Non-dialysis Dependent Chronic Kidney Disease Research Articles

The Relationship Between Myostatin, Inflammatory Markers, and Sarcopenia in Patients With Chronic Kidney Disease

To determine the prevalence of sarcopenia in patients with chronic kidney disease (CKD), investigate the relationship of the serum myostatin level with sarcopenia and inflammatory markers. The study was conducted with four patient groups: renal transplantation (TX), stage 3-5 non-dialysis-dependent CKD (NDD-CKD), hemodialysis (HD), and peritoneal dialysis (PD). Laboratory parameters, serum myostatin, C-reactive protein, and interleukin-6 levels were studied. Body composition was estimated using a multifrequency bioimpedance analysis. Handgrip strength (HGS) was evaluated with a handgrip dynamometer. The HGS and appendicular skeletal muscle index measurements were used to determine sarcopenia presence. The study included 130 patients (72 [55%] male patients). The patient distribution in groups was as follows: 37 in HD, 28 in PD, 37 in renal TX, and 28 in NDD-CKD. The highest level of myostatin was measured in the HD group, and the lowest in the TX group (P<.001). The HGS measurement in the PD group was significantly lower than that in the TX group (P=.025). The myostatin was negatively correlated with HGS, albumin, estimated glomerular filtration rate, and Kt/Vurea. However, myostatin had no correlation with inflammatory markers or appendicular skeletal muscle index. Sarcopenia was present in 37 (29%) patients: 15 (40%) in the HD group, nine (32%) in NDD-CKD, seven (25%) in PD, and six (16%) in TX. When the patients with and without sarcopenia were compared, only myostatin was higher in the former (P=.045). As a result of multivariate analysis, myostatin was the only independent factor which predicts sarcopenia (odds ratio: 1.002, 95% confidence interval: 1.001-1.005, P=.048). To prevent devastating events associated with sarcopenia in patients with CKD, renal transplantation seems to be the best treatment solution. For the early recognition of sarcopenia, the measurement of the serum myostatin level may be a promising diagnostic approach.

POS-252 THE DIFFERENTIAL IMPACT OF TWO NOVEL INTRAVENOUS IRON AGENTS ON FIBROBLAST GROWTH FACTOR 23, PHOSPHATE AND OTHER CLINICAL AND FUNCTIONAL MARKERS: METHODOLOGY AND BASELINE DATA

Third generation intravenous (IV) iron preparations are increasingly used in the treatment of non-dialysis dependent chronic kidney disease (CKD) associated iron deficiency. Such compounds allow rapid delivery of large concentrations of iron safely at a single sitting. Evidence suggests that their use may lead to improved cardiovascular outcomes. Nonetheless, concerns exist regarding the potential induction of hypophosphatemia via fibroblast-growth-factor 23 (FGF-23) following the use of certain compounds. Raised FGF-23 has been associated with mineral bone and cardiac disorders, alongside prognostic implications. No prior study has provided a head-to-head comparison between iron preparations in CKD. This pilot study is designed to primarily investigate the differential impact of two different IV iron compounds on FGF-23 and phosphate in patients with CKD; secondarily we examine the impact of these compounds on bone markers and functional status, quality of life and cardiovascular function. This is a randomized controlled double-blinded pilot study recruiting patients with CKD stage 3a – 5 (non-dialysis) and iron deficiency +/- anemia. Patients are randomized to receive either ferric carboxymaltose or ferric derisomaltose over two infusions (one-month apart) to achieve full repletion. The initial dose administered is 1000 mg for both medications, with 500 mg or 1000 mg reserved for the second dose depending on weight and hematinics. Follow up is over a period of three months following the first infusion with measurements of intact FGF-23, phosphate, phosphaturia, vitamin D, parathyroid hormone, bone metabolism markers, functional status and quality of life and cardiac markers (figure 1). 168 patients were referred to the specialist renal anemia services for pre-screening. Ninety-nine were contacted for interest to participate, with 64 individuals declining to join. The commonest reason for not participating, was the COVID-19 pandemic (43.3%) with patients not keen to travel. Thirty-five patients were screened, and 27 patients enrolled in the study, of which 26 were randomized to receive iron (figure 2). One patient withdrew from the study, as they were unable to attend appointments following successful screening. In our baseline cohort the median age was 67.9 (12.4) and 17 participants were male. Mean hemoglobin was 100.3 (13.5) and hematinic markers consistent were consistent with iron deficiency. Median eGFR was 18.0 (11.3) ml/min/1.73 m2; the population as expected had a raised intact FGF-23 (212.1 (116.4) pg/ml). Serum calcium and phosphate were within normal parameters, while parathyroid hormone and 1,25 (OH)2 Vitamin D were deranged (Table 1). ExplorIRON-CKD, like a number of trials, experienced significant disruption in recruitment due to COVID-19. This study will provide further insight to the potential induction of FGF-23 following administration of specific intravenous iron compounds, and identify whether such a differential effect exists in patients with CKD. The effect of such induction in terms of phosphate and other markers of bone metabolism, functional status and cardiac functioning will be observed. The results will aid in hypothesis generation for further studies to identify the potential long-term impact of iatrogenic FGF-23 increase in patients with CKD.

