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Background: Poor glycemic control in diabetic chronic kidney disease (CKD) patients on maintenance hemodialysis is of great challenge, resulting in increased risk of morbidity and mortality. This study aimed to determine the prevalence and determinants of poor glycemic control among diabetic CKD patients on maintenance hemodialysis., Methodology: A cross-sectional study was conducted in 12 dialysis centers located in four regions of Tanzania from March to June 2023. The study population was diabetic CKD patients above 18 years on maintenance hemodialysis for three months or more. A consecutive sampling technique was used for patient recruitment, and a semi-structured questionnaire was used to collect data. The primary outcome was poor glycemic control were considered when glycated hemoglobin (HbA1c) levels were <  6% or > 8%. Statistical Package for Social Sciences (SPSS) version 23 was used for data analysis. Univariate and multivariable regression models were used to evaluate the determinants of poor glycemic control. A p-value < 0.05 was considered statistically significant., Results: Out of 233 enrolled patients, the overall prevalence of poor glycemic control was 55.4%, whereby 27.0% had HbA1c < 6% and 28.33% had HbA1c > 8%. A high risk of HbA1c > 8% was observed among patients who were on antidiabetic medication (2.16 (95% CI: 1.06-4.41) p =  0.035) and those attending dialysis sessions less than 3 times a week (1.59 (95% CI: 1.02-2.48) p =  0.040). The lower risk of HbA1c < 6% was observed in patients dialyzed using glucose-containing dialysates than those dialyzed with glucose-free dialysate (0.57 (95% CI 0.36-0.87) p =  0.020)., Conclusion: The high prevalence of poor glycemic control among diabetic CKD patients, as revealed by this study, has significant implications. Patients on antidiabetic medication and those with less than three dialysis sessions per week are at a high risk of HbA1c > 8%. Conversely, patients dialyzed using glucose-free dialysates are at a high risk of HbA1c < 6%. Glycemic control in diabetic chronic kidney disease (CKD) patients is a great challenge due to altered glucose homeostasis, gluconeogenesis, tubular glucose reabsorption and inaccuracy of glycemic regulation metrics [1]. Furthermore, changed renal pharmacokinetics of antihyperglycemic agents (AHA), uremic milieu, and dialysis therapy also contribute to this challenge [2]. Based on the severe risk of hyperglycemia and hypoglycemia in patients with diabetic end-stage renal disease (ESRD), glycemic control is of paramount importance., Competing Interests: The authors declare that there is no competing interest., (Copyright: © 2025 Mfundo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Combination therapy, involving the use of multiple medications together, is becoming a new standard of care for chronic kidney disease (CKD). For people with CKD, combination therapy offers the promise of preventing kidney failure and reducing the risk of heart problems. This approach is appealing because different drugs target distinct mechanisms involved in CKD progression. For instance, some target immune responses, others reduce kidney inflammation and scarring, while others improve blood pressure within the kidneys. Data from large clinical trials suggest that each treatment works effectively on its own, regardless of other medications people are taking. Combining therapies can also reduce the risk of side effects of individual medications. This review highlights the evidence for combination therapy in CKD, explores how to improve its use, and discusses how future studies may answer remaining questions., Abstract: A range of therapies now exists to reduce the risk of kidney failure and cardiovascular events in people with type 2 diabetes, including renin-angiotensin system blockade, sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists. With multiple clinical trials underway, it is likely that at least some of these therapies-as well as additional agents such as endothelin receptor antagonists-will further demonstrate kidney-protective effects in people with CKD who do not have diabetes in the near future. For conditions such as IgA nephropathy, several therapies have recently been approved or are being evaluated in late phase trials. Thus combination therapy is emerging as a new standard for diabetic and non-diabetic chronic kidney disease (CKD). This approach is supported by randomized data suggesting that each therapeutic class offers independent and additive benefits in diabetic kidney disease, regardless of background therapy. Notably, the reduction in hyperkalaemia and fluid retention with SGLT2 inhibitors may enhance the tolerability and safety of other treatments. In this review, we present the rationale for combination therapy with evidence-based kidney therapies in diabetic and non-diabetic CKD. We also summarize randomized evidence supporting a multi-medicine approach, address safety considerations, review ongoing trials, and propose frameworks for implementing treatments aligned with patient risk to optimize person-centred care and reduce long-term risks of kidney failure and related complications., (© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.)

