The lived experience of renal cachexia: An interpretive phenomenological analysis.

Background: Chronic kidney disease is common, affecting up to 13 % of the global population, and is predicted to become the fifth leading cause of 'life years lost' by 2040. Individuals with end-stage kidney disease commonly develop complications such as protein-energy wasting and cachexia which further worsens their prognosis. The syndrome of 'renal cachexia' is poorly understood, under-diagnosed and even if recognised has limited treatment options. Objective: To explore the lived experience of renal cachexia for individuals with end-stage kidney disease and the interrelated experiences of their carers. Design: This interpretive phenomenological study was designed to facilitate an in-depth exploration of how patients and carers experience of renal cachexia. To improve and document the quality, transparency, and consistency of patient and public involvement in this study the Guidance for Reporting Involvement of Patients and the Public-Short Format was followed. Setting: The study was conducted across two nephrology directorates, within two healthcare trusts in the United Kingdom. Participants: Seven participants who met the inclusion criteria were recruited for this study, four patients (three female, one male) and three carers (two male, one female). Methods: We employed a purposive sampling strategy. Data collection was conducted between July 2022 and December 2023. Interviews were semi-structured, audio-recorded, transcribed verbatim and analysed in six steps by two researchers using interpretive phenomenological analysis. Ethical approval was approved by the Office for Research Ethics Committees Northern Ireland (Reference: 22/NI/0107). Results: Analysis generated six group experiential themes: the lived experience of appetite loss, functional decline and temporal coping, weight loss a visual metaphor of concern, social withdrawal and vulnerability, the emotional toll of eating challenges and psychological strain amidst a lack of information about cachexia. Conclusion: This is the first qualitative study exploring the lived experience of renal cachexia for patients and carers. Our study highlights that psycho-social and educational support is urgently needed. Additionally, healthcare professionals need better information provision to help them to recognise and respond to the needs of this population. Further research is required to develop models of holistic support which could help patients and carers cope with the impact of renal cachexia and optimally manage this syndrome within the family unit. Registration: N/A.

Dietary burden of phosphorus and aluminum in ready-to-eat wheat flour tortillas exceed that of corn tortillas: Implications for patients with renal or cardiovascular disease.

Ready-to-eat, shelf-stable tortillas contain several phosphorus- and aluminum-containing additives that may increase the risk of adverse events in patients with chronic kidney disease (CKD). The present study analyzes and compares the elemental content of wheat flour and corn tortillas with special reference to dietary aluminum and phosphorus burden. Twenty-one elements were quantified by ICP-MS and ICP-OES in 14 corn and 13 wheat flour tortilla brands purchased from local supermarkets in Southern California. The aluminum and phosphorus concentrations of many ready-to-eat tortilla brands can present a daily dietary load of up to approximately 100 mg aluminum and 700 mg phosphorus based on an average daily tortilla intake of 330 grams. Ready-to-eat wheat flour tortillas generally had more phosphorus than corn tortillas. Tortillas with aluminum listed as a food additive contained a higher aluminum content than those without such listing, exceeding the tolerable weekly intake. Despite conventional wisdom that CKD patients should avoid phosphorus-rich corn tortillas, ready-to-eat wheat flour tortillas consistently had a higher aluminum and phosphorus content due to additives. CKD patients and healthcare providers should pay attention to food labels, and regulatory authorities should monitor the use of approved food additives and mandate food label warnings for patients at risk.

The Relevance of Phytate for the Treatment of Chronic Kidney Disease.

Diets high in plant-based foods are commonly recommended for people with chronic kidney disease (CKD). One putative advantage of these diets is reduced intestinal phosphate absorption. This effect has been ascribed to phytic acid (myoinositol hexaphosphoric acid) and its anion, phytate, that are present in many plant foods, particularly in the seeds, nuts, grains and fruits of plants. This paper reviews the structure and many actions of phytate with particular reference to its potential effects on people with CKD. Phytate binds avidly to and can reduce gastrointestinal absorption of the phosphate anion and many macrominerals and trace elements including iron, zinc, calcium and magnesium. This has led some opinion leaders to label phytate as an "anti-nutrient." The human intestine lacks phytase; hence, phytate is essentially not degraded in the small intestine. A small amount of phytate is absorbed from the small intestine, although phytate bound to phosphate is poorly absorbed. Clinical trials in maintenance hemodialysis patients indicate that intravenously administered phytate may decrease hydroxyapatite formation, vascular calcification and calciphylaxis. Orally administered phytate or in vitro studies indicate that phytate may also reduce osteoporosis, urinary calcium calculi formation and dental plaque formation. Phytate appears to have anti-inflammatory and antioxidant effects, at least partly due to its ability to chelate iron. Other potential therapeutic roles for phytate, not definitively established, include suppression of cancer formation, reduction in cognitive decline that occurs with aging, and amelioration of certain neurodegenerative diseases and several gastrointestinal and metabolic disorders. These latter potential benefits of phytate are supported by cell or animal research or observational studies in humans. Many of the above disorders are particularly common in CKD patients. Definitive clinical trials to identify potential therapeutic benefits of phytate in CKD patients are clearly warranted.

