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Clinical Background: Hydration status, which is influenced by environment and self-behavior is associated with kidney health and disease. Epidemiology: Lack of safe water, sanitation, and high temperatures are environmental issues that affect a significant part of the worldwide population. Occupational factors that discourage proper hydration, as well as low water intake in favorable environment conditions, are also highly prevalent. As a consequence, inadequate water intake can lead to several kidney problems ranging from uncomplicated urinary tract infections to kidney stones, acute kidney injury, and chronic disorders with high mortality rates. Challenges: Increasing water intake is an individual effort when self-behavior is the main reason for inadequate hydration status. When the environment is an obstacle, it might require complex changes in a concerted multidisciplinary effort from employers, health authorities, researchers, and governments. Prevention and Treatment: Strategies can be implemented at global, local, and individual levels. Global efforts include actions to decrease poverty and climate change consequences, while increasing access to safe water and sanitation. Local actions can improve working conditions and access to water and toilets to workers. At an individual level, self-monitoring through regular observation of thirst sensation, acute weight loss, urine frequency, and urine color are recommended tools to monitor hydration status., (© 2021 S. Karger AG, Basel.)

Hyperkalemia is a common electrolyte disorder observed in the emergency department. It is often associated with underlying predisposing conditions, such as moderate or severe kidney disease, heart failure, diabetes mellitus, or significant tissue trauma. Additionally, medications, such as inhibitors of the renin-angiotensin-aldosterone system, potassium-sparing diuretics, nonsteroidal anti-inflammatory drugs, succinylcholine, and digitalis, are associated with hyperkalemia. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened a conference in 2018 to identify evidence and address controversies on potassium management in kidney disease. This review summarizes the deliberations and clinical guidance for the evaluation and management of acute hyperkalemia in this setting. The toxic effects of hyperkalemia on the cardiac conduction system are potentially lethal. The ECG is a mainstay in managing hyperkalemia. Membrane stabilization by calcium salts and potassium-shifting agents, such as insulin and salbutamol, is the cornerstone in the acute management of hyperkalemia. However, only dialysis, potassium-binding agents, and loop diuretics remove potassium from the body. Frequent reevaluation of potassium concentrations is recommended to assess treatment success and to monitor for recurrence of hyperkalemia.

Background: Kidney disease is prevalent in low-resource settings worldwide, but tests for its diagnosis are often unavailable. The saliva urea nitrogen (SUN) dipstick is a laboratory and electricity independent tool, which may be used for the detection of kidney disease. We investigated the feasibility and performance of its use in diagnosing kidney disease in community settings in Africa., Methods: Adult patients at increased risk of kidney disease presenting to three community health centres, a rural district hospital and a central hospital in Malawi were recruited between October 2016 and September 2017. Patients underwent concurrent SUN and creatinine testing at enrolment, and at 1 week, 1 month, 3 months and 6 months thereafter., Results: Of 710 patients who presented at increased risk of kidney disease, 655 (92.3%) underwent SUN testing at enrolment, and were included (aged 38 (29-52) years, 367 (56%) female and 333 (50.8%) with HIV). Kidney disease was present in 482 (73.6%) patients and 1479 SUN measurements were made overall. Estimated glomerular filtration rate (eGFR) correlated with SUN (r=-0.39; p<0.0001). The area under the receiver operating characteristics curve was 0.61 for presenting SUN to detect acute or chronic kidney disease, and 0.87 to detect severe (eGFR <15 mL/min/1.73 m 2 ) kidney disease (p<0.0001; sensitivity 82.3%, specificity 81.8%, test accuracy 81.8%). In-hospital mortality was greater if enrolment SUN was elevated (>test pad #1) compared with patients with non-elevated SUN (p<0.0001; HR 3.3 (95% CI 1.7 to 6.1)., Conclusions: SUN, measured by dipstick, is feasible and may be used to screen for kidney disease in low resource settings where creatinine tests are unavailable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Working conditions that impair sufficient water intake have been associated with kidney problems such as kidney stones, urinary symptoms and chronic kidney disease (CKD). Higher prevalence of these morbidities was linked to occupations that do not facilitate worker access to drinking water and toilets, as well as people who perform activities in a hot environment. In this mini-review, we aim to describe and interpret available evidence in the areas of occupation, hydration and kidney health. This review explores examples of documented kidney health problems affecting professions ranging from astronauts and teachers in developed countries to rural workers in low-income settings living in water-restricted or hot environments.

