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Contains fulltext : 232029.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 232029.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 232029.pdf (Publisher’s version ) (Open Access)

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term 'protein-energy wasting' for loss of body protein mass and fuel reserves. 'Kidney disease wasting' refers to the occurrence of protein-energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein-energy wasting that occurs infrequently in kidney disease. Protein-energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein-energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein-energy wasting but do not define protein-energy wasting. Clinical staging and potential treatment strategies for protein-energy wasting are to be developed in the future.

The recent research findings concerning syndromes of muscle wasting, malnutrition, and inflammation in individuals with chronic kidney disease (CKD) or acute kidney injury (AKI) have led to a need for new terminology. To address this need, the International Society of Renal Nutrition and Metabolism (ISRNM) convened an expert panel to review and develop standard terminologies and definitions related to wasting, cachexia, malnutrition, and inflammation in CKD and AKI. The ISRNM expert panel recommends the term 'protein-energy wasting' for loss of body protein mass and fuel reserves. 'Kidney disease wasting' refers to the occurrence of protein-energy wasting in CKD or AKI regardless of the cause. Cachexia is a severe form of protein-energy wasting that occurs infrequently in kidney disease. Protein-energy wasting is diagnosed if three characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid-arm muscle circumference). The kidney disease wasting is divided into two main categories of CKD- and AKI-associated protein-energy wasting. Measures of chronic inflammation or other developing tests can be useful clues for the existence of protein-energy wasting but do not define protein-energy wasting. Clinical staging and potential treatment strategies for protein-energy wasting are to be developed in the future.

Item does not contain fulltext, BACKGROUND: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex. METHODS: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression. RESULTS: Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies. CONCLUSION: Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.

Item does not contain fulltext, BACKGROUND: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex. METHODS: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression. RESULTS: Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies. CONCLUSION: Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.

Item does not contain fulltext, BACKGROUND: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with the general population by age group and sex. METHODS: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared with the European general population (WHO) were calculated. To identify risk factors, we used Cox regression. RESULTS: Infection-related mortality was increased 82-fold in dialysis patients and 32-fold in transplant recipients compared with the general population. Female sex, diabetes, cancer and multisystem disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2.9 times higher in dialysis patients and 1.7 times higher in transplant recipients than in the general population. Cancer and multisystem disease as primary causes of end-stage renal disease were associated with higher mortality from malignancies. CONCLUSION: Infection-related mortality is highly increased in dialysis and kidney transplant patients, while the risk of malignancy-related death is moderately increased. Young women on dialysis may deserve special attention because of their high excess risk of infection-related mortality. Further research into the mechanisms, prevention and optimal treatment of infections in this vulnerable population is required.

Item does not contain fulltext, BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated

Item does not contain fulltext, BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated

Background Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. Methods We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). Results A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. Conclusions Eculizumab inhibited complement-mediated thr

The pan-European ECHO observational study evaluated cinacalcet in adult dialysis patients with secondary hyperparathyroidism (SHPT) in "real-world" clinical practice. A sub-analysis compared data for 7 European countries/country clusters: Austria, CEE (Czech Republic and Slovakia), France, Italy, Netherlands, Nordics (Denmark, Finland, Norway, and Sweden), and the UK/Ireland.

The pan-European ECHO observational study evaluated cinacalcet in adult dialysis patients with secondary hyperparathyroidism (SHPT) in "real-world" clinical practice. A sub-analysis compared data for 7 European countries/country clusters: Austria, CEE (Czech Republic and Slovakia), France, Italy, Netherlands, Nordics (Denmark, Finland, Norway, and Sweden), and the UK/Ireland.

BACKGROUND: The use and effectiveness of cinacalcet in 'real-world' clinical practice was investigated in a pan-European observational study in dialysis patients with secondary hyperparathyroidism (SHPT) of varying severity. METHODS: Adult patients with chronic kidney disease on dialysis who had initiated cinacalcet treatment were enrolled. Data were collected 6 months before initiating cinacalcet, at baseline (initiation of cinacalcet) and up to 12 months after cinacalcet initiation. RESULTS: A total of 1865 patients [mean (SD) age 58 (15) years] were enrolled from 187 sites in 12 countries. Most patients had a dialysis vintage of > or =1 year (1-5 years, n = 833; >5 years, n = 748 versus <1 year, n = 265). The patients generally had severely uncontrolled intact parathyroid hormone (iPTH) serum levels (median 721 pg/ml) and elevated phosphorus (median 5.9 mg/dl) and calcium (median 9.6 mg/dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI(TM) (KDOQI(TM))] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium-phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received <60 mg/day cinacalcet at Month 12. Vitamin D sterol use remained fairly stable throughout the study. There was a 13% decrease in prescribed sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns. CONCLUSION: This analysis of current European clinical practice shows that-consistent with findings from randomized controlled trials and retrospective observational studies-cinacalcet improves attainment of KDOQI bone metabolism targets in dialysis patients with various stages of SHPT Udgivelsesdato: 2009/9

