Making the invisible visible: imaging techniques for assessing muscle mass and muscle quality in chronic kidney disease.

Muscle wasting and low muscle mass are prominent features of protein energy wasting (PEW), sarcopenia and sarcopenic obesity in patients with chronic kidney disease (CKD). In addition, muscle wasting is associated with low muscle strength, impaired muscle function and adverse clinical outcomes such as low quality of life, hospitalizations and increased mortality. While assessment of muscle mass is well justified, the assessment of skeletal muscle should go beyond quantity. Imaging techniques provide the means for non-invasive, comprehensive, in-depth assessment of the quality of the muscle such as the infiltration of ectopic fat. These techniques include computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Dual energy X-ray absorptiometry is also an imaging technique, but one that only provides quantitative and not qualitative data on muscle. The main advantage of imaging techniques compared with other methods such as bioelectrical impedance analysis and anthropometry is that they offer higher precision and accuracy. On the other hand, the higher cost for acquiring and maintaining the imaging equipment, especially CT and MRI, makes these less-used options and available mostly for research purposes. In the field of CKD and end-stage kidney disease (ESKD), imaging techniques are gaining attention for evaluating muscle quantity and more recently muscle fat infiltration. This review describes the potential of these techniques in CKD and ESKD settings for muscle assessment beyond that of muscle quantity.

A tool to predict the risk of lower extremity amputation in patients starting dialysis.

BACKGROUND AND HYPOTHESIS: Non-traumatic lower extremity amputation (LEA) is a severe complication during dialysis. To inform decision-making for physicians, we developed a multivariable prediction model for LEA after starting dialysis. METHODS: Data from the Swedish Renal Registry (SNR) between 2010 and 2020 were geographically split into a development and validation cohort. Data from NECOSAD between 1997 and 2009 were used for validation targeted at Dutch patients. Inclusion criteria were no previous LEA and kidney transplant and age ≥ 40 years at baseline. A Fine-Gray model was developed with LEA within 3 years after starting dialysis as outcome of interest. Death and kidney transplant were treated as competing events. One coefficient, ordered by expected relevance, per 20 events was estimated. Performance was assessed with calibration and discrimination. RESULTS: SNR was split into an urban development cohort with 4 771 individuals experiencing 201 (4.8%) events and a rural validation cohort with 4.876 individuals experiencing 155 (3.2%) events. NECOSAD contained 1 658 individuals experiencing 61 (3.7%) events. Ten predictors were included: female sex, age, diabetes mellitus, peripheral artery disease, cardiovascular disease, congestive heart failure, obesity, albumin, haemoglobin and diabetic retinopathy. In SNR, calibration intercept and slope were -0.003 and 0.912 respectively. The C-index was estimated as 0.813 (0.783-0.843). In NECOSAD, calibration intercept and slope were 0.001 and 1.142 respectively. The C-index was estimated as 0.760 (0.697-0.824). Calibration plots showed good calibration. CONCLUSION: A newly developed model to predict LEA after starting dialysis showed good discriminatory performance and calibration. By identifying high-risk individuals this model could help select patients for preventive measures.

The role of irisin in kidney diseases.

Irisin is a hormone that is produced mainly by skeletal muscles in response to exercise. It has been found to have a close correlation with obesity and diabetes mellitus for its energy expenditure and metabolic properties. Recent research has revealed that irisin also possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, which make it associated with major chronic diseases, such as chronic kidney disease (CKD), liver diseases, osteoporosis, atherosclerosis and Alzheimer s disease. The identification of irisin has not only opened up new possibilities for monitoring metabolic and non-metabolic diseases but also presents a promising therapeutic target due to its multiple biological functions. Studies have shown that circulating irisin levels are lower in CKD patients than in non-CKD patients and decrease with increasing CKD stage. Furthermore, irisin also plays a role in many CKD-related complications like protein energy wasting (PEW), cardiovascular disease (CVD) and chronic kidney disease-mineral and bone disorder (CKD-MBD). In this review, we present the current knowledge on the role of irisin in kidney diseases and their complications.

