Assessment of the cardiovascular system in pediatric chronic kidney disease: a pilot study

Long-term survival of children and adolescents with chronic kidney disease (CKD) is mainly limited by cardiovascular disease. Pediatric CKD patients (n = 26) on conservative treatment, dialysis and after renal transplantation were compared with healthy controls (n = 24) with respect to cardiovascular status. Mean baseline diameter of the brachial artery was significantly higher, and mean flow-mediated vasodilation (FMD) was significantly reduced, in CKD patients. CKD patients showed significantly increased left ventricular mass index, blood pressure (BP) values and age-related values of mean carotid intima-media thickness [intima-media thickness–standard deviation score (IMT-SDS)] compared with those of controls. Approximately 60% of patients presented with impaired FMD (≤ 5.79%), which was significantly associated with intima-media thickening, although only three patients (12%) presented with both, impaired FMD and increased age-related IMT. The latter was significantly associated with higher values for day-time BP. In contrast, duration and degree of CKD, mode of renal replacement therapy, homocysteine levels and concomitant medication showed no association with cardiovascular status. The majority of our pediatric CKD patients showed reduced endothelial function, which may have preceded the development of carotid arteriopathy. Therefore, routine assessment of FMD may be a useful tool to identify CKD patients at risk of progressive cardiovascular morbidity.     

Effects of exercise on markers of inflammation and indicators of nutrition in patients with chronic kidney disease: a systematic review and meta-analysis

International Urology and Nephrology - This meta-analysis aimed to reveal the effects of exercise training on markers of inflammation and indicators of nutrition in non-dialysis-dependent patients...     

Progression from acute kidney injury to chronic kidney disease: a pediatric perspective

Although emerging evidence indicates that the incidence of both acute kidney injury (AKI) and chronic kidney disease (CKD) in children is rising and the etiologies are dramatically changing, relatively little is currently known regarding the potential for transition from AKI to CKD. In both situations, early intervention can significantly improve the dismal prognosis. However, the lack of a uniform AKI definition and the paucity of early, predictive biomarkers have impaired our ability diagnose AKI early to institute potentially effective therapies in a timely manner. Fortunately, recent data has validated a multidimensional AKI classification system for children. In addition, the application of innovative technologies has identified candidates that are emerging as early biomarkers of both AKI and CKD. These include neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and kidney injury molecule-1. Studies to validate the sensitivity and specificity of these biomarkers in clinical samples from large cohorts and from multiple clinical situations are currently in progress, facilitated by the development of commercial tools for the reproducible measurement of these biomarkers across different laboratories.     

Effects of exercise training on physical impairment,arterial stiffness and health-related quality of life in patients with chronic kidney disease: a pilot study

Background  

Patients with chronic kidney disease (CKD) have impaired performance in physical tasks, lower health-related quality of life and high cardiovascular morbidity and mortality. Moderate intensity exercise has been shown to provide cardiovascular and metabolic benefits in healthy individuals and patients without CKD. Long-term exercise training is recommended as a vital component in the management of a number of chronic diseases. This randomized controlled pilot project examined the effects of exercise in predialysis CKD patients.     

The malnutrition and inflammation axis in pediatric patients with chronic kidney disease

Malnutrition and inflammation are closely linked in adult chronic kidney disease (CKD) patients and are both related to poor outcome, but data on pediatric patients are lacking. To describe the prevalence of inflammation, evaluate nutritional status, their correlation to each other, and their possible determinants in pediatric patients with CKD in predialysis, on hemodialysis (HD), and peritoneal dialysis (PD) who were submitted to demographic, nutritional, and inflammatory evaluations. Patients’ nutritional status was evaluated according to anthropometric parameters and body composition assessed by measurements of skinfold thickness and bioelectrical impedance. Inflammation was assessed by measurement of highly sensitive C-reactive protein (CRP), ferritin, and albumin. Patients with CRP >1 mg/l were considered inflamed. Sixty-four pediatric patients (mean age 9 ± 4 years-, 40% on HD, 22% on PD, and 38% predialysis) were studied. Mean CRP concentration was 3.4 ± 6.5 mg/l (median 0.78 mg/l, range 0.78−33.4 mg/l), and 41% presented CRP levels above 1 mg/l. Mean ferritin was 148 ± 197 mg/dl and was above the normal reference values in 28% of patients. On the other hand, mean albumin was 3.9 ± 0.5 mg/dl, below reference value in only 13% of patients. A larger proportion of HD patients (52%) were inflamed compared with those on PD (31%; p < 0.05). Malnutrition prevalence varied from 5% to 65% according to the method used. While inflamed patients presented lower serum bicarbonate and were on HD for a longer time, there were no consistent associations between malnutrition and inflammation. Inflammation is highly prevalent in the pediatric CKD population and was not consistently related to malnutrition. Other risk factors linked to high mortality and morbidity (acidosis and longer time on dialysis) were associated with inflammation. Prospective studies will need to analyze the predictive value of inflammation and malnutrition markers in the pediatric CKD population.     