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonist finerenone and glucagon-like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Diabetes is the commonest cause of end stage kidney disease globally, accounting for almost 40% of new cases requiring renal replacement therapy. Management of diabetes in people with advanced kidney disease on renal replacement therapy is challenging due to some unique aspects of assessment and treatment in this group of patients. Standard glycaemic assessment using glycated haemoglobin may not be valid in such patients due to altered red blood cell turnover or iron/erythropoietin deficiency, leading to changed red blood cell longevity. Therefore, use of continuous glucose monitoring may be beneficial to enable more focussed glycaemic assessment and improved adjustment of therapy. People with advanced kidney disease may be at higher risk of hypoglycaemia due to a number of physiological mechanisms, and in addition, therapeutic options are limited in such patients due to lack of experience or license. Insulin therapy is the basis of treatment of people with diabetes with advanced kidney disease due to many other drugs classes being contraindicated. Targets for glycaemic control should be adjusted according to co-morbidity and frailty, and continuous glucose monitoring should be used in people on dialysis to ensure low risk of hypoglycaemia. Post-transplant diabetes is common amongst people undergoing solid organ transplantation and confers a greater risk of mortality and morbidity in kidney transplant recipients. It should be actively screened for and managed in the post-transplant setting., (© 2024 Diabetes UK.)

Background: Pre-gestational diabetes occurs in approximately 1% of pregnancies in the UK and increases the risk of adverse maternal and fetal outcomes. More women with type 2 than type 1 diabetes are now becoming pregnant and tend to have higher rates of obesity and other multi-morbidities. Chronic kidney disease (CKD) affects approximately 5%-10% of pregnant women with type 1 diabetes and about 2%-3% with type 2 diabetes. Diabetic chronic kidney disease (DCKD) increases the risk of preeclampsia, preterm birth, Caesarean section, small for gestational age (SGA) infant and infant admission to neonatal intensive care unit (NICU), and risks are higher compared to those with diabetes without CKD and those with CKD from other causes. Definitions of CKD in pregnancy are not standardised, and studies are generally small, observational, heterogenous, mainly include women with type 1 diabetes and often predate modern diabetes management such as continuous glucose monitoring and insulin pumps. Therefore, there is a lack of robust data to guide practice and clinical guidelines offer conflicting advice, without precise detail., Aims: We present our approach to caring for women with diabetes and CKD in pregnancy based on available guidelines and clinical experience., Discussion and Conclusion: Our practice is to aim for intensive targets for blood pressure and glycaemic control pre and during pregnancy, lower than suggested in many guidelines. The importance of multidisciplinary team work and patient centred care is emphasised. Using standardised prospective data collection to better understand the prevalence and outcomes of diabetes and CKD in contemporary pregnancy populations, is recommended to drive future improvements in care., (© 2024 Diabetes UK.)

Diabetic nephropathy (DN) is a common complication of diabetes and a leading cause of end-stage renal disease, characterized by progressive kidney fibrosis and inflammation. The transforming growth factor-beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diabetes nephropathy, and SMAD7 is a key negative regulator of this pathway. Recent studies have highlighted the involvement of miRNA in the progression of DN. Computational analysis identified 11 potential miRNAs such as miR-424, miR-195, miR-216a, miR-503, miR-15a-5p, miR-15b-5p, miR-665, miR-520h, miR16-5p, miR-21 and miR-32-5p which are predicted to target 3'UTR of SMAD7 mRNA. This review aims to explore the role of these miRNAs in the progression of DN. Notably, these miRNAs have shown therapeutic potential in mitigating fibrosis and inflammation by modulating SMAD7 expression in DN. Future directions can be to investigate the mechanistic pathways through which these miRNAs exert their effects, as well as optimizing delivery systems for effective clinical application. Targeting miRNAs that modulate SMAD7 expression represents a promising strategy for developing specific and effective therapies for diabetic nephropathy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Despite the substantial progress in the management of diabetes mellitus (DM), chronic kidney disease (CKD) remains one of the most common complications. Although uncommon, diabetic emergencies [diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS)] can still occur in stage 4 and 5 CKD, at times with less typical clinical manifestations due to the altered pathophysiology, presence of chronic metabolic acidosis and effect of haemodialysis on glycaemic control and metabolic parameters. The purpose of this article is to review the current literature and provide recommendations for the diagnosis and treatment of DKA, euglycaemic DKA and HHS in people with advanced CKD., Methods and Results: Guidance on the management of diabetes-related emergencies mainly focuses on individuals with preserved renal function or early-stage CKD. Existing literature is limited, and recommendations are based on expert opinions and case reports. Given the clinical need for amended guidelines for this population, we are proposing a management algorithm for DKA and HHS based on clinical and metabolic parameters., Conclusions: In this review article, we propose treatment algorithms for diabetes-related hyperglycaemic emergencies in people with advanced CKD. Further research is needed to validate our proposed algorithms., (© 2024 Diabetes UK.)

