The relationship between neutrophil‐to‐lymphocyte ratio and vascular calcification in end‐stage renal disease patients

Chronic inflammation was found to be correlated with coronary (CAC) and thoracic peri‐aortic calcification (TAC) in end‐stage renal disease (ESRD) patients. Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and noncardiac disorders. Data regarding NLR and its association with TAC and CAC are lacking. We aimed to determine the relationship between NLR and vascular calcification in ESRD patients. This was a cross‐sectional study involving 56 ESRD patients (22 females, 34 males; mean age, 49.9 ± 14.2 years) receiving peritoneal dialysis or hemodialysis for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. TAC and CAC scores were measured by using an electrocardiogram‐gated 64‐multidetector computed tomography. NLR was calculated as the ratio of the neutrophils and lymphocytes. There was a statistically significant correlation between NLR, TACS and CACS in ESRD patients (r = 0.43, P = 0.001 and r = 0.30, P = 0.02, respectively). The stepwise linear regression analysis revealed that age, as well as NLR were independent predictors of TACS. However, increased age was the only independent predictor of CACS according to linear regression analysis. Simple calculation of NLR can predict vascular calcification in ESRD patients.     

Convective renal replacement therapies for acute renal failure and end-stage renal disease

Although hemodialysis remains the primary treatment modality for the management of patients with end‐stage renal disease (ESRD), its clearance of relatively large‐sized uremic toxins is limited due to its primarily diffusive nature. Moreover, recent studies suggesting conventional, diffusion‐based therapies may be limited in their ability to influence outcome in ESRD patients indicate the need for alternative chronic dialysis approaches, an example of which is convective therapies. In an analogous manner, a reassessment of the dialytic management of critically ill patients with acute renal failure (ARF) has also occurred recently based on clinical evidence that high‐dose continuous hemofiltration improves survival. These recent clinical results suggest the utilization of convective therapies in both ARF and ESRD will increase in the future. This article provides a review of convective therapies, with an initial discussion of the determinants of convective solute removal. This is followed by a comprehensive overview of the manner in which hemofiltration and hemodiafiltration are applied clinically.     

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end‐stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty‐one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid‐stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.     

Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end‐stage renal disease patients

Dyslipidemias may account for the excess of cardiovascular mortality in end‐stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride‐rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle‐aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE‐rich particles, lower high‐density lipoprotein (HDL) largest subclasses, and a smaller low‐density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL‐cholesterol levels, and a raise of small very‐low‐density lipoprotein, intermediate‐density lipoproteins (IDL), apoE‐rich particles, and non‐HDL‐cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation.     

Ledipasvir and Sofosbuvir for untreated HCV genotype 1 infection in end stage renal disease patients: A prospective observational study

Introduction: Hepatitis C virus (HCV) infection in end stage renal disease (ESRD) is associated with increased mortality. Recently, numerous directly acting antiviral agents have been approved for the management of HCV. Ledipasvir along with Sofosbuvir has been approved for management of genotype 1 infection in patients with eGFR ≥30 mL/min. However, there is paucity of data regarding its role in the management of patients on dialysis. Material and Methods: This is a single center prospective open label observational study to assess the safety and efficacy of Ledipasvir and Sofosbuvir in hemodialysis (HD) patients who were diagnosed with HCV genotype 1 infection. Eligibility criteria were treatment naive HD patients with normal liver histology. We administered Ledipasvir and Sofosbuvir combination tablet on alternate days for a period of 12 weeks. Primary efficacy end point was the assessment of sustained virological response (SVR12), and the safety end point was the discontinuation of therapy secondary to adverse drug effects. Results: A total of 21 patients were treated with this regimen. Two patients expired during the study period and are not related to the therapy. SVR12 was achieved in all the 19 patients. None of the patients in our study discontinued the therapy or had severe adverse drug effects. One patient had head ache and another patient had giddiness which were managed symptomatically. Conclusion: Ledipasvir and Sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions.     

