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.     

Hepatitis C virus infection in patients with end‐stage renal disease

Chronic hepatitis C virus (HCV) infection is a major global health problem affecting 3–5 million people in the United States and over 100 million worldwide. Chronic HCV infection, which can lead to cirrhosis and hepatocellular carcinoma, also results in numerous other complications, including impairment of renal function. Because HCV is most often transmitted via parenteral exposure to blood or blood products, patients with end‐stage renal disease (ESRD) treated with hemodialysis are at particular risk for infection. Historically, the medications available to treat HCV infection in these patients had significant side effects and were not particularly effective in generating a sustained virologic response. Since 2011, a number of direct‐acting antiviral therapies have emerged that can lead to virological cure in the vast majority of patients, with low pill burden and few side effects. Here, we describe the biology and pathophysiology of HCV infection, and summarize current information on new therapies, with a particular focus on their application in patients with chronic kidney disease including ESRD.     

Treatment of symptomatic coronary artery disease in patients with end‐stage renal disease on hemodialysis with paclitaxel‐eluting TAXUS stent

Percutaneous coronary intervention (PCI) utilizing drug‐eluting stents is becoming a very common revascularization technique in the dialysis cohort; therefore, we sought to identify the impact of dialysis on outcomes in this group of patients. This is a multicenter registry comparing results of 290 patients (186 with normal kidney function, 104 on dialysis) who underwent PCI with exclusive use of paclitaxel‐eluting TAXUS stent. The primary endpoint was an assessment of major adverse cardiac events (MACE) at 1‐ and 2‐year observation. Mean follow‐up was 23.3 ± 6.1 months. Results at 12 months showed: MACE 11.8% vs. 7.7% (P = not significant [ns]), composite major adverse cardiac and cerebrovascular events (MACCE) 12.4% vs. 11.5% (P = ns), all‐cause death 2.7% vs. 8.6% (P < 0.05), cardiac death 2.7% vs. 1.9% (P = ns), target vessel revascularization (TVR) 9.1% vs. 6.7% (P = ns), acute myocardial infarction (AMI) 3.8% vs. 2.9% (P = ns), cerebrovascular events (CVA) 0.5% vs. 1.0% (P = ns); and results at 24 months showed: MACE 17.7% vs. 18.3% (P = ns), MACCE 21.5% vs. 26.0% (P = ns), all‐cause death 4.3% vs. 14.4% (P < 0.01), cardiac death 3.2% vs. 1.9% (P = ns), TVR 14.0% vs. 16.3% (P = ns), AMI 5.4% vs. 5.8% (P = ns), CVA 3.2% vs. 2.9% (P = ns) for non–end‐stage renal disease (ESRD) and dialysis group, respectively. Prior coronary artery bypass graft (CABG) was found to be single risk factor for MACE, TVR, and MACCE in patients with ESRD, while dialysis and prior CABG were found to be single risk factors for death in the entire population. PCI with TAXUS is a feasible procedure and presents promising results in dialysis‐dependent patients.     

Association between depression and inflammatory/anti‐inflammatory cytokines in chronic kidney disease and end‐stage renal disease patients: A review of literature

Depression is a common psychiatric disorder in patients with advanced chronic kidney diseases (CKDs). Strong correlation has been reported between depression and patients' morbidity and mortality among dialysis patients. On the contrary, chronic inflammation may be a major contributor to morbidity and mortality in these patients. Elevated plasma levels of proinflammatory cytokines, especially C‐reactive protein and interleukin (IL)‐6, have been correlated with cardiovascular events, hospitalization, and all‐cause and cardiovascular‐associated mortality in dialysis patients. Studies suggested that inflammation‐mediated atherosclerotic cardiovascular diseases are the possible reasons for depression‐induced mortality among patients without renal diseases. Several studies found significant elevations in circulating levels of proinflammatory cytokines, particularly IL‐6 and tumor necrosis factor‐α, in patients with major depression. Furthermore, depressive mood and behaviors, including sadness and suicidal ideation, were observed in patients who received repeated injections of recombinant cytokines. A thorough literature review indicates that while depressive symptoms and elevated inflammatory cytokine levels coexist in CKD and dialysis patients, their association is uncertain. Depression seems to be more associated with elevated serum levels of IL‐6 than other cytokines in these patients. Further studies are needed to clarify the possibility of a causal relationship between inflammation and depressive symptoms in CKD and dialysis patients.     

