Sexual functioning in chronic kidney disease: the association with depression and anxiety

Sexual functioning is composed of both physiological and psychological factors among patients with chronic kidney disease (CKD). However, the role of depression and anxiety has not yet been studied extensively. This study aimed to investigate the relation of depressive and anxiety symptoms to sexual functioning among hemodialysis (HD) and peritoneal dialysis patients. A sample of 144 patients was recruited from three general hospitals in the broader area of Athens, consisting of 84 patients undergoing in-center HD and 60 patients in continuous ambulatory peritoneal dialysis. Measurements were conducted with the following instruments: the World Health Organization Quality of Life instrument, the General Health Questionnaire (GHQ-28), the State-Trait Anxiety Inventory (STAI 1/STAI 2), and the Center for Epidemiologic Studies Depression Scale. The results indicated that satisfaction about sexual life had negative association with all the subscales of GHQ-28 questionnaire (somatic symptoms, anxiety/insomnia, social dysfunction, severe depression). Sexual functioning was also related negatively to depression as well as state and trait anxieties. Findings provide evidence that the presence of depressive and anxiety symptoms relates significantly to the negative evaluation of sexual functioning in patients with CKD.     

Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end‐stage renal disease (ESRD) patients treated by hemodialysis (HD). Although traditional risk factors are common in dialysis patients, they may not alone be sufficient to account for the unacceptable high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor that is commonly observed in HD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The cause(s) of inflammation in HD patients is multifactorial and includes both dialysis‐related (such as graft and fistula infections, bioincompatibility, impure dialysate, and back‐filtration) and dialysis‐unrelated factors. Although inflammation may reflect underlying CVD, an acute‐phase reaction may also be a direct cause of vascular injury. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there is not yet any recognized, or even proposed, targeted treatment for ESRD patients with chronic inflammation; it would be of considerable interest to study the long‐term effect of various anti‐inflammatory treatment strategies on nutritional and cardiovascular status as well as outcome in these patients.     

Relationship between non‐alcoholic fatty liver disease and MIA syndrome

Non‐alcoholic fatty liver disease (NAFLD) is an important factor in the pathogenesis of cardiovascular diseases in the general population. Recently, it has been shown that NAFLD is highly prevalent in chronic kidney disease (CKD) patients. Ninety‐four hemodialysis (HD) patients were followed for a time period of 18 months or until death. Patient's survival rate was determined in relation to their nutritional and inflammatory state, and the presence of NAFLD. We also investigated the association between the presence of NAFLD and the patients' nutritional and inflammatory state. We did not find any significant association between the clinical parameters of nutritional status and the mortality rate. However, the mortality rate was statistically significantly higher in patients with low serum albumin and high high‐sensitive C‐reactive protein (hs‐CRP) levels and in those who had NAFLD. Surprisingly, patients who had received enteral nutrition did not have a better survival rate. The severity of liver steatosis was negatively correlated with the serum albumin levels, while it was positively correlated with hs‐CRP values. Furthermore, serum albumin levels showed a negative correlation with hs‐CRP levels. We did not find any significant association between the presence of NAFLD and clinical parameters of nutrition. We have shown that NAFLD could be one more possible example of reverse epidemiology in patients undergoing HD. NAFLD may be the missing link that causally ties malnutrition, inflammation, and atherosclerosis syndrome to the morbidity and mortality in patients undergoing HD.     

Physical function was related to mortality in patients with chronic kidney disease and dialysis

Previous studies have shown that exercise improves aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and health‐related quality of life (QOL) in patients with chronic kidney disease (CKD) and dialysis. Recently, additional studies have shown that higher physical activity contributes to survival and decreased mortality as well as physical function and QOL in patients with CKD and dialysis. Herein, we review the evidence that physical function and physical activity play an important role in mortality for patients with CKD and dialysis. During November 2016, Medline and Web of Science databases were searched for published English medical reports (without a time limit) using the terms “CKD” or “dialysis” and “mortality” in conjunction with “exercise capacity,” “muscle strength,” “activities of daily living (ADL),” “physical activity,” and “exercise.” Numerous studies suggest that higher exercise capacity, muscle strength, ADL, and physical activity contribute to lower mortality in patients with CKD and dialysis. Physical function is associated with mortality in patients with CKD and dialysis. Increasing physical function may decrease the mortality rate of patients with CKD and dialysis. Physicians and medical staff should recognize the importance of physical function in CKD and dialysis. In addition, exercise is associated with reduced mortality among patients with CKD and dialysis.     

