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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.

BACKGROUND: Pruritus is a common condition in chronic kidney disease (CKD), especially for patients receiving haemodialysis. CKD-associated pruritus (CKD-aP) can be distressing and have a negative impact on quality of life (QoL). This post hoc analysis aimed to assess the relationship between pruritus relief and QoL. METHODS: Data from phase 3 trials [(NCT03422653, NCT03636269 grouped), and NCT03998163] of the novel antipruritic difelikefalin (N = 914) were used to assess the relationship between reductions in pruritus intensity at Week 12 (24-h Worst Itching Intensity Numeric Rating Scale; WI-NRS), perceived improvement in itch (Patient Global Impression of Change, PGI-C) and pruritus-related QoL (Skindex-10 questionnaire). RESULTS: Patients receiving difelikefalin had greater improvements in Skindex-10 total scores than those receiving placebo [LS mean treatment difference -3.4; 95% confidence interval (CI) -5.5, -1.3; P = .002] and greater improvements across Skindex-10 domains (disease, mood and social functioning) at Week 12. In patients receiving difelikefalin, those with clinically meaningful improvements in pruritus (≥3-point reduction in WI-NRS score) at Week 12 had a greater improvement in Skindex-10 total score (mean difference 14.2; 95% CI 11.0, 17.3; P

Dialysis has been the dominant treatment regimen in end-stage kidney disease as a means to remove uremic waste products and to maintain electrolyte, acid base, and fluid balance. However, given that dialysis may not always provide a survival benefit nor improved quality of life in certain subpopulations, there is growing recognition of the need for conservative and preservative management as an alternative treatment strategy for advanced chronic kidney disease (CKD). Personalized nutritional management tailored to patients sociodemographics, social needs, psychological status, health literacy level, and preferences is a key component of conservative and preservative care, as well as in the management of patients transitioning from non-dialysis dependent CKD to dialysis. In this review, we discuss the nutritional and metabolic alterations that ensue in CKD; the rationale for low-protein diets in the conservative and preservative management of advanced CKD; the role of plant-based diets in kidney health; emerging data on dietary potassium and sodium intake on CKD outcomes; and the practical implementation of dietary interventions in advanced kidney disease.

BACKGROUND: We examined the real-world comparative safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. other newer anti-glycemic medications (dipeptidyl peptidase-4 inhibitors [DPP4i], glucagon-like peptide-1 receptor agonists [GLP1a]) in patients with and without chronic kidney disease (CKD). METHODS: Among US Veterans with diabetes receiving care from the Veterans Affairs (VA) healthcare system over 2004-19, we identified incident users of SGLT2i vs. DPP4i vs. GLP1a monotherapy. In analyses stratified by CKD status, defined by estimated glomerular filtration rate and albuminuria, we examined associations of SGLT2i vs. DPP4i vs. GLP1a use with risk of infection-related (primary outcome) and genitourinary infection hospitalizations (secondary outcome) using multivariable Cox models. FINDINGS: Among 92,269 patients who met eligibility criteria, 52% did not have CKD, whereas 48% had CKD. In the overall and non-CKD cohorts, compared to DPP4i use, SGLT2i use was associated with lower infection-related hospitalization risk (HRs [95% CIs] 0.74 [0.67-0.81] and 0.77 [0.67, 0.88], respectively), whereas GLP1a use demonstrated comparable risk. However, in the CKD cohort SGLT2i and GLP1a use were each associated with lower risk (HRs [95% CIs] 0.70 [0.61, 0.81] and 0.91 [0.84, 0.99], respectively). Propensity score-matched analyses showed similar findings in the non-CKD and CKD cohorts. In the overall, non-CKD, and CKD cohorts, SGLT2i use was associated with lower genitourinary infection hospitalization risk whereas GLP1a use showed comparable risk vs. DPP4i use. INTERPRETATION: In a national cohort of Veterans with diabetes, compared with DPP4i use, SGLT2i use was associated with lower infection-related and genitourinary infection hospitalization risk. FUNDING: VA Health Services Research and Development, USA.

