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.     

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.     

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.     

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.     

Effects of silymarin on biochemical and oxidative stress markers in end‐stage renal disease patients undergoing peritoneal dialysis

Introduction End‐stage renal disease (ESRD) patients especially those undergoing dialysis are vulnerable to several complications, in particular those related to oxidative stress. Silymarin is an herbal medicine commonly used as an antioxidant in different pathologies. Methods To evaluate the effect of silymarin on biochemical and oxidative stress markers, 50 ESRD patients undergoing peritoneal dialysis were randomly divided into two groups of silymarin (n = 28) and control (n = 22) and received silymarin (140 mg every 8 hours) or placebo for 2 months, respectively. Ferric reducing antioxidant power and total 8‐iso‐prostaglandin F_2α were measured in plasma, while catalase enzyme activity was measured in erythrocytes of both groups before and after treatment. Findings Ferric reducing antioxidant power values after treatment were significantly decreased in silymarin group compared to before treatment values (17.2 ± 2.9 and 15.9 ± 3.1 µM equivalent of quercetin/dL, respectively, P < 0.05). Conversely, catalase levels were increased 17.3% after silymarin consumption, while it was decreased 9.1% in control group. Further, hemoglobin (from 10.94 ± 2.17 to 11.54 ± 2.03 g/dL, P < 0.05) and albumin levels (from 3.48 ± 0.67 to 3.61 ± 0.53 g/dL, P < 0.05) were significantly increased after silymarin administration. Discussion It is concluded that silymarin could be regarded as a supplementary therapy for ESRD patients undergoing peritoneal dialysis in order to reduce complications.     

The effect of hemodialysis session on postural strategies in older end‐stage renal disease patients

Patients suffering from end‐stage renal disease experience multiple disabilities, such as muscle wasting, weakness, higher postural sway, and fall rates compared with healthy population, which has a negative effect on physical functioning and autonomy. The vital treatment of hemodialysis is recognized to induce important post‐hemodialysis fatigue, hypotension, cramps, and headache due to the rapid fluid redistribution, among others. Nevertheless, even the well‐known negative effect of aforementioned consequences of hemodialysis treatment, its effect on physical function, especially postural balance, is unclear. Thus, this study hypothesized the adverse effect of hemodialysis treatment on postural sway in 12 end‐stage renal disease patients (mean age 63.3 ± 11 years) through the analysis of center‐of‐pressure (COP) trajectories recorded before and immediately after hemodialysis session. Evident postural alterations were observed at post‐hemodialysis balance assessment for COP position‐based (Fs < 7.7, P < 0.02) and COP velocity‐based variables (Fs > 2.33, P < 0.05), without changes in complexity of COP time series in anteroposterior and mediolateral directions. These results suggest that period after hemodialysis treatment is particularly unsafe, as evidenced by important disability in postural control, and highlight the importance of the medical support and falls‐related prevention strategies of these older frail patients after hemodialysis treatment.     

Effects of end‐stage renal disease and dialysis modalities on blood ammonia level

Introduction: Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10‐fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Methods: Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. Findings: No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre‐ and post‐hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). Discussion: Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure.     

Two additional cases of metformin‐associated encephalopathy in patients with end‐stage renal disease undergoing hemodialysis

We report on two additional cases of metformin‐associated encephalopathy in patients with end‐stage renal disease (ESRD) undergoing hemodialysis. Two patients were seen at our hospital with abnormal neurological signs and symptoms. Magnetic resonance imaging (MRI) revealed the same pattern of high signal intensity in both basal ganglia in T2‐weighted images in the two patients. The two patients had started taking metformin 5 and 6 weeks earlier at the same dose of 1000 mg per day. Metformin was immediately stopped, and regular hemodialysis was conducted. Their signs and symptoms resolved completely after these measures. The high signal intensity in both ganglia in T2‐weighted MRI also disappeared. We should suspect metformin‐induced encephalopathy and withdraw the drug when presented with diabetic patients with chronic kidney disease and neurological signs and symptoms of unknown cause.     