Automated Peritoneal Dialysis With Remote Patient Monitoring: Clinical Effects and Economic Consequences for Poland.

OBJECTIVES: Remote patient monitoring (RPM) of patients treated with automated peritoneal dialysis (APD) at home allows clinicians to supervise and adjust the dialysis process remotely. This study aimed to review recent scientific studies on the use of RPM in patients treated with APD and based on extracted relevant data assess possible clinical implications and potential economic value of introducing such a system into practice in Poland. METHODS: A systematic literature review was performed in the MEDLINE, EMBASE, and Cochrane databases. The model of clinical effects and costs associated with APD was built as a cost-effectiveness analysis with a 10-year time horizon from the Polish National Health Fund perspective. Cost-effectiveness analysis compared 2 strategies: APD with RPM versus APD without RPM. RESULTS: Thirteen publications assessing the clinical value of RPM among patients with APD were found. The statistical significance of APD with RPM compared with APD without RPM was identified for the main clinical outcomes: frequency and length of hospitalizations, APD technique failure, and death. An incremental cost-effectiveness ratio was equal to €27 387 per quality-adjusted life-year. The obtained incremental cost-effectiveness ratio is below the willingness-to-pay threshold for the use of medical technologies in Poland (€36 510 per quality-adjusted life-year), which means that APD with RPM was a cost-effective technology. CONCLUSIONS: RPM in patients starting APD is a clinical option that is worth considering in Polish practice because it has the potential to decrease the frequency of APD technique failure and shorten the length of hospitalization.

Prevalence and associated factors of frailty in patients with chronic kidney disease: a cross-sectional analysis of PEAKING study.

AIM:  Frailty is common and is reported to be associated with adverse outcomes in patients with chronic diseases in Western countries. However, the prevalence of frailty remains unclear in individuals with chronic kidney disease (CKD) in China. We examined the prevalence of frailty and factors associated with frailty in patients with CKD. METHODS:  This was a cross-sectional analysis of 177 adult patients (mean age 54 ± 15 years, 52% men) with CKD from the open cohort entitled Physical Evaluation and Adverse outcomes for patients with chronic Kidney disease IN Guangdong (PEAKING). Frailty at baseline were assessed by FRAIL scale which included five items: fatigue, resistance, ambulation, illnesses, and loss of weight. Potential risk factors of frailty including age, sex, body mass index, and daily step counts recorded by ActiGraph GT3X + accelerometer were analyzed by multivariate logistic regression analysis. RESULTS: The prevalence of prefrailty and frailty was 50.0% and 11.9% in patients with stages 4-5 CKD, 29.6% and 9.3% in stage 3, and 32.1% and 0 in stages 1-2. In the multivariate logistic regression analysis, an increase of 100 steps per day (OR = 0.95, 95% CI 0.91-0.99, P = 0.01) and an increase of 5 units eGFR (OR = 0.82, 95% CI 0.68-0.99, P = 0.045) were inversely associated with being frail; higher BMI was associated with a higher likelihood of being frail (OR = 1.52, 95% CI 1.11-2.06, P = 0.008) and prefrail (OR = 1.25, 95% CI 1.10-1.42, P = 0.001). CONCLUSION:  Frailty and prefrailty were common in patients with advanced CKD. A lower number of steps per day, lower eGFR, and a higher BMI were associated with frailty in this population.

High Osmol Gap Hyponatremia Caused by Icodextrin: A Case Series Report.

Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.

Needs, barriers and facilitators for a healthier lifestyle in haemodialysis patients: The GoodRENal project.