BRD4 plays an antiaging role in the senescence of renal tubular epithelial cells.

Background: Age-related kidney failure is often induced by a decrease in the bioavailability of tubular epithelial cells in elderly chronic kidney disease (CKD) patients. BRD4, an epigenetic regulator and a member of the bromodomain and extraterminal (BET) protein family, acts as a super-enhancer (SE) organizing and regulating genes expression during embryogenesis and cancer development. But the physiological function of BRD4 in normal cells has been less studied. This study aimed to research certain biological roles of BRD4 in the process of normal cell aging and discuss the potential mechanisms. Methods: In this study, we investigated the biological functions of BRD4 proteins in the aging of renal tubular cells. At first, we used a D-galactose (D-gal) and BRD4 inhibitor (Abbv-075) to replicate kidney senescence in vivo. D-gal and Abbv-075 were then used to measure the aging-related changes, such as changes in cell cycle, ß-galactosidase activity, cell migration, and p16 protein expression in vitro. At last, we knocked down and over-expressed BRD4 to investigate the aging-related physiological phenomena in renal tubular cells. Results: In vitro, D-gal treatment induced noticeable aging-related changes such as inducing cell apoptosis and cell cycle arrest, increasing ß-galactosidase activity as well as up-regulating p16 protein expression in primary human tubular epithelial cells. In the aging mice model, D-gal significantly induced renal function impairment and attenuated BRD4 protein expression. At the same time, the BRD4 inhibitor (Abbv-075) was able to mimic D-gal-induced cell senescence. In vivo, Abbv-075 also decreased kidney function and up-regulated p21 protein expression. When we knocked down the expression of BRD4, the senescence-associated ß-galactosidase (SA-ß-gal) activity increased dramatically, cell migration was inhibited, and the proportion of cells in the G0/G1 phase increased. Additionally, the knockdown also promoted the expression of the senescence-related proteins p16. When the renal tubular cells were overexpressed with BRD4, cell aging-related indicators were reversed in the D-gal-induced cell aging model. Conclusions: BRD4 appears to have an active role in the aging of renal tubular cells in vivo and in vitro. The findings also suggest that BRD4 inhibitors have potential nephrotoxic effects for oncology treatment. BRD4 may be a potential therapeutic biomarker and drug target for aging-related kidney diseases, which warrants additional studies.

Frailty in patients on dialysis.

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

Anti-Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease.

Importance: Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. Objective: To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. Design, Setting, and Participants: This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Exposures: Incident use of TNF inhibitors. Main Outcomes and Measures: The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Results: Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. Conclusions and Relevance: In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.

Association of oral iron replacement therapy with kidney failure and mortality in CKD patients.

Background: Oral iron is the predominant route of iron replacement (IRT) but its benefits and safety are unclear in patients with chronic kidney disease (CKD). Methods: We examined the association of oral IRT vs no IRT with end-stage kidney disease (ESKD) and mortality in a national cohort of US Veterans. We identified 17 413 incident new users of oral IRT with estimated glomerular filtration rates <60 mL/min/1.73 m2 and 32 530 controls who did not receive any IRT during 2004-18. We used propensity score-overlap weighting to account for differences in key baseline characteristics associated with the use of oral IRT. We examined associations using competing risk regression and Cox models. Results: In the cohort of 49 943 patients, 1616 (3.2%) patients experienced ESKD and 28 711 (57%) patients died during a median follow-up of 1.9 years. Oral IRT was not associated with ESKD [subhazard ratio (HR) (95% confidence interval, CI) 1.00 (0.84-1.19), P = .9] and was associated with higher risk of all-cause mortality [HR (95% CI) 1.06 (1.01-1.11), P = .01]. There was significant heterogeneity of treatment effect for mortality, with oral IRT associated with higher mortality in the subgroups of patients without congestive heart failure (CHF), anemia or iron deficiency. In patient with blood hemoglobin <10 g/dL oral IRT was associated with significantly lower mortality. Conclusion: Oral IRT was associated with lower mortality only in patients with anemia. In patients without anemia, iron deficiency or CHF, the risk-benefit ratio of oral IRT should be further examined.