Aim: Since the impact of peritonitis on long-term non-infectious mortality has not been investigated until the present, the aim of this study was to analyze the impact of peritonitis on long-term cardiovascular (CV) mortality in a large peritoneal dialysis (PD) cohort., Methods: The analysis was based on BRAZPD II, a national prospective cohort study that recruited patients in Brazilian centres from December 2004 to January 2011. Incident adult PD patients with at least 90 days on treatment were included in the analysis. Cardiovascular death occurring after a minimum of 30 days after a peritonitis episode was considered the primary endpoint. Cox regression analysis for time-dependent variables was used for the adjustments., Results: There were 2405 episodes of peritonitis in 5707 patients (48% males, 44% diabetes, 73% hypertensive). Patients with one episode of peritonitis presented a 22% increase in the hazard ratio of late CV mortality compared to those who never experienced peritonitis (HR1.22; CI95%1.01-1.47). Adjusted hazard for CV mortality showed a stepwise negative effect on survival for each additional peritonitis episode of infection: two episodes (HR1.78; CI95%1.31-2.42), three episodes (HR2.81; CI95%1.83-4.32) and four episodes (HR3.84; CI95%2.01-7.32)., Conclusion: Peritonitis was an independent predictor of CV mortality and the frequency of peritonitis was strongly associated with an increase in this risk. This is the first study to demonstrate the impact of peritonitis on late cardiovascular mortality of PD patients, suggesting a link between acute inflammation and cardiovascular outcomes., (© 2016 Asian Pacific Society of Nephrology.)

Systemic arterial hypertension is an important risk factor for cardiovascular disease that is frequently observed in populations with declining renal function. Initiation of renal replacement therapy at least partially decreases signs of fluid overload; however, high blood pressure levels persist in the majority of patients after dialysis initiation. Hypervolemia due to water retention predisposes peritoneal dialysis (PD) patients to hypertension and can clinically manifest in several forms, including peripheral edema. The approaches to detect edema, which include methods such as bioimpedance, inferior vena cava diameter and biomarkers, are not always available to physicians worldwide. For clinical examinations, the presence of pitting located in the lower extremities and/or over the sacrum to diagnose the presence of peripheral edema in their patients are frequently utulized. We evaluated the impact of edema on the control of blood pressure of incident PD patients during the first year of dialysis treatment. Patients were recruited from 114 Brazilian dialysis centers that were participating in the BRAZPD study for a total of 1089 incident patients. Peripheral edema was diagnosed by the presence of pitting after finger pressure was applied to the edematous area. Patients were divided into 2 groups: those with and without edema according to the monthly medical evaluation. Blood arterial pressure, body mass index, the number of antihypertensive drugs and comorbidities were analyzed. We observed an initial BP reduction in the first five months and a stabilization of blood pressure levels from five to twelve months. The edematous group exhibited higher blood pressure levels than the group without edema during the follow-up. The results strongly indicate that the presence of a simple and easily detectable clinical sign of peripheral edema is a very relevant tool that could be used to re-evaluate not only the patient's clinical hypertensive status but also the PD prescription and patient compliance.

Cardiovascular disease is the leading cause of death in the set of chronic kidney disease (CKD) patients, whether on renal replacement therapy or conservative treatment. A better understanding of cardiovascular risk factors, diagnostic approach and management are central keys to develop strategies to reduce cardiovascular mortality among those patients. This review article discusses some aspects of pathophysiology, investigation methods and current treatment of cardiovascular disease in CKD patients.

Peritoneal dialysis (PD) patients are at high risk of developing cardiovascular disease, resulting from both traditional and nontraditional cardiovascular risk factors, including factors related to uremia and dialysis. Glucose metabolism is altered in chronic kidney disease patients even in the earlier stages and the most common manifestations are insulin resistance and dyslipidemia, known factors in the pathogenesis of hypertension and atherosclerosis. Exposure to high glucose concentration solutions during PD intensifies these metabolic abnormalities, which are extremely common in PD patients and potentially have an impact on cardiovascular outcome. Life style and dietary modification and pharmacological interventions may be particularly important to revert these risk factors and glucose sparing solutions may represent an additional strategy to change the PD-induced metabolic profile. Together, these approaches may have a positive impact in reducing the risk of mortality in PD patients.

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.

