Objective: The aim of this study was to evaluate daily magnesium intake and the relation to its serum concentration in hemodialysis (HD) patients with chronic kidney disease (CKD).Design: This is a prospective, open-label, cross-sectional clinical study analyzing daily magnesium intake based on nutritional questionnaire.Participants: A total of 101 HD patients with CKD were screened for hypermagnesemia. All patients with serum magnesium >1.5 mmol/L were asked to fill in the standard 3-day nutritional questionnaire. The control group consisted of twice as many randomly selected HD patients with serum magnesium concentration <1.5 mmol/L and 20 subjects with normal kidney function on usual diet.Results: Mean (±standard deviation) serum magnesium concentration in HD patients was 1.32 ± 0.18 mmol/L. Hypermagnesemia >1.5 mmol/L was found in 17 (16.8%) patients. There was no one case of severe hypermagnesemia (>2.0 mmol/L). The daily intake of magnesium was higher by 31.7% in the group with serum magnesium >1.5 mmol/L. Hypermagnesemia was observed in patients ingesting >281 mg of magnesium daily. In univariate analysis, there was a strong positive correlation between magnesium intake and serum concentration in the whole group (r = 0.870, P < .001). No correlation between Kt/V or residual diuresis and serum magnesium concentration was found.Conclusions: Magnesium consumption is the most important determinant of serum magnesium concentration in HD patients with CKD. Magnesium-containing phosphate binders can be considered in the therapy of hyperphosphatemia in HD patients without hypermagnesemia.

Relationship Between Appetite and Symptoms of Depression and Anxiety in Patients on Chronic Hemodialysis

2011-06-20

Objective: We aimed at evaluating the association between appetite and symptoms of depression and anxiety, cognitive dysfunction, fatigue, and comorbidities in patients on hemodialysis (HD).Design: A cross-sectional study was conducted.Setting: The study was conducted in an outpatient HD service of a tertiary level academic hospital.Patients: A total of 90 patients on HD were evaluated for appetite (during the past week, how would you rate your appetite?), symptoms of depression (Beck Depression Inventory [BDI]) and anxiety (Hamilton Anxiety Rating Scale [HARS]), cognitive dysfunction (Mini Mental State Examination [MMSE]), and comorbidities (Charlson Comorbidity Index).Main Outcome Measure: Relationship between appetite and symptoms of depression and/or anxiety, cognitive dysfunction, and comorbidities was assessed.Results: In 43 patients, the appetite was very good/good (group 1), in 22, it was fair (group 2), and in 25, it was poor/very poor (group 3). Mean and median BDI were significantly higher in group 3 as well as the percentage of patients with BDI ≥16. Mean and median HARS and the percentage of patients with HARS >13 were significantly higher in group 3. MMSE was significantly lower in group 3 as well as the percentage of patients with MMSE ≤23. Multiple linear regression analysis showed a dependence of appetite by age and BDI (P = .007 and P = .002, respectively).Conclusions: Anorexia is associated with older age and symptoms of depression in patients on HD.

Converting to Doxercalciferol Capsules From Intravenous Paricalcitol or Doxercalciferol

2011-06-09

Objective: The purpose of the 2 studies presented in this article was to determine the clinically appropriate dose of doxercalciferol capsules that is required to maintain similar intact parathyroid hormone control when converting from intravenous (IV) paricalcitol or doxercalciferol.Design: Both studies were multicenter, open-label, randomized designs comprising the following 3 periods: a screening period, a 5-week run-in period, and a 5-week treatment period.Setting: Dialysis centers in the United States.Patients: Patients with stage 5 chronic kidney disease receiving dialysis 3 times weekly for a minimum of 6 months and with recent intact parathyroid hormone measurements between 15.9 and 63.7 pmol/L (150 to 600 pg/mL) were included.Intervention: After a 5-week fixed-dose IV paricalcitol or doxercalciferol run-in period, subjects were randomized to doxercalciferol capsules for the 5-week treatment period. Conversion factors for the paricalcitol study were 0.5, 1.0, and 1.5 times the current paricalcitol dose. Conversion factors for the doxercalciferol study were 1.0, 1.5, and 2.0 times the current doxercalciferol injection dose.Results: The predicted conversion factor for paricalcitol injection to doxercalciferol capsules was 0.92, whereas the factor for doxercalciferol injection to doxercalciferol capsules was 1.49. No statistically significant changes in serum calcium and phosphorus levels were found in either study. The nature of adverse events was consistent with the administration of an active vitamin D therapy to patients with chronic kidney disease receiving dialysis.Conclusion: The studies demonstrate patients on dialysis can be safely and effectively converted from IV paricalcitol or doxercalciferol to oral doxercalciferol.

Interdialytic Weight Gain Does Not Influence the Nutrition of New Hemodialysis Patients

Yu-Wei Chen, Han-Hsiang Chen, Chi-Feng Pan, Chiung-Ying Chang, Chih-Jen Wu — 2011-05-27

Objective: The aim of the present study was to assess the relationship between interdialytic weight gain (IDWG) and nutrition markers in hemodialysis (HD) patients, by means of repeated measures analysis.Methods: The records of 255 patients, who had recently received conventional HD for a minimum of 1 year, were retrospectively reviewed. Nutrition markers, including serum albumin, serum phosphate, blood urea nitrogen, and creatinine, were recorded at monthly intervals and subjected to repeated measures analysis.Results: Patients with higher IDWG/dry weight (IDWG%) (>5%) had significantly lower body mass index throughout the study. Repeated measures analysis of variance indicated no significant difference in these nutrition markers for patients with different IDWG%. At the end of the study, neither IDWG nor IDWG% were found to be associated with albumin or phosphate, on linear regression analysis.Conclusions: There was no evidence of better nutrition in new HD patients with higher IDWG%. Although increased intake is promoted as critical for improving nutritional status in HD patients, it may be inappropriate to focus solely on the benefits of higher IDWG%, which can also lead to the development of hypertension, left ventricular hypertrophy, and intradialytic hypotension.