BACKGROUND: Malnutrition, sedentary lifestyle, cognitive dysfunction and poor psychological well-being are often reported in patients on haemodialysis (HD). AIMS: We aimed to explore needs, barriers and facilitators-as perceived by patients, their carers, and healthcare professionals (HCPs) for increasing the adherence to the diet, to physical activity and cognition and psychological well-being. METHODS: This is an observational cross-sectional study following the STROBE statement. This study is part of an ERASMUS+ project, GoodRENal-aiming to develop digital tools as an educational approach to patients on HD. For that, the GoodRENal comprises HD centers located in four Belgium, Greece, Spain and Sweden. Exploratory questionnaires were developed regarding the perceived needs, barriers and facilitators regarding the diet, physical activity, cognition and psychological well-being from the perspective of patients, their carers and HCPs. RESULTS: In total, 38 patients, 34 carers and 38 HCPs were included. Nutrition: For patients and carers, the main needs to adhere to the diet included learning more about nutrients and minerals. For patients, the main barrier was not being able to eat what they like. Physical activity: As needs it was reported information about type of appropriate physical activity, while fatigue was listed as the main barrier. For Cognitive and emotional state, it was perceived as positive for patients and carers perception but not for HCPs. The HCPs identified as needs working as a team, having access to specialised HCP and being able to talk to patients in private. CONCLUSIONS: Patients and their carers listed as needs guidance regarding nutrition and physical activity but were positive with their cognitive and emotional state. The HCPs corroborated these needs and emphasised the importance of teamwork and expert support.

Ultraprocessed foods and chronic kidney disease-double trouble.

High energy intake combined with low physical activity generates positive energy balance, which, when maintained, favours obesity, a highly prevalent morbidity linked to development of non-communicable chronic diseases, including chronic kidney disease (CKD). Among many factors contributing to disproportionately high energy intakes, and thereby to the obesity epidemic, the type and degree of food processing play an important role. Ultraprocessed foods (UPFs) are industrialized and quite often high-energy-dense products with added sugar, salt, unhealthy fats and food additives formulated to be palatable or hyperpalatable. UPFs can trigger an addictive eating behaviour and is typically characterized by an increase in energy intake. Furthermore, high consumption of UPFs, a hallmark of a Western diet, results in diets with poor quality. A high UPF intake is associated with higher risk for CKD. In addition, UPF consumption by patients with CKD is likely to predispose and/or to exacerbate uraemic metabolic derangements, such as insulin resistance, metabolic acidosis, hypertension, dysbiosis, hyperkalaemia and hyperphosphatemia. Global sales of UPFs per capita increased in all continents in recent decades. This is an important factor responsible for the nutrition transition, with home-made meals being replaced by ready-to-eat products. In this review we discuss the potential risk of UPFs in activating hedonic eating and their main implications for health, especially for kidney health and metabolic complications of CKD. We also present various aspects of consequences of UPFs on planetary health and discuss future directions for research to bring awareness of the harms of UPFs within the CKD scenario.

Early outcomes of peritoneal dialysis in a middle-income country: A retrospective cohort study of a large dialysis network in Colombia.

BACKGROUND: The first year of dialysis is critical given the significant risk for complications following dialysis initiation. We analysed complications during the first year among incident peritoneal dialysis (PD) patients. METHODS: This retrospective cohort study comprised adult kidney failure patients starting PD in Baxter Renal Care Services in Colombia, receiving their first PD catheter between 1 January 2017 and 31 December 2020 and were followed up for up to 1 year. We analysed incidence, causes and factors associated with complications using logistic regression and transfer to haemodialysis (HD) using the Fine-Gray regression model. RESULTS: Among 4743 patients receiving their first PD catheter: 4628 (97.6%) of catheter implantations were successful; 377 (7.9%) patients experienced early complications. The incidence rate of complications during the year was 0.51 events per patient-year (95% CI: 0.48-0.54). Age, obesity and urgent start were associated with higher probability of complications after catheter implantation. The cumulative incidence of transfer to HD within 1 year of PD initiation was 10.1% [95% CI: 9.2-11.1%]. The hazard function for transfer to HD showed an accelerating pattern during the first month followed by progressive decrease during the first year. CONCLUSIONS: In this large population of incident PD patients, there is a high primary catheter placement success rate. Urgent start, age ≥65 years, obesity, centre size ≥150 PD patients and diabetes were risk factors associated with early complications. The follow-up of the cohort from day 1 of PD treatment showed that the risk for transfer to HD was higher during the first month.