Platelet‐to‐lymphocyte ratio better predicts inflammation than neutrophil‐to‐lymphocyte ratio in end‐stage renal disease patients

Neutrophil‐to‐lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end‐stage renal disease (ESRD) patients. Recently, platelet‐to‐lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross‐sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C‐reactive protein, TNF‐α, IL‐6 levels were measured. PLR, NLR, serum high sensitive C‐reactive protein, IL‐6, and TNF‐α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL‐6, and TNF‐α levels when compared to patients with PLR < 139. In the bivariate correlation analysis, PLR was positively correlated with NLR, IL‐6, and TNF‐α in this population. When we compared the association of PLR and NLR with IL‐6 (r = 0.371, P = 0.003 vs. r = 0.263, P = 0.04, respectively) and TNF‐α (r = 0.334, P = 0.008 vs. r = 0.273, P = 0.032, respectively), PLR was found to be superior to NLR in terms of inflammation in ESRD patients. Simple calculation of PLR can predict inflammation better than NLR in ESRD patients.     

Outcomes of patients with end‐stage renal disease (ESRD) under chronic hemodialysis requiring continuous renal replacement therapy (CRRT) and patients without ESRD in acute kidney injury requiring CRRT: A single‐center study

In most continuous renal replacement therapy (CRRT) studies, end‐stage renal disease (ESRD) patients were excluded and the outcomes of patients with ESRD treated with chronic hemodialysis (HD) were unknown. The purposes of this study were to (1) evaluate short‐term patient survival and (2) compare the survival of conventional HD patients needing CRRT with the survival of non‐ ESRD patients in acute kidney injury (AKI) requiring CRRT. We evaluated adults (>18 years) requiring CRRT who were treated in the intensive care unit (ICU) at Kosin University Gospel Hospital from January 1, 2009 to December 31, 2010. A total of 100 (24 ESRD, 76 non‐ESRD) patients underwent CRRT during the study period. Patients were divided into two major groups: patients with ESRD requiring chronic dialysis and patients without ESRD (non‐ESRD) with AKI. We compared the survival of conventional HD patients requiring CRRT with the survival of non‐ ESRD patients in AKI requiring CRRT. For non‐ESRD patients, the 90‐day survival rate was 41.6%. For ESRD patients, the 90‐day survival rate was 55.3%. Multivariate Cox proportional hazards analyses demonstrated that conventional HD was not a significant predictor of mortality (hazard ratio [HR]: 0.334, 95% confidence interval [CI]: 0.063–1.763, P = 0.196), after adjustment for age, gender, presence of sepsis, APACHE score, use of vasoactive drugs, number of organ failures, ultrafiltration rate, and arterial pH. The survival rates of non‐ESRD and ESRD patients requiring CRRT did not differ; ESRD with conventional HD patients may be not a significant predictor of mortality.     

Pyogenic liver abscess in end‐stage renal disease patients: A nationwide longitudinal study

End‐stage renal disease (ESRD) patients are more prone to infectious disease because of their immunocompromised status. However, the association between pyogenic liver abscess (PLA) and ESRD remains not clear. The aim of our study is to evaluate the incidence, risk factors, and outcomes of PLA in ESRD patients. We recruited all incident ESRD patients from the Taiwan National Health Insurance database from 1998 to 2006. The incidence rate of PLA in ESRD patients was compared with that of a randomly selected non‐ESRD control group matched for age, sex gender, Charlson comorbidity score, diabetes mellitus, and cirrhosis. Among the 57,761 incident dialysis patients, there were 538 cases of PLA. The incidence rate of PLA was 18.20 per 10,000 person‐years in the ESRD cohort and 6.34 per 10,000 person‐years in matched control cohort. The rate of PLA was significantly higher in the ESRD cohort (hazard ratio 3.63, 95% confidence interval 2.83–4.65, P < 0.001). The mortality rates of PLA were higher in the ESRD cohort than those in matched control cohort. Diabetes mellitus was an independent risk factor for mortality of PLA. Compared with non‐ESRD patients, ESRD patients have a higher risk of PLA and poorer outcomes.     