Older Patients with Advanced Chronic Kidney Disease and Their Perspectives on Prognostic Information: a Qualitative Study.

Prognostic information is key to shared decision-making, particularly in life-limiting illness like advanced chronic kidney disease (CKD). To understand the prognostic information preferences expressed by older patients with CKD. Qualitative study of 28 consecutively enrolled patients over 65years of age with non-dialysis dependent CKD stages 3b-5, receiving care in a multi-disciplinary CKD clinic. Semi-structured telephone or in-person interviews to explore patients' preference for and perceived value of individualized prognostic information. Interviews were analyzed using inductive content analysis. We completed interviews with 28 patients (77.7 ± SD 6.8years, 69% men). Patients varied in their preference for prognostic information and more were interested in their risk of progression to end-stage kidney disease (ESKD) than in life expectancy. Many conflated ESKD risk with risk of death, perceiving a binary choice between dialysis and quick decline and death. Patients expressed that prognostic information would allow them to plan, take care of important business, and think about their treatment options. Patients were accepting of prognostic uncertainty and imagined leveraging it to nurture hope or motivate them to better manage risk factors. They endorsed the desire to receive prognosis of life expectancy even though it may be hard to accept or difficult to talk about but worried it could create helplessness for other patients in their situation. Most, but not all, patients were interested in prognostic information and could see its value in motivating behavior change and allowing planning. Some patients expressed concern that information on life expectancy might cause depression and hopelessness. Therefore, prognostic information is most appropriate as part of a clinical conversation that fosters shared decision-making and helps patients consider treatment risks, benefits, and burdens in context of their lives.

È possibile una gestione “ideale” della pandemia da malattia renale cronica?

Chronic Kidney Disease (CKD) is recognized as one of the major categories of noncommunicable epidemic diseases and in the last decades it has been largely growing in incidence and prevalence all over the world. Ideal management of CKD pandemic should be comprehensive of measures of tertiary, secondary, primary and primordial prevention. So, it should include prompt diagnosis and treatment of traditional and non-traditional risk factors for CKD, optimal conservative treatment for non-dialysis dependent CKD patients and appropriated dialysis therapy or renal transplantation for patients with end-stage renal disease. However, these goals are not easy to obtain on a global scale. It would be possible only by a broad and holistic approach, ranging from good governance to achievement of the sustainable development goals (SDGs).

Frequency and risk factors of frailty in nondialyzable chronic kidney disease geriatric patients

Background Frailty is an additional clinical and economic burden in the setting of chronic kidney disease (CKD). In this study, we aimed to determine the frequency and the risk factors for the occurrence of frailty in nondialyzable CKD geriatric patients' (stages 3–4). Patients and methods We conducted a cross-sectional, analytical study, which included consecutive patients with CKD, who attended the Nephrology Unit of Assiut University Hospital from April 2017 to April 2020. The total number of cases is 77 (21 of the control group and 56 of the patient group). Geriatric patients with aged more than or equal to 60 years and CKD stages 3–4 nondialysis dependent patients were included. The patients will be followed-up for 1 year. Results In terms of the frequency of frailty in geriatric CKD patients, the present study showed that 14.3% of the nondialyzable geriatric CKD patients had frailty. Regarding the predictors of frailty, the present study showed that nondialysis patients with frailty had significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, lymphocyte count, monocyte count, higher blood urea, higher serum creatinine, and higher basophil count. Notably, a lower serum magnesium level was noticed in the frail group. Conclusion In conclusion, frailty is not common in geriatric nondialysis dependent CKD patients. Independent risk factors for frailty in CKD include low serum magnesium and high serum creatinine.