Oral Supplementation of Turmeric Decreases Proteinuria, Hematuria, and Systolic Blood Pressure in Patients Suffering From Relapsing or Refractory Lupus Nephritis: A Randomized and Placebo-controlled Study

2011-07-11

Objective: Despite highly expensive treatments, lupus nephritis remains a major cause of morbidity and mortality in patients with relapsing or refractory lupus nephritis. Meanwhile, experimental studies indicate that curcumin attenuates both the binding of autoantibodies from systemic lupus erythematosus patients to their cognate antigens and also the inflammatory responses of tumor necrosis factor-alpha-stimulated human endothelial cells. Therefore, in this study we investigated effect(s) of oral curcumin supplementation on patients suffering from relapsing or refractory lupus nephritis.Design: A randomized and placebo-controlled study was carried out.Setting: The present study was conducted in Lupus clinic of Hafez Hospital, Out-Patient Department of Shiraz University of Medical Sciences.Patients: A total of 24 patients with relapsing or refractory biopsy-proven lupus nephritis, who were randomized in 2 groups (trial [n = 12] and control [n = 12] groups) were included in this study.Intervention: With each meal, each patient in the trial group received 1 capsule for 3 months, which contained 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (3 capsules daily). The control group received 3 capsules (1 with each meal) for the same period, which contained starch and were identical in color and size to capsules given to patients in the trial group.Main Automatic Measure: Data were analyzed using Statistical Package for the Social Sciences software version 15.0.Results: A significant decrease in proteinuria was found when comparing pre- (954.2 ± 836.6) and 1, 2, and 3 months supplementation values (448.8 ± 633.5, 235.9 ± 290.1, and 260.9 ± 106.2, respectively) in the trial group. Also, systolic blood pressure and hematuria were found to decrease significantly when pre- and post-turmeric supplementation values were compared in the trial group. However, placebo capsules did not exert any statistically significant effect on measured variables in the control group over 3 months of the study. No adverse effect related to turmeric supplementation was observed during the trial.Conclusion: Short-term turmeric supplementation can decrease proteinuria, hematuria, and systolic blood pressure in patients suffering from relapsing or refractory lupus nephritis and can be used as an adjuvant safe therapy for such patients.

Association Between Vascular Calcification Scores on Plain Radiographs and Fatty Acid Contents of Erythrocyte Membrane in Hemodialysis Patients

2011-05-27

Objective: Vascular calcification (VC) scores determined by using simple plain radiographic films are known to be associated with coronary artery disease and mortality in patients undergoing hemodialysis (HD). Omega-3 fatty acid (FA) has been shown to reduce ectopic calcifications in an animal model, and it has also been shown that erythrocyte membrane omega-3 FA content is an independent discriminator of coronary artery disease. The present study was designed to demonstrate relations between VC scores and erythrocyte membrane FA contents in patients undergoing HD.Design: A cross-sectional study was carried out.Setting: The study was carried out at an outpatient hemodialysis unit at Dong-A University Hospital, Busan, Republic of Korea.Patients: A total of 31 patients undergoing HD were recruited. Patients with significant malnutrition, a short duration of dialysis (<12 months), a history of recent infection, malignancy, or liver disease were excluded.Main Outcome Measures: Plain radiographic films of the feet, hands, pelvis, and lateral lumbar spine were examined and VC scores were determined using previously reported methods. Erythrocyte membrane FA contents were analyzed by gas chromatography.Results: The erythrocyte membrane contents of eicosapentaenoic acid and docosahexaenoic acid were not found to be related with VC on simple plain radiographic films. However, erythrocyte membrane contents of oleic acid and total monounsaturated FA (MUFA) were significantly higher in patients with significant VC scores. Furthermore, erythrocyte membrane contents of MUFA and oleic acid were found to be negatively associated with high-density lipoprotein cholesterol level and positively associated with triglyceride level.Conclusion: Erythrocyte membrane contents of MUFA and oleic acid were found to be associated with VC scores determined using plain radiographs and with dyslipidemia in patients undergoing HD.

Seasonal Changes in Phosphorus Content of Fish Tissue as They Relate to Diets of Renal Patients

Sana Ghaddar, I. Patrick Saoud — 2011-07-11

Objective: To investigate seasonal variations in tissue phosphorus (P) levels, P to protein ratio, and P to omega-3 fatty acid (ω3-FA) ratio in 2 species of fish that are commonly consumed in Lebanon. We aim to determine suitability for dietary management of renal patients.Design and Setting: Siganus rivulatus (rabbitfish) and Diplodus sargus (white seabream) were caught in traps off the coast of Beirut and transported on ice to the laboratory during various seasons. Fillets of fish were removed, dried to constant weight at 95°C, finely ground, and stored at −20°C. Protein, P, P to protein ratio, and P to ω3-FA ratio were determined.Results: Compared with white seabream (carnivore), rabbitfish (algaevore) had a significantly lower mean P content (±SE) (895 ± 32 mg/100 g vs. 1,132 ± 23 mg/100 g; P < .0001), a significantly lower P to protein ratio (±SE) (10.35 ± 0.39 vs. 13.15 ± 0.34 mg P/g of protein; P < .001), and a significantly lower P to ω3-FA ratio (±SE) (2.81 ± 0.29 vs. 5.93 ± 1.05 g of ω3-FA/g of P; P < .005). P content in flesh of both species varied significantly with season (P < .0001). Rabbitfish P content was least in August and greatest in June (P < .05), whereas white seabream P content was greatest in April and least in June (P < .05). Rabbitfish muscle P to protein ratio and P to ω3-FA ratio was least in August, with a significantly greater P to ω3-FA ratio during the rest of the year. White seabream exhibited wider seasonal variation in P to protein ratio and P to ω3-FA ratio as compared with rabbitfish.Conclusion: Because of differences and seasonal variations in P levels that exist among fish species, renal dietitians may need to identify the seasonal proximate composition of individual fish species in various habitats and formulate dietary regimens accordingly. Such advice notwithstanding, oily marine fish remain a healthy food choice for dialysis patients if the fillet is consumed without bones.

Call to Arms…

Lisa Gutekunst — 2012-01-01

MY FELLOW RENAL dietitian, if ever there was a time to stand up, make noise, and be heard, it is now. We as renal healthcare professionals can no longer sit by in the wings as Medicare and dialysis units make policies that negatively impact our patients’ lives and outcomes. I am outraged by the changes that I have seen in the past year. I am disappointed that policies are made and implemented without thinking about how they will affect those that we serve. I am disheartened that one day, I, a family member, or a friend will have to submit to the suboptimal care that these policies have created. We, as a profession, knew that there would be changes in how we treat our patients when the bundled reimbursement plan came into effect last year. I could never imagine the turn that it would take.

January 2012 Meeting Announcements

2012-01-01

February 14-17, 2012 17th Continuous Renal Replacement Therapies (CRRT) Conference, Sans Diego, California. Visit www.crrtonline.comor call 858-272-1018. February 26-28, 2012 32nd Annual Dialysis Conference, San Antonio, Texas. Visit http://som.missouri.edu/dialysis or call 573-882-4105.

Nutrition Supplementation and Chronic Kidney Disease: What Are the Options?