Individuals afflicted with advanced kidney dysfunction who require dialysis for medical management exhibit different degrees of native kidney function, called residual kidney function (RKF), ranging from nil to appreciable levels. The primary focus of this manuscript is to delve into the concept of RKF, a pivotal yet under-represented topic in nephrology. To begin, we unpack the definition and intrinsic nature of RKF. We then juxtapose the efficiency of RKF against that of hemodialysis in preserving homeostatic equilibrium and facilitating physiological functions. Given the complex interplay of RKF and overall patient health, we shed light on the extent of its influence on patient outcomes, particularly in those living with advanced kidney dysfunction and on dialysis. This manuscript subsequently presents methodologies and measures to assess RKF, concluding with the potential benefits of targeted interventions aimed at preserving RKF.

BACKGROUND: Poor sleep quality is associated with higher mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis (HD). This post hoc analysis of the Phase 3 difelikefalin studies (Study 3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in individuals with CKD-aP improved sleep quality. METHODS: Itch intensity was assessed in patients undergoing HD who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1 and -2) or placebo (N = 425, KALM-1 and -2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D Itch Scale (5-D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS). RESULTS: Greater improvements in sleep quality were observed in patients with ≥3-point versus

BACKGROUND: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care. METHODS: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment. RESULTS: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up). CONCLUSIONS: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.

INTRODUCTION: Information on whether race and ethnicity are associated with a greater risk of recurrent hyperkalemia is limited. The aim of this study was to examine the association between race or ethnicity and recurrent hyperkalemia in a population of US veterans. METHODS: This retrospective study used the US Veterans Affairs database to identify adults (aged ≥18 years) with at least one serum potassium measurement during the study period who ever experienced hyperkalemia (serum potassium > 5.0 mmol/L). The proportion of patients with hyperkalemia recurrence (≥1 subsequent event) within one year was determined for different race and ethnicity groups. The association between patient race and ethnicity and the risk of hyperkalemia recurrence within one year after the index hyperkalemia event was analyzed using competing risk regression. RESULTS: Among a total of 1,493,539 veterans with incident hyperkalemia (median age (interquartile range): 61.0 years (54.0, 71.0)), recurrence within one year occurred in 19.1% of Black, 16.0% of Native Hawaiian/other Pacific Islander, 15.1% of White, 14.9% of American Indian/Alaska Native, and 13.1% of Asian patient groups. Recurrent hyperkalemia occurred in 18.1% of Hispanic and 15.6% of non-Hispanic patient groups. In a fully-adjusted regression model, recurrent hyperkalemia risk was significantly higher in Black versus White patient groups (subhazard ratio (sHR), 1.17; 95% confidence interval (CI), 1.16-1.19; p< 0.0001) and in Hispanic versus non-Hispanic patient groups (sHR, 1.30; 95% CI, 1.28-1.33; p< 0.0001). DISCUSSION/CONCLUSION: Among US veterans with incident hyperkalemia, the risk of recurrent hyperkalemia was higher in Black and Hispanic patient groups. This information may be useful for health system screenings to risk stratify patient groups and both guide the frequency of serum potassium monitoring and better understand the root causes of group differences.

Vaccinating patients receiving dialysis may prevent morbidity and mortality in this vulnerable population. The National Forum of End-Stage Renal Disease Networks (the Forum) published a revised vaccination toolkit in 2021 to update evidence and recommendations on vaccination for patients receiving dialysis. Significant changes in the last 10 years include more data supporting the use of a high-dose influenza vaccine, the introduction of the Heplisav-B vaccine for hepatitis B, and changes in pneumococcal vaccines, including the approval of the PCV15 and PCV20 to replace the PCV13 and PPSV23 vaccines. Additional key items include the introduction of vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19), and a new vaccine to prevent respiratory syncytial virus disease. Historically, influenza and pneumococcal vaccinations were routinely administered by dialysis facilities, and because of possible risks of hematogenous spread of hepatitis B, dialysis providers often have detailed hepatitis B vaccine protocols. In March 2021, COVID-19 vaccines were made available for dialysis facilities to administer, although with the end of the public health emergency, vaccine policies by dialysis facilities against COVID-19 remains uncertain. The respiratory syncytial virus vaccine was authorized in 2023, and how dialysis facilities will approach this vaccine also remains uncertain. This review summarizes the Forums vaccination toolkit and discusses the role of the dialysis facility in vaccinating patients to reduce the risk of severe infections.