Value of troponin T as a screening test of cardiac structure and function in chronic kidney disease

Background: Cardiovascular disease starts early in the course of chronic kidney disease (CKD) and is the leading cause of death in patients with end-stage renal disease. Since high-sensitivity cardiac troponin T (hs-cTnT) can detect much lower levels of myocardial injury than conventional assays, it may be useful for studying the earliest stages of heart disease in patients with CKD.Objective: To evaluate the association of circulating hs-cTnT with LV structural and functional abnormalities detected by echocardiography among dialysis dependent and non-dialysis dependent CKD patients.Methods: This study was conducted on 107 subjects divided into three groups.Group I consisted of CKD patients on conservative treatment (n=42), Group II: hemodialysis patients (n=42), Group III: control group: age and sex matched healthy volunteers (n=23). All subjects were subjected to clinical examination, biochemical evaluation including estimation of hs-cTnT and Echo-Doppler study of cardiac structure and function.Results: There was a significant increase in LAV (p&lt;0.01), LVM (p&lt;0.01) in both patient groups compared to the control group. Mitral annular plane systolic excursion (MAPSE) was significantly decreased in both patient groups compared to the control group (p&lt;0.01, p&lt;0.05) and in group I compared to group II (p&lt;0.05) with a significant decrease in S velocity in group I compared to groups II and III (p&lt;0.01). There was a significant decrease in Vp (p&lt;0.01) with a significant increase in AEF (p&lt;0.01) in both patients’ groups compared to the control group and AEF was significantly increased in group II compared to group I (p&lt;0.01). Ea velocity and Ea/Aa decreased significantly (p&lt;0.01) with significant increase in Aa velocity (p&lt;0.05, p&lt;0.01), E/Ea (p&lt;0.01) and E/Vp (p&lt;0.05) in both patient groups compared to the control group. There was a significant increase in hs-cTnT levels in both patient groups compared to the control group (P&lt;0.01). We found a positive correlation between hs-cTnT levels and LAV (r=0.291, p&lt;0.03), IVST (r=0.374, p&lt;0.004), PWT (r=0.309, p&lt;0.02), LVM (r=0.282, p&lt;0.03), A wave velocity (r=0.271, p&lt;0.04), E/Ea (r=0.506, p&lt;0.0001), PCWP (r=.507, p&lt; 0.0001) and a negative correlation between hs-cTnT and MAPSE (r=-0.300, p&lt;0.02), S wave velocity (r= -0.259, p&lt;0.05), Ea (r=-626, p&lt;0.0001), Ea/Aa (r=-0.543, p&lt;0.0001). Troponin at the cut-off value of &gt;5 ng/L, revealed 100% sensitivity and 95% specificity with areas under curve (AUC) of 0.998 and accuracy of 95.65% (P&lt;0.01) for discrimination of Group I vs control group and 76.2% sensitivity and 95.7% specificity with AUC 0.796 and accuracy 71.84% (P&lt;0.01) for discrimination of group II vs control group. Conclusion: Structural and functional cardiac abnormalities are common in CKD patients. Serum hs-cTnT levels increased in CKD patients and was associated with LVH, LAV and some of the echocardiographic parameters of LV systolic and diastolic dysfunction. Our research suggests that hs-cTnT levels may be important for early screening of cardiac structure and function in CKD patients to provide evidence for early intervention.

Value of troponin T as a screening test of cardiac structure and function in chronic kidney disease.