Malnutrition‐inflammation‐coronary calcification in pediatric patients receiving chronic hemodialysis

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1–21.2 years) receiving hemodialysis for ≥2 months. Inflammation was assessed by serum IL‐6, IL‐8, and C‐reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time‐averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice‐weekly; mean single pool Kt/V 1.48±0.13; and mean normalized protein catabolic rate 1.27±0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1±2.1 vs. 15.4±3.1 months; P=0.03), had longer dialysis vintage (49.4±15.3 vs. 17.2±10.5 months, P=0.0002), lower serum cholesterol (122±17.7 vs. 160.4±10.6 mg/dL, P=0.02), and higher phosphorus (9.05±1.2 vs. 6.1±0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL‐6 and IL‐8 levels compared with healthy norms; the mean IL‐6, IL‐8, and C‐reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.     

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

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

Protecting the endothelium: a new focus for management of chronic kidney disease

It is being increasingly recognized that cardiovascular disease (CVD) and its complications are the most important cause of morbidity and mortality in patients with chronic kidney disease (CKD) and dialysis patients. If outcomes for these patients are to be improved, therapeutic strategies at all stages of CKD will have to target the etiologies and mechanisms that lead to CVD. In this review, we focus on the central role of endothelial dysfunction as the critical precursor of CVD. We argue that a better understanding of endothelial dysfunction by nephrologists and dialysis physicians is necessary if there is to be success in limiting the CVD epidemic that kills and maims our patients. The extensive studies to explain the high prevalence of vascular disease in patients with CKD have shown the close relationship among endothelial dysfunction, inflammation, and atherosclerosis. The pathogenesis starts with endothelial cell injury from any of many possible causes, and strategies to reduce the burden of CVD in uremic and dialysis patients must be directed at restoring normal endothelial function or, at the least, preventing aggravation of endothelial damage. At the center of the exploration of endothelial dysfunction and atherosclerosis are oxidative stress and inflammation. Of these, which is the chicken and which is the egg is unknown, but in the setting of uremia, endothelial injury because of free radical, oxidative stress is likely to precede inflammation. The issues raised here are highly complex and most renal practitioners may not have been adequately exposed to the background research underlying current thinking of the pathogenesis of vascular disease. Clearly, progress in management of CVD in patients with CKD will require collaboration with experts in the research and treatment of vascular disease. Nephrologists seeking optimum outcomes for patients with CKD will need to become "endotheliologists" or, at the least, subscribe to a mission "to protect the endothelium."     

Hypomagnesemia,chronic kidney disease and cardiovascular mortality: Pronounced association but unproven causation

Magnesium is as an essential metal implicated in numerous physiological functions of human cells. The kidney plays a crucial role in magnesium homeostasis. In advanced chronic kidney disease, serum magnesium levels are increased. Data from experimental and observational studies suggest that low levels of magnesium are associated with several factors, such as insulin resistance, diabetes, oxidative stress, hypertension, atherosclerosis, and inflammation which are implicated in the progression of chronic kidney disease. Moreover, low levels of magnesium have been correlated with cardiovascular disease and all‐cause mortality in end‐stage renal disease patients. Hypomagnesemia has also been associated with poorer renal allograft and transplant recipients' outcomes. The causality of these relationships has not been completely elucidated. A thorough review of the current literature indicates that low magnesium levels in dialysis patients may reflect a poorer nutritional status and/or are the result of systemic inflammation. Further studies in chronic kidney disease and dialysis patients are needed in order to clarify the causality of these associations.     