Amy Braglia Tarpey — 2012-01-01

LOW SERUM ALBUMIN and low protein intake are independently associated with increased risk of mortality in the hemodialysis and peritoneal dialysis populations. In a hypothetical theoretical model, interventions to improve serum albumin by just 0.2 g/dL in 50% of all dialysis patients with albumin levels less than 3.5 g/dL were projected to potentially save 1,400 lives and decrease hospitalizations by 6,300 per year. However, dialysis patients may underestimate the importance of these factors in their overall health at the onset of dialysis. One of these factors may include being overwhelmed with information from various health care practitioners, including physicians, nurses, dietitians, and social workers. Nutrition counseling focused on increasing protein intake is often undertaken in the face of many obstacles. Some of these obstacles may include lack of patient readiness to make changes in food intake, inadequate monetary funds, dysgeusia, poor gastrointestinal function, poor appetite, depression, and low energy levels between dialysis treatments. As a result, nutritional supplementation has become a routine part of life for many dialysis patients. Given that mortality rises significantly as albumin levels decrease below 3.8 g/dL, it is important for the dietitian to start implementing nutritional supplementation in the earlier stages of malnutrition. In general, oral supplementation is the first and most frequently used nutrition intervention, followed or supplemented by enteral tube feeding. If these treatments fail to improve albumin levels and stabilize weight, are deemed unacceptable or medically inappropriate for the patient, or if additional supplementation is required, intradialytic parenteral nutrition or intraperitoneal nutrition may be an option for patients.

Medication Reminder Systems: An Adjunct Technique in Improving Phosphate Binder Adherence

Thessa Obrero Churillo — 2012-01-01

IT IS A known fact that hyperphosphatemia is one of the risk factors for cardiovascular disease among patients with chronic kidney disease (CKD). According to the Kidney Disease Outcome and Quality Initiative (K-DOQI) Bone Metabolism and Chronic Kidney Disease Guidelines, recommended serum phosphorus levels should be maintained between 3.5 and 5.5 mg/dL. The Kidney Disease Improving Global Outcomes (KDIGO) suggests lowering elevated phosphorus levels toward the normal range.

Uremia Research and Toxicity

Shaul G. Massry, Toshimitsu Niwa, Boleslaw Rutkowski — 2012-01-01

We are pleased to provide the readers of the Journal of Renal Nutrition with the Proceedings of the Seventh International Congress on Uremia Research and Toxicity, which was held in Nagoya, Japan on May 12 to 14, 2011. The Congress was sponsored by the International Society of Uremia Research and Toxicity, and it was attended by 290 clinicians and scientists from 20 countries, including Belgium, China, Czech Republic, France, Germany, Hong Kong, Indonesia, Italy, Japan, Poland, Singapore, Slovakia, South Korea, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, and United States of America.

Dysregulated Oxygen Metabolism of the Kidney by Uremic Toxins: Review

Chih-Kang Chiang, Tetsuhiro Tanaka, Masaomi Nangaku — 2012-01-01

Because kidneys consume a large amount of oxygen and are relatively inefficient in oxygen uptake, they are susceptible to hypoxia, especially in patients with advanced chronic kidney disease accompanied by loss of peritubular capillaries. Accumulating evidence suggests that chronic tubulointerstitial hypoxia acts as a final common pathway leading to end-stage renal disease. Some biologically active uremic retention molecules, considered as uremic toxins, accumulate as the renal function declines, and at this moment, more than 90 bioactive uremic toxins have been identified. Uremic toxins per se have been proven to accelerate the progression of renal failure. However, the causal relationship between uremic toxin and tubulointerstitial hypoxia remains unclear. Our studies provided direct evidence that uremic toxin dysregulates oxygen metabolism in the kidney. Indoxyl sulfate (IS), a representative protein-bound uremic toxin, increased oxygen consumption in proximal renal tubules, decreased renal oxygenation, and consequently aggravated hypoxia in the remnant rat kidneys. The increase in tubular oxygen consumption by IS was dependent on sodium–potassium adenosine triphosphatase and oxidative stress. Our work also indicated a possible connection between IS and the desensitization of the oxygen-sensing mechanism in erythropoietin-producing cells, which may partly explain inadequate erythropoietin production in hypoxic kidneys of end-stage renal disease patients. Studies of uremic toxins will open a new avenue in development of novel therapeutic approaches of kidney disease.

Adipokines as Uremic Toxins

Daniel Teta — 2012-01-01

The adipose tissue has pleiotropic functions far beyond the mere storage of energy, and it secretes a number of hormones and cytokines, called adipokines, which have biological effects that impact heath and disease. Adipokines are markedly elevated in the plasma of uremic patients, mainly due to decreased renal excretion. They have pluripotent signaling effects on inflammation/oxidative stress (leptin, adiponectin, resistin), protein-energy wasting (leptin, adiponectin), insulin signaling (adiponectin, leptin, visfatin), endothelial dysfunction (visfatin), and vascular damage (adiponectin, leptin, resistin), which are prevalent in uremic patients. Obesity superimposed to uremia may further aggravate hyperadipokinemia, with the exception of adiponectinemia, which is mitigated by adiposity. Among adipokines and until more data become available, only leptin may be considered as a full uremic toxin owing to adverse effects on protein-energy wasting, cardiovascular damage, inflammation, and the immune system, which have been documented both clinically and experimentally. Resistin and visfatin display some features of uremic toxins, but more data are needed to consider these adipokines as true uremic toxins. In contrast, high levels of adiponectin and chemerin seen in uremia appear to be beneficial. Further research is needed to investigate whether selective removal of leptin, resistin, and visfatin and increments of adiponectin and chemerin levels may have clinical relevance in uremic patients.

Indoxyl Sulfate Induces Endothelial Cell Senescence by Increasing Reactive Oxygen Species Production and p53 Activity

2012-01-01

Background/Aim: We have reported that indoxyl sulfate (IS), a uremic toxin, accelerates proximal tubular cell senescence. Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been reported to induce endothelial cell senescence. This study aimed to determine whether IS induces endothelial cell senescence in comparison with ADMA, and to investigate its molecular mechanism.Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with IS (250 μM) and/or ADMA (10 μM). These concentrations were comparable with their mean serum levels in hemodialysis patients. Cell senescence was evaluated by measuring senescence-associated beta-galactosidase (SA-β-gal) activity. N-acetylcysteine, an antioxidant, and pifithrin alpha p-nitro, a p53 inhibitor, were used to determine the role of reactive oxygen species (ROS) and p53 in the induction of cell senescence.Results: Both IS and ADMA significantly increased SA-β-gal activity in HUVECs. Further, some additional increase in SA-β-gal activity was observed when IS and ADMA were co-incubated. Preincubation of N-acetylcysteine or pifithrin alpha p-nitro significantly inhibited SA-β-gal activity induced by IS and ADMA in HUVECs. Thus, both IS and ADMA induced endothelial senescence through ROS and p53.Conclusion: IS induces endothelial cell senescence by increasing ROS production and p53 activity, like ADMA.