Background: Cardiovascular disease starts early in the course of chronic kidney disease (CKD) and is the leading cause of death in patients with end-stage renal disease. Since high-sensitivity cardiac troponin T (hs-cTnT) can detect much lower levels of myocardial injury than conventional assays, it may be useful for studying the earliest stages of heart disease in patients with CKD.Objective: To evaluate the association of circulating hs-cTnT with LV structural and functional abnormalities detected by echocardiography among dialysis dependent and non-dialysis dependent CKD patients.Methods: This study was conducted on 107 subjects divided into three groups.Group I consisted of CKD patients on conservative treatment (n = 42), Group II: hemodialysis patients (n = 42), Group III: control group: age and sex matched healthy volunteers (n = 23). All subjects were subjected to clinical examination, biochemical evaluation including estimation of hs-cTnT and Echo-Doppler study of cardiac structure and function.Results: There was a significant increase in LAV (p < 0.01), LVM (p < 0.01) in both patient groups compared to the control group. Mitral annular plane systolic excursion (MAPSE) was significantly decreased in both patient groups compared to the control group (p < 0.01, p < 0.05) and in group I compared to group II (p < 0.05) with a significant decrease in S velocity in group I compared to groups II and III (p < 0.01). There was a significant decrease in Vp (p < 0.01) with a significant increase in AEF (p < 0.01) in both patients’ groups compared to the control group and AEF was significantly increased in group II compared to group I (p < 0.01). Ea velocity and Ea/Aa decreased significantly (p < 0.01) with significant increase in Aa velocity (p < 0.05, p < 0.01), E/Ea (p < 0.01) and E/Vp (p < 0.05) in both patient groups compared to the control group.There was a significant increase in hs-cTnT levels in both patient groups compared to the control group (P < 0.01). We found a positive correlation between hs-cTnT levels and LAV (r = 0.291, p < 0.03), IVST (r = 0.374, p < 0.004), PWT (r = 0.309, p < 0.02), LVM (r = 0.282, p < 0.03), A wave velocity (r = 0.271, p < 0.04), E/Ea (r = 0.506, p < 0.0001), PCWP (r = .507, p < 0.0001) and a negative correlation between hs-cTnT and MAPSE (r = − 0.300, p < 0.02), S wave velocity (r = − 0.259, p < 0.05), Ea (r = − 626, p < 0.0001), Ea/Aa (r = − 0.543, p < 0.0001).Troponin at the cut-off value of >5 ng/L, revealed 100% sensitivity and 95% specificity with areas under curve (AUC) of 0.998 and accuracy of 95.65% (P < 0.01) for discrimination of Group I vs control group and 76.2% sensitivity and 95.7% specificity with AUC 0.796 and accuracy 71.84% (P < 0.01) for discrimination of group II vs control group.Conclusion: Structural and functional cardiac abnormalities are common in CKD patients. Serum hs-cTnT levels increased in CKD patients and was associated with LVH, LAV and some of the echocardiographic parameters of LV systolic and diastolic dysfunction.Our research suggests that hs-cTnT levels may be important for early screening of cardiac structure and function in CKD patients to provide evidence for early intervention.

A Mobile App to Support Self-management of Chronic Kidney Disease: Development Study.

BackgroundChronic kidney disease (CKD) is a common and costly condition that is usually accompanied by multiple comorbidities including type 2 diabetes, hypertension, and obesity. Proper management of CKD can delay or prevent kidney failure and help mitigate cardiovascular disease risk, which increases as kidney function declines. Smart device apps hold potential to enhance patient self-management of chronic conditions including CKD.ObjectiveThe objective of this study was to develop a mobile app to facilitate self-management of nondialysis-dependent CKD.MethodsOur stakeholder team included 4 patients with stage 3-4 nondialysis-dependent CKD; a kidney transplant recipient; a caretaker; CKD care providers (pharmacists, a nurse, primary care physicians, a nephrologist, and a cardiologist); 2 health services and CKD researchers; a researcher in biomedical informatics, nutrition, and obesity; a system developer; and 2 programmers. Focus groups and in-person interviews with the patients and providers were conducted using a focus group and interview guide based on existing literature on CKD self-management and the mobile app quality criteria from the Mobile App Rating Scale. Qualitative analytic methods including the constant comparative method were used to analyze the focus group and interview data.ResultsPatients and providers identified and discussed a list of requirements and preferences regarding the content, features, and technical aspects of the mobile app, which are unique for CKD self-management. Requirements and preferences centered along themes of communication between patients and caregivers, partnership in care, self-care activities, adherence to treatment regimens, and self-care self-efficacy. These identified themes informed the features and content of our mobile app. The mobile app user can enter health data including blood pressure, weight, and blood glucose levels. Symptoms and their severity can also be entered, and users are prompted to contact a physician as indicated by the symptom and its severity. Next, mobile app users can select biweekly goals from a set of predetermined goals with the option to enter customized goals. The user can also keep a list of medications and track medication use. Our app includes feedback mechanisms where in-range values for health data are depicted in green and out-of-range values are depicted in red. We ensured that data entered by patients could be downloaded into a user-friendly report, which could be emailed or uploaded to an electronic health record. The mobile app also includes a mechanism that allows either group or individualized video chat meetings with a provider to facilitate either group support, education, or even virtual clinic visits. The CKD app also includes educational material on CKD and its symptoms.ConclusionsPatients with CKD and CKD care providers believe that a mobile app can enhance CKD self-management by facilitating patient-provider communication and enabling self-care activities including treatment adherence.