Association of obesity with inflammation in chronic kidney disease: a cross-sectional study.

OBJECTIVE: As adipose tissue releases inflammatory cytokines, obesity is associated with elevated C-reactive protein (CRP) levels in the general population. We examined the cross-sectional association of body mass index (BMI) with CRP in patients with chronic kidney disease (CKD). DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Ninety-four CKD patients with varying levels of renal function seen at the University of Utah outpatient renal clinic were studied. METHODS: Data on demographics (age, gender, race), comorbidity (diabetes mellitus, hypertension, myocardial infarction/angina, cerebrovascular disease, peripheral vascular disease, and smoking) and anthropometry (height and weight) were obtained by patient interview and chart reviews. High-sensitivity CRP was measured by the N-latex assay on a BN II nephelometer. MAIN OUTCOME MEASURE: Risk factors of high CRP. RESULTS: In a multivariable logistic regression model, when compared with patients with a BMI < 25, the odds of CRP > 3.0 mg/L were 2.5-fold (95% CI, 1.02 to 5.99) higher in patients with BMI > or = 30. In a stepwise multiple linear regression model, BMI (regression coefficient [beta] = 0.06; 95% CI, 0.03 to 0.1; P < .01), serum creatinine (beta = 0.16; 95% CI, 0.04 to 0.3; P = .01) and age (beta = 0.01; 95% CI, -0.001 to 0.03; P = .05) were significantly associated with log transformed CRP. CONCLUSION: These data suggest that as in the general population, in CKD patients, obesity, a traditional risk factor for atherosclerosis, is associated with inflammation, a novel risk factor for atherosclerosis.     

Acute exercise during hemodialysis prevents the decrease in natural killer cells in patients with chronic kidney disease: a pilot study

Purpose

To evaluate the acute response of natural killer (NK) cell subsets of chronic kidney disease patients submitted to intradialytic exercise in a randomized crossover study.

Methods

Nine patients were submitted to a single bout of 20-min intradialytic exercise and a control hemodialysis (HD) session with an interval of 7 days between them. Peripheral blood sample was collected at baseline, during HD and immediately after HD in each trial to evaluate the peripheral frequency of NK cells and their subsets (CD3-CD56^bright and CD3-CD56^dim), systemic cortisol concentrations, C-reactive protein (CRP), creatine kinase activity (CK), and urea and creatinine levels.

Results

HD therapy induced a significant decrease in NK cells frequency (p = 0.039), NK CD3-CD56^bright cells (p = 0.04), and CD3-CD56^dim cells (p = 0.036). On the other hand, no significant alterations were observed in NK cells and NK subsets during and after intradialytic exercise trial (p > 0.05). Neither trial altered CRP levels or serum CK activity during and after HD therapy (p > 0.05). However, HD therapy increased cortisol concentrations after HD therapy (p = 0.034).

Conclusions

This study suggests the potential role of intradialytic exercise to prevent the decrease in peripheral frequency of NK cell subsets during HD therapy. Moreover, moderate intensity intradialytic exercise did not exacerbate the systemic inflammation or induce muscle damage during HD therapy.