Genetic polymorphisms and the risk of progressive renal failure in elderly Hungarian patients

The relationship between renal disease progression and genetic polymorphism of enzymes influencing endothelial function remains incompletely understood. We genotyped three cohorts of elderly Hungarian patients: 245 patients with end‐stage renal disease (ESRD) on chronic hemodialysis (HD), 88 patients with mild chronic kidney disease (CKD), and 200 healthy controls. The underlying diagnoses of renal diseases were primary glomerulonephritis, interstitial nephritis, hypertension, diabetic nephropathy, and hereditary diseases. We examined genetic polymorphisms of eight candidate genes associated with endothelial function: endothelial constitutive nitric oxide synthase (ecNOS) T‐786C, endothelin‐1 G5727T, methylenetetrahydrofolate reductase (MTHFR) C677T, paraoxonase‐1 Q192R and M55L, angiotensinogen M235T, angiotensin‐converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C gene. Six gene polymorphisms were detected by real‐time polymerase chain reaction with melting‐point analysis, and two via allele‐specific amplification and gel electrophoresis. Control group patients were in Hardy‐Weinberg equilibrium for all tested genotypes. In ESRD patients attributed to hypertension, the endothelin gene G5727T GG genotype occurred significantly less but GT genotype more frequently (P < 0.01 for both). In ESRD patients attributed to primary glomerulonephritis, more ACE DD and less ID genotypes were found (P < 0.02 for both) than in the controls. The underlying diagnosis may modify the association of genetic polymorphism and dialysis‐dependent ESRD.     

Hepatitis C in dialysis units: the Saudi experience

Hepatitis C virus (HCV) infection is a significant health problem, as it can lead to chronic active hepatitis, liver cirrhosis, and hepatic carcinoma. Patients undergoing hemodialysis treatment are at increased risk of contracting HCV and other viral infections. This is primarily due to their impaired cellular immunity, underlying diseases, and blood exposure for a prolonged period. Transmission of viral hepatitis, and in particular HCV in dialysis units, has been showing a progressive increase worldwide, ranging between 5% in some western countries and up to 70% in some developing countries. The annual rate of HCV seroconversion in Saudi Arabia is 7% to 9%, while its prevalence is variable between 15% and 80%. This prevalence remained at almost 50% in recent years, despite the further increase in number of patients with end-stage renal disease and the expansion of dialysis services. The most prevalent genotypes in Saudi Arabia are genotype 4 followed by genotypes 1a and 1b, whereas genotypes 2a/2b, 3, 5, and 6 are rare. Genotypes 1 and 4 were associated with different histological grades of liver disease. Mixed infections with more than one genotype were observed in some studies. Isolation of dialysis machines and infected patients, together with strict application of infection-control policies and procedures and continuous education and training of nursing staff, remain the cornerstone in prevention and control of the spread of HCV infection in dialysis units. Interferon (INF)-alpha or pegylated INF, alone or in combination with ribavirin, have shown great promise in the treatment of chronic HCV in dialysis patients.     

End‐stage renal disease from hemolytic uremic syndrome in the United States, 1995–2010

Management of hemolytic uremic syndrome (HUS) has evolved rapidly, and optimal treatment strategies are controversial. However, it is unknown whether the burden of end‐stage renal disease (ESRD) from HUS has changed, and outcomes on dialysis in the United States are not well described. We retrospectively examined data for patients initiating maintenance renal replacement therapy (RRT) (n = 1,557,117), 1995–2010, to define standardized incidence ratios (SIRs) and outcomes of ESRD from HUS) (n = 2241). Overall ESRD rates from HUS in 2001–2002 were 0.5 cases/million per year and were higher for patients characterized by age 40–64 years (0.6), ≥65 years (0.7), female sex (0.6), and non‐Hispanic African American race (0.7). Standardized incidence ratios remained unchanged (P ≥ 0.05) between 2001–2002 and 2009–2010 in the overall population. Compared with patients with ESRD from other causes, patients with HUS were more likely to be younger, female, white, and non‐Hispanic. Over 5.4 years of follow‐up, HUS patients differed from matched controls with ESRD from other causes by lower rates of death (8.3 per 100 person‐years in cases vs. 10.4 in controls, P < 0.001), listing for renal transplant (7.6 vs. 8.6 per 100 person‐years, P = 0.04), and undergoing transplant (6.9 vs. 9 per 100 person‐years, P < 0.001). The incidence of ESRD from HUS appears not to have risen substantially in the last decade. However, given that HUS subtypes could not be determined in this study, these findings should be interpreted with caution.     