Role of turmeric in oxidative modulation in end‐stage renal disease patients

Oxidative stress is considered as a major player in uremia‐associated morbidity and mortality in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of turmeric on oxidative stress markers in HD patients. This study was a prospective and double‐blind randomized clinical trial. Fifty HD patients aged 18–60 years were recruited after fulfilling the inclusion criteria. Patients were randomly categorized into 2 groups: trial group received turmeric and control group received placebo for 8 weeks. Each patient in the trial group received turmeric, whereas the control group received starch for the same 8 weeks. Plasma malondialdehyde (MDA), red blood cell (RBC) antioxidant enzyme activities as glutathione peroxidase (GPX), glutathione reductase (GR), and catalase (CAT), cholesterol, high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol, triglyceride, albumin, and hemoglobin were also measured before and after study. Although MDA level was reduced in both groups, the ratio of decrease was significantly higher in the turmeric group (0.2 vs. 0.1, P = 0.040). Three enzymes of GPX, GR, and CAT levels were increased in both groups; the ratio of increased was significantly higher in the turmeric group for the CAT enzyme (0.73 vs. 0.54; P = 0.02). Also, significant elevation of albumin level in the turmeric group compared with the control group was observed (P = 0.001). Regular ingestion of turmeric reduces plasma MDA and increases RBC CAT activity and plasma albumin levels in HD patients. Turmeric showed no adverse effects.     

Esophageal actinomycosis in a patient with end‐stage renal disease

Actinomycosis of esophagus is uncommon. Herpes simplex virus, cytomegalovirus, candidiasis, tuberculosis, and other fungal infections are the commonly reported infections in both immunocompromised and immunocompetent patients. We report a case of esophageal actinomycosis in an end‐stage renal disease patient. A 28‐year‐old lady, known case of systemic lupus erythematosus, hepatitis B virus infection with end‐stage renal disease on regular maintenance hemodialysis since 5 years presented with history of epigastric pain and odynophagia for 1 week. Her upper gastrointestinal endoscopic examination revealed extensive necrotic areas with membrane in the esophagus. Histopathology revealed actinomycotic colonies and bacterial clumps. She was treated with intravenous penicillin followed by oral ampicillin for 6 months. She showed marked clinical improvement, and repeat endoscopy showed healing of ulceration and no evidence of actinomycosis.     

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.     

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.     

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.     

Acute hemodialysis complications in end‐stage renal disease patients: The burden and implications for the under‐resourced Sub‐Saharan African health systems

Little is known about the challenges of routine renal replacement therapy in Sub‐Saharan Africa. We investigated the fatal and nonfatal acute hemodialysis (HD) complications in patients with end‐stage renal disease (ESRD) in two main dialysis centers in Cameroon. 1000 consecutive HD sessions incurred over a 4‐month period by 129 patients (96 men, 74%) with ESRD, receiving two weekly HD sessions of 4 hours each, were considered. Personal and clinical profiles before, during, and within 24 hours after HD sessions were used to diagnose complications. Participants were aged 7 to 80 years (mean 46 years). In all, 452 acute complications were recorded in 411 (41%) of the 1000 HD sessions. Of the 11 types of complications, hypotension (25%), muscular cramps (22%), hypertensive crisis (14%), pruritus (10%), and fever (7%) were the most frequent. Three hundred and six complications (67.7%) occurred during understaffed nighttime. The vascular access was the main bleeding site with 64%. Being diabetic and ultrafiltration rate >1000 mL/h were associated with hypotension and muscle cramps. The shorter duration in dialysis was associated with the risk of bleeding and the disequilibrium syndrome while longer duration was associated with muscle cramps. Four deaths (three from bleeding and one from disequilibrium syndrome) occurred, all during nighttime. Nearly half of dialysis sessions in these settings are associated with acute complications, some of which are fatal. Those complications occurred mostly during understaffed periods. Urgent strategies are needed to quickly solve the human capital crisis in the health care sector.     

Management of pain in end‐stage renal disease patients: Short review

Pain management in end stage renal disease (ESRD) patients is a complex and challenging task to accomplish, and effective pain and symptom control improves quality of life. Pain is prevalent in more than 50% of hemodialysis patients and up to 75% of these patients are treated ineffectively due to its poor recognition by providers. A good history for PQRST factors and intensity assessment using visual analog scale are the initial steps in the management of pain followed by involvement of palliative care, patient and family counseling, discussion of treatment options, and correction of reversible causes. First line should be conservative management such as exercise, massage, heat/cold therapy, acupuncture, meditation, distraction, music therapy, and cognitive behavioral therapy. Analgesics are introduced according to WHO guidelines (by the mouth, by the clock, by the ladder, for the individual, and attention to detail) using three‐step analgesic ladder model. Neuropathic pain can be controlled by gabapentin and pregabalin. Substitution/addition of opioid analgesics are indicated if pain control is not optimal. Commonly used opioids in ESRD patients are tramadol, oxycodone, hydromorphone, fentanyl, methadone, and buprenorphine. Methadone, fentanyl, and buprenorphine are the ideal analgesics in ESRD. However, complex pain syndrome requires multidrug analgesic regimen comprising opioids, non‐opioids, and adjuvant medication, which should be individualized to the patient to achieve adequate pain control.     