An Update on Protein-Bound Uremic Retention Solutes

2012-01-01

Although protein-bound uremic retention solutes are recognized as 1 of the 3 main categories of uremic retention solutes, they only recently have been submitted to thorough analysis. In vitro and ex vivo data link both p-cresyl sulfate and indoxyl sulfate, two of the main compounds of this solute group, to negative impact on the cardiovascular system and progression of kidney failure. Recent in vivo observational data also relate concentration of these compounds to survival outcome, inflammation, and vascular disease in different, even moderate, stages of chronic kidney disease. Removal by different dialysis strategies, even high-flux hemodialysis, is difficult, and only by applying convection, some improvement of removal has been obtained. The other strategy with the potential to decrease concentration is by influencing intestinal generation and/or absorption. The sorbent Kremezin (AST-120) has been shown in controlled studies to decrease protein-bound solute concentration. In pilot controlled studies, AST-120 has been shown to be superior on outcome parameters to placebo. Results from large randomized trials are awaited, before these data can be considered as solid enough to warrant the recommendation to use these compounds for overall therapeutic purposes.

Cellular Toxicity of Nicotinamide Metabolites

2012-01-01

There are almost 100 different substances called uremic toxins. Nicotinamide derivatives are known as new family of uremic toxins. These uremic compounds play a role in an increased oxidative stress and disturbances in cellular repair processes by inhibiting poly (ADP-ribose) polymerase activity. New members of this family were discovered and described. Their toxic properties were a subject of recent studies. This study evaluated the concentration of 4-pyridone-3-carboxamid-1-β-ribonucleoside-triphosphate (4PYTP) and 4-pyridone-3-carboxamid-1-β-ribonucleoside-monophosphate (4PYMP) in erythrocytes of patients with chronic renal failure.Serum and red blood cells were collected from chronic renal failure patients on conservative treatment, those treated with hemodialysis, and at different times from those who underwent kidney transplantation. Healthy volunteers served as a control group. Nicotinamide metabolites were determined using liquid chromatography with mass spectrometry based on originally discovered and described method. Three novel compounds were described: 4-pyridone-3-carboxamid-1-β-ribonucleoside (4PYR), 4PYMP, and 4PYTP.4PYR concentration was elevated in the serum, whereas 4PYMP and 4PYTP concentrations were augmented in erythrocytes of dialysis patients. Interestingly, concentrations of these compounds were less elevated during the treatment with erythropoietin-stimulating agents (ESAs). After successful kidney transplantation, concentrations of 4PYR and 4PYMP normalized according to the graft function, whereas that of 4PYTP was still elevated. During the incubation of erythrocytes in the presence of 4PYR, concentration of 4PYMP rose very rapidly while that of 4PYTP increased slowly. Therefore, we hypothesized that 4PYR, as a toxic compound, was actively absorbed by erythrocytes and metabolized to the 4PYMP and 4PYTP, which may interfere with function and life span of these cells.

Role of Uremic Toxins and Oxidative Stress in the Development of Chronic Kidney Disease–Mineral and Bone Disorder

2012-01-01

The kidney plays an important role in the regulation of mineral metabolism. As kidney function declines, there is a progressive deterioration in mineral homeostasis, along with various abnormalities, including bone disease and vascular calcification, which has recently been named as “Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).” Although the precise mechanisms of this systemic disorder remain to be elucidated, accumulating evidence suggest that uremic toxins contribute substantially to the development of CKD–MBD, partly through evoking oxidative stress in the bone and cardiovascular systems. This brief review summarizes recent work on the role of uremic toxins and oxidative stress in the development of CKD–MBD.

Indoxyl Sulfate Induces Nephrovascular Senescence

Toshimitsu Niwa, Hidehisa Shimizu — 2012-01-01

Indoxyl sulfate is markedly accumulated in the serum of chronic kidney disease (CKD) patients. The oral sorbent AST-120 reduces serum levels of indoxyl sulfate in CKD patients by adsorbing indole, a precursor of indoxyl sulfate, in the intestine. Indoxyl sulfate is taken up by proximal tubular cells through organic anion transporters (OAT1, OAT3), and it induces reactive oxygen species (ROS) with impairment of cellular antioxidative system. Indoxyl sulfate stimulates progression of CKD by increasing renal expression of profibrotic cytokines such as transforming growth factor beta 1. Further, it promotes the expression of p53 by ROS-induced activation of nuclear factor kappa B, thereby accelerating senescence of proximal tubular cells with progression of CKD. Administration of indoxyl sulfate to hypertensive rats reduces renal expression of Klotho and promotes cell senescence, with expression of senescence-associated beta-galactosidase, p53, p21, p16, and retinoblastoma protein, accompanied by kidney fibrosis. Indoxyl sulfate downregulates Klotho expression in the kidneys through production of ROS and activation of nuclear factor kappa B in proximal tubular cells. It promotes cell senescence, with expression of senescence-associated beta-galactosidase, p53, p21, p16, and retinoblastoma protein, in the aorta of hypertensive rats. It also promotes aortic calcification and aortic wall thickening in hypertensive rats with expression of osteoblast-specific proteins, induces ROS in vascular smooth muscle cells and vascular endothelial cells, stimulates proliferation and osteoblastic transdifferentiation of vascular smooth muscle cells, and inhibits viability and nitric oxide production of vascular endothelial cells. Thus, indoxyl sulfate accelerates the progression of not only CKD but also of cardiovascular disease by inducing nephrovascular cell senescence.

A Nexus of Progression of Chronic Kidney Disease: Tryptophan, Profibrotic Cytokines, and Charcoal

Gerald Schulman — 2012-01-01

Fibrosis plays a major role in the pathogenesis of progressive chronic kidney disease (CKD). The inhibition of the renin-angiotensin system, which promotes fibrosis, has become the standard of care in the treatment of patients with CKD. The use of alternative agents capable of blocking the actions of profibrotic cytokines such as transforming growth factor-beta (TGF-β) is also an important strategy that is in its early stages of development. An example of such a drug is AST-120, a charcoal compound that ultimately inhibits the synthesis of TGF-β in the kidney. The inhibition is mediated by blocking the intestinal absorption of tryptophan-derived indole by AST-120. This reduces the hepatic conversion of indole to indoxyl sulfate (IS). IS stimulates the production of TGF-β in the renal parenchyma, and lowering the level of IS with AST-120 appears to slow progression of CKD. The status of recent trials examining the safety and efficacy of AST-120 has been described, including a multicenter, randomized, placebo-controlled, phase III trial of approximately 2,000 subjects being conducted to gain approval of this drug by the U.S. Food and Drug Administration.