Components of the diet related to changes in eating habits that characterize the modern Western world are important factors in the increasingly high prevalence of chronic disease, including obesity, diabetes, hypertension and as a consequence, chronic kidney disease. The healthy diets recommended for the general population to promote longevity (such as the Mediterranean diet), are defined based on epidemiological and intervention studies and are usually characterized by a relatively higher amount of protein than the usual Western diet. Unfortunately, very few clinical studies focused on diet-based strategies of prevention of kidney disorders. Furthermore, this review will propose that the concept that protein restricted diets decrease the risk of developing kidney disease in the general population is not supported by the scientific literature. Indeed, preliminary studies showing a positive effect of relatively high protein diets on risk factors for chronic kidney disease (particularly on obesity, hypertension and diabetes) point to the need for future studies addressing diets that could prevent the increasingly high prevalence of kidney disease in the Western world. On the other hand, there is a potential role for protein restriction in patients with established kidney disease, particularly in patients with significant decrease in glomerular filtration rate. The exact protective action of protein restriction in patients with established renal disease needs further analysis, taking into account the more broad effects of protein restriction (lower phosphate, acidosis, uric acid) and a more current definition of malnutrition.

Background: Inflammation and malnutrition are common in chronic kidney disease (CKD) patients, and plasma concentrations of free amino acids (AAs) in these patients are often abnormal. Malnutrition contributes to alterations in AA concentrations., Objective: The objective was to study the effects of inflammation on plasma AA concentrations., Design: Concentrations of plasma AAs, serum albumin, and several inflammatory markers were analyzed in 200 fasting, nondiabetic CKD patients who were close to the start of renal replacement therapy. The nutritional status of these patients was assessed by a subjective global assessment., Results: The patients with inflammation [C-reactive protein (CRP) concentrations >10 mg/L] or malnutrition had lower AA concentrations than did the patients with no inflammation or malnutrition. The presence of both inflammation and malnutrition was associated with more marked reductions in AA concentrations than was malnutrition alone. Significant inverse correlations were observed between the plasma concentrations of most of the essential and nonessential AAs and inflammatory markers, whereas serum albumin concentrations were positively correlated with several AA concentrations. A stepwise multivariate regression analysis showed that serum CRP concentrations were independently associated with low concentrations of the sums of both nonessential AAs and all AAs. An analysis of all-cause mortality with a Kaplan-Meier test showed that the patients with higher AA concentrations had significantly better survival than did the patients with lower AA concentrations., Conclusions: Plasma AA concentrations are low in CKD patients with inflammation and are inversely correlated with concentrations of inflammatory markers. Although inflammation and malnutrition are closely related, CRP concentrations were independently associated with low concentrations of the sums of both nonessential AAs and all AAs, which suggests an independent role of inflammation as a cause of low plasma AA concentrations in CKD patients.

Signs of an activated immune system can be observed already in the early stages of chronic kidney disease (CKD). Markers of a chronically activated immune system are closely linked to several complications of CKD, such as accelerated atherosclerosis, vascular calcification, insulin resistance, increased muscle catabolism, loss of appetite, bone remodeling, and increased peritoneal permeability. Interestingly, all the aforementioned pathological states resemble a state of accelerated ageing and are strongly associated with increased morbidity and mortality in CKD patients. In recent studies, signs of inflammation have been shown as predictors for mortality in dialysis patients, and the role of inflammation as a risk factor for complications of CKD in children has emerged. Although preliminary findings suggest that inflammation is highly prevalent in the pediatric population with CKD, information related pathogenic links and to clinical outcomes is lacking. For the future, it is crucial for investigations to address the mechanisms and complications of inflammation that are manifested in pediatric patients with CKD in all stages. Since early identification and intervention may generate the most efficient strategies for prevention and treatment of cardiovascular disease in CKD patients, the pediatric population deserves special attention in future studies. In this review, we discuss the mechanisms involved in the inflammatory activation and the main causes and consequences of the inflammatory state observed in the CKD patient, with special emphasis on the pediatric population.

Background: Inflammation and malnutrition are common findings in patients with chronic kidney disease (CKD). We hypothesized that in inflamed and malnourished patients, respiratory and peripheral muscle dysfunction may have significant consequences on pulmonary function. The aim of this study was to investigate possible associations between pulmonary function and inflammation and malnutrition in patients with CKD., Methods: We studied 109 patients (63% males; 53+/-12 years) at the initiation of dialysis treatment (GFR 7.5+/-2.5 ml/min). Pulmonary function tests [forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and peak expiratory flow (PEF)] were performed and the percentages of predicted values were calculated (%FEV(1), %FVC and %PEF). Systemic inflammation, assessed by high-sensitivity C-reactive protein (hsCRP) and nutritional status assessed by subjective global assessment (SGA), lean body mass (LBM) (estimated with dual energy X-ray absorptiometry) and hand-grip strength (HGS), were evaluated at the same time., Results: Significant negative correlations were found between hsCRP and the percent predicted values for all pulmonary function tests [%FEV(1) (Rho = -0.45), %FVC (Rho = -0.43) and %PEF (Rho = -0.38)], respectively. Malnourished patients defined as SGA >or=2 had lower %FEV(1) (64+/-19 vs 82+/-23%; P<0.001) and %FVC (67+/-18 vs 83+/-21%; P<0.001) than well nourished patients. Significant correlations were observed between HGS and %FVC (Rho = 0.38; P <0.001), %FEV(1) (Rho = 0.37; P<0.001) and %PEF (Rho = 0.22; P<0.05) and between LBM and %PEF (Rho = 0.20; P<0.05). Multivariate Cox analysis showed that cardiovascular disease and low %FVC were associated with poor survival., Conclusions: Impaired pulmonary function is associated with malnutrition and inflammation, and predicts mortality in CKD patients. This may reflect an impact of malnutrition and inflammation on respiratory muscle performance, leading to pulmonary dysfunction, which could influence the clinical outcome.