Dilemma Facing Patients Aged 75 Years and Older on Fluid Restriction When Drug Package Inserts Advise Use of a Lot of Water: A Cross-Sectional, Descriptive, and Hypothesis-Generating Study Using a Large Claims Database.

BACKGROUND: Several oral drugs are recommended to be taken with large amounts of water for reasons such as peptic ulcer prophylaxis. On the other hand, there are many patients with diseases that restrict water intake, and the actual frequency of patients receiving prescriptions in these conflicting situations is not clear. OBJECTIVE: Using a large claims database in Japan, this study aimed to determine the proportion of patients aged ≥ 75 years on fluid restriction who received drugs whose drug package insert mentioned "a large amount of water intake is needed when taking the drug". METHODS: We performed a prescription survey of older patients over 75 years of age using the Japan Medical Data Centre (JMDC) claims database. Out of approximately 8800 oral drugs used in Japan, we defined 29 drugs for which package inserts noted that a large amount of water intake is recommended during drug administration. We defined diagnosis codes for some common diseases for which restricted water intake is likely recommended: heart failure (NYHA class III or IV), liver cirrhosis with ascites, and chronic kidney disease stage 5, including dialysis patients. RESULTS: Of 5968 patients aged ≥ 75 years (men 47.7%), 320 (5.4%) patients with heart failure (2.8%, n = 170), liver cirrhosis (0.7%, n = 40), or chronic kidney disease (1.9%, n = 113), diagnoses likely associated with the need for fluid restriction, were prescribed drugs for which abundant fluid at intake was recommended. Among 29 identified drugs, 15 drugs were administered to older patients over 75 years with fluid restriction due to said diseases. CONCLUSIONS: Of patients 75 years and older with disease likely requiring water restriction, 5.4% faced the dilemma of following advice to restrict fluid intake due to their diagnoses or to adhere to instructions in drug package inserts to have abundant fluid intake when taking the drug. Our study raises awareness regarding the dilemma of water restriction and intake in clinical settings, highlighting the importance of considering individual patient needs. These real-world findings emphasize the need for information and guidelines to assist healthcare professionals in navigating this dilemma and making informed decisions for the benefit of their patients.

Results of the first nationwide cohort study of outcomes in dialysis and kidney transplant patients before and after vaccination for COVID-19.

BACKGROUND: Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign. METHODS: Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started. RESULTS: On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7-2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4-0.7)] compared with KTRs. CONCLUSIONS: The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives.

Interleukin-6-to-Albumin Ratio as a Superior Predictor of Mortality in End-Stage Kidney Disease Patients.

INTRODUCTION: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients. METHODS: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. RESULTS: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality. CONCLUSIONS: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD.

GLIM in chronic kidney disease: What do we need to know?

The lack of consensus on diagnostic criteria for malnutrition has hampered developments in research and clinical practice pertaining to nutrition. This opinion paper describes the applicability and other aspects of using the Global Leadership Initiative on Malnutrition (GLIM) criteria for diagnosing malnutrition in patients with chronic kidney disease (CKD). We examine the purpose of GLIM, the particularities of CKD that can affect the nutritional and metabolic status and the diagnosis of malnutrition. In addition, we make an appraisal of previous studies that used GLIM in the context of CKD and discuss the value and relevance of using the GLIM criteria in patients with CKD.

Modelling of icodextrin hydrolysis and kinetics during peritoneal dialysis.

In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by α-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by α-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naïve at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and α-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by α-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naïve and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by α-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in α-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells.

Central obesity as assessed by conicity index and a-body shape index associates with cardiovascular risk factors and mortality in kidney failure patients.

Background: Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated. Methods: In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST). Results: Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time. Conclusion: Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.

Gut microbiota disturbances and protein-energy wasting in chronic kidney disease: a narrative review.