     

Angiotensin receptor blockade and arterial compliance in chronic kidney disease: a pilot study

BACKGROUND: Almost 20 million people in the US have chronic kidney disease (CKD). Cardiovascular disease and arterial wall abnormalities are common in this population. Because angiotensin II may have adverse effects on the arterial wall, we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial compliance as compared with placebo in subjects with CKD. METHODS: We performed a double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2 or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg. Arterial compliance was measured at baseline and at 8 weeks. RESULTS: Baseline characteristics were similar between the groups and included mean estimated glomerular filtration rate 63 +/- 14 ml/min/1.73 m(2), heart rate 76 +/- 10 beats/min, BP 142 +/- 12/81 +/- 8 mm Hg, 64% diabetic, 44% male, and 40% white, though subjects in the eprosartan group were younger (60 +/- 12 vs. 70 +/- 6 years, p = 0.01). There were no significant differences between the groups in large or small artery compliance measurements either at baseline or at 8 weeks, but there was a statistically significant improvement from baseline in small artery compliance in the eprosartan group (from median 2.5 ml/mm Hg x 100 [90% CI (1.1, 4.7)] to 4.0 ml/mm Hg x 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the placebo group. CONCLUSION: Use of an ARB to achieve recommended BP is associated with improved small artery compliance in people with CKD, though larger studies are needed to confirm these findings.     

Hemoglobin target in chronic kidney disease: a pediatric perspective

Erythropoietin has transformed the treatment of the anemia of chronic kidney disease (CKD) by preventing the need for blood transfusions and improving the quality of life in all patients, including children. Anemia in children, in the age group 1–19 years, may be defined as hemoglobin (Hgb) levels < 12.1–13.5 g/dl for boys and < 11.4–11.5 g/dl for girls, based on the National Health and Nutrition Examination Survey (NHANES) norms. The prevalence of anemia in children ranges from 31.2% in stage 1 CKD to 93.3% in stages 4 and 5 CKD. The recent publication of trials evaluating the optimal hemoglobin level in adult CKD patients has generated considerable uncertainty about the target Hgb level in children with CKD. It is unclear whether generalizing of results from these trials in adults to children is appropriate. Adequately powered, randomized, controlled studies have not been conducted on children, and none to our knowledge are currently planned. The Food and Drug Administration (FDA) offers scant guidance on the Hgb target level for children, other than implying that it should be no different from that for adults. The purpose of this editorial is to critically scrutinize whether there is a benefit to the normalization of anemia in children with CKD and whether adoption of the results from adult studies is appropriate.     

Transition from acute kidney injury to chronic kidney disease: a single-centre cohort study

Background

The incidence of acute kidney injury (AKI) is increasing. AKI is currently recognised as an inducer of chronic kidney disease (CKD) and this is known as the ‘AKI–CKD transition’. This study aimed to evaluate the rate of decline in estimated glomerular filtration rate (eGFR) associated with AKI events in individuals with and without pre-existing CKD.

Methods

Inpatients aged 18–80 years were retrospectively enrolled. AKI was diagnosed according to the kidney disease improving global outcomes (KDIGO) criteria using serum creatinine levels. Patients with a history of AKI events were divided into four groups according to eGFR before and after the AKI events. In each group, the eGFR levels after an AKI event were compared to those before the AKI event. Patients were further divided into eight groups according to clinical background based on underlying diseases, medications, and surgical history.

Results

We analysed data from 9651 patients with AKI. Not surprisingly, we found that eGFR levels during the first AKI event were significantly lower than levels before the event in each group. Furthermore, eGFR levels after the first AKI event were significantly lower than those before the first AKI event, and the eGFR levels after the second AKI event were significantly lower than those after the first AKI event. These trends were similar in each group irrespective of clinical background.

Conclusions

Our study revealed that AKI events can cause a decline in kidney function and, as more AKI events occur, acceleration of this decline.

     

Effects of acute resistance exercise on acyl-ghrelin and obestatin levels in hemodialysis patients: a pilot study

Abstract

Chronic physical exercises may be beneficial to modulate appetite hormones as acyl-ghrelin (orexigenic) and obestatin (anorexigenic) in chronic kidney disease (CKD) patients; however, there are no data about the effects of acute exercises on these hormones. Thus, the aim of the present study was to assess the effect of acute resistance exercise on appetite hormones (acyl-ghrelin and obestatin) of patients undergoing hemodialysis (HD). Twenty-five patients (44.7?±?12.9 years, 68% women) on regular HD program were enrolled into two groups, 16 patients performed exercises and 9 patients comprised the control group. The patients performed the exercises in both lower limbs with ankle-cuffs and elastic bands, 30?min after the initiation of hemodialysis session. Blood samples of both the groups were drawn in the morning before and after 30?min with exercise session (exercise group) and, before and after the same time without exercise (control group). Acyl-ghrelin and obestatin plasma levels were measured using an enzyme immunometric assay. Acyl-ghrelin plasma levels did not change in both the groups. However, when stratified by gender the acyl-ghrelin increased significantly right after exercise in men [32.1?pg/mL (25.6–41.2) to 46.0?pg/mL (39.0–59.5)] (p?=?0.04). Obestatin plasma levels reduced after a single bout of exercise and changes remained significantly when the sample was stratified by gender. There was no change in obestatin plasma levels in control group. A single bout of resistance exercise seems to modulate the levels of appetite hormones in HD patients.     