SIRTUIN 1 Gene Polymorphisms are Associated With Cholesterol Metabolism and Coronary Artery Calcification in Japanese Hemodialysis Patients

2012-01-01

Objectives: Sirtuin 1 (SIRT1), a longevity gene, protects cells against oxidative and genotoxic stress. This study aimed to investigate the association of SIRT 1 gene single-nucleotide polymorphisms, namely, rs7895833, rs7069102, and rs2273773 with lipid profiles and coronary artery calcification score in 219 Japanese hemodialysis (HD) patients.Methods: Genotyping of these polymorphisms was performed using polymerase chain reaction with confronting two-pair primers assay.Results: The A allele frequency of rs7895833 and G allele frequency of rs7069102 were significantly lower in HD patients (0.228 and 0.131, respectively) than those in 803 control subjects (general population) (0.289 and 0.181, respectively) (P = .010 and P = .012, respectively). However, the allele frequency of rs2273773 was not significantly different from that in the control subjects. Multivariate analysis adjusted for age and duration on HD demonstrated that the serum levels of total and low-density lipoprotein cholesterol were significantly high in G allele carriers of rs7069102 compared with CC genotype in male HD patients. Coronary artery calcification score was significantly high in C allele carriers of rs2273773 in all and male HD patients.Conclusions: SIRT 1 polymorphisms, rs7069102 and rs2273773, are associated with abnormal cholesterol metabolism and coronary artery calcification, respectively, in Japanese HD patients, especially in males.

Cardiovascular Biomarkers in Chronic Kidney Disease

Sun-Hee Park, Peter Stenvinkel, Bengt Lindholm — 2012-01-01

Cardiovascular disease (CVD) is the major cause of death in patients with advanced chronic kidney disease (CKD). Recent studies have suggested that novel risk factors, uremia- or dialysis-related, are of great importance, as they act synergistically with the highly prevalent traditional risk factors for CVD in CKD patients. Whereas an ideal single biomarker, i.e., one that adds relevant prognostic information in clinical practice over and above that provided by conventional (Framingham) risk factors, has yet to be identified, combinations of several biomarkers or repeated measurements of biomarkers may increase the explanatory power of prognostic information provided by traditional risk factors to predict cardiovascular outcomes. However, because the increase of predictive power is modest, clinical assessment of patient status still remains the cornerstone tool for predicting risk for CVD. On the other hand, the search for better biomarkers may reveal novel pathways linked to CVD that need to be explored in CKD patients. This brief review summarizes some emerging and potentially clinically applicable CVD biomarkers in CKD patients, especially focusing on inflammation and vascular calcification that may provide additional information to conventional risk factors.

AGEs and Cardiovascular Diseases in Patients With End-Stage Renal Diseases

Yoshiki Nishizawa, Hidenori Koyama, Masaaki Inaba — 2012-01-01

Cardiovascular disease is the major cause of death in patients with renal insufficiency, accounting for 50% of all deaths in renal replacement therapy patients. Mortality from cardiovascular diseases in these patients is approximately 9% per year, which is about 30 times the risk in the general population. So far, intensive interventions to the general risk factors, such as high levels of low-density lipoprotein -cholesterol or C-reactive protein, have not been successful in improving their cardiovascular outcomes, suggesting that the beneficial effect of risk reduction may be overwhelmed by accumulated risk memorized by long-term exposure to oxidative stress during the progression of renal failure. This irreversible memory effect may be mediated by advanced glycation end products (AGEs), the generation of which has been implicated to be deeply associated with increased oxidative stress. To examine whether circulating AGEs predict future cardiovascular events, a cohort containing 386 (243 male, 142 female) hemodialysis patients was set up. The patients were examined for plasma pentosidine at registration (December 2005) and were followed until March 2010. Patients with high tertile for plasma pentosidine exhibited significantly higher risk for cardiovascular events (hazard risk: 1.74, 95% confidence interval: 1.11 to 2.74, P = .017). Comparisons of the risk of high plasma pentosidine in key subgroups showed that the risk of the high tertile was more prominent in patients with low serum albumin levels. Thus, AGE levels could represent accumulated oxidative stress during the progression of CKD, and their measurements would be useful for stratification of the cardiovascular risks in patients with ESRD.

Carbamylated Low-Density Lipoprotein: Nontraditional Risk Factor for Cardiovascular Events in Patients With Chronic Kidney Disease

Eugene O. Apostolov, Alexei G. Basnakian, Ercan Ok, Sudhir V. Shah — 2012-01-01

The high cardiovascular morbidity and mortality associated with chronic kidney disease (CKD) cannot be explained entirely by traditional risk factors. Urea spontaneously dissociates to form cyanate, which modifies proteins in a process referred to as carbamylation. Carbamylated low-density lipoprotein (cLDL) has been shown to have all of the major biological effects relevant to atherosclerosis, including endothelial cell injury, increased expression of cell adhesion molecules, and vascular smooth muscle cell proliferation. Recent studies indicate that cLDL leads to endonuclease G activation, which participates in cellular injury. In addition, cLDL has been shown to enhance generation of oxidants. Limited human data have demonstrated high levels of cLDL in hemodialysis patients, with the highest levels in patients who have atherosclerosis. In 2 separate clinical studies, plasma levels of carbamylated protein independently predicted an increased risk of coronary artery disease, future myocardial infarction, stroke, and death. Future prospective studies to examine the association and/or predictive value of cLDL and studies to establish cause–effect relationship in patients with CKD are needed.