Metabolic and nutritional derangements are prominent features of the uremic syndrome. Recent evidence suggest that several large-molecular-weight molecules that often are elevated in uremia, such as leptin, ghrelin, and proinflammatory cytokines, may have nutritional impact in this patient group. On the basis of present knowledge, these compounds could be regarded as suspected but not established uremic toxins. The discovery of the ob gene, its product leptin, and cerebral leptin receptors has undoubtedly widened our understanding of obesity and the underlying molecular and physiologic mechanisms that regulate food intake and body weight. Moreover, the recent discovery of leptin receptor isoforms in several peripheral organs suggests that leptin besides having a central function also has several important peripheral biological functions. Because uremic patients in general have an inappropriate elevation of circulatory leptin, further research is necessary to determine the potential biological effects of elevated leptin levels in end-stage renal disease. Also, because many symptoms and findings prevalent in the uremic syndrome are known to be associated with elevated levels of proinflammatory cytokines, such as interleukin-6, future studies are needed to evaluate the role of specific anti-inflammatory treatment strategies in malnourished uremic patients.

Background The prevalence and incidence of hyperkalaemia, a potassium abnormality that can potentially have life-threatening consequences, are unclear. Methods The objective was to provide the most comprehensive overview of the epidemiology of hyperkalaemia to date within the general population, across different continents, in different healthcare settings and within pre-specified subgroups. Embase and MEDLINE were searched from database inception to 2 February 2021 using the Ovid SP platform. Relevant congress proceedings from 2018 to 2020 were also reviewed for inclusion. There was no language constraint applied. Observational studies from any time period and language reporting prevalence or incidence of hyperkalaemia within both adult and paediatric populations. Four investigators independently screened abstracts and assessed study quality of those meeting the pre-determined inclusion/exclusion criteria. Data extraction was conducted by the lead author with oversight from the senior author and data were pooled using a random-effects model. The measures assessed were the prevalence and incidence of hyperkalaemia. Prevalence was reported as a percentage, whilst incidence was reported as the rate per 100 person years. Results In total, 542 articles were included from an initial search of 14 112 articles. Across all adult studies, we report a prevalence of hyperkalaemia (by any definition/threshold) of 6.3% [95% confidence interval (CI): 5.8–6.8%], with an incidence of hyperkalaemia in the adult population of 2.8 (2.3–3.3) cases per 100 person years. Prevalence within the general population was 1.3% (1.0–1.8%), whilst incidence was 0.4 (0.2–0.8) cases per 100 person years. There was a variation by sex with a prevalence of 6.3% (4.9–8.0%) in males and 5.1% (4.0–6.6%) in females. Prevalence also varied according to the definition/threshold of hyperkalaemia used: >5 mmol/L—8.0% (7.2–8.9), ≥5.5 mmol/L—5.9% (3.5–10.0) and ≥6.0 mmol/L—1.0% (0.8–1.4); hyperkalaemia (by any definition/threshold) was highest amongst patients with end-stage kidney disease (21.5%; 18.3–25.3), kidney transplant patients (21.8%; 16.1–29.5) and patients with acute kidney injury (24.3%; 19.3–30.7). Conclusions This novel review provides a comprehensive and valuable resource on the prevalence and incidence of hyperkalaemia to better inform clinicians, healthcare providers and health policy makers on the burden of hyperkalaemia across different healthcare settings, patient populations and continents. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide, contributing to a great burden across a variety of patient‐reported and clinical outcomes. New interventions for DKD management have been established in recent years, unleashing a novel paradigm, in which kidney‐dedicated trials yield informative and robust data to guide optimal clinical management. After unprecedented results from groundbreaking randomized controlled trials were released, a new scenario of evidence‐based recommendations has evolved for the management of diabetic patients with CKD. The current guidelines place great emphasis on multidimensional and interdisciplinary approaches, but the challenges of implementation are just starting and will be pivotal to optimize clinical results and to understand the new threshold for residual risk in DKD. We thereby provide an updated review on recent advances in DKD management based on new guideline recommendations, summarizing recent evidence while projecting the landscape for innovative ongoing initiatives in the field. Specifically, we review current insights on the natural history, epidemiology, pathogenesis, and therapeutics of DKD, mapping the new scientific information into the recently released Kidney Disease – Improving Global Outcomes Guidelines translating results from major novel randomized controlled trials to the clinical practice. Additionally, we approach the landscape of new therapeutics in the field, summarizing ongoing phase IIb and III trials focused on DKD. Finally, reflecting on the past and looking into the future, we highlight unmet needs in the current DKD management based on real‐world evidence and offer a nephrologist's perspective into the challenge of fostering continuous improvement on clinical and patient‐reported outcomes for individuals living with DKD. [ABSTRACT FROM AUTHOR]