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality, and lower quality of life. It is a complex syndrome, in which inflammation and retention of uremic toxins are two main factors. Causes of inflammation and uremic toxin retention in CKD are multiple; however, gut dysbiosis plays an important role, serving as a link between those entities and PEW. Besides, there are several pathways by which microbiota may influence PEW, e.g., through effects on appetite mediated by microbiota-derived proteins and hormonal changes, or by impacting skeletal muscle via a gut-muscle axis. Hence, microbiota disturbances may influence PEW independently of its relationship with local and systemic inflammation. A better understanding of the complex interrelationships between microbiota and the host may help to explain how changes in the gut affect distant organs and systems of the body and could potentially lead to the development of new strategies targeting the microbiota to improve nutrition and clinical outcomes in CKD patients. In this review, we describe possible interactions of gut microbiota with nutrient metabolism, energy balance, hunger/satiety signals and muscle depletion, all of which are strongly related to PEW in CKD patients.

Muscle fat infiltration in chronic kidney disease: a marker related to muscle quality, muscle strength and sarcopenia.

Muscle fat infiltration (MFI) also known as myosteatosis refers to any deposit of lipids found in the skeletal muscle. MFI is preferably assessed by image-based methods like computed tomography (CT), magnetic resonance image (MRI) and ultrasound, normally from muscle groups located in the legs, arms and in the trunk. MFI is understood as a marker of muscle quality, where a muscle with higher fat deposition has lower contraction power and capacity to produce force per unit of muscle mass. This concept supports the hypothesis that a decrease in muscle strength is not always explained by a decrease in muscle mass, but also by other factors, including lipid deposition in the muscle. In the general population, MFI is associated with older age, physical inactivity and with insulin resistance and inflammation. In chronic kidney disease (CKD), MFI has been associated with a decrease in muscle strength and impaired muscle quality as well as with metabolic abnormalities, cardiovascular disease and increased mortality. Interventions aimed at reducing MFI in CKD are incipient, but it seems that guided exercise can ameliorate muscle quality in patients on hemodialysis. The aim of this narrative review about MFI in CKD is to draw attention to a still not often addressed complication in CKD. We conclude that more studies are warranted to investigate mechanisms and factors promoting MFI in CKD. Thus, clinical trials aimed at understanding the type, frequency and intensity of exercise that can diminish MFI and improve the clinical condition of the patients are needed.

Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimer's dementia.

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years (64% women) and the mean eGFR was 68 ml/min/1.73m2. During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of CKD progression (1,231 events, adjusted hazard ratio 0.82; 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

Low-Plasma Insulin-Like Growth Factor-1 Associates With Increased Mortality in Chronic Kidney Disease Patients With Reduced Muscle Strength.

OBJECTIVES: Chronic kidney disease (CKD) leads to metabolic and nutritional abnormalities including resistance to insulin-like growth factor-1 (IGF-1) action, and reduced muscle mass and strength. Low IGF-1 as well as low hand-grip muscle strength (HGS) are independent predictors of increased mortality in CKD patients. METHODS: In 685 patients (CKD Stage 3-5, median age 58 years; 62% men), baseline measurements of IGF-1, HGS, subjective global assessment (SGA), lean body mass index (LBMI), and metabolic and inflammatory biomarkers potentially linked to IGF-1 were analyzed in relation to mortality during 5 years of follow-up. We compared survival in 4 groups with high or low (cut-offs defined by receiver operating characteristic curve analysis) levels of IGF-1 and HGS. RESULTS: Patients with low IGF-1 were older; had lower BMI, HGS, and LBMI, were more likely to have diabetes, cardiovascular disease (CVD), and malnutrition (SGA >1); and had high-sensitivity C-reactive protein levels. During 5 years of follow-up, 208 patients died. The mortality rate was highest among patients with Low IGF-1 + Low HGS. In competing-risk regression analysis, Low IGF-1 + Low HGS was independently associated with 2.8 times higher all-cause mortality risk than Low IGF-1 + High HGS, after adjusting for Framingham's CVD risk score, presence of CVD, SGA, dialysis status, high-sensitivity C-reactive protein, albumin, LBMI, and sample time in freezer. CONCLUSION: Low IGF-1 was associated with increased all-cause mortality in patients who also had low HGS but not in those with high HGS, suggesting that the association of IGF-1 with survival in CKD patients depends on nutritional status.