Association of iron therapy with incidence of chronic kidney disease.

OBJECTIVE: We investigated the association of oral iron replacement with the incidence of chronic kidney disease (CKD) in a population with normal kidney function to study the effects of iron replacement on the development of new onset CKD. METHODS: In a national cohort of US Veterans with no pre-existing CKD, we identified 33 894 incident new users of oral iron replacement and a comparable group of 112 780 patients who did not receive any iron replacement during 2004-2018. We examined the association of oral iron replacement versus no iron replacement with the incidence of eGFR <60 mL/min/1.73 m2 and the incidence of urine albumin creatinine ratio (UACR) ≥30 mg/g in competing risk regressions and in Cox models. We used propensity score weighing to account for differences in key baseline characteristics associated with the use of oral iron replacement. RESULTS: In the cohort of 146 674 patients, a total of 18 547 (13%) patients experienced incident eGFR <60 mL/min/1.73 m2 , and 16 117 patients (11%) experienced new onset UACR ≥30 mg/g. Oral iron replacement was associated with significantly higher risk of incident eGFR <60 mL/min/1.73 m2 (subhazard ratio, 95% confidence interval [CI]: 1.3 [1.22-1.38], p < .001) and incident albuminuria (subhazard ratio, 95% CI: 1.14 [1.07-1.22], p < .001). CONCLUSION: Oral iron replacement is associated with higher risk of new onset CKD. The long-term kidney safety of oral iron replacement should be tested in clinical trials.

Kidney function in cachexia and sarcopenia: Facts and numbers.

Cachexia, in the form of unintentional weight loss >5% in 12 months or less, and secondary sarcopenia in the form of muscle wasting are serious conditions that affect clinical outcomes. A chronic disease state such as chronic kidney disease (CKD) often contributes to these wasting disorders. The purpose of this review is to summarize the prevalence of cachexia and sarcopenia, their relationship with kidney function, and indicators for evaluating kidney function in patients with CKD. It is estimated that approximately half of all persons with CKD will develop cachexia with an estimated annual mortality rate of 20%, but few studies have been conducted on cachexia in CKD. Hence, the true prevalence of cachexia in CKD and its effects on kidney function and patient outcomes remain unclear. Some studies have highlighted the concept of protein-energy wasting (PEW) which usually include sarcopenia and cachexia. Several studies have examined kidney function and CKD progression in patients with sarcopenia. Most studies use serum creatinine levels to estimate kidney function. However, creatinine may be influenced by muscle mass, and creatinine-based glomerular filtration rate may overestimate kidney function in patients with reduced muscle mass or muscle wasting. Cystatin C, which is least affected by muscle mass, has been used in some studies, and creatinine-to-cystatin-C ratio has emerged as an important prognostic marker. A previous study incorporating 428 320 participants reported that participants with CKD and sarcopenia had a 33% higher hazard of mortality compared with those without (7% to 66%, P = 0.011), and that those with sarcopenia were twice as likely to develop end-stage kidney disease (hazard ratio: 1.98; 1.45 to 2.70, P < 0.001). Future studies on cachexia and sarcopenia in patients with CKD are needed to report rigorously defined cachexia concerning kidney function. Moreover, in studies on sarcopenia with CKD, it is desirable to accumulate studies using cystatin C to accurately estimate kidney function.

A randomized study to compare oral potassium binders in the treatment of acute hyperkalemia.

BACKGROUND: The KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy. METHODS: Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics). DISCUSSION: The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04585542 . Registered 14 October 2020.

Hypophosphataemia risk associated with ferric carboxymaltose in heart failure: A pooled analysis of clinical trials.