Aim: The co-existence of diabetes and CKD poses significant challenges to healthcare systems, current frameworks often inadequately address the complex needs of individuals with both conditions. Recognising these gaps, we introduced a new diabetes care model for people with advanced CKD in renal satellite units.This paper aims to evaluate this new diabetes model care., Method: We conducted a prospective audit of a new integrated diabetes kidney care model. Data were presented as mean ± SD or counts/percentages, and pre- and post-intervention differences were assessed using paired samples t-tests., Results: A total of 291 individuals with diabetes and advanced CKD stages 4 or 5, or undergoing haemodialysis, were included. The mean age was 68.5 (±13.0) years, 58.4% were males. Nearly half of the cohort had four or more long-term conditions, while two-thirds experienced mild/severe frailty. Only 6% were receiving ongoing diabetes care from secondary care diabetes specialist services. For patients with CKD not receiving dialysis, comparing pre- and post-intervention, there were improvements in HbA1c (-13.0 mmol/mol, p < 0.001), SBP (-13.7 mm Hg, p < 0.0001), and weight (-2.9 kg, p < 0.0001). Furthermore, there was an increase in guideline-directed therapies, with notable usage of SGLT2i (62.9%) and GLP1-RA (28.4%), while access to diabetes technology increased to 89%., Conclusion: This new model of care resulted in improved metabolic outcomes, increased utilisation of guideline-directed therapies, and enhanced access to diabetes technologies. However, the model also revealed significant unmet clinical needs in areas such as access to diabetes care, diabetes eye screening and foot surveillance., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Diabetic nephropathy represents a predominant etiology of end-stage renal disease (ESRD) on a global scale, significantly impacting the morbidity and mortality rates of individuals with diabetes. The primary objective of this analysis is to furnish a comprehensive examination of the etiology, fundamental mechanisms, and treatment modalities for DN. The development of DN stems from a multitude of factors, encompassing a intricate interplay involving metabolic irregularities induced by hyperglycemia, alterations in hemodynamics, inflammatory responses, oxidative stress, and genetic susceptibility. Principal mechanisms encompass the generation of advanced glycation end products (AGEs), activation of protein kinase C (PKC), and overexpression of the renin-angiotensin-aldosterone system (RAAS). These processes precipitate glomerular hyperfiltration, hypertrophy, and eventually, fibrosis and scarring of the renal parenchyma. Initially, hyperglycemia triggers mesangial proliferation and thickening of the glomerular basement membrane in the incipient stages of DN, subsequently leading to progressive glomerular sclerosis and tubulointerstitial fibrosis. Inflammatory cascades, notably involving cytokines like TGF-β and NF-κB, play pivotal roles in the advancement of DN by fostering the accumulation of extracellular matrix and renal fibrosis. Inflammation pathways, particularly those involving cytokines like TGF-β and NF-κB, play essential roles in diabetic nephropathy progression by stimulating extracellular matrix accumulation and renal fibrosis. The presence of oxidative stress, worsened by dysfunctional mitochondria, contributes further to renal injury via lipid peroxidation and DNA damage. Current therapeutic approaches for diabetic nephropathy concentrate on optimizing glycemic control, controlling hypertension, and suppressing the renin-angiotensin-aldosterone system. Among antihypertensive medications, ACE inhibitors and angiotensin II receptor blockers are crucial for decelerating disease advancement., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

People treated with peritoneal dialysis (PD) often have complicating conditions that require careful management. Three such conditions are reviewed in this article-diabetes mellitus, polycystic kidney disease, and chronic liver disease. Each of these conditions requires an understanding of both its effect on the delivery of the PD and the effect of the PD on the condition itself. In diabetes, glucose absorption from the dialysate complicates metabolic control and affects salt and water management and patient outcome. There is particular benefit in clinical care being delivered through a multidisciplinary team that involves both kidney and diabetes experts. In relation to polycystic kidney disease, a key issue is the potential for increased intraperitoneal pressure due to the combined effect of the enlarged polycystic organs and the presence of the dialysis solution, and therefore, the PD prescription requires to be managed with a particular focus on limiting that pressure. For patients with liver disease, key issues include nutritional support because PD can add to protein losses already consequent on the liver disease itself. Considered approaches are required to manage ascites and reduce infection risk and the potential for hernias and leaks to develop. Mortality in this group is unfortunately high-however, PD may present a better management option than hemodialysis in many patients-particularly in those where the liver disease is complicated by low BP, clotting abnormalities, or troublesome ascites. Overall, the choice to use PD in patients with these complicating conditions should be based on shared decision making with the patient and their family members informed by high-quality information in which risks, benefits, and management strategies are clearly presented., (Copyright © 2024 by the American Society of Nephrology.)