BACKGROUND: There are knowledge gaps about factors associated with acute kidney injury (AKI) among COVID-19 patients. To examine AKI predictors among COVID-19 patients, a retrospective longitudinal cohort study was conducted between January 2020 and December 2022. Logistic regression models were used to examine predictors of AKI, and survival analysis was performed to examine mortality in COVID-19 patients. RESULTS: A total of 742,799 veterans diagnosed with COVID-19 were included and 95,573 were hospitalized within 60 days following COVID-19 diagnosis. A total of 45,754 developed AKI and 28,573 AKI patients were hospitalized. Use of vasopressors (OR = 14.73; 95% CL 13.96-15.53), history of AKI (OR = 2.22; CL 2.15-2.29), male gender (OR = 1.90; CL 1.75-2.05), Black race (OR = 1.62; CL 1.57-1.65), and age 65+ (OR = 1.57; CL 1.50-1.63) were associated with AKI. Patients who were vaccinated twice and boosted were least likely to develop AKI (OR = 0.51; CL 0.49-0.53) compared to unvaccinated COVID-19 patients. Patients receiving two doses (OR = 0.77; CL = 0.72-0.81), or a single dose (OR = 0.88; CL = 0.81-0.95) were also less likely to develop AKI compared to the unvaccinated. AKI patients exhibited four times higher mortality compared to those without AKI (HR = 4.35; CL 4.23-4.50). Vaccinated and boosted patients had the lowest mortality risk compared to the unvaccinated (HR = 0.30; CL 0.28-0.31). CONCLUSION: Use of vasopressors, being unvaccinated, older age, male gender, and Black race were associated with post COVID-19 AKI. Whether COVID-19 vaccination, including boosters, decreases the risk of developing AKI warrants additional studies.

OBJECTIVE: To examine the relationship between thyroid status and incident kidney dysfunction/chronic kidney disease (CKD) progression. PATIENTS AND METHODS: We examined incident thyroid status, ascertained by serum thyrotropin (TSH) levels measured from January 1, 2007, through December 31, 2018, among 4,152,830 patients from the Optum Labs Data Warehouse, containing deidentified retrospective administrative claims data from a large national health insurance plan and electronic health record data from a nationwide network of provider groups. Associations of thyroid status, categorized as hypothyroidism, euthyroidism, or hyperthyroidism (TSH levels >5.0, 0.5-5.0, and 5.0-10.0, >10.0-20.0, and >20.0 mIU/L, respectively) were associated with increasingly higher risk of the composite end point (reference: TSH level, 0.5 to

Ketogenic metabolic therapy (KMT) is a medical nutrition therapy to address certain health and disease conditions. It is increasingly used for many non-communicable diseases that are rooted in abnormal metabolic health. Since chronic kidney disease (CKD) is commonly caused by overnutrition leading to hyperglycemia, insulin resistance and diabetes mellitus, the carbohydrate restriction inherent in KMT may offer a therapeutic option. Numerous studies have found that various forms of KMT are safe for individuals with CKD and may lead to improvement of renal function. This is in contrast to the current standard pharmacological approach to CKD that only slows the relentless progression towards renal failure. Kidney care providers, including physicians and dietitians, are usually not aware of non-standard dietary interventions, including KMT, and often criticize KMT due to common misconceptions and uncertainty about the underlying science, including the common misconception that KMT must involve high protein or meat consumption. This review article discusses the rationales for using KMT, including plant-dominant KMT, for treatment of CKD, clarifies common misconceptions, summarizes the results of clinical studies and discusses why KMT is emerging as an effective medical nutrition therapy (MNT) to consider for patients with kidney disease. KMT, including its plant-dominant versions, can expand a practitioners kidney health toolbox and will likely become a first-line therapy for CKD in certain CKD-associated conditions such as obesity, metabolic syndrome and polycystic kidney disease.