Hepatitis B and C in dialysis units in Iran: changing the epidemiology

Hepatitis B (HBV) and C (HCV) viruses are the most important infections transmitted by the parenteral route in patients receiving maintenance dialysis. The prevalence varies markedly from country to country. The aim of this study is to review the efficacy of the strategies to reduce the incidence of these infections and the trend of results in Iran. As a routine, all hemodialysis patients in Iran have biannual blood samples for assessment of serum HBSAg, HBS Abs, and HCV Abs. The data are collected in the Ministry of Health. For statistical analysis, prevalence, and incidence were calculated. There is an increasing prevalence/incidence of end-stage renal disease (ESRD) in Iran, from 238/49.9 pmp in 2000 to 357/63.8 pmp in 2006. The prevalence of positive HBSAg and HCV Abs decreased from 3.8% and 14.4% in 1999 to 2.6% and 4.5% in 2006, respectively. Regarding the genotype distribution in Iran, no one was found with genotype 2. On the subject of decreasing HBV infection, our next strategy should be mandatory vaccination in dialysis centers and in the pre-ESRD period. Concerning HCV infection prevention, 2 approaches may be recommended: the first is decrease of duration of the hemodialysis period by possible early transplantation of suitable patients. The next is a strictly enforced isolation policy for HCV-positive patients, which may play a role in limiting HCV transmission in HD units, and universal precaution in dialysis units should be under constant close surveillance.     

Comparison of Preventive Care Provided to Dialysis Patients by Nephrologists and to Patients Followed in General Medical Clinics: Compliance with American College of Physicians Guidelines

Most end‐stage renal disease (ESRD) patients do not have primary‐care providers, and preventive medicine often is provided by their nephrologists. Little has been written about their success in providing this care. We studied all patients on dialysis at our hospital and compared their preventive care to a control group followed in the general medical clinic. The general medical group showed higher compliance with Pap smears (89% vs 48%), mammography (87% vs 62%), fecal occult blood testing (75% vs 50%), and pneumococcal vaccination (55% vs 28%). The ESRD group had better compliance with influenza vaccination (70% vs 55%) and lipid profile (100% vs 75%). When the subgroup of patients on hemodialysis (HD) was compared with patients on peritoneal dialysis (PD), it was shown that HD patients were more likely than PD patients to receive preventive care. We also compared diabetes‐specific care. The ESRD group had a higher rate of HbA _1C (100% vs 78%) and lipid monitoring (100% vs 76%), diabetes education (100% vs 84%), and podiatry visits (70% vs 38%). There was no difference in ophthalmologic examination or influenza vaccination. We found that nephrologists provide preventive care to ESRD patients with success approximately equal to primary‐care physicians in our institution, although in different parameters. Ready access to dialysis patients and their blood and unit‐specific policies contribute to compliance that is above national averages. Further improvements can be made by additional preventative measures policies, by physician and patient education, and by monitoring primary‐care compliance in the chart.     