Background: Hypertension affects almost all chronic kidney disease patients and is related to poor outcomes. Sodium intake is closely related to blood pressure (BP) levels in this population and decreasing its intake consistently improves the BP control particularly in short-term controlled trials. However, most patients struggle in following a controlled diet on sodium according to the guidelines recommendation due to several factors and barriers discussed in this article. Summary: This review article summarizes the current knowledge related to the associations between sodium consumption, BP, and the risk of cardiovascular disease and chronic kidney disease (CKD); it also provides recommendations of how to achieve sodium intake lowering. Key Messages: Evidences support the benefits in decreasing sodium intake on markers of cardiovascular and renal outcomes in CKD. Trials had shorter follow-up and to maintain long-term sodium intake control is a major challenge. Larger studies with longer follow-up looking at hard endpoints will be important to drive future recommendations. [ABSTRACT FROM AUTHOR]

Background/Aims: Neighborhood walkability is associated with indicators of health in the general population. We explored the association between neighborhood walkability and daily steps in hemodialysis (HD) patients. Methods: We measured daily steps over 5 weeks using Fitbit Flex (Fitbit, San Francisco, CA, USA) and retrieved Walk Score® (WS) data by patient’s home ZIP code (www.walkscore.com; 0 = poorest walkability; 100 = greatest walkability). Results: HD patients took a mean of 6,393 ± 3,550 steps/day (n = 46). Median WS of the neighborhood where they resided was 28. Patients in an above-median WS (n = 27) neighborhood took significantly more daily steps compared to those (n = 19) in a below-median WS neighborhood (7,514 ± 3,900 vs. 4,800 ± 2,228 steps/day; p < 0.001, t test). Daily steps and WS were directly correlated (R = 0.425; p = 0.0032, parametric test; R = 0.359, p = 0.0143, non-parametric test). Conclusion: This is the first study conducted among HD patients to indicate a direct relationship between neighborhood walkability and the actual steps taken. These results should be considered when designing initiatives to increase and improvise exercise routines in HD populations. [ABSTRACT FROM AUTHOR]

Background: We performed this study to evaluate the incidence, risk factors, microbiology, treatment, and outcome of peritonitis in pediatric Peritoneal dialysis (PD) patients at a nationwide prospective study. Methodology: Patients younger than 18 years recruited in the BRAZPD II study from 2004 to 2011, who presented their first peritonitis episode, were included in the study. Results: We found 125 first episodes of peritonitis in 491 children PD patients (0.43 episodes/patient-year). Patients free of peritonitis episode constituted 75.6% in 1 year. Culture-negative episodes were very high (59.2%) and gram-positive (GP) bacteria were the most commonly found organisms (58.8%). First-generation cephalosporin was the initial choice to cover GP (40.5%) and aminoglycosides was the most prescribed antibiotics used for gram-negative agents (27.5%). Treatment failure was 26.4%. Technique failure (TF) occurred in 12.1% and peritonitis was the main cause (65.1%). Pseudomonas (p = 0.04) and negative cultures (p < 0.001) were identified as predictors of TF. Conclusion: Peritonitis remains a common complication of PD in children and negative cultures and pseudomonas had a negative impact on TF. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) progression and complications are associated with increased oxidative stress, as well as with Nrf2 inactivation. Lipoic acid (LA) has been considered an inducer of Nrf2 antioxidant response. We tested whether oral administration of LA provides beneficial effects in experimental CKD in rats. Wistar rats underwent 5/6 nephrectomy (CKD group) or sham laparotomy. Seven days later, CKD group was divided into three subgroups that received: (i) LA continuously in the drinking water (100 mg/kg/day), (ii) LA by gavage every other day (100 mg/kg), or (iii) no LA treatment. LA treatment lasted until day 60. Plasma urea and creatinine, 24 h-proteinuria, glomerulosclerosis, interstitial fibrosis/tubular atrophy, and Nrf2 activation were analyzed. All parameters measured were significantly altered in the untreated CKD group, compared with the sham group, as expected. Oral LA administration, either in the drinking water or by gavage, did not improve significantly any parameter, comparing the treated-groups with the untreated CKD group. These results indicate that oral LA administration for 53 days was ineffective to reactivate Nrf2 in the remnant kidney of uremic rats, likely preventing improvements in biochemical and histopathological markers of renal function. [ABSTRACT FROM AUTHOR]

Background/Aims: Oxidative stress has been considered a nontraditional risk factor for cardiovascular disease in the chronic kidney disease (CKD) population, possibly triggered by uremic toxicity. Methods: A chromatographic method with coulometric detection was adapted to directly and simultaneously determine cysteine (Cys) and cystine (Cyss) in plasma samples. Healthy subjects and CKD subjects in different stages were analyzed. The free Cys and free Cyss levels in their plasma were determined, and the reduction potential [Eh(Cyss/2Cys)] was calculated with the Nernst equation. Results: Healthy plasma presented Eh(Cyss/2Cys) of -123 ± 7 mV. Plasma Eh(Cyss/2Cys) correlated significantly with creatinine levels (p < 0.0001, r = 0.62). Conclusion: Plasma Eh(Cyss/2Cys) correlated with increased levels of plasma creatinine, supporting the view that uremia triggers oxidative stress. In addition, it may be used as a quantitative oxidative stress biomarker in uremic conditions. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Heart failure (HF) is very common in the general population, and risk factors for HF, such as coronary artery disease, diabetes, obesity, and hypertension, are frequently present in patients with CKD. Therefore, HF is also an important cause of morbidity and mortality in this population. Diastolic heart failure (DHF), also called HF with preserved ejection fraction, refers to a clinical syndrome in which patients have symptoms and signs of HF, normal or near normal left ventricular (LV) systolic function, and evidence of diastolic dysfunction (e.g., abnormal LV filling and elevated filling pressure). Recent data suggest that HF with normal ejection fraction is even more common in patients than HF with low ejection fraction, including those on hemodialysis. Not surprisingly, DHF is a strong predictor of death in CKD patients. In this article, we review the information available on the mechanisms, clinical presentation, impact, and potential interventions in DHF based on evidence from CKD patients, as well as evidence from the general population potentially applicable to the CKD population. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease in chronic kidney disease (CKD) has peculiar characteristics. The aim of this study was to analyze atherosclerosis, vascular calcification and nitration in arteries from CKD patients. Methods: External iliac and renal artery segments from 27 stage 5 CKD patients and 25 donor controls, respectively, were collected during the transplantation procedure. Results: CKD patients presented a significantly higher degree of lesion. In a large proportion (72%) of CKD patients, we observed vascular calcifications. Immunohistochemistry for nitrotyrosine revealed a significant increase in nitrotyrosine production in arteries from CKD patients compared with control donors. In addition, within CKD patients, nitrotyrosine staining was significantly stronger in arteries with media calcification when compared with arteries without media calcification. Conclusion: The arteriopathy in the CKD patients appears in an early age and seems to be distinct from the arteriopathy of the general population, especially due to intense calcification and vascular oxidative stress. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic inflammation is closely linked to several complications of chronic kidney disease (CKD), such as vascular calcification, accelerated atherosclerosis, loss of appetite, insulin resistance, increased muscle catabolism and anemia. As a consequence, inflammation is a predictor of mortality in this group of patients. Specific causes of the activation of the immune system in CKD are largely unknown. Endotoxin (ET) release to the circulation represents a potentially important target for interventions aiming to reduce mortality in CKD patients. In this minireview, we propose that there are several potential sources of endotoxemia in CKD and that gut translocation, leading to the generation of ligands of the innate immune response, represents a potentially reversible cause. Prevention of endotoxemia, through treating foci of ET (periodontal disease, catheters, vascular access) or reducing translocation from the gut, will potentially reduce the inflammatory response. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Chronic kidney disease (CKD) and periodontitis (PD) are serious public-health concerns. Vitamin D is a fat-soluble steroid hormone that interacts with its nuclear receptor (VDR) to regulate a variety of biological processes, such as bone metabolism, immune response modulation and transcription of several genes involved in CKD and PD disease mechanisms. The aim of this work was to investigate the association between polymorphisms in the VDR gene and end-stage renal disease (ESRD) and PD. Methods: 222 subjects with and without ESRD (in hemodialysis) were divided into groups with and without PD. Polymorphisms TaqI and BsmI in the VDR gene were analyzed by PCR restriction fragment length polymorphism. The significance of differences in allele, genotype and haplotype frequencies between groups was assessed by the χ2 test (p value <0.05) and odds ratio (OR). Results: Allele G was associated with protection against ESRD: groups without versus with ESRD (GG) × (GA+AA): OR = 2.5, 95% CI = 1.4-4.6, p = 0.00; (G × A): OR = 1.5, 95% CI = 1.0-2.3, p = 0.02; (TG + CG) × (TA + CA): OR = 1.5, 95% CI = 1.0-2.3, p = 0.02. No association was observed between the study polymorphisms and susceptibility to or protection against PD. Conclusion: Allele G of the VDR BsmI polymorphism was associated with protection against ESRD. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Endothelial dysfunction in uremia can result in cell-to-cell junction loss and increased permeability, contributing to cardiovascular diseases (CVD) development. This study evaluated the impact of the uremic milieu on endothelial morphology and cell junction's proteins. We evaluated (i) serum levels of inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on endothelial cells (ECs) of arteries removed from CKD patients during renal transplant; (ii) ECs morphology in vitro under different uremic conditions, and (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and ZO-1 gene and protein expression in cultured ECs. We found that the uremic arteries had lost their intact and continuous endothelial morphology, with a reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia alters cell-to-cell junctions leading to an increased endothelial damage. This gives a new perspective regarding the pathophysiological role of uremia in intercellular junctions and opens new avenues to improve cardiovascular outcomes in CKD patients. [ABSTRACT FROM AUTHOR]