There is rising interest globally with respect to the health implications of vegetarian or plant-based diets. A growing body of evidence has demonstrated that higher consumption of plant-based foods and the nutrients found in vegetarian and plant-based diets are associated with numerous health benefits, including improved blood pressure, glycemic control, lipid levels, body mass index, and acid-base parameters. Furthermore, there has been increasing recognition that vegetarian and plant-based diets may have potential salutary benefits in preventing the development and progression of chronic kidney disease (CKD). While increasing evidence shows that vegetarian and plant-based diets have nephroprotective effects, there remains some degree of uncertainty about their nutritional adequacy and safety in CKD (with respect to protein-energy wasting, hyperkalemia, etc.). In this review, we focus on the potential roles of and existing data on the efficacy/effectiveness and safety of various vegetarian and plant-based diets in CKD, as well as their practical application in CKD management.

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis.

Most patients receiving dialysis rely on dietary restriction and phosphate binders to minimize the risk of hyperphosphatemia, which is associated with increased mortality. However, dietary restriction is difficult because of hidden phosphate additives in processed foods and medications. Restriction of dietary phosphate sources such as protein may increase the risk of malnutrition. Phosphate binders, the only pharmacologic option for phosphate management since aluminum salts were introduced several decades ago, are often insufficient for binding the 1400-2500 mg of phosphate potentially consumed daily. Over the last decade, serum phosphate levels in the United States have risen, and >69% of patients receiving dialysis exhibited a most recent phosphate level >4.5 mg/dl (above the normal range), indicating an urgent need for new, more effective therapies to manage phosphate burden. Novel, nonbinder therapies such as transcellular and paracellular phosphate absorption inhibitors may be used for phosphate management, and future studies should examine whether they allow fewer dietary restrictions for patients receiving dialysis, potentially improving patient quality of life and nutritional status. It is imperative that we collaborate to move beyond the restrictive approaches available today and provide patients and clinicians with an array of strategies so that they may choose the most appropriate patient-centered therapy.

BackgroundOral iron is the predominant route of iron replacement (IRT) but its benefits and safety are unclear in patients with chronic kidney disease (CKD).MethodsWe 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

INTRODUCTION: The survival benefit of residual kidney function (RKF) in patients on hemodialysis is presumably due to enhanced fluid management and solute clearance. However, data are lacking on the association of renal urea clearance (CLurea) with specific causes of death. METHODS: We conducted a longitudinal cohort study of 39,623 adults initiating thrice-weekly in-center hemodialysis from 2007 to 2011 and had data on renal CLurea and urine volume. Multivariable cause-specific proportional hazards model was used to examine the associations between baseline RKF and cause-specific mortality, including sudden cardiac death (SCD), non-SCD cardiovascular death (CVD), and non-CVD. Restricted cubic splines were fitted for change in RKF over 6 months after initiating hemodialysis. RESULTS: Among 39,623 patients with data on baseline renal CLurea and urine volume, there was a significant trend toward a higher mortality risk across lower RKF levels, irrespective of cause of death in a case-mix adjustment model (Ptrend < 0.05). Adjustment for ultrafiltration rate (UFR) slightly attenuated the association between low renal CLurea and high cause-specific mortality, whereas adjustment for highest potassium did not have substantial effect. Among 12,169 patients with data on change in RKF, a 6-month decline in renal CLurea showed graded associations with SCD, non-SCD CVD, and non-CVD risk, whereas the graded associations between faster 6-month decline in urine output and higher death risk were clear only for SCD and non-CVD. CONCLUSION: Lower RKF and loss of RKF were associated with higher cause-specific mortality among patients initiating thrice-weekly in-center hemodialysis.