Association of Polypharmacy with Kidney Disease Progression in Adults with CKD.

Polypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT. We retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5-9 and ≥10 medications per day, respectively. The median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality. The use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.

The Impact of Intravenous Iron on Renal Injury and Function Markers in Patients With Chronic Kidney Disease and Iron Deficiency Without Anemia

The Impact of Intravenous Iron on Renal Injury and Function Markers in Patients With Chronic Kidney Disease and Iron Deficiency Without Anemia

Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study.

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.

Plant-based Diets in Kidney Disease: Nephrology Professionals' Perspective

Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and co-morbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. However, it is unclear how often plant-based diets are recommended to patients with kidney disease. The objective of this study was to understand nephrology professionals' familiarity, perception, and recommendation of plant-based diets to people with kidney disease. A survey to understand perception of recommendation of plant-based diets for patients with CKD was developed. Nephrology professionals from the National Kidney Foundation's member directory were e-mailed a link to complete the survey online. This directory includes professionals who work in a variety of nephrology settings, including both CKD and end-stage renal disease care. Survey items were evaluated with descriptive statistics. Differences across items were determined using chi-square tests and t-tests. A total of 3,901 professionals were sent the survey, and 644 completed the survey. A majority were dietitians (58%) and worked in dialysis clinics (54%). Most (88%) had heard of using plant-based diets for kidney disease treatment, and a majority (88%) believed it could improve CKD management, cardiovascular disease (90%), hypertension (90%), diabetes (84%), high cholesterol (90%), and obesity (84%). Dietitians were more likely to report plant-based diets as beneficial for each health condition (P<.05). Professionals were most confident that a plant-based diet could help control hypertension (3.75±0.99 on a scale of 1-5), compared with delaying progression of CKD (3.68±1.15) or treating acidosis (3.68±1.13). Dietitians felt more confident in their ability to plan a balanced plant-based diet compared with other specialties (3.49 vs. 2.74, P<.001). Nephrology professionals who work in nondialysis-dependent CKD settings, and those who work with patients on dialysis, are aware of the benefits of plant-based diets in kidney disease. However, plant-based diets are not routinely being offered as a treatment option. Nephrology practices should work to increase dietitian referrals to offer patients support in transitioning to a plant-based diet.

Current status of the assessment of sarcopenia, frailty, physical performance and functional status in chronic kidney disease patients.

Low physical function, frailty, and sarcopenia are common complications of chronic kidney disease (CKD). In this article, we review the epidemiology and pathogenesis of low physical function, as well as its associations with adverse outcomes in CKD patients. Additionally, we present various traditional and novel methods for assessment of physical function in CKD patients. In nondialysis dependent (NDD) and dialysis-dependent CKD patients, the prevalence of low physical function, frailty, and sarcopenia are substantially higher than in the general population. The potential mechanisms of low physical function, frailty, and sarcopenia in CKD patients are due to various factors including underlying kidney disease, co-existing comorbidities, and certain therapeutic interventions utilized in CKD. Increasing evidence has also uncovered the ill effects of impaired physical function on clinical outcomes in CKD patients. Routine assessment of physical function is an under-utilized yet important component in the management of CKD patients. Future studies are needed to determine how prescription of exercise and increased daily physical activity can be tailored to optimize the health and well-being of NDD and dialysis-dependent CKD patients in pursuit of successful aging.