Since the introduction of continuous ambulatory peritoneal dialysis during the late 1970s as a form of home-based, self-care renal replacement therapy, peritoneal dialysis (PD) has become an appealing alternative for the treatment of patients with end-stage renal disease. A significant amount of research over the last 25 years has resulted in continuous improvements in the quality of PD treatment. This review will focus on the benefits beyond the membrane, i.e., the systemic benefits that may be achieved with the new biocompatible PD solutions.

Adiponectin in renal disease: Relationship to phenotype and genetic variation in the gene encoding adiponectin. Background. The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. Methods. In a cohort of 204 (62% males) ESRD patients aged 52 ± 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin ( N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions –11391, –11377, 45, and 276. Thirty-six age- (52 ± 2 years) and gender-matched (64% males) healthy subjects served as control subjects. Results. Markedly ( P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 μg/mL), especially type 1 diabetic patients (36.8 μg/mL), compared to control subjects (12.2 μg/mL). Log plasma adiponectin correlated to visceral fat mass ( R=−0.29; P < 0.01) and Log hs-CRP ( R=−0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes ( P < 0.001) and visceral fat mass ( P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene –11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype. Conclusion. The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD. [ABSTRACT FROM AUTHOR]

Renin-angiotensin system inhibitors (RASi) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials. CKD-REIN cohort study. We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France. The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age. Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction =.72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction =.28). This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects. [ABSTRACT FROM AUTHOR]

Abstract: Chronic kidney disease (CKD) and periodontitis (PD) are complex inflammatory disturbances, influenced by genetic factors. Interleukin (IL)-1 genes code for inflammatory mediators involved in the physiopathogenesis of both diseases. Functional polymorphisms in IL1 genes modulate cytokine levels and have been associated with susceptibility to immune-inflammatory conditions. Objectives: The aim of this study was investigate the association of functional IL1 gene polymorphisms and transcript levels with susceptibility to CKD and PD. Design: The sample consisted of 246 individuals, mean age 44.8years, divided into: group 1 (64 patients without CKD and without PD), group 2 (58 without CKD and with PD), group 3 (52 with CKD and without PD) and group 4 (72 with CKD and with PD). DNA was obtained from cells of oral mucosa and polymorphisms IL1AC−889T, IL1BC−511T, IL1BC+3954T and IL1RN (intron 2) were analyzed by PCR-RFLP. Transcript levels from gingival tissues were analyzed by real-time PCR. Results: IL1RN *1 allele was associated with almost 4-fold increased risk for CKD (OR 3.92 95% CI=1.6–9.4, p =0.002). IL1RN *2 allele was associated with 3-fold increased risk for PD in CKD patients (OR 3.08 95% CI=1.2–7.9, p =0.019). Allele T for polymorphism IL1B+3954 was associated with CKD in PD patients (OR 2.28 95% CI=1.1–4.7, p =0.019). Significantly increased levels of transcripts of IL1A, IL1B and IL1RN genes were found in PD patients. Conclusions: It was observed an evidence for association of IL1B and IL1RN alleles with susceptibility to CKD and PD. Higher levels of IL1 gene transcripts were found in PD patients. [Copyright &y& Elsevier]

