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.     

Intermittent pneumatic compression in patients with ESRD. A systematic review

Introduction: Patients with end‐stage renal disease (ESRD) experience frequent hemodialysis (HD) complications. Intradialytic hypotension (IDH) is a common complication presenting in approximately between 20 and 50% of HD sessions. Available interventions such as volume replacement or vasoactive medications are associated with significant side effects. Intermittent pneumatic compression (IPC) has been proposed as a feasible intervention for the prevention of IDH, treatment of peripheral arterial disease and venous ulcers. These devices apply intermittent pressure to the legs improving arterial blood flow, mobilization of pooled blood with an increase in venous return increasing the effective circulatory volume. Our goal was to identify the published clinical evidence on whether IPC has a circulatory benefit and is it well‐tolerated among patients receiving HD. Methods: We conducted a systematic review to identify studies assessing the efficacy and safety of IPC in patients with ESRD. Our primary outcome was IDH. Secondary outcomes such as HD comfort, ultrafiltration volume, and physical activity were collected. No restrictions where used and we included all observational and interventional studies. Two reviewers performed screening and study quality assessment. Findings: We included seven studies. Out of the seven studies, five addressed IDH, and the rest were included for secondary outcomes such as physical capacity and HD comfort. In one randomized crossover trial comparing exercise against IPC, 21 patients were randomized to 3 different arms (no intervention, cycling, IPC) a decrease in the rates of IDH with IPC was described (43%, 38%, and 24% respectively P = 0.014). The smaller studies corroborated these results. All studies where at high risk of bias. Discussion: IPC might offer significant benefits for patients undergoing HD not limited to prevention of IDH but also improvement of hemodialysis comfort and physical capacity. However, our results should be interpreted in the context of its limitations.     

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.     

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.     

Chronic pain is underestimated and undertreated in dialysis patients: A retrospective case study

Significant chronic pain is highly prevalent in chronic kidney disease patients and is associated with morbidity and mortality. In this study, we retrospectively evaluated the incidence and treatment of pain in the dialysis unit of our tertiary referral center. The cohort included 147 patients. Over 66% reported significant (VAS >40) chronic pain during the preceding 3 months, most often characterized as stabbing (38%) and with concurrent itching (44%). Only 33% of patients received chronic pain medications, while 55.6% of patients with severe pain and 45.9% with pain characterized as the worst imaginable did not receive any analgesics. Pregabalin or weak opioids were the most frequently used. In conclusion, chronic pain is highly prevalent and markedly undertreated in dialysis patients, despite its significant adverse impact.     

A rare case of Actinomyces skin and soft tissue infection in an end‐stage kidney disease patient with a review of the literature

End‐stage kidney disease (ESKD) patients are a commonly overlooked immunocompromised population that places them at risk for rare infections. We describe the case of a 78‐year‐old man with a history of ESKD managed with thrice weekly in‐center hemodialysis who had a prolonged episode of left elbow pain and drainage and was eventually found to have a skin and soft tissue infection from Actinomyces radingae. We review the bacteriology of Actinomyces spp. and the experiences of other providers who have treated actinomycosis in individuals with ESKD. The anatomic sites and demographics of these individuals are heterogeneous, but they all generally require a long antibiotic course with a beta‐lactam and portend to a good prognosis. High index of suspicion is needed to identify rare and atypical infections in the ESKD population.     

Time trends in the association of ESRD incidence with area‐level poverty in the US population