Depressive symptom severity,contributing factors,and self‐management among chronic dialysis patients

Despite the high prevalence of depressive symptoms in patients receiving chronic dialysis, there has been inadequate attention to patient‐related barriers to management of depressive symptoms, such as factors identified by these patients as contributing to their symptoms, and how they responded to the symptoms. Participants (N = 210) in an ongoing longitudinal observational study of multidimensional quality of life in patients receiving chronic dialysis completed a battery of measures monthly for 12 months. For each patient at each measurement point, an event report was generated if he or she scored outside of the normal range on the depressive symptom scale (Center for Epidemiologic Studies Depression Scale‐Short Form [CESD‐SF] ≥10) or expressed suicidal ideation. Of the 210 participants, 100 (47.6%) had a CESD‐SF score ≥10 at least once resulting in 290 event reports. Of these 100 participants, 15 (15%) had also reported suicidal ideation in addition to having depressive symptoms. The most frequently stated contributing factors included “managing comorbid conditions and complications” (56 event reports, 19.3%), “being on dialysis” (50, 17.2%), “family or other personal issues” (37, 12.8%), and “financial difficulties” (31, 10.7%). On 11 event reports (3.8%) participants had been unaware of their depressive symptoms. On 119 event reports (41%) participants reported that they discussed these symptoms with their dialysis care providers or primary care providers, while on 171 event reports (59%) symptoms were not discussed with their health‐care providers. The prevalence of depressive symptoms is high and many patients lack knowledge about effective self‐management strategies.     

Is there any interaction of resistin and adiponectin levels with protein‐energy wasting among patients with chronic kidney disease

The aim of this study was to evaluate the effects of adipocytokines including adiponectin, leptin, resistin, neuropeptide Y and ghrelin in chronic kidney disease (CKD) patients on appearance of protein‐energy wasting (PEW). One hundred fifty patients with mean age of 45.4 ± 15.9 years, without active infections or chronic inflammatory conditions were recruited into the study. Study groups were control group (consisting of 30 healthy volunteers with normal kidney functions), hemodialysis group, predialysis group, peritoneal dialysis group and kidney transplant group. Fasting morning serum leptin, ghrelin, acylated ghrelin, neuropeptide Y, adiponectin, resistin levels of all of the groups were measured. Anthropometric and nutritional assessments of all patients were obtained. Diagnosis of PEW was made according to definition recommended by the International Society of Renal Nutrition and Metabolism. Presence of PEW in hemodialysis (23.3%) and peritoneal dialysis (26.7%) groups were significantly higher than those of predialysis (3.3%), and transplantation (0%) groups. Adiponectin and resistin levels in predialysis, peritoneal dialysis and hemodialysis patients were significantly higher than control group (p: 0.0001). This study had given significant positive correlations between presence of PEW and serum resistin (r: 0.267, p: 0.001), and serum adiponectin levels (r: 0.349, p: 0.0001). There were no relationship between presence of PEW and ghrelin, acylated‐ghrelin, neuropeptide Y, and leptin levels of the groups. CKD patients except transplant patients had higher adiponectin and resistin levels than control group. PEW was found to be linearly correlated with resistin and adiponectin. High serum resistin and adiponectin levels might have a role in development of PEW among dialysis patients.     

D‐dimer levels in maintenance hemodialysis patients: High prevalence of positive values also in the group without predisposing diseases

We aimed to estimate the prevalence of elevated D‐dimer levels in all chronic hemodialysis patients and those without additional disease, and to identify factors associated with increased D‐dimer. In 167 chronic hemodialysis patients from our center, D‐dimer was measured before dialysis. The effects of age, C‐reactive protein (CRP), recent acute illness, vascular access, anticoagulation type, dialysis vintage, and chronic diseases, considered to predispose for increased D‐dimer levels, were analyzed. The median D‐dimer in the whole group was 966 (inter‐quartile range [IQR] 524–1947) μg/L and was positive (>500 μg/L) in 75% of cases. D‐dimer was positive in 91% of patients with acute illness, 76% of those with predisposing chronic diseases, but was still positive in 52% of patients without additional disease (i.e., acute illness or predisposing chronic diseases) – median D‐dimer was 538.5 (IQR 359–966) μg/L. D‐dimer was correlated to patients' age, but not dialysis vintage. In univariate analysis, the D‐dimer levels were significantly higher in patients with atrial fibrillation, ischemic heart disease, recent acute illness, increased CRP, dialyzed over a catheter, and on citrate anticoagulation. Multivariate logistic regression showed that only age >65 years (odds ratio [OR] 2.93), catheter (OR 4.86), and positive CRP (OR 4.07) were independently associated with positive D‐dimer at 500 μg/L cut‐off, while the significance of age disappeared at 2000 μg/L cut‐off. To conclude, the high prevalence of positive D‐dimer values even in hemodialysis patients without additional disease limits the use of D‐dimer for exclusion of thromboembolic diseases in hemodialysis patients.     