Coronary Artery Calcification Score is Associated With Mortality in Japanese Hemodialysis Patients

Yasuhiko Shimoyama, Yoshinari Tsuruta, Toshimitsu Niwa — 2012-01-01

Objective: Coronary artery calcification has been associated with higher mortality in coronary artery disease and chronic kidney disease. This study aimed to correlate coronary artery calcification score (CACS) with all-cause and cardiovascular mortalities in hemodialysis (HD) patients.Design, Setting, Subjects: A survival analysis was conducted in 200 HD patients. CACS was assessed by multidetector-row computed tomography and stratified as tertiles: group 1 (0∼105 U), group 2 (110∼1067 U), and group 3 (1094∼15481 U). The duration of follow-up was 7 years and 4 months. Kaplan–Meier method and Cox proportional hazard analysis adjusted for age and HD duration were performed to examine the impact of CACS on survival.Main Outcome Measure: All-cause and cardiovascular mortalities were measured.Results: The cumulative all-cause and cardiovascular mortalities of group 1 were significantly lower than those of groups 2 and 3 (all-cause mortality: 7.6% vs. 43.3% and 52.2%, respectively, cardiovascular mortality: 3.0% vs. 22.4% and 26.9%, respectively). Cox proportional hazard analysis adjusted for age and HD duration revealed that all-cause and cardiovascular mortalities of group 1 were significantly lower than those of groups 2 and 3.Conclusion: CACS is helpful to predict prognosis of HD patients independently of age and HD duration.

Advanced Oxidation Protein Products and Advanced Glycation End Products in Children and Adolescents With Chronic Renal Insufficiency

2012-01-01

Objective: Advanced oxidation protein products (AOPPs) represent dityrosine-containing cross-linked protein modifications formed mainly via myeloperoxidase reaction, supposed to accelerate the uremia-associated atherogenesis and renal fibrosis.Design, Subjects, and Main Outcome Measures: In a cross-sectional study, we investigated the accumulation of AOPPs and advanced glycation end product (AGE)-specific fluorescence corrected for albumin in children and adolescents with chronic renal failure (CRF, n = 42), end-stage renal disease (ESRD, n = 12), kidney transplanted patients (Tx, n = 16), and age-matched healthy controls (n = 38).Results: AOPP levels were 2.4-fold higher in the CRF and ESRD patients, and 1.6-fold higher in the transplanted subjects when compared with the controls (P < .001). In comparison with healthy controls, AGE levels rose 2-fold in the CRF, 7-fold in the ESRD, and 5-fold in the kidney transplanted children and adolescents, (P < .001). Patients with cardiovascular affliction presented with higher AGE levels than those without diagnosed cardiovascular disease (P < .02). In patients with stabilized renal function, AOPP and AGE levels did not change significantly during 12 months.Conclusion: Pattern of accumulation of AOPP and AGE in children and adolescents with chronic renal disease differs. Accelerated rise in AOPP levels in some children and adolescents in predialysis stage of chronic renal insufficiency, inadequate to deterioration of renal function, might require further attention.

Effect of Uremia on Structure and Function of Immune System

Nosratola D. Vaziri, Madeleine V. Pahl, Albert Crum, Keith Norris — 2012-01-01

End-stage renal disease (ESRD) is simultaneously associated with immune activation, marked by systemic inflammation, and immune deficiency. Systemic inflammation contributes to atherosclerosis, cardiovascular disease, cachexia, and anemia, whereas immune deficiency leads to impaired response to vaccination, and increased incidence and severity of microbial infections. ESRD-associated inflammation and immune deficiency are associated with the following: (a) general expansion of monocytes and elevations of their basal integrin, Toll-like receptor (TLR)-2, TLR-4 expression, cytokine production, and reactive oxygen species (ROS) generation and reduced phagocytic capacity, (b) depletion and impaired inhibitory activity of regulatory T cells, (c) spontaneous activation, degranulation, increased basal ROS production, decreased phagocytic capacity, and increased apoptosis of the circulating polymorphonuclear leukocytes, (d) upregulation of ROS production machinery and chemokine expression in the cellular constituents of various tissues, highlighting participation of nonimmune cells in the prevailing inflammatory state, (e) depletion of the antigen-presenting dendritic cells, (f) reduced CD4/CD8 T cell ratio and depletion of naïve and central memory T cells, (g) diffuse B cell lymphopenia leading to impaired humoral immunity, and (h) increased proinflammatory activity of low-density lipoprotein and reduced anti-inflammatory capacity of high-density lipoprotein. Thus, ESRD-associated inflammation is due to activation of innate immune system, orchestrated by monocytes, macrophages, granulocytes, and cellular constituents of other organs/tissues. This is coupled with immune deficiency that is caused by depletion of dendritic cells, naïve and central memory T cells and B cells, and impaired phagocytic function of polymorphonuclear leukocytes and monocytes.

International Evaluation of Unrecognizably Uglifying Human Faces in Late and Severe Secondary Hyperparathyroidism in Chronic Kidney Disease. Sagliker Syndrome. A Unique Catastrophic Entity, Cytogenetic Studies for Chromosomal Abnormalities, Calcium-Sensing Receptor Gene and GNAS1 Mutations. Striking and Promising Missense Mutations on the GNAS1 Gene Exons 1, 4, 10, 4

2012-01-01

Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS.

New-Onset Posttransplant Diabetes Mellitus Begins in the Dialysis Period

Katarzyna Madziarska, Marian Klinger — 2012-01-01

Objectives: New-onset posttransplant diabetes mellitus (PTDM) affects >20% of transplant recipients at 1 year and is associated with increased risk of mortality. From the pathogenetic point of view, PTDM can be considered as the consequence of predisposing factors existing in the dialysis period, which are triggered by immunosuppressive drugs, calcineurin inhibitors, mTOR inhibitors, and steroids.Design, Patients, and Main Outcome Measure: In our own study, the independent predictors of PTDM were recipient age, a positive family history of diabetes, and treatment by peritoneal dialysis. Other clinical investigations have added the presence of metabolic syndrome components and hepatitis C infection to this list.Conclusions: Estimation of the risk of development of PTDM should be an integral element in the qualification process for the waiting list. An intensive lifestyle modification program should be offered to candidates with impaired glucose tolerance.

Muscle and Fat Metabolism in Obesity After Kidney Transplantation: No Effect of Peritoneal Dialysis or Hemodialysis

2012-01-01

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 μg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 μmol/L; P < .01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.

Ghrelin and Muscle Metabolism in Chronic Uremia

2012-01-01

Patients with chronic kidney disease (CKD) are prone to nutritional complications with negative prognostic impact. In particular, protein–energy wasting is a major CKD-associated clinical burden, and emerging evidence indicates that clustered metabolic alterations, including inflammation, oxidative stress, and insulin resistance, contribute to loss of skeletal muscle mass. Ghrelin is a gastric hormone discovered in its acylated form and extensively studied for its appetite-stimulating effect. Further studies have shown that ghrelin may positively modulate systemic inflammation and insulin action. In addition, a role of ghrelin in the regulation of redox state has been described in vitro. Ghrelin treatment could therefore represent a potential comprehensive therapeutic approach for CKD-related metabolic and nutritional complications, and evidence supporting this hypothesis has emerged in clinical and experimental CKD. Clinical trials of ghrelin administration are needed to test the hypothesis that ghrelin may chronically improve nutritional status and outcome in CKD patients.