AIMS: Iron deficiency is a common finding among patients with heart failure (HF) and is associated with adverse outcomes, including decreased quality of life, increased risk of hospitalization, and decreased survival. Intravenous ferric carboxymaltose (FCM) has been shown to improve outcomes among patients with HF and concomitant iron deficiency, but FCM is associated with an increased risk of hypophosphataemia. We aimed to better characterize this risk among HF populations. METHODS AND RESULTS: This pooled analysis examined data from 41 studies of adults with iron deficiency across disease states and therapeutic areas. Among the 7931 patients treated with FCM available for analysis, 14% made up the HF subgroup. Additional subgroups included women's health (36%), non-dialysis-dependent chronic kidney disease (NDD-CKD; 27%), haemodialysis-dependent chronic kidney disease (HD-CKD; 1%), gastrointestinal (10%), neurology (3%), and other (10%). The incidence of post-baseline moderate or severe hypophosphataemia (i.e. serum phosphate [PO4 3- ] level <2.0 mg/dL) varied across the therapeutic areas, with the lowest incidences observed in the HD-CKD (0%), HF (8.1%), and NDD-CKD (12.8%) subgroups. The prevalence of moderate or severe hypophosphataemia among the women's health, other, gastrointestinal, and neurology subgroups was 30.1%, 40.6%, 51.0%, and 55.6%, respectively. In the HF subgroup, one patient (<0.1%) had a serum PO4 3- of <1.0 mg/dL recorded, compared with 4.8% and 4.0% of the subjects in the neurology and gastrointestinal groups, respectively. With the exception of the HD-CKD subgroup, mean serum PO4 3- levels decreased through weeks 2 to 4, and then returned toward baseline and plateaued by week 8. The strongest predictor of hypophosphataemia was preserved kidney function (estimated glomerular filtration rate: >60 mL/min/1.73 m2 vs. <30 mL/min/1.73 m2 ; odds ratio: 12.2). Among patients in the HF subgroup, the incidence of treatment-emergent adverse events potentially related to hypophosphataemia (e.g. cardiac failure, ventricular tachyarrhythmias, fatigue, muscle weakness, bone pain, neurological symptoms, and muscle pain) was lower among FCM-treated patients than among those receiving placebo, and lower among patients with a post-baseline PO4 3- <2 mg/dL vs. those not meeting such criteria. CONCLUSIONS: The risk of laboratory-assessed hypophosphataemia in HF patients treated with FCM was lower than that seen in patients in other therapeutic areas treated with FCM, and clinical events associated with hypophosphataemia are uncommon with FCM therapy in this population. Appropriate monitoring, particularly soon after administration in the unlikely event of repeated dosing in HF patients, will allow for further refinement of management strategies. [Correction added on 24 February 2023, after first online publication: In the preceding sentence, "…administration, will allow…" has been corrected to "…administration in the unlikely event of repeated dosing in HF patients, will allow…" in this version.].

Prognostic Nutritional Index as a Predictor of Mortality in 101,616 Patients Undergoing Hemodialysis.

High mortality in dialysis patients is linked to malnutrition and inflammation. Prognostic nutritional index (PNI), calculated from serum albumin level and total lymphocyte count, has been developed as a prognostic marker for cancer patients. We investigated the clinical utility of PNI in predicting mortality in patients undergoing hemodialysis. Thus, 101,616 patients who initiated hemodialysis in United States dialysis centers between 2007 and 2011 were included in this retrospective cohort study. Using the Cox regression model, we assessed the relationship between PNI and mortality. Further, the predictive value of PNI for one-year mortality was compared with that of its constituent using area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. Higher PNI quartiles were incrementally associated with lower mortality; in patients with PNI values of 39.5−<43.1, 43.1−<46.6, and ≥46.6 (reference: PNI < 39.5), case-mix adjusted hazard ratios (95% confidence intervals) were 0.66 (0.64, 0.68), 0.49 (0.48, 0.51), and 0.36 (0.34, 0.37), respectively. PNI predicted mortality better than serum albumin level or total lymphocyte count alone. In the subgroup analysis, PNI performed well in predicting mortality in patients aged < 65 years. Our results indicate that PNI is a simple and practical prognostic marker in patients undergoing hemodialysis.

Serum Creatinine-to-Cystatin-C Ratio as a Potential Muscle Mass Surrogate and Racial Differences in Mortality.