Title: Efficacy and Safety of Ferric Derisomaltose for Treatment of Anemia in Chronic Kidney Disease Patients: A Systematic Review

BackgroundAnemia in chronic kidney disease (CKD) patients develop primarily due to iron and erythropoietin deficiency, factors contributing to this include uremia induced inhibition of erythropoiesis, shortened red cell survival and nutritional deficiency. Erythropoietin stimulating agents (ESA) used in CKD increases iron demand for the production of new red blood cells (RBCs). Oral iron does not provide a reliable route to meet the demand of the iron required and poses the risk of side effects. The intravenous formulation provides the fastest route, although multiple intravenous formulations are available they require multiple dosing and still carry a risk of an adverse event. Ferric derisomaltose/iron isomaltoside (IIM) is an intravenous formulation of iron recently approved by the Food and drug administration (FDA) for patients intolerant to oral iron and non-dialysis dependent CKD patients. FDI is administered in high dose usually in a single administration. In this systematic review, we evaluated the published literature for the efficacy and safety of ferric derisomaltose in both dialysis-dependent and dialysis independent patients.Material/MethodsA literature search was done using the following databases: PubMed, Cochrane, Embase, Clinical trials.gov, and Web of Science. The search was completed without using any filter and we used the Mesh Terms for “anemia”, “iron deficiency anemia” “chronic kidney disease” and “ferric compounds”. Total of 316 which were further screened and we included 2 trials, and 2 prospective studies. Case reports, preclinical trials, meta-analyses, and review articles were excluded. We followed the PRISMA guidelines for literature search and selection of studies. We only included the trial studies that were completed. We excluded the studies that did not report efficacy and safety.ResultsIn total, amongst the four studies, 1558 CKD patients received ferric derisomaltose in a single dose. Patients in all stages of CKD were studied but most patients were between stages I to stage III CKD, stage IV and V(dialysis-dependent) were studied by Kalra et al (2020). A single dose of 1000 mg/dl of IIM, was administered intravenously. The mean pre-treatment haemoglobin level varied from 9.6g/dl to 10.6 g/dl. The mean serum ferritin ranged from 82.4 µg/L to 161.9 µg/L and the mean transferrin saturation ranged in patients from 15.8% to 18.51%. IIM receiving patients were compared with iron sucrose receiving patients by Bhandari et al, and oral iron by Kalra et al (2015). The remaining two studies compared single IIM with multiple IIM dosages. The results are summarised in the table below.Efficacy: The increase in haemoglobin ranged between 0.9 g/dL to 6.58 g/dL from baseline measured at 8 weeks. At the same time, serum ferritin showed an increase in baseline serum ferritin from 104 µg/L to 277 µg/L and transferrin saturation (TSAT) increased in the range of 5.3%-11.4 %. All markers of iron deficiency showed significant improvement. It achieved a greater Hb response irrespective of ESA treatment in both haemodialysis dependent and non-dependent patients. In the comparison group by Bhandari et al, iron sucrose receiving patients also had similar efficacy as IIM. On the other hand, those receiving oral iron in the study by Kalra et al (2015) had much poorer efficacy as compared to IIMSafety: Severe adverse effect was seen in a total of 10 (0.6%) patients who developed hypersensitivity reaction, acute myocardial infarction and injection site-related adverse effects with hypersensitivity being the most common. 15 (0.9%) patients discontinued the treatment. 21 (1.3%) died, and the death was attributed to end-stage renal disease.ConclusionFerric derisomaltose is an effective parenteral iron therapy to treat iron deficiency when compared to oral iron therapy, however, its efficacy is very similar to other parenteral iron formulations. In terms of safety, being used as a single dose it relatively has lesser adverse events but can seldom lead to discontinuation of the drug. This drug can be recommended for iron therapy especially considering single-dose administration but more studies need to be carried out in comparison to other parenteral formulations to further clarify its efficacy in dialysis-dependent CKD patients. [Display omitted] DisclosuresAnwer: BMS / Celgene: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding; Allogene Therapeutics: Research Funding.