End-stage renal disease patients on hemodialysis: a study from a tertiary care center in a developing country

The exact number of patients with chronic renal failure requiring renal replacement therapy in developing world is not known. Unlike the developed world, most developing countries lack renal registries. This study was initiated to know demographic and clinical data of end-stage renal disease (ESRD) patients presenting to maintenance hemodialysis (MHD) at a government funded tertiary care centre in a developing country. A prospective analysis of all new ESRD patients attending to hemodialysis at our centre from 2004 to 2007 had been done. There were 237 new hemodialysis patients during a three-year period. Males were 153 and females were 84, with the mean age 44.92 years. Diabetes mellitus (31.22%) was the most common cause of ESRD. Only 29.95% of patients had education on renal replacement therapy. 65.40% patients had emergency hemodialysis. Internal jugular catheter was the most common form of vascular access at initiation of hemodialysis. Arteriovenous fistula was secured in 29.95% of patients at presentation. Catheter-related infection appeared in 13.55% of patients on catheter. The most common infection in dialysis patients was urinary tract infection (37.14%). Renal transplantation was opted by 9.7% patients and continuous ambulatory peritoneal dialysis in 20.25% and 103 (43.45%) were lost to follow up. The rest (8.86%) continued on MHD. There were 42 (17.72%) deaths over a three-year period. The present study provided the information of the practice of hemodialysis, its population characteristics and outcomes from a developing country.     

Coronary artery calcification in Korean patients with incident dialysis

Introduction: Patients with chronic kidney disease have an extremely high risk of developing cardiovascular disease (CVD). In patients with end‐stage renal disease (ESRD), coronary artery calcification (CAC) is associated with increased mortality from CVD. Methods: The present study aimed to investigate the risk factors for CAC in Korean patients with incident dialysis. Data on 423 patients with ESRD who started dialysis therapy between December 2012 and March 2014 were obtained from 10 university‐affiliated hospitals. CAC was identified by using noncontrast‐enhanced cardiac multidetector computed tomography. The CAC score was calculated according to the Agatston score, with CAC‐positive subjects defined by an Agatston score >0. Findings: Patients' mean age was 55.6 ± 14.6 years, and 64.1% were men. The CAC‐positive rate was 63.8% (270 of 423). Results of univariate analyses showed significant differences in age, sex, etiology of ESRD and comorbid conditions according to the CAC score. However, results of multiple regression analysis showed that only a higher age was significantly associated with the CAC score. Receiver operating characteristic curves showed that the sensitivity and specificity of L‐spine radiography for diagnosing CAC were 56% and 91%, respectively, for diagnosing CAC (area under the curve, 0.735). Discussion: CAC was frequent in patients with incident dialysis, and multiple regression analysis showed that only age was significantly associated with the CAC score. In addition, L‐spine radiography could be a helpful modality for diagnosing CAC in patients with incident dialysis.     

Kidney embolization induces prompt organ response in a 86‐year‐old patient with MGRS‐related AL‐amyloidosis

Despite substantial improvements following the introduction of novel agents and antibodies, amyloid light‐chain (AL)‐amyloidosis still carries a grim prognosis. Here, we report on the case of a severely frail 86‐year‐old patient suffering from monoclonal gammopathy of renal significance (MGRS)‐associated AL‐amyloidosis with a diuretic‐refractory nephrotic syndrome. In this patient, treatment with bortezomib–dexamethasone effectively induced a serological response, but was unfortunately poorly tolerated and failed to promote renal recovery fast enough to prevent secondary complications. Facing ongoing nephrotic syndrome, we performed unilateral kidney embolization and observed a substantial improvement of hypoalbuminemia accompanied by a significant gain in overall quality of life despite the necessity for thrice weekly dialysis. It can be concluded that systemic drugs in MGRS typically do not lead to instantaneous organ recovery but may initially rather be associated with substantial treatment‐related morbidity. In this setting, unilateral renal artery embolization is effective to treat nephrotic syndrome and its secondary complications. The risk of potentially adverse effects, including post‐embolization syndrome, can be minimized by unilateral embolization, still noting that also one‐sided renal ablation has to be balanced against the requirement for life‐long renal replacement therapy. Prospective controlled trials in a more comprehensive cohort will be needed to estimate the overall benefit of kidney embolization relative to novel agent therapies in frail patients with MGRS‐related AL‐amyloidosis.     