OBJECTIVES: Serum creatinine-based estimated glomerular filtration rate equations and muscle mass are powerful markers of health and mortality risk. However, the serum creatinine-to-cystatin-C ratio may be a better indicator of health status. The objective of this study was to describe the relationship between creatinine-to-cystatin-C ratio and all-cause mortality when stratifying patients as per race and as per chronic kidney disease status. METHODS: This was a retrospective cohort study examining black and nonblack US veterans between October 2004 and September 2019, with baseline cystatin C and creatinine data from those not on dialysis during the study period. Veterans were divided into four creatinine-to-cystatin-C ratio groups: <0.75, 0.75-<1.00, 1.0-<1.25, and ≥1.25. The primary outcome of interest was all-cause mortality subsequent to the cystatin C laboratory measure. RESULTS: Among 22,316 US veterans, the mean (± standard deviation) age of the cohort was 67 ± 14 years, 5% were female, 82% were nonblack, and 18% were black. The proportion of black veterans increased across creatinine-to-cystatin-C ratio groups. In the fully adjusted model, compared with the reference (creatinine-to-cystatin-C ratio: 1.00-<1.25), a creatinine-to-cystatin-C ratio <0.75 had the highest mortality risk among both black and nonblack veterans (nonblack: hazard ratio [HR] [95% confidence interval {CI}]: 3.01 [2.78-3.26] and black: 4.17 [3.31-5.24]). A creatinine-to-cystatin-ratio ≥1.25 was associated with lower death risk than the referent in both groups (nonblack: HR [95% CI]: 0.89 [0.80-0.99] and black: HR [95% CI]: 0.55 [0.45-0.69]). However, there was a significant difference in the effect by race (Wald's P-value: <0.01). CONCLUSIONS: Higher creatinine-to-cystatin-C ratios indicate better health status and are strongly associated with lower mortality risk regardless of the kidney function level, and the relation was similar for both black and nonblack veterans, but with different strengths of effect across racial groups. Thereby, use of a fixed race coefficient in estimating kidney function may be biased.

Novel insights in classic versus relative glomerular hyperfiltration and implications on pharmacotherapy.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) assessment and its estimation (eGFR) is a long-lasting challenge in medicine and public health. Current eGFR formulae are indexed for standardized body surface area (BSA) of 1.73 m2, ignoring persons and populations wherein the ratio of BSA or metabolic rate to nephron number might be different, due to increased BSA, increased metabolic rate or reduced nephron number. These equations are based on creatinine, cystatin C or a combination of the two, which adds another confounder to eGFR assessment. Unusually high GFR values, also known as renal hyperfiltration, have not been well defined under these equations. RECENT FINDINGS: Special conditions such as solitary kidney in kidney donors, high dietary protein intake, obesity and diabetes are often associated with renal hyperfiltration and amenable to errors in GFR estimation. In all hyperfiltration types, there is an increased intraglomerular pressure that can be physiologic, but its persistence over time is detrimental to glomerulus leading to progressive glomerular damage and renal fibrosis. Hyperfiltration might be underdiagnosed due to BSA standardization embedded in the formula. Hence, timely intervention is delayed. Reducing intraglomerular pressure in diabetes can be achieved by SGLT2 inhibitors or low protein diet to reverse the glomerulopathy process. SUMMARY: Accurate identification of glomerular hyperfiltration as a pre-CKD condition needs accurate estimation of GFR in the above normal range should establish a threshold for timely intervention.

Traditions and innovations in assessment of glomerular filtration rate using creatinine to cystatin C.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) is the best index for kidney function and estimated GFR (eGFR) calculated from endogenous filtration markers like serum creatinine and cystatin C is widely used in clinical practice for chronic kidney disease diagnosis and prognostication. We sought to review the evolution of GFR estimating equations, nuances of eGFR interpretation, and utility of eGFR in drug dosing. RECENT FINDINGS: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) serum creatinine eGFR equation was recently updated to exclude the race variable and the CKD-EPI creatinine-cystatin C equation demonstrated the highest reliability. Although calculated creatinine clearance by Cockcroft Gault has been traditionally used for drug dosing, the use of eGFR is slowly being adapted by the Food and Drug Administration for pharmacokinetic studies. However, the individual-level accuracy of eGFR using the CKD-EPI 2021 equations remained low, with the distribution of measured GFR at a given eGFR value spanning several CKD stages. SUMMARY: Although current methods of estimating GFR have improved in population measures of reliability, all have significant individual-level inaccuracies that can be an issue when clinical decision-making is contingent on the actual level of GFR. Modern methods of GFR measurements should be made widely available to enhance individualized patient decision-making.

Developing an Evidence and Theory Based Multimodal Integrative Intervention for the Management of Renal Cachexia: A Theory of Change.

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.

Exploring the lived experience of renal cachexia for individuals with end-stage renal disease and the interrelated experience of their carers: Study protocol.