Resumo A elevada carga da doença renal, disparidades globais no cuidado renal e desfechos ruins da insuficiência renal impõem uma sobrecarga crescente aos indivíduos afetados e suas famílias, cuidadores e a própria comunidade geral. Educação em saúde é o grau em que indivíduos e organizações têm, ou que igualmente permitem que indivíduos tenham, capacidade de encontrar, compreender e utilizar informações e serviços para tomar decisões e ações conscientes relacionadas à saúde para si e outros. Mais do que enxergar educação em saúde como um problema dos pacientes, a melhoria dessa educação depende principalmente da comunicação e educação efetiva dos profissionais em parceria com aqueles que apresentam doença renal. Para formuladores de políticas renais, educação em saúde é pré-requisito para que organizações migrem para uma cultura que coloque a pessoa no centro dos cuidados. A crescente capacidade e acesso à tecnologia oferecem novas oportunidades para melhorar educação e conscientização sobre doença renal para todas as partes interessadas. Avanços nas telecomunicações, incluindo redes sociais, podem ajudar a melhorar a educação de pessoas e provedores. O Dia Mundial do Rim declara 2022 como o ano da "Saúde dos Rins para Todos" promovendo trabalho em equipe global no avanço de estratégias para preencher a lacuna na educação e conhecimento em saúde renal. Organizações renais devem trabalhar para mudar a narrativa da educação em saúde como um problema de pacientes, para sendo responsabilidade dos profissionais e formuladores de políticas. Ao engajar-se e apoiar formulação de políticas centradas na saúde renal, planejamento de saúde comunitária e abordagens de educação em saúde para todos, comunidades renais esforçam-se para prevenir doenças renais e permitir viver bem com elas.

In chronic kidney disease (CKD), metabolic derangements resulting from the interplay between decreasing renal excretory capacity and impaired gut function contribute to accelerating disease progression and enhancing the risk of complications. To protect residual kidney function and improve quality of life in conservatively managed predialysis CKD patients, current guidelines recommend protein-restricted diets supplemented with essential amino acids (EAAs) and their ketoanalogues (KAs). In clinical studies, such an approach improved nitrogen balance and other secondary metabolic disturbances, translating to clinical benefits, mainly the delayed initiation of dialysis. There is also increasing evidence that a protein-restricted diet supplemented with KAs slows down disease progression. In the present review article, recent insights into the role of KA/EAA-supplemented protein-restricted diets in delaying CKD progression are summarized, and possible mechanistic underpinnings, such as protein carbamylation and gut dysbiosis, are elucidated. Emerging evidence suggests that lowering urea levels may reduce protein carbamylation, which might contribute to decreased morbidity and mortality. Protein restriction, alone or in combination with KA/EAA supplementation, modulates gut dysbiosis and decreases the generation of gut-derived uremic toxins associated, e.g., with cardiovascular disease, inflammation, protein energy wasting, and disease progression. Future studies are warranted to assess the effects on the gut microbiome, the generation of uremic toxins, as well as markers of carbamylation.

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

Epigenetic mechanisms are implicated in transcriptional programs driving chronic kidney disease (CKD). Apabetalone is an orally available inhibitor of bromodomain and extraterminal (BET) proteins, which are epigenetic readers that modulate gene expression. In the phase 3 BETonMACE trial, apabetalone reduced risk of major adverse cardiac events (MACE) by 50% in the CKD subpopulation, indicating favorable effects along the kidney-heart axis. Activation of human renal mesangial cells (HRMCs) to a contractile phenotype that overproduces extracellular matrix (ECM) and inflammatory cytokines, and promotes calcification, frequently accompanies CKD to drive pathology. Here, we show apabetalone downregulated HRMC activation with TGF-β1 stimulation by suppressing TGF-β1-induced α-smooth muscle actin (α-SMA) expression, α-SMA assembly into stress fibers, enhanced contraction, collagen overproduction, and expression of key drivers of fibrosis, inflammation, or calcification including thrombospondin, fibronectin, periostin, SPARC, interleukin 6, and alkaline phosphatase. Lipopolysaccharide-stimulated expression of inflammatory genes IL6, IL1B, and PTGS2 was also suppressed. Transcriptomics confirmed apabetalone affected gene sets of ECM remodeling and integrins. Clinical translation of in vitro results was indicated in CKD patients where a single dose of apabetalone reduced plasma levels of key pro-fibrotic and inflammatory markers, and indicated inhibition of TGF-β1 signaling. While plasma proteins cannot be traced to the kidney alone, anti-fibrotic and anti-inflammatory effects of apabetalone identified in this study are consistent with the observed decrease in cardiovascular risk in CKD patients.

AimsIron 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 resultsThis 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 60 mL/min/1.73 m2 vs.

BackgroundThe 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.MethodsEmergency 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).DiscussionThe findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia.Trial registrationClinicalTrials.gov Identifier: NCT04585542 . Registered 14 October 2020.

ObjectivesThis double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19.MethodsCOVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory).ResultsIn all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment.ConclusionERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.

Background: The current social and legal landscape is likely to foster the medicinal and recreational use of cannabis. Synthetic cannabinoid use is associated with acute kidney injury (AKI) in case reports; however, the association between natural cannabis use and AKI risk in patients with advanced chronic kidney disease (CKD) is unknown. Materials and Methods: From a nationally representative cohort of 102,477 U.S. veterans transitioning to dialysis between 2007 and 2015, we identified 2215 patients with advanced CKD who had undergone urine toxicology (UTOX) tests within a year before dialysis initiation and had inpatient serial serum creatinine levels measured within 7 days after their UTOX test. The exposure of interest was cannabis use compared with no use as ascertained by the UTOX test. We examined the association of this exposure with AKI using logistic regression and inverse probability of treatment weighting with extensive adjustment for potential confounders. Results: The mean age of the overall cohort was 61 years; 97% were males, 51% were African Americans, 97% had hypertension, 76% had hyperlipidemia, and 75% were diabetic. AKI occurred in 56% of the cohort, and in multivariable-adjusted analysis, cannabis use (when compared with no substance use) was not associated with significantly higher odds of AKI (odds ratio 0.85, 95% confidence interval 0.38-1.87; p=0.7). These results were robust to various sensitivity analyses. Conclusions: In this observational study examining patients with advanced CKD, cannabis use was not associated with AKI risk. Additional studies are needed to characterize the impact of cannabis use on risk of kidney disease and injury.

Since the breakthrough of kidney replacement therapy, increases in life expectancy for patients with end-stage kidney disease have been limited. However, patients have become increasingly vocal that, although mortality and life expectancy matter to them, the quality of their life, and particularly the relief of symptoms associated with their treatment, are in many cases more important. The majority of dialysis-associated symptoms and adverse effects do not currently have any approved treatments in this patient population, with the few treatments that are available used off-label, frequently without proven efficacy, yet still potentially adding further adverse effects to patients' current symptom burden. This article will illustrate how understanding the pathophysiology of a single, particularly burdensome symptom of dialysis (chronic kidney disease-associated pruritus) resulted in the design, development and regulatory approval of a treatment for that symptom. The pathway described here can be applied to other symptoms associated with dialysis, meaning that if we cannot add years to patients' lives, we can at least add life to their remaining years.

INTRODUCTION: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. METHODS: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. RESULTS: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR

BACKGROUND: Several studies suggest that Asian-American and Native Hawaiian and Other Pacific Islander (NHOPI) racial/ethnic groups have a heightened risk of chronic kidney disease (CKD), but provide limited inference due to the aggregation of these groups into a single racial/ethnic category. We thus examined the association of granularly defined racial/ethnic groups with specific CKD indicators among a diverse group of participants from the National Kidney Foundation of Hawaiis Kidney Early Detection Screening (KEDS) Program. METHODS: Among 1,243 participants enrolled in 19 KEDS screening events over 2006-2009, we examined the association between Asian-American and NHOPI groups and specific CKD indicators, defined as self-reported CKD, microalbuminuria, and macroalbuminuria, using multivariable logistic regression. We then examined associations of race/ethnicity with various CKD risk factors. RESULTS: The most predominant racial/ethnic groups were White (22.0%), Multiracial (18.9%), Japanese (19.2%), Filipino (13.4%), NHOPI (8.4%), and Chinese (4.5%) participants. NHOPI and Chinese participants had a higher risk of microalbuminuria (adjusted ORs [aORs] [95% CIs] 2.48 [1.25-4.91] and 2.37 [1.07-5.27], respectively), while point estimates for all other minority groups suggested higher risk (reference: Whites). NHOPI participants also had a higher risk of macroalbuminuria and self-reported CKD. While most minorities had a higher risk of diabetes and hypertension, NHOPI and Multiracial participants had a higher risk of obesity, whereas the East Asian groups had a lower risk. CONCLUSIONS: In this community-based cohort, compared with Whites, Asian-Americans had a higher risk of early CKD indicators, whereas NHOPIs had a higher risk of more severe CKD indicators. Further studies are needed to elucidate the distinct pathways leading to CKD across diverse racial/ethnic groups in Hawaii.

BACKGROUND: Chronic microinflammation contributes to the progression of chronic kidney disease (CKD). Aspirin (ASA) has been used to treat inflammation for centuries. The effects of long-term low-dose ASA on CKD progression are unclear. METHODS: We examined the association of long-term use of newly initiated low-dose ASA (50-200 mg/day) with all-cause mortality using Cox proportional hazard models; with cardiovascular/cerebrovascular (CV) mortality and with end stage kidney disease (ESKD) using Fine and Gray competing risk regression models; with progression of CKD defined as patients eGFR slopes steeper than -5 mL/min/1.73m2/year using logistic regression models in a nationwide cohort of US Veterans with incident CKD. Among 831,963 patients, we identified 385,457 who either initiated ASA (N = 21,228) within 1 year of CKD diagnosis or never received ASA (N = 364,229). We used propensity score matching to account for differences in key characteristics, yielding 29,480 patients (14,740 in each group). RESULTS: In the matched cohort, over a 4.9-year median follow-up period, 11,846 (40.2%) patients (6,017 vs. 5,829 ASA users vs. non-users) died with 25.8% CV deaths, and 934 (3.2%) patients (476 vs. 458) reached ESKD. ASA users had a higher risk of faster decline of kidney functions, i.e., steeper slopes (OR 1.30 [95%CI: 1.18, 1.44], p

PURPOSE OF REVIEW: There has been a decline in living kidney donation over the last two decades. Donors from low-income families or racial/ethnic minorities face greater disproportionate geographic, financial, and logistical barriers to completing lengthy and complex evaluations. This has contributed to the decreased proportion of these subgroups. The authors view telemedicine as a potential solution to this problem. RECENT FINDINGS: Since the initial decline of donors in 2005, biologically related donors have experienced a lack of growth across race/ethnicity. Conversely, unrelated donors have emerged as the majority of donors in recent years across race/ethnicity, except for unrelated black donors. Disparities in access to living kidney donation persist. Telemedicine using live-video visits can overcome barriers to access transplant centers and facilitate care coordination. In a U.S. survey, nephrologists, surgeons, coordinators, social workers, and psychologists/psychologists across transplant centers are favorably disposed to use telemedicine for donor evaluation/follow-up beyond the coronavirus disease 2019 pandemic. However, with the waning of relaxed telemedicine regulations under the Public Health Emergency, providers perceive payor policy and out-of-state licensing as major factors hindering telemedicine growth prospects. SUMMARY: Permanent federal and state policies that support telemedicine services for living kidney donation can enhance access to transplant centers and help overcome barriers to donor evaluation.

National strategies for addressing chronic kidney disease (CKD) are crucial to improving kidney health. We sought to describe country-level variations in non-communicable disease (NCD) strategies and CKD-specific policies across different regions and income levels worldwide. The International Society of Nephrology Global Kidney Health Atlas (GKHA) was a multinational cross-sectional survey conducted between July and October 2018. Responses from key opinion leaders in each country regarding national NCD strategies, the presence and scope of CKD-specific policies, and government recognition of CKD as a health priority were described overall and according to region and income level. 160 countries participated in the GKHA survey, comprising 97.8% of the worlds population. Seventy-four (47%) countries had an established national NCD strategy, and 53 (34%) countries reported the existence of CKD-specific policies, with substantial variation across regions and income levels. Where CKD-specific policies existed, non-dialysis CKD care was variably addressed. 79 (51%) countries identified government recognition of CKD as a health priority. Low- and low-middle income countries were less likely to have strategies and policies for addressing CKD and have governments which recognise it as a health priority. The existence of CKD-specific policies, and a national NCD strategy more broadly, varied substantially across different regions around the world but was overall suboptimal, with major discrepancies between the burden of CKD in many countries and governmental recognition of CKD as a health priority. Greater recognition of CKD within national health policy is critical to improving kidney healthcare globally.

Purpose of reviewGlomerular 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 findingsThe 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.SummaryAlthough 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.

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−

Phosphorus is an essential micromineral with a key role in cellular metabolism and tissue structure. Serum phosphorus is maintained in a homeostatic range by the intestines, bones, and kidneys. This process is coordinated by the endocrine system through the highly integrated actions of several hormones, including FGF23, PTH, Klotho, and 1,25D. The excretion kinetics of the kidney after diet phosphorus load or the serum phosphorus kinetics during hemodialysis support that there is a "pool" for temporary phosphorus storage, leading to the maintenance of stable serum phosphorus levels. Phosphorus overload refers to a state where the phosphorus load is higher than is physiologically necessary. It can be caused by a persistently high-phosphorus diet, renal function decline, bone disease, insufficient dialysis, and inappropriate medications, and includes but is not limited to hyperphosphatemia. Serum phosphorus is still the most commonly used indicator of phosphorus overload. Trending phosphorus levels to see if they are chronically elevated is recommended instead of a single test when judging phosphorus overload. Future studies are needed to validate the prognostic role of a new marker or markers of phosphorus overload.

ObjectivesSerum 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.MethodsThis 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:

BackgroundEmerging data suggest that sodium disarrays including hyponatremia are potential risk factors for infection ensuing from impairments in host immunity, which may be exacerbated by coexisting conditions (i.e. mucosal membrane and cellular edema leading to breakdown of microbial barrier function). While dysnatremia and infection-related mortality are common in dialysis patients, little is known about the association between serum sodium levels and the risk of bloodstream infection in this population.MethodsAmong 823 dialysis patients from the national Biospecimen Registry Grant Program who underwent serum sodium testing over the period January 2008-December 2014, we examined the relationship between baseline serum sodium levels and subsequent rate of bloodstream infection. Bloodstream infection events were directly ascertained using laboratory blood culture data. Associations between serum sodium level and the incidence of bloodstream infection were estimated using expanded case mix-adjusted Poisson regression models.ResultsIn the overall cohort, ∼10% of all patients experienced one or more bloodstream infection events during the follow-up period. Patients with both lower sodium levels

Traditionally, diets for kidney disease were low in potassium. This recommendation was based on outdated research and often wrong assumptions that do not reflect current evidence. In fact, studies conducted over the past decades show patients with CKD, including kidney failure, do not benefit from the restriction of plant foods relative to control. Generally, dietary potassium does not correlate with serum potassium, and we posit that this is due to the effects of fiber on colonic potassium absorption, the alkalinizing effect of fruits and vegetables on metabolic acidosis, and the bioavailability of dietary potassium in plant foods. Also, consumption of plant foods may provide pleiotropic benefits to patients with CKD. Emerging dietary recommendations for kidney health should be devoid of dietary potassium restrictions from plant foods so that patient-centered kidney recipes can be encouraged and promoted.

BackgroundHyperkalemia is associated with kidney function decline in patients with non-dialysis dependent chronic kidney disease, but this relationship is unclear for residual kidney function (RKF) among hemodialysis (HD) patients.MethodsWe conducted a retrospective cohort study of 6655 patients, who started HD January 2007 and December 2011 and who had data on renal urea clearance (KRU). Serum potassium levels were stratified into four groups (i.e. ≤4.0, >4.0 to ≤4.5, >4.5 to ≤5.0 and >5.0 mEq/L) and 1-year KRU slope for each group was estimated by a linear mixed-effects model.ResultsHigher serum potassium was associated with a greater decline in KRU, and the greatest decrease in KRU (-0.20, 95% confidence interval -0.50 to -0.06) was observed for baseline potassium >5.0 mEq/L in the fully adjusted model. Mediation analysis showed that KRU slope mediated 1.78% of the association between serum potassium and mortality.ConclusionsHyperkalemia is associated with a decline in RKF amongst incident HD patients. These findings may have important clinical implications in the management of hyperkalemia in advanced CKD if confirmed in additional clinical trials.

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