Objectives: To observe the effect of electroacupuncture (EA) preconditioning on podocytes and phosphatase and tension homologous protein (PTEN)/phosphoinositide-3-kinase (PI3K) signaling pathway in rats with type 2 diabetic kidney injury, so as to explore its potential mechanisms., Methods: Fifty male Wistar rats were randomly divided into control, model, EA, inhibitor, and sham EA groups, with 10 rats in each group. Diabetes model was established by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin (40 mg/kg). For rats in the EA group, EA (2 Hz, 1 mA) preconditioning was applied to "Guanyuan" (CV4), "Zhongwan" (CV12), and bilateral "Zusanli" (ST36), "Fenglong" (ST40) for 15 min, once every other day for 8 weeks. And rats in the sham EA group were given acupuncture at the subcutaneous areas of the same acupoints without EA stimulation. Rats of the inhibitor group were given intraperitoneal injection of BPV (HOpic, 0.6 mg/kg, 0.5 mg/mL) combined with the same EA stimulation as EA group once a week for 8 weeks. The blood glucose level of rats was recorded. Urinary albumin (ALB) content in rats was detected by ELISA. The contents of serum urea (Urea), creatinine (Crea), total cholesterol (TC) and triglyceride (TG) were detected by automatic biochemical analyzer. HE staining, PAS staining and Masson staining were used to observe the pathological changes of renal tissues. The ultrastructural changes of podocytes were observed by transmission electron microscopy. The relative expression levels of Synaptopodin, microtubule-associated protein light chain 3 Ⅱ(LC3-Ⅱ), PTEN and PI3K proteins in kidney were detected by Western blot., Results: Compared with the control group, the blood glucose, content of serum ALB, Urea, Crea, TC, TG and renal PI3K protein expression in the model group were significantly increased ( P <0.01), while the expression levels of renal Synaptopodin, LC3-Ⅱ and PTEN proteins were decreased ( P <0.01). Compared with the model group, the blood glucose, content of serum ALB, Urea, Crea, TC, TG and renal PI3K protein expression in the EA group decreased ( P <0.01, P <0.05), while the expression levels of renal Synaptopodin, LC3-Ⅱ and PTEN proteins increased ( P <0.01). In comparison with the EA group, the blood glucose, ALB, Urea, Crea, TC, TG content and PI3K protein expression level were increased ( P <0.05, P <0.01), while the expression levels of Synaptopodin, LC3-Ⅱ and PTEN proteins were decreased ( P <0.01) in the inhibitor group；whereas, the blood glucose, ALB, Urea, TC, TG content and PI3K protein expression level were increased ( P <0.05, P <0.01), while the expression levels of Synaptopodin, LC3-Ⅱ and PTEN proteins were decreased ( P <0.01) in the sham EA group. HE staining and PAS staining showed glomerular hypertrophy and glomerular glycogen deposition；and Masson staining displayed an enhancement of glomerular fibrosis；and electron microscope revealed foot process fusion, basement membrane thickening and autophagosomes reduction in the rat' s kidney of the model, inhibitor and sham EA groups, which were relatively milder in the EA group., Conclusions: EA promotes the expression of PTEN gene-encoded protein in the kidneys of type 2 diabetic rats, thereby inhibiting the activation of PI3K, increasing the autophagy level and protecting the podocytes.