IL-10, IL-6, and TNF-α: Central factors in the altered cytokine network of uremia—The good, the bad, and the ugly. It has been increasingly apparent that wasting and cardiovascular disease (CVD) is associated with a persistent systemic inflammatory response in end-stage renal disease (ESRD) patients. The reasons for the increased risk of inflammation in ESRD patients appear to be complex, including nondialysis as well as dialysis-related factors. The combination of an impaired immune response coupled with persistent immune stimulation may have a role in the low-grade systemic inflammation and altered cytokine balance that characterizes the uremic state and which may translate into increased risk for vascular disease. The accelerated atherosclerotic process of ESRD may involve several interrelated processes, such as oxidative stress, endothelial dysfunction, and vascular calcification, in a milieu of constant low-grade inflammation with impaired function of neutrophils and T cells, as well as a dysregulated cytokine network. Although a large number of pro- and anti-inflammatory cytokines are of importance, available data suggest that the anti-inflammatory cytokine interleukin (IL)-10 and the mainly proinflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α) may play important roles in the development of Th imbalance, CVD and wasting in the uremic milieu. Given the strong association between proinflammatory cytokines and complications common in ESRD, such as vascular calcification and wasting, the potential role of both general and targeted anticytokine treatment strategies in ESRD patients needs further evaluation. [ABSTRACT FROM AUTHOR]

Reduced gene expression of adiponectin in fat tissue from patients with end-stage renal disease. Background. Cardiovascular disease (CVD) is the main cause of death in end-stage renal disease (ESRD) patients. It has been suggested that inflammation plays a key role in the development of both atherosclerosis and malnutrition (MIA), a combination of complications associated with poor outcome. Although plasma levels of adiponectin, a recently discovered anti-inflammatory and antiatherogenic adipocytokine, are markedly elevated in ESRD, gene expression of adiponectin (ApM1) has not been analyzed in ESRD patients. Methods. We analyzed the ApM1 gene expression in adipose tissue from 18 ESRD patients of whom 9 (7 males, 60 ± 8 years, BMI 24 ± 6 kg/m2) had a high prevalence of MIA complications, and 9 age- (55 ± 9 years), gender- (7 males) and BMI- (24 ± 2 kg/m2) matched ESRD patients had few MIA complications. The results were compared with age- (59 ± 11 years), gender- (7 males), and BMI- (24 ± 6 kg/m2) matched healthy control patients. Information on CVD was obtained at the recruitment based on a detailed medical history. Malnutrition was defined as a subjective global assessment (SGA) score >1. Inflammation was defined as CRP ≥10 mg/L. Gene expression analysis was performed using the in situ hybridization technique. Results. Gene expression of ApM1 was lower in ESRD patients compared with healthy control patients ( P= 0.001). On the other hand, when comparing the gene expression between ESRD patients with and without MIA complications, respectively, no difference in the ApM1 gene expression was detected. Conclusion. Adiponectin gene expression is significantly down-regulated in ESRD patients compared with healthy control patients. We propose that the decrease in expression may be the result of a negative feedback regulation, as a result of elevated levels of circulating adiponectin caused by renal failure. [ABSTRACT FROM AUTHOR]

Mortality, malnutrition, and atherosclerosis in ESRD: What is the role of interleukin-6? There is growing evidence that increased plasma concentrations of CRP strongly predict cardiovascular death in both non-renal and renal patient populations. The interleukin-6 (IL-6) system activity, which is the major mediator of the acute phase response, is often markedly up-regulated in uremic patients and has also been shown to predict outcome. This raises the issue of whether or not IL-6 per se may contribute to increased mortality from malnutrition and atherosclerotic cardiovascular disease in uremic patients. The causes of elevated IL-6 levels in the uremic circulation are not fully understood, although a number of factors prevalent in uremic patients, such as hypertension, adiposity, infections, and chronic heart failure may all contribute. However, factors associated with the dialysis procedure, such as bioincompatibility and non-sterile dialysate, may stimulate IL-6 production. Furthermore, available evidence suggests that genetic factors may also have an impact on circulating plasma IL-6 levels. We advance the hypothesis that IL-6 may play a central role in the genesis of inflammatory-driven malnutrition and that it may be regarded as a significant proatherogenic cytokine. This hypothesis may provide a rationale to test if targeted anti-cytokine therapy may be one way to combat the unacceptable high cardiovascular mortality rate among dialysis patients. [ABSTRACT FROM AUTHOR]