Lipoprotein (a) in Chronic Renal Failure: Effect of Maintenance Hemodialysis

Background:  Coronary artery disease accounts for significant morbidity and mortality in patients with chronic kidney disease (CKD). Besides the higher prevalence of traditional risk factors, several uremia-related factors may play a role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a) (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well understood. The present work was carried out to study the Lp(a) levels in Stage 4 and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients with Stage 5 CKD.
Methods:  The study subjects included 15 patients with Stage 4 CKD, 15 patients with Stage 5 CKD, and 15 age- and sex-matched healthy controls. Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD were dialyzed two to three times weekly for 4 hr during each session.
Results:  Mean Lp(a) levels were significantly higher in patients with CKD than in control patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 ± 19.5 mg/dL, whereas in Stage 5 CKD the level was 49.0 ± 30.9 and in healthy controls it was 22.2 ± 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant fall in Lp(a) levels by 23.6% (P < 0.001).
Conclusions:  The results of this study show that increases in Lp(a) levels start early during the course of CKD and become more pronounced with increased severity of disease. Initiation of MHD lowers Lp(a) levels and may have a long-term beneficial effect on cardiovascular morbidity and mortality.     

Disease‐Triggered Drug Release Effectively Prevents Acute Inflammatory Flare‐Ups,Achieving Reduced Dosing

For conditions with inflammatory flare‐ups, fast drug‐release from a depot is crucial to reduce cell infiltration and prevent long‐term tissue destruction. While this concept has been explored for chronic diseases, preventing acute inflammatory flares has not been explored. To address this issue, a preventative inflammation‐sensitive system is developed and applied to acute gout, a condition where millions of inflammatory cells are recruited rapidly, causing excruciating and debilitating pain. Rapid drug release is first demonstrated from a pH‐responsive acetalated dextran particle loaded with dexamethasone (AcDex‐DXM), reducing proinflammatory cytokines in vitro as efficiently as free drug. Then, using the air pouch model of gout, mice are pretreated 24 h before inducing inflammation. AcDex‐DXM reduces overall cell infiltration with decreased neutrophils, increases monocytes, and diminishes cytokines and chemokines. In a more extended prophylaxis model, murine joints are pretreated eight days before initiating inflammation. After quantifying cell infiltration, only AcDex‐DXM reduces the overall joint inflammation, where neither free drug nor a conventional drug‐depot achieves adequate anti‐inflammatory effects. Here, the superior efficacy of disease‐triggered drug‐delivery to prevent acute inflammation is demonstrated over free drug and slow‐release depots. This approach and results promise exciting treatment opportunities for multiple inflammatory conditions suffering from acute flares.     

Causes and consequences of inflammation on anemia management in hemodialysis patients

Inflammation is common among hemodialysis patients, and evidence is accumulating to suggest that inflammation is a major contributor to morbidity and mortality. Several factors have been suggested as potential causes of inflammation, including infections and the atherosclerosis process, as well as etiologies directly related to kidney disease such as reduced renal function and dialysis. Among several inflammatory biomarkers investigated, serum C-reactive protein (CRP) is the most widely used. In hemodialysis patients, raised CRP levels have been shown to be predictive of cardiovascular events, hospitalization, and all-cause and cardiovascular mortality. Elevated CRP levels may correlate with comorbidities and intercurrent events, all of which may impact the response to erythropoiesis-stimulating agents (ESAs) and lead to higher ESA doses. Most dialysis facilities do not routinely measure CRP, despite recommendations by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. Regular measurement of CRP levels may help providers to understand change in ESA dosing and identify patients at risk for cardiovascular events. This review explores the inter-relationships between inflammation, CRP levels, and anemia management in patients receiving hemodialysis.     

Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: A multicenter longitudinal study

Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients and is associated with poor survival. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb proinflammatory cytokines and to decrease amino acids and antioxidants loss. These features could be helpful in MHD patients affected by idiopathic chronic inflammation, but this issue remains to be elucidated. We performed a multicenter longitudinal study to assess the effect of the switching from bicarbonate HD to HFR in patients with serum C‐reactive Protein (CRP) > 5 mg/L coupled with albumin <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20 patients were assessed at 4 months and 18 completed the study. We excluded 11 patients with evident causes of inflammation. At baseline, serum levels of CRP (18.7[7.0–39.4] mg/L) and albumin (3.5[3.3–3.7] g/dL) were significantly correlated (r = ?0.49; P = 0.028). The effect on CRP and albumin was almost evident in the first 4 months and remained stable until to eighth month. A strict correlation (R = ?0.49; 0.040) between percentage change of CRP (?35%) and albumin (+14%) after 8 months of HFR. These effects were associated with the reduction of IL‐6, IL‐1β, and TNF‐α and the increment of pre‐albumin and leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained unchanged. In MHD patients affected by idiopathic chronic inflammation the switching from BHD to HFR is associated with improvement of inflammation. Whether these favorable effects may modify the outcomes of these high‐risk patients needs to be confirmed by studies ad hoc.     

Risk of major depression in patients with chronic renal failure on different treatment modalities: A matched‐cohort and population‐based study in Taiwan

The influence of different treatment modalities on the risk of developing major depression in patients with chronic renal failure (CRF) is not well understood. We aimed to explore the incidence of major depression among patients with CRF who were on different dialysis modalities, who had received renal transplantation (RT), and those who had not yet received any of the aforementioned renal replacement therapies. We conducted a population‐based retrospective cohort study using a national health insurance research database. This study investigated 89,336 study controls, 17,889 patients with chronic kidney disease on conservative treatment, 3823 patients on hemodialysis (HD), 351 patients on peritoneal dialysis (PD), and 322 patients who had RT. We followed all individuals until the occurrence of major depression or the date of loss to follow‐up. The PD group had the highest risk (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.26–4.69), whereas the RT group had the lowest risk (HR 0.18; 95% CI 0.03–1.29) of developing major depression compared with the control group. Patients initiated on PD had a higher risk of developing major depression than patients initiated on HD (pairwise comparison: HR 2.20; 95% CI 1.09–4.46). Different treatment modalities are associated with different risks of developing major depression in patients with CRF. Among renal replacement therapies, patients who have had RT have the lowest risk of developing major depression. Patients who initiate renal therapy on PD may have a higher risk of major depression compared with patients who initiate renal therapy on HD.     

Self‐perceived quality of sleep and mortality in Norwegian dialysis patients

Sleep complaints are prevalent and associated with poor health‐related quality of life (HRQoL), depression and possibly mortality in dialysis patients. This study aimed to explore possible associations between sleep quality, daytime sleepiness and mortality in dialysis patients. In this study, 301 dialysis patients were followed up to 4.3 years. HRQoL was evaluated at baseline with the Kidney Disease and Quality of Life—Short Form (KDQoL‐SF), depression with Beck Depression Inventory (BDI), sleep quality with Pittsburgh Sleep Quality Index and daytime sleepiness with Epworth Sleepiness Scale. The single item “on a scale from 0–10, how would you evaluate your sleep?” in the sleep subscale in KDQoL‐SF was used to identify poor (0–5) and good sleepers (6–10). A total of 160 patients (53.3%) were characterized as poor sleepers. They were younger (r = 0.241, P < 0.001), had more depression (BDI: 8.72 ± 6.79 vs. 13.60 ± 8.04, P < 0.001), a higher consumption of hypnotics and antidepressants and reduced HRQoL (Mental Component Summary score: 45.4 ± 11.0 vs. 50.0 ± 10.4, P < 0.001. Physical Component Summary score: 35.0 ± 9.9 vs. 38.5 ± 10.5, P = 0.004). In multivariate analyses, poor sleepers had nearly a twofold increase in mortality risk (hazard ratio [HR] 1.92, confidence interval [CI] 1.10‐3.35, P = 0.022). Daytime sleepiness was not related to mortality (HR 1.01, CI 0.95‐1.08, P = 0.751). Sleep complaints predicted increased mortality risk in dialysis patients and should therefore be routinely assessed. Further studies are needed to find suitable treatment options for poor sleep in dialysis patients as it may affect both HRQoL and survival.     