The objective of this study was to examine the temporal trends of the association between area‐level poverty status and end‐stage renal disease (ESRD) incidence. We hypothesized that the association between area‐level poverty status and ESRD incidence has increased significantly over time. Patient data from the United States Renal Data System were linked with data from the 2000 and 2010 US census. Area‐level poverty was defined as living in a zip code‐defined area with ≥20% of households living below the federal poverty line. Negative binomial regression models were created to examine the association between area‐level poverty status and ESRD incidence by time period in the US adult population while simultaneously adjusting for the distribution of age, sex, and race/ethnicity within a zip code. Time was categorized as January 1, 1995 through December 31, 2004 (Period 1) and January 1, 2005 through December 31, 2010 (Period 2). The percentage of adults initiating dialysis with area‐level poverty increased from 27.4% during Period 1 to 34.0% in Period 2. After accounting for the distribution of age, sex, and race/ethnicity within a zip code, area‐level poverty status was associated with a 1.24 (95% confidence interval [CI] 1.22, 1.25)‐fold higher ESRD incidence. However, this association differed by time period with 1.04‐fold (95% CI 1.02, 1.05) higher ESRD incidence associated with poverty status for Period 2 compared with the association between ESRD and poverty status in Period 1. Area‐level poverty and its association with ESRD incidence is not static over time.     

Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac,endothelial function,and arterial stiffness in ESRD (CERES) study

Introduction: Recent studies suggest that women with end‐stage renal disease (ESRD) may have higher rates of mortality than men, but it is unknown whether sex differences in vascular function explain this disparity. The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study is an ongoing, prospective observational study designed to investigate vascular function, myocardial injury, and cardiovascular outcomes in ESRD. Methods: Among 200 CERES participants (34% women), we evaluated arterial wave reflections as augmentation index normalized to a heart rate of 75 (AIx75), arterial stiffness as pulse wave velocity, and macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation and velocity time integral (VTI). Over a median of 14 months, participants were followed for the composite outcome of cardiovascular hospitalization or all‐cause death. Findings : Women had higher arterial wave reflection (Mean, SD AIx75 30% ± 9% for women vs. 21% ± 10% for men; P < 0.001) and worse microvascular function (VTI 55 ± 30 cm for women vs. 70 ± 27 cm for men; P = 0.007). After multivariable adjustment, female sex remained associated with a 0.5‐SD higher AIx75 (95% CI [0.01, 0.9]) and 0.3‐SD lower VTI (95%CI [0.1, 0.7]). Women experienced higher adjusted rates of the composite outcome (HR 2.5; 95%CI [1.1, 5.6]; P = 0.03), and further adjustment for arterial wave reflection attenuated this risk. Discussion: Vascular dysfunction may partly explain the association of female sex with higher cardiovascular risk and mortality in patients with ESRD. Further studies are needed to explore whether sex differences in vascular function predict long‐term outcomes, and whether hormonal or inflammatory factors explain these associations.     

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.     

Intensive dialysis and pregnancy

Pregnancy in women with end stage renal disease on renal replacement therapy is uncommon due to the physiologic changes associated with renal failure as well as the complexities and risk involved in managing these patients. As most of these women had long periods of illness with chronic kidney disease, the effects of their chronic illness together with the current societal trends to delay child bearing to a more advanced maternal age can hamper fertility. For those able to conceive, intensified hemodialysis (HD), through longer and/or more frequent dialysis sessions, offers improved maternal and neonatal outcomes. Intensified HD is most conveniently offered in the patient's home, where possible. This review expands the scope of the Implementing Hemodialysis in the Home website and associated supplement published previously in Hemodialysis International and includes information tailored to women of reproductive age. We describe the necessary counseling that women should receive before conception and before intensification of HD, and provide a detailed management strategy that includes nephrologic and obstetric care, should pregnancy occur.     

Modification of cardiovascular risk in hemodialysis patients: an evidence-based review

Cardiovascular disease accounts for 40% to 50% of deaths in dialysis populations. Overall, the risk of cardiac mortality is 10-fold to 20-fold greater in dialysis patients than in age and sex-matched controls without chronic kidney disease. The aim of this paper is to review critically the evidence that cardiac outcomes in dialysis patients are modified by cardiovascular risk factor interventions. There is limited, but as yet inconclusive controlled trial evidence that cardiovascular outcomes in dialysis populations may be improved by antioxidants (vitamin E or acetylcysteine), ensuring that hemoglobin levels do not exceed 120 g/L (especially in the setting of known cardiovascular disease), prescribing carvedilol in the setting of dilated cardiomyopathy, and by using cinacalcet in uncontrolled secondary hyperparathyroidism. Similarly, there are a number of negative controlled trials, which have demonstrated that statins, high-dose folic acid, angiotensin-converting enzyme inhibitors, multiple risk factor intervention via multidisciplinary clinics, and high-dose or high-flux dialysis are ineffective in preventing cardiovascular disease. Although none of these studies could be considered conclusive, the negative trials to date should raise significant concerns about the heavy reliance of current clinical practice guidelines on extrapolation of findings from cardiovascular intervention trials in the general population. It may be that cardiovascular disease in dialysis populations is less amenable to intervention, either because of the advanced stage of chronic kidney disease or because the pathogenesis of cardiovascular disease in dialysis patients is different from that in the general population. Large, well-conducted, multicenter randomized-controlled trials in this area are urgently required.     