Epidemiology of pediatric chronic kidney disease

In contrast to the adult population, in whom a variety of registries have confirmed the incidence, prevalence, and diagnoses associated with chronic kidney disease (CKD), the epidemiological information on pediatric CKD is currently imprecise and flawed by methodological differences between the various data sources. Obstructive uropathy and congenital aplasia/hypoplasia/dysplasia are responsible for almost one half of all cases of CKD in children, underscoring the fact that a substantial percentage of the pediatric CKD population develops renal insufficiency very early in life. However, there are distinct geographic differences in the reported causes of CKD, in part because of environmental, racial, genetic, and cultural (consanguinity) differences. Furthermore, despite apparently comparable incidence rates, high mortality in countries that lack health care resources results in a low prevalence of CKD in those locations. In countries where renal replacement therapy is readily available, the most favored treatment modality is renal transplantation in all pediatric age groups. Additional efforts to define the epidemiology of pediatric CKD worldwide in a more uniform manner are necessary if a better understanding of the full extent of the problem, areas for study, and the potential impact of intervention is desired.     

Effects of intradialytic exercise on systemic cytokine in patients with chronic kidney disease

Abstract

Background: Immunological dysfunctions and a pro-inflammatory environment are associated with higher risk of cardiovascular diseases in chronic kidney disease (CKD). Physical exercise can be an important anti-inflammatory strategy, but the effects in CKD remain poorly investigated. Objective: Evaluate the acute inflammatory response to intradialytic exercise in the peripheral blood of individuals with CKD. Methods: Nine patients, of both genders, with CKD and allocated in the ambulatory of hemodialysis of Hospital Ernesto Dornelles (Brazil), performed two sessions of hemodialysis (HD) in random form: aerobic intradialytic exercise sessions (EX, 20?min of moderate exercise in cycle-ergometer) and a control hemodialysis session (CON). Peripheral blood collection was made at the baseline, during and immediately after HD to evaluate the cytokine profile: interleukin-6, interleukin-10 (IL-10), interleukin-17a (IL-17a), interferon-gamma (INF-γ) and tumoral necrosis factor-alpha (TNF-α). Results: INF-γ decreased during HD when compared with the pre moment in both sessions, while an increase in post HD was only found in the CON session. IL-17 was higher in post when compared with during HD in both sessions. In addition to the time effect, IL-10 presented a time?×?group interaction and the relative changes were significantly higher in EX when compared with the CON session. The relative changes in TNF-α tended to be higher in CON when compared with EX immediately post HD session. Conclusions: These data indicate that 20?min of intradialytic exercise have modest effect in systemic inflammation. However, the significant increase in IL-10 may indicate an immunoregulatory effect of physical exercise.     

Sodium ferric gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study.

BACKGROUND: Intravenous (i.v) iron is widely used to treat anaemia in patients with chronic kidney disease (CKD). Although beneficial and usually well tolerated, concerns have been raised about its ability to cause oxidative stress and renal injury. METHODS: To determine if i.v. iron causes oxidative stress [as assessed by plasma and urine malondialdehye (MDA)] and/or renal injury (as assessed by urinary albumin, total protein and enzymuria), we conducted a prospective, four-way randomized crossover, blinded end-point trial in eight patients with CKD. Two widely used doses of sodium ferric gluconate (125 mg infused over 1 h and 250 mg infused over 2 h) were given with or without the antioxidant N-acetylcysteine (NAC), resulting in four treatment dose-antioxidant/placebo combinations in each patient. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, MDA by high performance liquid chromatography, and albuminuria and proteinuria by standard clinical methods. Enzymuria was assessed by measurement of N-acetyl-beta-D-glucosaminidase (NAG) excretion by colorimetric assay. RESULTS: I.v. ferric gluconate infusion at both doses resulted in a marked increase in transferrin saturation and a significant increase in plasma MDA levels. Urinary MDA levels also increased at the higher dose of iron. There was no evidence of acute renal injury, as assessed by albuminuria, proteinuria or enzymuria. Pre-treatment with NAC had no effect on oxidative stress or the above urinary parameters. CONCLUSIONS: I.v. ferric gluconate caused oxidative stress (as reflected by increased MDA), but this was not associated with biochemical manifestations of acute renal injury.     

