Thyroid function in end stage renal disease and effects of frequent hemodialysis

Introduction: End‐stage renal disease (ESRD) is associated with perturbations in thyroid hormone concentrations and an increased prevalence of hypothyroidism. Few studies have examined the effects of hemodialysis dose or frequency on endogenous thyroid function. Methods: Within the Frequent Hemodialysis Network (FHN) trials, we examined the prevalence of hypothyroidism in patients with ESRD. Among those with endogenous thyroid function (without overt hyper/hypothyroidism or thyroid hormone supplementation), we examined the association of thyroid hormone concentration with multiple parameters of self‐reported health status, and physical and cognitive performance, and the effects of hemodialysis frequency on serum thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri‐iodothyronine (FT3) levels. Conventional thrice‐weekly hemodialysis was compared to in‐center (6 d/wk) hemodialysis (Daily Trial) and Nocturnal (6 nights/wk) home hemodialysis (Nocturnal Trial) over 12 months. Findings: Among 226 FHN Trial participants, the prevalence of hypothyroidism was 11% based on thyroid hormone treatment and/or serum TSH ≥8 mIU/mL. Among the remaining 195 participants (147 Daily, 48 Nocturnal) with endogenous thyroid function, TSH concentrations were modestly (directly) correlated with age (r = 0.16, P = 0.03) but not dialysis vintage. Circulating thyroid hormone levels were not associated with parameters of health status or physical and cognitive performance. Furthermore, frequent in‐center and nocturnal hemodialysis did not significantly change (baseline to month 12) TSH, FT4, or FT3 concentrations in patients with endogenous thyroid function. Discussion: Among patients receiving hemodialysis without overt hyper/hypothyroidism or thyroid hormone treatment, thyroid indices were not associated with multiple measures of health status and were not significantly altered with increased dialysis frequency.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

The path to a paradigm shift in hemodialysis

About 1 out of 4 American conventional dialysis patients die in the first year and 3 out of 5 die within 5 years with no favorable trend in sight. Largely ignored in practice is the evidence accumulated over decades that longer, more frequent dialysis can immediately slash this grim result in half or more. Pierratos has called for a paradigm shift—a disruptive change—in dialysis practice from conventional treatment to daily nocturnal dialysis, performed at home, to realize this dramatic improvement. We examine here how such a paradigm shift might be brought about and suggest that changes in 3 perspectives must occur. First, new dialysis guidelines must be recast from the old goal of minimally adequate to a new goal of best possible . Second, the body of dialysis research must be interpreted through the lens of best possible patient survival and well being, and the near-impossibility of demonstrating dialysis survival advantage through randomized clinical trials must be acknowledged. Finally, dialysis modality must be seen as, most importantly, a survival and well-being choice, not merely a "Lifestyle" choice; hence, it must be the nondelegatable responsibility of the physician, not dialysis center personnel, to advise and prescribe. Many old perspectives, which might stand in the way of this sorely needed paradigm shift are also examined. These old perspectives make up a fabric of excuses that has delayed—and, if not discarded, will continue to delay—progress toward a survival and well-being outlook for dialysis patients just as favorable as might be achieved through kidney transplant.     

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.     

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.     

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.     

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.     

CathAway fistula vascular access program achieves improved outcomes and sets a new standard of treatment for end‐stage renal disease