Renal cachexia is an important consideration in the person-centred care that is needed in end-stage renal disease (ESRD). However, given that clinical guidelines relating to renal cachexia are largely absent, this is an unmet care need. To inform guidelines and future renal service planning, there is an urgency to understand individuals' experiences of renal cachexia and the interrelated experiences of the carers in their lives. We report here the protocol for an interpretative phenomenological study which will explore this lived experience. A purposive sampling strategy will recruit individuals living with ESRD who have cachexia and their carers. A maximum of 30 participants (15 per group) dependent on saturation will be recruited across two nephrology directorates, within two healthcare trusts in the United Kingdom. Individuals with renal cachexia undergoing haemodialysis will be recruited via clinical gatekeepers and their carers will subsequently be invited to participate in the study. Participants will be offered the opportunity to have a face-to-face, virtual or telephone interview. Interviews will be audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. NVivo, will be used for data management. Ethical approval for this study was granted by the Office for Research Ethics Committees Northern Ireland (REC Reference: 22/NI/0107). Scientific evidence tends to focus on measurable psychological, social and quality of life outcomes but there is limited research providing in-depth meaning and understanding of the views of individuals with renal disease who are experiencing renal cachexia. This information is urgently needed to better prepare healthcare providers and in turn support individuals with ESRD and their carers. This study will help healthcare providers understand what challenges individuals with ESRD, and their carers face in relation to cachexia and aims to inform future clinical practice guidelines and develop supportive interventions which recognise and respond to the needs of this population.

Dietary potassium intake, kidney function, and survival in a nationally representative cohort.

BACKGROUND: In healthy adults, higher dietary potassium intake is recommended given that potassium-rich foods are major sources of micronutrients, antioxidants, and fiber. Yet among patients with advanced kidney dysfunction, guidelines recommend dietary potassium restriction given concerns about hyperkalemia leading to malignant arrhythmias and mortality. OBJECTIVES: Given sparse data informing these recommendations, we examined associations of dietary potassium intake with mortality in a nationally representative cohort of adults from the NHANES. METHODS: We examined associations between daily dietary potassium intake scaled to energy intake (mg/1000 kcal), ascertained by 24-h dietary recall, and all-cause mortality among 37,893 continuous NHANES (1999-2014) participants stratified according to impaired and normal kidney function (estimated glomerular filtration rates <60 and ≥60 mL · min-1 · 1.73 m-2, respectively) using multivariable Cox models. We also examined the impact of the interplay between dietary potassium, source of potassium intake (animal- compared with plant-based sources), and coexisting macronutrient and mineral consumption upon mortality. RESULTS: Among participants with impaired and normal kidney function, the lowest tertile of dietary potassium scaled to energy intake was associated with higher mortality (ref: highest tertile) [adjusted HR (aHR): 1.18; 95% CI: 1.02, 1.38 and aHR: 1.17; 95% CI: 1.06, 1.28, respectively]. Compared with high potassium intake from plant-dominant sources, participants with low potassium intake from animal-dominant sources had higher mortality irrespective of kidney function. Among participants with impaired kidney function, pairings of low potassium intake with high protein, low fiber, or high phosphorus consumption were each associated with higher death risk. CONCLUSIONS: Lower dietary potassium scaled to energy intake was associated with higher mortality, irrespective of kidney function. There was also a synergistic relation of higher potassium intake, plant-based sources, and macronutrient/mineral consumption with survival. Further studies are needed to elucidate pathways linking potassium intake and coexisting dietary factors with survival in populations with and without chronic kidney disease.

Thrombotic Microangiopathy Syndromes-Common Ground and Distinct Frontiers.

Thrombotic microangiopathies (TMAs) have in common a terminal phenotype of microangiopathic hemolytic anemia with end-organ dysfunction. Thrombotic thrombocytopenic purpura results from von Willebrand factor multimerization, Shiga toxin-mediated hemolytic uremic syndrome causes toxin-induced endothelial dysfunction, while atypical hemolytic uremic syndrome results from complement system dysregulation. Drug-induced TMA, rheumatological disease-induced TMA, and renal-limited TMA exist in an intermediate space that represents secondary complement activation and may overlap with atypical hemolytic uremic syndrome clinically. The existence of TMA without microangiopathic hemolytic features, renal-limited TMA, represents an undiscovered syndrome that responds incompletely and inconsistently to complement blockade. Hematopoietic stem cell transplant-TMA represents another more resistant form of TMA with different therapeutic needs and clinical course. It has become apparent that TMA syndromes are an emerging field in nephrology, rheumatology, and hematology. Much work remains in genetics, molecular biology, and therapeutics to unravel the puzzle of the relationships and distinctions apparent between the different subclasses of TMA syndromes.