Chronic obstructive pulmonary disease in patients with end‐stage kidney disease on hemodialysis

The objectives of this study were to assess the prevalence of chronic obstructive pulmonary disease (COPD) in hemodialysis patients with spirometry and to examine the effects of fluid removal by hemodialysis on lung volumes. Patients ≥18 years at two Danish hemodialysis centers were included. Forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC ratio were measured with spirometry before and after hemodialysis. The diagnosis of COPD was based on both the GOLD criteria and the lower limit of normal criteria. There were 372 patients in treatment at the two centers, 255 patients (69%) completed spirometry before dialysis and 242 of these (65%) repeated the test after. In the initial test, 117 subjects (46%) had airflow limitation indicative of COPD with GOLD criteria and 103 subjects (40.4%) with lower limit of normal criteria; COPD was previously diagnosed in 24 patients (9%). Mean FVC and FEV₁ decreased mildly after dialysis (FVC: 2.84 to 2.79 L, P < 0.01. FEV₁: 1.97 to 1.93 L, P < 0.01) Hemodialysis did not affect the FEV₁/FVC ratio or number of subjects with airflow limitation indicative of COPD (113 vs. 120, P = 0.324; n = 242). COPD is a frequent and underdiagnosed comorbidity in patients on chronic hemodialysis. Spirometry should be considered in all patients on dialysis in order to address dyspnea adequately. Hemodialysis induced a small fall in mean FEV₁ and FVC, which was more pronounced in patients with little or no fluid removal, but the FEV₁/FVC ratio and the number of subjects with airflow limitation indicative of COPD were not affected by dialysis.     

Hyperprolactinemia in end‐stage renal disease and effects of frequent hemodialysis

Introduction: End‐stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods: The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in‐center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health‐related quality of life, self‐reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12‐month follow‐up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings: Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th–75th percentile 48–195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion: Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one‐year period.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Kienböck's disease associated with radiocephalic fistula formation in a patient with end‐stage renal disease

Kienböck's disease, which consists of osteonecrosis and collapse of the lunate bone, causes chronic pain and dysfunction of the wrist. Patients on hemodialysis are occasionally present with wrist pain, but Kienböck's disease is rarely reported in dialysis patients. This case study describes Kienböck's disease in a patient with end‐stage renal disease on hemodialysis. A 39‐year‐old male with a 1‐year history of hemodialysis presented with left wrist pain that increased progressively over 6 months. The patient had no history of trauma or any other risk factors known to be associated with Kienböck's disease. Physical examination of the wrist at the site of the arteriovenous fistula showed swelling and tenderness with decreased range of motion. Radiographic examination showed articular collapse and fracture of the body of lunate consistent with stage IIIb Kienböck's disease. An intercarpal arthrodesis with autogenous bone graft was performed.     

Confounding factors for early death in incident end‐stage renal disease patients: Role of emergency dialysis start

Hemodialysis (HD) has been associated with higher 1‐year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1‐year and ≥1‐year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (<6 months), 167 (33.7%) started dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1‐year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1‐year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1‐year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1‐year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1‐year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival.     

Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all‐cause mortality in hemodialysis patients: A prospective cohort study

Introduction: Patients with chronic kidney disease, especially those with end‐stage renal disease, have an increased risk of death. Previous studies have suggested neutrophil/lymphocyte ratio (NLR) was related to worse outcome in patients undergoing hemodialysis (HD). However, monocyte/lymphocyte ratio (MLR) has not been evaluated in HD patients. In this study, we prospectively studied the predictive value of MLR for all‐cause and cardiovascular mortality in HD patients and compared it with NLR. Methods: Patients who had been on a HD treatment for at least 6 months were enrolled. MLR was calculated by dividing the monocyte count by the lymphocyte count. Survival outcomes were estimated using the Kaplan‐Meier method and compared by the log‐rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of MLR and other clinical factors on all‐cause and cardiovascular mortality. Results: Mortality rates for the lowest, middle, and highest MLR tertile group were 3.65, 7.02, and 11.15, respectively per 100 patient‐years. The Kaplan‐Meier analysis revealed that survival rates were significantly different among three MLR groups (P < 0.001). In multivariate Cox regression analyses, MLR was independently associated with all‐cause mortality (HR 4.842; 95% CI, 2.091–11.214; P < 0.001) and cardiovascular mortality (HR 6.985, 95% CI 1.943–25.115, P = 0.003) as continuous variables. NLR was not an independent predictor of all‐cause nor cardiovascular mortality after adjusted with MLR. Conclusions: The main finding of the study suggest that higher MLR was a strong and independent predictor of all‐cause and cardiovascular mortality and overwhelmed NLR among HD patients.