An evaluation of roxadustat for the treatment of anemia associated with chronic kidney disease

ABSTRACT Introduction Anemia is one of the major complications of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) have been the mainstay of renal anemia treatment. However, there are several safety drawbacks, and a safer and more effective alternative treatment has been sought. Areas covered Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been developed as a novel orally active therapeutic agent for renal anemia. HIF-PHIs stimulate endogenous EPO and optimize iron utilization. Roxadustat is a first-in-class HIF-PHI for the treatment of anemia in CKD patients approved in China, Japan, South Korea, and Chile. The authors herein evaluate the pharmacology of roxadustat and give their expert perspectives on its use. Expert opinion Phase 3 clinical trials have demonstrated that roxadustat effectively increases and maintains hemoglobin (Hb) levels in both nondialysis-dependent and dialysis-dependent CKD patients. Roxadustat also improved iron metabolism and reduced intravenous (IV) iron requirements. However, pooled analyses of phase 3 studies have revealed frequent thromboembolic events in the roxadustat group, which might be attributed to rapid changes in Hb and inadequate iron supplementation. Roxadustat is an attractive alternative treatment especially for patients with ESA hyporesponsive due to impaired iron utilization, and so appropriate selection of target patients and its proper use are crucially important.

Serum Osteoprotegerin Is an Independent Marker of Metabolic Complications in Non-DialysisDependent Chronic Kidney Disease Patients.

Background: Osteoprotegerin (OPG) belongs to the tumour necrosis factor superfamily and is known to accelerate endothelial dysfunction and vascular calcification. OPG concentrations are elevated in patients with chronic kidney disease. The aim of this study was to investigate the association between OPG levels and frequent complications of chronic kidney disease (CKD) such as anaemia, protein energy wasting (PEW), inflammation, overhydration, hyperglycaemia and hypertension. Methods: One hundred non-dialysis-dependent men with CKD stage 3–5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure overhydration, fat amount and lean body mass. We also measured the serum concentrations of haemoglobin, albumin, total cholesterol, C-reactive protein (CRP), fibrinogen and glycated haemoglobin (HgbA1c), as well as blood pressure. Results: We observed a significant, positive correlation between OPG and age, serum creatinine, CRP, fibrinogen, HgbA1c concentrations, systolic blood pressure and overhydration. Negative correlations were observed between OPG and glomerular filtration rate (eGFR), serum albumin concentrations and serum haemoglobin level. Logistic regression models revealed that OPG is an independent marker of metabolic complications such as anaemia, PEW, inflammation and poor renal prognosis (including overhydration, uncontrolled diabetes and hypertension) in the studied population. Conclusion: Our results suggest that OPG can be an independent marker of PEW, inflammation and vascular metabolic disturbances in patients with chronic kidney disease.

Factors Affecting Doses of Roxadustat Versus Darbepoetin Alfa for Anemia in Nondialysis Patients

Introduction: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia of chronic kidney disease (CKD). This post hoc analysis of a Japanese, open-label, partially randomized, phase 3 study in nondialysis-dependent (NDD) CKD patients treated with traditional erythropoiesis-stimulating agents (ESAs) evaluated dosing trends of roxadustat and darbepoetin alfa (DA) required to maintain target hemoglobin concentrations in patients with risk factors associated with ESA hyporesponsiveness. Methods: Patients enrolled in the 1517-CL-0310 study (NCT02988973) that demonstrated noninferiority of roxadustat to DA for change in average hemoglobin levels of week 18–24 from baseline who had used human recombinant erythropoietin or DA before conversion and who were randomized to either roxadustat or DA were included. The endpoints were the average allocated dose of roxadustat and DA per administration in the last 6 weeks (AAD/6W), assessed by subgroups known to be associated with ESA hyporesponsiveness. The analysis of variance was performed by the treatment group to test the influence of subgroup factors on the AAD/6W of study drug. The ratios between the mean AAD/6W in each subgroup category and the within-arm mean AAD/6W were calculated. Results: Two hundred and sixty-two patients were randomized to either the roxadustat or DA comparative group and received treatment (roxadustat, n = 131; DA, n = 131). Higher mean (standard deviation) doses of both roxadustat (63.15 [24.84] mg) and DA (47.33 [29.79] μg) were required in the highest ESA resistance index (≥6.8) quartile (p = 0.003 and p < 0.001, respectively). Patients with adequate iron repletion had the lowest doses for both roxadustat (45.54 [18.01] mg) and DA (28.13 [20.98] μg). High-sensitivity C-reactive protein ≥28.57 nmol/L and the estimated glomerular filtration rate <15 mL/min/1.73 m² were associated with requiring higher DA but not roxadustat doses. Discussion/Conclusion: The roxadustat dose required to maintain target hemoglobin in NDD patients in Japan with anemia of CKD relative to DA dose may not be impacted by low-grade inflammation. Roxadustat may be beneficial for ESA-hyporesponsive NDD CKD patients.