Predialysis volume overload and patient‐reported sleep duration and quality in patients receiving hemodialysis

Introduction: Previous studies of patients with end‐stage renal disease have examined the role of fluid shifts on apnea‐hypopnea episodes, but the association between volume overload and patient‐reported sleep quality or duration has not been well‐established. Methods: We studied the association between predialysis bioimpedance spectroscopy‐derived volume estimates and self‐reported sleep quality and duration in 638 patients in the United States Renal Data System ACTIVE/ADIPOSE study receiving hemodialysis from 2009 to 2011. We used questionnaires to assess self‐reported sleep duration and quality. We used relative hydration status (fluid overload/extracellular water; FO/ECW) as the primary predictor and examined associations with hours of sleep duration using linear regression. We used multivariable ordinal logistic regression to determine the association between categories of relative hydration status (normal hydration [FO/ECW < 6.8%], mild overhydration [FO/ECW 6.8%–15%], and hyperhydration [FO/ECW > 15%]) and four levels of difficulty with falling asleep, waking, and returning to sleep. Findings: Higher relative hydration status was associated with fewer hours of sleep (?0.31 hours per 10%, 95% confidence interval (CI) ?0.49 to ?0.13). Compared to the normal hydration group, there was a statistically significant association between higher relative hydration status category and more frequent nighttime waking (OR: mild overhydration 1.92 [95% CI 1.23–2.99], hyperhydration 1.87 [95% CI 1.16–2.99]), a trend toward more difficulty returning to sleep (OR: mild overhydration 1.46 [95% CI 0.94–2.27], hyperhydration 1.52 [95% CI 0.95–2.43]), and no association between relative hydration category and difficulty falling asleep. Discussion: Hydration status was associated with self‐reported sleep duration in patients on dialysis. Future studies should prospectively examine the effects of optimizing fluid status on sleep duration and quality.     

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.     

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.     

The influence of socioeconomic status on patient survival on chronic dialysis

Socioeconomic status (SES) has been linked to worse end‐stage kidney disease survival. The effect of SES on survival on chronic dialysis, including the impact of transplantation, was examined. A retrospective, observational study investigated the association of SES with dialysis patient survival, with censoring at time of transplantation. Adult patients commencing dialysis from 1990 to 2009 in an Irish tertiary center received a spatial SES score using the 2011 Pobal Haase‐Pratschke Deprivation Index and were compared by quartile. Cox proportional hazard models and Kaplan–Meier survival analysis examined any association of SES with survival. The 1794 patients included had a median follow‐up of 3.8 years. Patients in the lowest SES area quartile were significantly younger than the highest, mean age 56.7 vs. 59 years, P = 0.006, respectively. There was no association between SES area score and survival in an unadjusted model (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.99–1.01). Survival in the highest SES area quartile was superior to the lowest SES in a multivariable adjusted model including age, gender, and dialysis modality (HR 0.83, 95% CI 0.70–0.99, P = 0.04). These results were only mildly attenuated by censoring at time of transplantation (highest SES area quartile deprived vs. lowest SES area quartile, HR 0.85, 95% CI 0.70–1.03, P = 0.09). Superior patient survival was identified in the highest SES areas compared with the lowest following age‐adjusted analyses, despite the older population in the most affluent areas. Further research should focus on identifying modifiable targets for intervention that account for this socioeconomic‐related survival advantage.