This study explores the application and advancements of precision nursing model (PNM) in hemodialysis for diabetic nephropathy patients. Diabetic nephropathy is a severe complication of diabetes, frequently leading to end-stage renal disease and necessitating long-term hemodialysis. The PNM aims to enhance treatment outcomes and patient quality of life through individualized care plans, multidisciplinary collaboration, and continuous quality improvement. Research indicates that this model significantly improves clinical indicators and patient satisfaction, demonstrating broad applicability. This paper provides a detailed overview of the definition, theoretical foundation, implementation strategies, and specific interventions of the PNM, and evaluates its effectiveness in hemodialysis. Additionally, it addresses the challenges faced in implementation and suggests future research directions. Emphasis is placed on the need for long-term studies, technological innovations, and cost-effectiveness analyses to further integrate precision nursing into clinical practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Diabetic nephropathy (DN) is one of the most relevant and prevalent microvascular complications associated with Diabetes Mellitus. In recent years, hyperbaric oxygen therapy (HBO) has been used to mitigate tissue damage caused by hypoxia, thereby attenuating inflammatory processes. This study aimed to explore morphological aspects associated with DN in rats subjected to HBO. Forty-eight Wistar rats were divided into the following groups: C (normoglycemic animals), n = 12; C + HBO (normoglycemic animals submitted to HBO), n = 12; D (diabetic animals) n = 12; D + HBO (diabetic animals submitted to HBO), n = 12. The C + HBO and D + HBO groups were daily treated with HBO at 2.5 atmospheres absolute pressure (ATA) for 60 min, 5 days a week, for 5 weeks. Kidneys were collected for assessment of structural changes in the tissue parenchyma, assessment of renal fibrosis and renal protein expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). Our results showed that group D had hyperglycemia and weight loss, and that there was also an increase in the renal corpuscle, Bowman's space, and distal tubular epithelium, as well as accumulation of collagen. HBO administration effectively prevented glomerular hypertrophy and attenuated the expression of TNF-α and TGF-β1. It also positively affected renal tubules, inhibiting the development of tubular atrophy. These findings suggest that HBO was effective in attenuating the initial alterations observed in DN., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Diabetes-related foot ulceration (DFU), a serious but preventable complication of diabetes, is a leading cause of hospitalisation, lower extremity amputation and disability worldwide. People with DFU have a greater burden of cardiovascular risk factors, heart failure and chronic kidney disease, resulting in over two-fold higher risk of cardiovascular death compared with people with diabetes without DFU. Here, we propose a "cardio-renal-metabolic-foot" connection in people with diabetes based on shared pathophysiological mechanisms linking DFU with cardiovascular and renal disease. Whilst these mechanistic links remain to be fully elucidated, systemic inflammation and infection in the context of DFU are postulated as key mediators in the development, and progression of, cardiovascular and renal disease. However, cardiovascular and renal disease are also implicated in the pathogenesis of DFU, highlighting the multi-directional interplay between conditions. The impact of screening, prevention, and early management of cardiovascular complications associated with DFU requires further research. Multi-modality cardiac imaging could play a role in unravelling disease mechanisms leading to novel therapeutic strategies, as well as facilitating personalised risk assessment and management. Recent clinical trials have transformed the therapeutic landscape for people with type 2 diabetes, by demonstrating that sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 agonists and non-steroidal mineralocorticoid receptor antagonists improve cardiovascular and renal outcomes. Although dedicated research in people with DFU is warranted, these therapies could target multiple facets of the "cardio-renal-metabolic-foot" connection. The holistic, person-centred approach to managing DFU should incorporate new multidisciplinary models of care focusing on the prevention and management of cardiovascular and kidney disease., Competing Interests: Declarations. Competing interests: NSRL has received research funding from Sanofi as part of a Clinical Fellowship in Endocrinology and Diabetes, education support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Seqirus, Eli Lilly, Novartis and Pfizer, speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis and Sanofi, and has participated in advisory boards for Eli Lilly. PGF has received paid lectures from Novo Nordisk. GD reports paid lectures from AstraZeneca, Pfizer and Amgen and provides consultancy services and has equity interest in Artrya Ltd., (© 2024. The Author(s).)