AST-120 Ameliorates Epithelial-to-Mesenchymal Transition and Interstitial Fibrosis in the Kidneys of Chronic Kidney Disease Rats

Dilinaer Bolati, Hidehisa Shimizu, Toshimitsu Niwa — 2012-01-01

Objective: Indoxyl sulfate (IS), a uremic toxin, is a risk factor for progression of chronic kidney disease (CKD). AST-120 reduces serum IS and delays the progression of CKD. This study aimed to examine whether AST-120 inhibits epithelial-to-mesenchymal transition (EMT) in the kidneys of CKD rats.Methods: CKD rats were produced by 5/6 nephrectomy and were divided into 2 groups: (1) CKD rats and (2) AST-120-treated CKD rats at a dosage of 4 g/kg body weight/day. After 10 weeks, their kidneys were excised for histological and immunohistochemical analysis. EMT was evaluated by immunohistochemistry of zonula occludens (ZO-1), an epithelial marker, and alpha-smooth muscle actin (α-SMA), a mesenchymal marker. Interstitial fibrosis was evaluated by Masson’s trichrome staining.Results: CKD rats showed reduced expression of ZO-1 and enhanced expression of α-SMA as compared with normal rats. Administration of AST-120 to CKD rats increased expression of ZO-1 and decreased expression of α-SMA as compared with CKD rats. Further, CKD rats showed enhanced extent of interstitial fibrosis as compared with normal rats, and administration of AST-120 to CKD rats ameliorated interstitial fibrosis. CKD rats showed increased serum level of IS as compared with normal rats, whereas administration of AST-120 to CKD rats decreased both serum and urine levels of IS.Conclusion: We conclude that AST-120 ameliorated EMT and interstitial fibrosis in the kidneys of CKD rats, probably by alleviating IS overload on the kidneys.

Chemical and Physiological Relevance of Glucose Degradation Products in Peritoneal Dialysis

Stefan Mittelmaier, Toshimitsu Niwa, Monika Pischetsrieder — 2012-01-01

Fibrosis and vascular sclerosis are main complications that limit the long-term application of peritoneal dialysis (PD). Low biocompatibility has been largely attributed to the presence of glucose degradation products (GDPs), which are formed during the heat sterilization of PD fluids. GDPs readily modify proteins in the peritoneum, leading to a decline of their biological function. After absorption, GDPs can also promote systemic protein glycation. Additionally, GDPs may augment DNA glycation, a process enhanced in uremia. Apart from their glycating activity, GDPs induce cytotoxicity and interfere with cell signaling in peritoneal mesothelial cells. Targeted screening revealed the nature of the 6 major GDPs with α-dicarbonyl structure as 3-deoxyglucosone, 3-deoxygalactosone, glucosone, glyoxal, methylglyoxal, and 3,4-dideoxyglucosone-3-ene. Valid quantification of these GDPs was achieved by ultrahigh-performance liquid chromatography/diode array detector/tandem mass spectrometry. Identification and quantification of single GDPs allow a structure-dependent risk evaluation. As a consequence, PD fluids and processes can be improved to reduce the GDP burden of patients undergoing PD.

A Brief Review of External Mass Balance and Internal Calcium Redistribution in Dialysis Patients—Is Calcium a Uremic Toxin?

Jochen G. Raimann, Stephan Thijssen, Nathan W. Levin — 2012-01-01

Recent debates between 2 schools of thought on calcium mass balance in dialysis patients and its relevance to disease—one emphasizing external calcium mass balance, and the other, internal calcium redistribution—have created controversy. Due to decreased ability to excrete calcium and loss of endocrine function by the kidney, patients suffering from chronic kidney disease, particularly when requiring dialysis, demonstrate varying degrees of positive or negative calcium balance, vitamin D deficiency, and secondary hyperparathyroidism. Consequently, patients are prone to bone demineralization, with diminished bone strength, and are thus prone to fractures that substantially worsen morbid outcomes in this population. However, intra- and interdialytic positive calcium mass balance creates complications of a different kind, which include the occurrence of vascular and cardiac disease and reduced survival. This review aims to shed light on the mechanisms of and relationships between external calcium mass balance and internal calcium redistribution and their consequences. It also discusses the potential to improve current regimens by means of diffusive and convective calcium mass transfer for the achievement of neutral calcium mass balance.

Hyperhomocysteinemia in Chronic Renal Failure: Alternative Therapeutic Strategies

2012-01-01

Chronic renal failure and uremia represent states wherein high blood levels of homocysteine, a cardiovascular risk factor, are largely resistant to folate therapy. Indeed, normalization of homocysteine levels through vitamin administration is rarely achieved in this population, and this fact could explain, among other causes, the negative results of intervention trials designed to lower cardiovascular risk. Dialysis itself lowers homocysteine levels, albeit transitorily. N-acetylcysteine therapy could induce an additional decrease in homocysteine removal during dialysis, thus representing an alternative approach in the attempt to lower cardiovascular risk in these patients.

Dietary and Synthetic Activators of the Antistress Gene Response in Treatment of Renal Disease

Paul J. Thornalley, Naila Rabbani — 2012-01-01

Renal failure is associated with increased vascular inflammation, oxidative stress and dicarbonyl stress linked to development of cardiovascular disease, and other complications. The endogenous defense to inflammatory, oxidative, and dicarbonyl challenge to vascular function is coordinated by nuclear factor E2–related factor 2 (nrf2), kelch-related erythroid cell-derived protein with CNC homology (ECH) protein 1 (keap1), and antioxidant response element–linked gene expression in the antistress gene response. Intervention trials of the synthetic nrf2 activator, bardoloxone methyl, in patients with advanced diabetic nephropathy, showing improvement of renal function and decreased inflammation, suggest that nrf2 activators may have therapeutic benefit in chronic renal failure. Activators of nrf2 are of both synthetic and dietary origin. The aim of this review is to describe the “nrf2/keap1/antioxidant response element” transcriptional system and studies of this system in renal failure, and to assess the current status and future prospects that dietary nrf2 activators may be of benefit to patients with chronic renal failure.

The Removal of Protein-Bound Solutes by Dialysis

Timothy W. Meyer — 2012-01-01

Protein-bound solutes that accumulate in plasma when the kidneys fail are poorly cleared by conventional dialysis. Means have been developed to reduce the levels of such solutes, either by modifying the dialysis procedure to increase their clearance or by limiting their production. A trial testing whether reducing bound solute levels clinically benefits dialysis patients is required to determine whether these measures should be adopted in routine clinical practice.