Cardiovascular complications of pediatric chronic kidney disease

Cardiovascular disease (CVD) mortality is a leading cause of death in adult chronic kidney disease (CKD), with exceptionally high rates in young adults, according to the Task Force on Cardiovascular Disease. Recent data indicate that cardiovascular complications are already present in children with CKD. This review summarizes the current literature on cardiac risk factors, mortality and morbidity in children with CKD.     

The impact of inflammation on metabolic regulation in chronic kidney disease: a review.

Chronically uremic patients are characterized by a low-grade systemic inflammation that reflects the consequences of an unbalanced production of proinflammatory and anti-inflammatory cytokines and contributes to the progression of atherosclerotic vascular disease and malnutrition. The causes of inflammation in end-stage kidney disease have been studied in details. Nonetheless, the degree of activation of the systemic inflammatory response shows great interindividual variability that cannot be explained by renal disease or dialysis. The amount of cytokine that is produced on a definite stimulus varies among individuals. Single nucleotide polymorphisms in the promoter or coding regions of cytokine genes lead to high or low productions of these mediators and may genetically explain this heterogeneity. The "low-producer" genotypes for the anti-inflammatory cytokine interleukin-10 are more permissive for a greater level of systemic inflammation and for increased cardiovascular morbidity and mortality in patients on hemodialysis. Potential pharmacologic and nutritional approaches for treatment of systemic inflammation have been identified in recent years. In addition, physical exercise training may reduce the systemic inflammatory response. Definition of the relationships between different cytokine gene polymorphisms and systemic inflammation in chronically uremic patients will improve efficacy of targeted anti-inflammatory treatments.     

Nutrition, inflammation and chronic kidney disease

PURPOSE OF REVIEW: Protein-energy wasting and chronic inflammation are important comorbid conditions that predict poor clinical outcome in patients with advanced chronic kidney disease. The current article aims to provide a brief overview of the etiology and nutritional consequences of chronic inflammation with an outline of potential treatment options. RECENT FINDINGS: The exact mechanisms leading to these unfavorable conditions are not fully elucidated and are most likely multifactorial. Irrespective of the specific etiologic mechanisms, it appears that the common pathway for all the metabolic derangements is related to exaggerated protein degradation relative to protein synthesis. Several studies suggest that chronic inflammation can predispose advanced chronic kidney disease patients to a catabolic state leading to worsening of protein-energy wasting by both increasing protein breakdown and decreasing protein synthesis. Chronic administration of nutritional supplementation, both parenterally and orally, improves nutritional status even in inflamed hemodialysis patients. Several pilot studies indicate that antiinflammatory intervention can also improve the metabolic and nutritional profiles. SUMMARY: While a single common etiology has not been identified in this complex process, nutritional and antiinflammatory interventions can provide potential treatment options to improve the high mortality and morbidity in patients with advanced chronic kidney disease.     

Sleep disorders in pediatric chronic kidney disease patients

The prevalence of sleep disorders during childhood has been estimated to range from 25 to 43 %. The aim of this review is to determine the prevalence of sleep disorders and possible associations with chronic kidney disease (CKD)-related factors and health-related quality of life (HRQOL) in children with CKD. An electronic systematic literature search for sleep disorders in children with CKD in Pubmed, Embase and the Cochrane Library Databases identified seven relevant articles for review, all of which reported an increased prevalence of sleep disorders in children with CKD. Five studies included children with CKD undergoing dialysis, and two studies included only non-dialysis patients. In all studies the presence of sleep disturbances was assessed by questionnaires; only one study compared the results of a validated questionnaire with laboratory-based polysomnography. The prevalence of any sleep disorder ranged from 77 to 85 % in dialysis patients, to 32–50 % in transplanted patients and 40–50 % in non-dialysis patients. The most commonly studied disorder was restless legs syndrome, which presented at a prevalence of 10–35 %. Three studies showed significant associations between presence of sleep disorders and HRQOL. We found consistent evidence of an increased prevalence of sleep disturbances in children with CKD, and these seemed to play a critical role in HRQOL.     

Genome-wide association studies in pediatric chronic kidney disease

The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression.