Clinical practice guideline for the management of lipids in adults with diabetic kidney disease: abbreviated summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2024.

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD.

The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease.

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.

Evaluating the effect of a digital health intervention to enhance physical activity in people with chronic kidney disease (Kidney BEAM): a multicentre, randomised controlled trial in the UK.

BACKGROUND: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life. METHODS: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933. FINDINGS: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001). INTERPRETATION: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions. FUNDING: Kidney Research UK.

Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis.

BACKGROUND: Poor sleep quality is associated with increased 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. This post hoc analysis of Phase 3 studies (3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in CKD-aP improved sleep quality. METHODS: Itch intensity was assessed in patients undergoing haemodialysis, 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/-2) or placebo (N = 425, KALM-1/-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 (5­D 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 < 3-point WI-NRS improvement using SQ-NRS in Study 3105 (mean [95% confidence interval]: -5.2 [-5.6, -4.8] vs -1.5 [-2.0, -1.0]) and 5-D SDQ in KALM-1/-2 (-1.8 [-2.1, -1.6] vs -0.8 [-1.1, -0.4]). SQ-NRS and WI-NRS scores correlated strongly at baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM­1/­2. CONCLUSIONS: In patients undergoing haemodialysis with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

Assessment and management of chronic kidney disease in people living with obesity.

Obesity and chronic kidney disease (CKD) are common and frequently coexisting medical conditions. Already well known to be a risk factor for type 2 diabetes mellitus (T2DM), ischaemic heart disease, stroke, hypertension, malignancy and premature death, obesity also predisposes to CKD. Elevated weight leads to declining renal function through several mechanisms, including established pathways via metabolic syndrome, hypertension and T2DM, but also through relatively recently understood glomerulosclerosis, directly related to obesity. Compared with non-obese comparators, people living with obesity and established CKD develop faster decline in glomerular filtration, progression to end-stage renal disease (ESRD) and death. Importantly, treatment of obesity can influence these crucial renal outcomes and significantly improve quality of life. Declining renal function also impacts the medical and surgical treatment options available to treat patients with overweight and obesity. In this article, we briefly outline the epidemiology of obesity and renal disease and review the pathological interactions between these diseases before focusing on considerations for assessment and evidence-based treatments for obesity and renal disease.

Gut Dysbiosis in Experimental Kidney Disease: A Meta-Analysis of Rodent Repository Data.

SIGNIFICANCE STATEMENT: Alterations in gut microbiota contribute to the pathophysiology of a diverse range of diseases, leading to suggestions that chronic uremia may cause intestinal dysbiosis that contributes to the pathophysiology of CKD. Various small, single-cohort rodent studies have supported this hypothesis. In this meta-analysis of publicly available repository data from studies of models of kidney disease in rodents, cohort variation far outweighed any effect of experimental kidney disease on the gut microbiota. No reproducible changes in animals with kidney disease were seen across all cohorts, although a few trends observed in most experiments may be attributable to kidney disease. The findings suggest that rodent studies do not provide evidence for the existence of "uremic dysbiosis" and that single-cohort studies are unsuitable for producing generalizable results in microbiome research. BACKGROUND: Rodent studies have popularized the notion that uremia may induce pathological changes in the gut microbiota that contribute to kidney disease progression. Although single-cohort rodent studies have yielded insights into host-microbiota relationships in various disease processes, their relevance is limited by cohort and other effects. We previously reported finding metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. METHODS: To attempt to identify common microbial signatures that transcend batch variability and that may be attributed to the effect of kidney disease, we downloaded all data describing the molecular characterization of the gut microbiota in rodents with and without experimental kidney disease from two online repositories comprising 127 rodents across ten experimental cohorts. We reanalyzed these data using the DADA2 and Phyloseq packages in R, a statistical computing and graphics system, and analyzed data both in a combined dataset of all samples and at the level of individual experimental cohorts. RESULTS: Cohort effects accounted for 69% of total sample variance ( P <0.001), substantially outweighing the effect of kidney disease (1.9% of variance, P =0.026). We found no universal trends in microbial population dynamics in animals with kidney disease, but observed some differences (increased alpha diversity, a measure of within-sample bacterial diversity; relative decreases in Lachnospiraceae and Lactobacillus ; and increases in some Clostridia and opportunistic taxa) in many cohorts that might represent effects of kidney disease on the gut microbiota . CONCLUSIONS: These findings suggest that current evidence that kidney disease causes reproducible patterns of dysbiosis is inadequate. We advocate meta-analysis of repository data as a way of identifying broad themes that transcend experimental variation.

The management of dialysis access thrombosis during the COVID-19 pandemic.

BACKGROUND: Maintaining patent access is essential for haemodialysis dependent end stage renal failure patients. The COVID-19 pandemic has significantly affected surgical and interventional radiology services worldwide. We aimed to review the impact COVID-19 has caused to the management of acute dialysis access thrombosis. METHODS: We conducted a single centre retrospective review of outcomes of patients with arteriovenous fistula and arteriovenous graft thrombosis between March and May 2020, which coincided with the first peak of the COVID-19 pandemic in London, and a similar period in the previous year, March-May 2019. Outcomes in both cohorts of patients were compared, including attempts at salvage, salvage success, 1-month patency rates after salvage and subsequent surgery on the same access. We also analysed the use of tunnelled haemodialysis lines (THL), either due to failed salvage attempts or when salvage was not attempted. RESULTS: There was a similar incidence of access thrombosis in both periods (26 cases in 2019, 38 in 2020). There were 601 patients dialysing via an arteriovenous fistula or graft in 2019, and 568 patients in 2020. Access salvage, when attempted, had similar success rates and 1-month patency (salvage success 74% vs 80%, p = 0.39; 1-month patency 55% vs 62%, p = 0.69). The proportion of patients where access salvage was not attempted and a THL inserted was significantly higher in 2020 compared to 2019 (32% vs 4%, p = 0.007). There were more patients who subsequently had surgery to salvage or revise the same access in 2019 compared to 2020 (62% vs 13%, p < 0.001). CONCLUSIONS: During the peak of the COVID-19 pandemic, there were fewer attempts at access salvage. This was a conscious decision due to increased pressure on the healthcare system, access to emergency interventional radiology or operative theatres and the perceived risk/benefit ratio of access salvage. The long-term effects of this change in practice remain unknown.