Anxiety and Depression in Maintenance Dialysis Patients: Preliminary Data of a Cross-sectional Study and Brief Literature Review

2012-01-01

Background: Anxiety and depression affect the quality of life of maintenance dialysis (MD) patients. There is little information concerning the extent to which the experience of individual hemodialysis treatments engenders anxiety in this patient population. This preliminary study examined the prevalence and severity of anxiety and depression in MD patients and the incidence of anxiety related to dialysis treatment.Methods: One hundred seventy patients, 155 undergoing maintenance hemodialysis and 15 undergoing chronic peritoneal dialysis, were examined. Inclusion criteria included dialysis vintage of at least 6 months. Patients completed the Beck Anxiety Inventory and Beck Depression Inventory and questionnaires that examined their feelings of anxiety related to individual hemodialysis sessions.Results: Patients’ mean age was 56 ± standard deviation of 16 years; dialysis vintage, 55 ± 48 months; 46% were female. The data confirmed a high prevalence of anxiety and depression in MD patients. Many MD patients become anxious, often severely, by merely going for routine hemodialysis treatment and also owing to such common events as being connected to the hemodialyzer by a new person or on hearing their hemodialyzer alarm sound.Conclusion: Anxiety and depression are common in MD patients. Many patients who are well established on MD experience anxiety during individual maintenance hemodialysis treatments.

Survival Is Not Enough

2012-01-01

Survival is not enough is a yearly international event started in 2007 in Naples, Italy, in the week of the World Kidney Day to discuss the needs of renal patients and the quality of life of a category of patients living a machine-dependent life. Renal patients and their associations, philosophers, economists, nephrologists, and health care managers are enrolled to discuss about the possibility to grant the best cures and care without reducing the quality and the quantity of the services the patients need. Various quests have arisen for (1) a new cadre of managers capable of keeping health accounts in balance without cutting expenditure but by reducing waste of resources, (2) the promotion of prevention as the only measure capable of reducing costs in the long run, and (3) the promotion of clinical and translational research. The changes occurring in the health system should be viewed as a window of opportunity, including the advent of the medical–industrial complex firstly described in 1980, an event originating in the United States of America and now spreading worldwide.

Masthead

2012-01-01

Editorial Board

2012-01-01

Guidelines for Contributing Authors

2012-01-01

Journal of Renal Nutrition

Nephrology and Nutrition Leaders Coming to Hawaii for the World Renal Nutrition Week: Why is the 16th Congress in Renal Nutrition and Metabolism in Honolulu, Hawai’i, June 2012, Worth Attending?

Risk Factors for Hypovitaminosis D in Nondialyzed Chronic Kidney Disease Patients

Persistent Homocysteine Metabolism Abnormality Accelerates Cardiovascular Disease in Hemodialyzed Patients—the Nishinomiya Study

Daily Magnesium Intake and Hypermagnesemia in Hemodialysis Patients With Chronic Kidney Disease

Relationship Between Appetite and Symptoms of Depression and Anxiety in Patients on Chronic Hemodialysis

Converting to Doxercalciferol Capsules From Intravenous Paricalcitol or Doxercalciferol

Interdialytic Weight Gain Does Not Influence the Nutrition of New Hemodialysis Patients

Oral Supplementation of Turmeric Decreases Proteinuria, Hematuria, and Systolic Blood Pressure in Patients Suffering From Relapsing or Refractory Lupus Nephritis: A Randomized and Placebo-controlled Study

Association Between Vascular Calcification Scores on Plain Radiographs and Fatty Acid Contents of Erythrocyte Membrane in Hemodialysis Patients

Seasonal Changes in Phosphorus Content of Fish Tissue as They Relate to Diets of Renal Patients

Call to Arms…

January 2012 Meeting Announcements

Nutrition Supplementation and Chronic Kidney Disease: What Are the Options?

Medication Reminder Systems: An Adjunct Technique in Improving Phosphate Binder Adherence

Uremia Research and Toxicity

Dysregulated Oxygen Metabolism of the Kidney by Uremic Toxins: Review

Adipokines as Uremic Toxins

Indoxyl Sulfate Induces Endothelial Cell Senescence by Increasing Reactive Oxygen Species Production and p53 Activity

An Update on Protein-Bound Uremic Retention Solutes

Cellular Toxicity of Nicotinamide Metabolites

Role of Uremic Toxins and Oxidative Stress in the Development of Chronic Kidney Disease–Mineral and Bone Disorder

Indoxyl Sulfate Induces Nephrovascular Senescence

A Nexus of Progression of Chronic Kidney Disease: Tryptophan, Profibrotic Cytokines, and Charcoal

SIRTUIN 1 Gene Polymorphisms are Associated With Cholesterol Metabolism and Coronary Artery Calcification in Japanese Hemodialysis Patients

Cardiovascular Biomarkers in Chronic Kidney Disease

AGEs and Cardiovascular Diseases in Patients With End-Stage Renal Diseases

Carbamylated Low-Density Lipoprotein: Nontraditional Risk Factor for Cardiovascular Events in Patients With Chronic Kidney Disease

Coronary Artery Calcification Score is Associated With Mortality in Japanese Hemodialysis Patients

Advanced Oxidation Protein Products and Advanced Glycation End Products in Children and Adolescents With Chronic Renal Insufficiency

Effect of Uremia on Structure and Function of Immune System

New-Onset Posttransplant Diabetes Mellitus Begins in the Dialysis Period

Muscle and Fat Metabolism in Obesity After Kidney Transplantation: No Effect of Peritoneal Dialysis or Hemodialysis

Ghrelin and Muscle Metabolism in Chronic Uremia

AST-120 Ameliorates Epithelial-to-Mesenchymal Transition and Interstitial Fibrosis in the Kidneys of Chronic Kidney Disease Rats

Chemical and Physiological Relevance of Glucose Degradation Products in Peritoneal Dialysis

A Brief Review of External Mass Balance and Internal Calcium Redistribution in Dialysis Patients—Is Calcium a Uremic Toxin?

Hyperhomocysteinemia in Chronic Renal Failure: Alternative Therapeutic Strategies

Dietary and Synthetic Activators of the Antistress Gene Response in Treatment of Renal Disease

The Removal of Protein-Bound Solutes by Dialysis

Anxiety and Depression in Maintenance Dialysis Patients: Preliminary Data of a Cross-sectional Study and Brief Literature Review

Survival Is Not Enough

Masthead

Editorial Board

Table of Contents

Guidelines for Contributing Authors