Antithrombotic therapy in end‐stage renal disease

The delicate balance of risk vs. benefit of using antiplatelet and antithrombotic agents in the general population is well established. The decision to use these agents in the end stage renal disease (ESRD) population remains complex and difficult. The concomitant association of a prothombotic state with high risk of bleeding in the ESRD population requires individualization and careful clinical judgment before implementing such therapy. There remains a paucity of clinical trials and lack of substantial evidence in literature for safe and effective use of antithrombotic drugs in patients with advanced chronic kidney disease. The current review summarizes the pros and cons of using antiplatelet and antithrombotic agents in primary and secondary prevention of cardiovascular events, evaluate the risks with routine use of anticoagulation for cerebrovascular stroke prevention with nonvalvular atrial fibrillation and role of newer oral anticoagulants as alternate agents in the dialysis population.     

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.     

Effects of hemodialysis on ventricular activation time in children with end‐stage renal disease

Patients with end‐stage renal disease are affected by cardiovascular complications, including disturbances of the heart intraventricular conduction. Body surface potential mapping is a non‐invasive electrocardiographic detection method of initial disturbances in heart activation propagation. A goal of the study was to analyze the effects of single hemodialysis (HD) session on ventricular activation time (VAT) maps obtained from hemodialyzed children. The study group consisted of 13 hemodialyzed children (age: 6–18 years). The control group is composed of 26 healthy subjects. In each HD patient, 12‐lead electrocardiogram and echocardiography examinations were performed. Isochrone heart maps, reflecting body surface distribution of VAT isolines, were recorded from an 87‐electrode HPM‐7100 system for body surface potential mapping, before (group B) and after HD session (group A). The distribution of isochrones and VAT values, as recorded in the HD patients, differed significantly from the reference VAT map for controls. The highest VAT maximal value was noted in group B (Me: 110 vs. 62 ms in the control group; P < 0.001), becoming significantly lower after HD session (Me: 98 ms for group A vs. 110 ms for group B; P < 0.001). Ventricular activation time maps, recorded before HD session, showed significant VAT delays with isochrone arrangement specific for the left bundle branch block. After HD session, VAT maps presented significant changes, suggesting a normalization process. Ventricular activation time maps in children with end‐stage renal disease exhibited disturbances of intraventricular conduction within the left bundle branch block, undetectable on standard electrocardiogram. A single HD session resulted in VAT map improvement related to overall HD treatment duration.     

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.     

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.     

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.     

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.     

Epidemiology of end‐stage renal disease and hemodialysis treatment in Serbia at the turn of the millennium

The study presents the epidemiological features of patients treated with renal replacement therapy (RRT) in Serbia from 1997 to 2009 and compares the results of hemodialysis treatment in 1999 and 2009. Epidemiological data were obtained from the National Registry of RRT patients and data on hemodialysis treatment from special surveys conducted in 1999 and 2009. Within the period 1997–2009 the incidence of patients on RRT increased from 108 to 179 per million population (pmp), prevalence rose from 435 to 699 pmp, while mortality rate fell from 20.7% to 16.7%. The frequency of patients with glomerulonephritis decreased, while that of patients with diabetes and hypertensive nephropathy increased. In late 2009 there were 5208 patients receiving RRT in Serbia. Within the examined period new hemodialysis and reverse osmosis equipment were purchased, high‐flux dialyzers with synthetic membranes were increasingly used and the number of patients receiving hemodiafiltration increased to 17.6%. Kt/V greater than 1.2 was recorded in 16% of the patients in 1999 but 52% in 2009. Options for correction of anemia and mineral disorders have also improved. The percentage of patients with HbsAg (13.8% vs. 4.8%) as well as anti‐hepatitis C virus antibodies positive patients (23.2% vs. 12.7%) was significantly lower in 2009 than in 1999. Both the incidence and prevalence of RRT patients in Serbia are rising continuously, while the mortality rate is falling. More favorable conditions for dialysis treatment have brought about significant improvement in the results over the last 10 years.