Hemodialysis patients using central venous catheters (CVCs) for vascular access are at greater risk of infection and death vs. arterial venous fistula (AVF). In 2008, DaVita initiated the CathAway quality improvement initiative, a multidisciplinary program to reduce CVC use in favor of AVF. Our retrospective analysis examined CVC use for incident (≤90 days) and prevalent (>90 days) patients receiving hemodialysis in the years 2006 to 2010. Outcomes included annual mean percentage of patients with CVCs, new CVC placements per 100 patient years, CVC survival, and percentage patient days with CVC. Over 152,000 patient records were reviewed. Between 76.2% and 79.7% of incident patients used a CVC annually, but for prevalent patients, the proportion decreased from 41.1% in 2006 to 33.5% in 2010. The number of new CVC placements per 100 patient years increased slightly for incident patients but fell annually from 64.8 in 2006 to 55.2 in 2010 for prevalent patients. The percentage of treatment days with CVCs was stable among incident patients (70.4%–74.3%) but fell among prevalent patients from 26.1% in 2006 to 16.5% in 2010. The mean duration of CVC use in incident patients was between 53.0 days (SD, 27.8) in 2006 and 54.1 days (SD, 28.1) in 2009, and for prevalent patients between 158.9 days (SD, 123.0) in 2006 and 128.1 days (SD, 112.0) in 2010. CathAway significantly decreased CVC use in prevalent hemodialysis patients. Decreasing incident patient use will require improvements in predialysis care.     

Tuberculosis in end-stage renal disease patients on hemodialysis

Recent studies have shown that there is an increase in the incidence of mycobacterium tuberculosis (MBT). This is more prevalent among immune compromised patients (those on dialysis) and recipients of organ transplants. Furthermore, extra-pulmonary presentation appears to be more common and difficult to diagnose. We aimed in this study to assess and evaluate the presentation of MBT in a retrospective study conducted among 256 hemodialysis (HD) patients where 18 of them were diagnosed and managed for tuberculosis over a 10-year period between 1990 and 2000. The mean age of the patients was 38 years (21-75 years). The mean interval between the onset of HD and the time of diagnosis was about 24 months (1-120 months). The diagnosis of tuberculosis was made either by isolation of acid-fast bacilli (AFB), the typical caseating granuloma on biopsy, or by recovery of tubercle bacilli from the culture of the biopsy material. Extra-pulmonary tuberculosis was more common (77.8%) than pulmonary tuberculosis (22.2%). The various extra-pulmonary tuberculosis sites noted were cervical lymphadenitis (16.7%), gastrointestinal (16.7%), genitourinary (11.1%), peritonitis (11.1%), pleural effusion (5.6%), pericardial effusion (5.6%), miliary tuberculosis (5.6%), and pyrexia of unknown origin (5.6%). None of the patients with extra-pulmonary tuberculosis had evidence of pulmonary tuberculosis. The atypical presentation with insidious onset was quite common. Anergy to tuberculin skin test was noticed in 56% of cases. All of our patients received modified antituberculosis treatment for 1 year with adequate response, and without undue side effects. We conclude that a high index of suspicion is required especially in the diagnosis of extra-pulmonary tuberculosis, and when there is a high percentage of anergy to tuberculin skin test. Tissue biopsy both for characteristic histology and demonstration of MTB, either by staining or culture, remains the main criteria for the diagnosis of extra-pulmonary tuberculosis.     

Vascular access for chronic hemodialysis in a patient with epidermolysis bullosa dystrophica Hallopeau‐Siemens

Epidermolysis bullosa is a rare genetic hereditary disease characterized with mechanobullous dermatosis. Except cutaneous, these patients have various extracutaneous manifestations and some types of epidermolysis bullosa comprise almost all organ systems. Because of prolonged life span, chronic renal insufficiency has become an important cause of morbidity and death in these patients. Establishment of functional vascular dialysis access is a great challenge for both the doctors and the patients. Multidisciplinary approach is essential. We present a case of successful establishment of dialysis access via Tesio catheter in a young woman suffering from epidermolysis bullosa dystrophica Hallopeau‐Siemens and end‐stage renal disease. Since then, the Tesio catheter inserted via the right internal jugular vein has been the functional mean of dialysis. The patient was given the opportunity to lead a quality and active life in spite of disabling disease. Several cases of successful dialysis access establishment with dialysis catheters via central veins have been reported. We report the successful establishment of long‐term dialysis access via Tesio catheter and suggest this approach as ideal for these patients. This is the first report dealing with vascular access in this group of patients.     

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.