BACKGROUND: The use and effectiveness of cinacalcet in 'real-world' clinical practice was investigated in a pan-European observational study in dialysis patients with secondary hyperparathyroidism (SHPT) of varying severity. METHODS: Adult patients with chronic kidney disease on dialysis who had initiated cinacalcet treatment were enrolled. Data were collected 6 months before initiating cinacalcet, at baseline (initiation of cinacalcet) and up to 12 months after cinacalcet initiation. RESULTS: A total of 1865 patients [mean (SD) age 58 (15) years] were enrolled from 187 sites in 12 countries. Most patients had a dialysis vintage of > or =1 year (1-5 years, n = 833; >5 years, n = 748 versus <1 year, n = 265). The patients generally had severely uncontrolled intact parathyroid hormone (iPTH) serum levels (median 721 pg/ml) and elevated phosphorus (median 5.9 mg/dl) and calcium (median 9.6 mg/dl) at baseline, despite being prescribed conventional therapies. The proportions of patients achieving the recommended [NKF-K/DOQI(TM) (KDOQI(TM))] targets increased from baseline [4%, 39%, 40% and 46% for iPTH, phosphorus, calcium and calcium-phosphorus product (Ca x P), respectively] to Month 12 (28%, 48%, 51% and 68%, respectively). At Month 12, 18% of patients had achieved the combined target for iPTH + Ca x P compared with 2% at baseline. Most patients (65%) received <60 mg/day cinacalcet at Month 12. Vitamin D sterol use remained fairly stable throughout the study. There was a 13% decrease in prescribed sevelamer; use of calcium-based phosphate binders increased by 5.6%. There was no unexpected safety or tolerability concerns. CONCLUSION: This analysis of current European clinical practice shows that-consistent with findings from randomized controlled trials and retrospective observational studies-cinacalcet improves attainment of KDOQI bone metabolism targets in dialysis patients with various stages of SHPT Udgivelsesdato: 2009/9

In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team's cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management.

OBJECTIVES: Haemodialysis (HD) patients suffer from nutritional problems, which include muscle wasting, weakness, and cachexia, and are associated with poor clinical outcomes. The European Working Group for Sarcopenia in Older People (EWGSOP) and Foundations for the National Institute of Health (FNIH) have developed criteria for the assessment of sarcopenia, including the use of non-invasive techniques such as bioelectrical impedance assessment (BIA), anthropometry, and hand grip strength (HGS) dynamometry. This study investigated the prevalence of muscle wasting, weakness, and sarcopenia using the EWGSOP and FNIH criteria. METHODS: BIA was performed in 24 females (f) and 63 males (m) in the post-dialysis period. Total skeletal muscle mass and appendicular skeletal muscle mass were estimated and index values (i.e., muscle mass divided by height2 [kg/m2]) were calculated (Total Skeletal Muscle Index (TSMI) and Appendicular Skeletal Muscle Index (ASMI)). Mid-arm circumference and triceps skin-fold thickness were measured and mid-upper arm muscle circumference (MUAMC) calculated. HGS was measured using a standard protocol and Jamar dynamometer. Suggested cut-points for low muscle mass and grip strength were utilized using the EWGSOP and FNIH criteria with prevalence estimated, including sarcopenia. RESULTS: The prevalence varied depending on methodology: low TSMI (moderate and severe sarcopenia combined) was 55% for whole group: 21% (f) and 68% (m). Low ASMI was 32% for whole group: 25% (f) and 35% (m). Low MUAMC was 25% for whole group: 0% (f) and 30% (m). ASMI highly correlated with Body Mass Index (r = 0.78, P < .001) and MUAMC (r = 0.68, P < .001). Muscle weakness was high regardless of cut-points used (50-71% (f); 60-79% (m)). CONCLUSIONS: Internationally, this is the first study comparing measures of muscle mass (TSMM and ASMM by BIA and MUAMC) and muscle strength (HGS) using this specific methodology in a hemodialysis population. Future work is required to confi

BACKGROUND: Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. METHODS: A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. DISCUSSION: Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in c