Efficacy and Safety of Roxadustat in Patients with Anemia of Non-Dialysis-Dependent CKD (NDD-CKD) Treated Continuously for ≥2 Years

Efficacy and Safety of Roxadustat in Patients with Anemia of Non-Dialysis-Dependent CKD (NDD-CKD) Treated Continuously for ≥2 Years

Electrophysiological study of peripheral neuropathies in chronic kidney disease patients and relation of severity of peripheral neuropathy with degree of renal failure

Background: Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. Peripheral neuropathy occurs in 60-100% patients of CKD. Nerve conduction study is the gold standard method to diagnose uremic neuropathy. In this study we have examined the correlation of nerve conduction latency, amplitude and nerve conduction velocity with serum creatinine, blood urea, serum uric acid levels and compared these parameters among dialysis and non-dialysis dependent CKD patients.Methods: The present cross-sectional study was conducted on 100 adult patients diagnosed to have and treated for CKD. All cases were subjected to nerve conduction study (NCS) which was performed on median nerve, ulnar nerve, common peroneal nerve, tibial nerve and sural nerve.Results: The prevalence of neuropathy was 68% in both dialysis and non-dialysis dependent groups. The most involved nerve was sural nerve. On NCS, there was prolongation of nerve latency, decrease in nerve amplitude and nerve conduction velocity with rising blood urea and serum creatinine levels. All these abnormalities were more evident in dialysis dependent patients as compared to non-dialysis dependent patients. Depressed amplitude was the most common abnormality in all the tested nerves.Conclusions: The nerve latency, amplitude and nerve conduction velocity worsened with rise in blood urea, serum creatinine and decrease in eGFR suggesting that neuropathy progress with increased severity of renal failure. Nerve conduction abnormalities were more prominent in dialysis dependent patients and therefore was associated with more advanced stage of CKD.

ASSOCIATION BETWEEN ANEMIA AND BONE PROFILE IN NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE ANEMIA AND BONE PROFILE IN CKD

Objective: To determine association between iron deficiency anemia and bone profile in cases of chronic kidney disease not undergoing dialysis.&#x0D; Study Design: Comparative cross sectional study.&#x0D; Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology in collaboration with department of Nephrology, Armed Forces Institute of Urology, Rawalpindi, from Sep 2018 to Oct 2019.&#x0D; Methodology: A total of 300 chronic kidney disease patients who were not dependent on any kind of dialysis were included in our study. Chronic kidney disease was confirmed according to National Kidney Foundation/Kidney Disease Outcome Quality Initiative criteria. Hemoglobin, Mean corpuscular volume and ferritin levels were used to diagnose iron deficiency anemia. Association of Calcium, inorganic Phosphorous, Magnesium, Alkaline phosphatase and Parathyroid Hormone (PTH) was determined with iron deficiency anemia.&#x0D; Results: Out of 300 patients studied 201 (67%) were females while 99 (33%) were males. Mean age of participants was 43.51 ± 5.652 years. Mean duration of chronic kidney disease was 4.36 ± 3.712 years. One hundred and forty one (47%) patients had no anemia while 159 (53%) had presence of iron deficiency anemia. After applying binary logistic regression analysis hypocalcemia, hypophosphatemia and hypomagnesemia were noted to have a statistically significant association with iron deficiency anemia in the target sample size.&#x0D; Conclusion: This study revealed a high frequency of iron deficiency anemia in non-dialysis chronic kidney disease patients. Hypocalcemia, hypophosphatemia and hypomagnesemia were found having strong association with presence of iron deficiency anemia in non-dialysis dependent chronic kidney disease patients.