Anemia management in chronic kidney disease

Anemia is common in chronic kidney disease (CKD) due to a state of erythropoietin deficiency. Erythropoietin therapy has been used for approximately 20 years to correct anemia in CKD and to improve both subjective and objective outcomes. Guidelines that establish a hemoglobin (Hb) goal for anemia correction in CKD patients are largely based on observational data. Controversy still exists, however, because outcomes have not been consistent with various degrees of anemia correction. The number of prospective randomized trials investigating the effects of anemia correction on cardiovascular (CV) morbidity and mortality in CKD patients, an already high-risk group, is limited. With respect to improving CV outcomes in the CKD population, the currently available trial data caution against raising Hb levels in CKD patients to approach more "normal" physiologic ranges. The disappointing experience with the trial data must be weighed against the beneficial associations of erythropoietin therapy that have been generated from observational data. Establishing the ideal target Hb ranges for anemia correction in CKD patients remains a dynamic process and leaves many gray areas to be further elucidated. Here, we present a case that underscores the need to consider the study design when reviewing the data at a population level in order to determine what is most appropriate for our patient.     

Left ventricular geometric patterns in end‐stage kidney disease: Determinants and course over time

Introduction : While concentric left ventricular hypertrophy (cLVH) predominates in non–dialysis‐dependent chronic kidney disease (CKD), eccentric left ventricular hypertrophy (eLVH) is most prevalent in dialysis‐dependent CKD stage 5 (CKD5D). In these patients, the risk of sudden death is 5× higher than in individuals with cLVH. Currently, it is unknown which factors determine left ventricular (LV) geometry and how it changes over time in CKD5D. Methods : Data from participants of the CONvective TRAnsport Study who underwent serial transthoracic echocardiography were used. Based on left ventricular mass (LVM) and relative wall thickness (RWT), 4 types of left ventricular geometry were distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of eLVH were assessed with logistic regression. Left ventricular geometry of patients who died and survived were compared. Long‐term changes in RWT and LVM were evaluated with a linear mixed model. Findings : Three hundred twenty‐two patients (63.1 ± 13.3 years) were included. At baseline, LVH was present in 71% (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively associated with eLVH and ß‐blocker use inversely. None of the putative volume parameters showed any relationship with eLVH. Although eLVH was most prevalent in non‐survivors, the distribution of left ventricular geometry did not vary over time. Discussion : The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long‐term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings.     

Serum matrix metalloproteinase-3 in hemodialysis patients with dialysis-related amyloidosis

Background: Matrix metalloproteinase‐3 (MMP‐3) has been linked to osteoarticular destruction in rheumatic arthritis. To investigate the role of MMP‐3 in dialysis‐related amyloidosis (DRA), we determined serum MMP‐3 in long‐term hemodialysis (HD) patients with and without clinical manifestations of DRA. Methods: Thirty‐three subjects (63% female, 3% diabetic) enrolled in the study between September 2001 and June 2003. All patients underwent standard HD three times per week, using high‐flux dialyzers. Four patients had active DRA complications (DRA patients), whereas the others (n = 29) had no evidence of DRA. We determined serum concentrations of MMP‐3, C‐reactive protein (CRP), β₂‐microglobulin (β₂M), and interleukin‐6 (IL‐6). We also studied the effects of hemodiafiltration (HDF) on inflammatory measures by transferring the DRA patients from regular HD to predilution HDF. Results: The DRA group had been on dialysis significantly longer than the control group. Significant positive correlations were observed between MMP‐3 and IL‐6 (R² = 0.5143, p < 0.0001) and MMP‐3 and CRP (R² = 0.6492, p < 0.0001). IL‐6 levels increased after a single dialysis treatment, but this effect was minimal with predilution HDF (the increment of IL‐6 levels did not exceed 10 pg/mL). Serum MMP‐3 levels decreased in parallel with the decrease of IL‐6. Conclusions: MMP‐3 serum levels increase in accordance with clinical manifestations of DRA and elevated circulating levels of IL‐6. For the evaluation of the pathophysiologic state of DRA, serum MMP‐3 may be a useful predictor indicative of chronic inflammation and osteoarticular disorders in DRA patients.