Associations of microvascular dysfunction with cardiovascular outcomes: The cardiac,endothelial function and arterial stiffness in ESRD (CERES) cohort

Introduction: Patients with end‐stage renal disease (ESRD) have reduced endothelial function, but whether macro‐ and microvascular endothelial function correlate with baseline risk factors and cardiovascular outcomes in this population is not well understood. Methods: Among 146 participants of the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study, we evaluated macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation (FMD) and velocity time integral (VTI), respectively. We examined cross‐sectional correlations of baseline characteristics, inflammatory and cardiac markers with FMD and VTI. We followed participants for the composite outcome of cardiovascular hospitalization or all‐cause death over fourteen months. Cox survival analyses were adjusted for demographics, comorbidities, medications, systolic blood pressure, inflammation, high‐sensitivity troponin T (hs‐TnT), and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP). Findings: Impaired VTI was associated with older age and Black race (P < 0.05), as well as female gender, atherosclerosis, and hemodialysis (as opposed to peritoneal dialysis) (P < 0.2). Myocardial injury, measured as hs‐TnT, inflammatory markers and NT‐proBNP correlated with impaired VTI. In unadjusted analyses, VTI was significantly associated with the composite outcome (HR per SD VTI 0.65 [95%CI 0.45, 0.95]), but FMD was not (HR per SD FMD 0.97 [95%CI 0.69, 1.4]). When VTI was calculated as the ratio of (hyperemic VTI‐baseline VTI)/baseline VTI, its association with the outcome persisted after multivariable adjustment. Discussion: Microvascular function was associated with higher rates of cardiovascular hospitalizations and all‐cause mortality among individuals with ESRD on dialysis. Further research is needed to learn whether novel therapies that target microvascular endothelial function could improve outcomes in this high‐risk population.     

Rationale and study design of a three‐period, 58‐week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis

Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end‐stage renal disease. One of the cornerstones of treatment is the use of phosphate‐binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three‐period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2‐week washout period, a 52‐week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4‐week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end‐stage renal disease patients who have been treated with thrice‐weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three‐period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.     

Positive association between plasma levels of oxidized low‐density lipoprotein and myeloperoxidase after hemodialysis in patients with diabetic end‐stage renal disease

End‐stage renal disease (ESRD) patients undergoing hemodialysis (HD) have a high prevalence of cardiovascular events. Low‐density lipoprotein (LDL) in dialysis patients has been shown to be susceptible to in vitro peroxidation; therefore, oxidized‐LDL (ox‐LDL) could be generated in these patients. Moreover, myeloperoxidase (MPO) released from activated neutrophils may play a role in the induction of LDL oxidation. The purpose of this study was to investigate the relationship between plasma ox‐LDL levels, plasma MPO levels, and serum high‐sensitivity C‐reactive protein (hs‐CRP) levels during initial HD in patients with diabetic ESRD. Patients (n = 28) had serial venous blood samples drawn before and after HD at the initial, second, and third sessions. Plasma ox‐LDL levels were measured using a specific monoclonal antibody (DLH3), and plasma MPO levels were measured using an enzyme‐linked immunosorbent assay kit. Plasma ox‐LDL levels and MPO levels after a single HD session increased significantly (ox‐LDL, P < 0.005; MPO, P < 0.0001) compared with levels before that HD session. However, the increase was transient since the levels returned to pre‐HD session levels. Additionally, plasma MPO levels showed a positive correlation with plasma ox‐LDL levels during HD (R = 0.62, P = 0.0029). No significant change was observed in serum hs‐CRP levels before and after each HD session. This study demonstrates that plasma MPO levels are directly associated with plasma ox‐LDL levels in diabetic ESRD patients during initial HD. These findings suggest a pivotal role for MPO and ox‐LDL in the progression and acceleration of atherosclerosis in patients undergoing HD.