Diabetic kidney disease (DKD) is a significant and growing global health concern, affecting a substantial proportion of individuals with diabetes mellitus. This position paper of Scientific societies of endocrinologists, nephrologists and cardiologists has been consensually brought at a couple of mutual meetings, aiming to synthesize current knowledge on screening, diagnosis and staging of DKD, emphasizing the need for an early detection and intervention in order to prevent progression to end-stage renal disease (ESRD). The role of glycemic control, blood pressure management, lipid management and the use of reno and cardioprotective agents, including angiotensin-converting enzyme inhibitors, sodium-glucose co-transporter 2 inhibitors and non-steroidal mineralocorticisteroid receptor antagonist has been entirely considered. Furthermore, we highlight the importance of a multidisciplinary approach in the care of patients with DKD, integrating lifestyle modifications and patient education into the clinical practice. This paper advocates for the implementation of standardized screening protocols and the development of personalized treatment strategies to optimize patient outcomes. By addressing the complexities of DKD, we aim to provide a comprehensive framework for healthcare professionals to enhance the quality of care for individuals at risk of or living with this condition., (© 2024 Goce Spasovski et al., published by Sciendo.)

Objective: This systematic review and meta-analysis aimed to synthesize the role of exosomes in the pathogenesis and management of diabetic kidney disease., Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched for studies that compared the levels of exosomes between patients with diabetic kidney disease and controls published up to 27 November 2023. Methodological quality was assessed using the JBI Appraisal Checklist for Case-Control Studies. The methodology of the samples and the main results were summarized. A meta-analysis of the diagnostic performance of exosomes was performed using estimates of test sensitivity and specificity, and these values were summarized using summary receiver-operating characteristic curves. The results were reported following the PRISMA 2020 checklist., Results: A total of 32 studies, including 1,119 patients with diabetic kidney disease and 1,328 controls, met the inclusion criteria. A total of 78 upregulated and 22 downregulated microRNAs, 2 upregulated and 4 downregulated mRNAs, 6 upregulated and 1 downregulated proteins, and 4 upregulated lipids were identified. The miR-126, miR-145, miR-150, miR-21, and WT1 mRNA dysregulation were consistently reported in at least two studies. The overall sensitivity and specificity of the exosomes in diabetic kidney disease diagnosis were 0.70 (95% CI: 0.59-0.80) and 0.79 (95% CI: 0.70-0.85), respectively. The summary receiver operating characteristic curve was plotted to assess diagnostic accuracy with the area under the curve (AUC) of 0.82 (95% CI: 0.78-0.85)., Conclusion: Exosomes have great potential to become effective diagnostic biomarkers for diabetic kidney disease. Panels of exosomes or the combination of exosomes with other clinical indicators seemed more accurate than single exosomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Xu and Jin.)

To the best of our knowledge, bibliometric analysis has not been performed for studies related to diabetic kidney disease (DKD) and hemodialysis using healthcare big data. Herein, the aim of this bibliometric analysis was to identify emerging research trends in DKD and hemodialysis within healthcare insurance databases by exploring authors, co-author networks, and countries to discover new potential research areas. A bibliometric study was conducted, utilizing data obtained from the Scopus database. Keywords such as diabetic kidney disease, hemodialysis, insurance or big data, and prediction were employed. Inclusion criteria were original articles and review articles written in English published between 2010 and 2022. VOSviewer and the Bibliometrix package in R were used for comprehensive bibliometric analysis. VOSviewer facilitated keyword co-occurrence analysis to identify clusters and visualize relationships among keywords, emphasizing distinct research themes, keyword density, and network visualization. Meanwhile, Bibliometrix allowed exploration of key metrics such as prolific authors and institutions, publication trends, co-authorship networks, citations, document types, emerging trends through keyword analysis, and network visualizations, including co-authorship and keyword co-occurrence. Results from both tools were integrated for a thorough analysis. The present study yielded 2,199 articles, which was reduced to 1,828 after removing duplicates and applying inclusion criteria. This bibliometric analysis found that machine learning and artificial intelligence are emerging yet remain relatively under-researched in the context of hemodialysis and DKD. The prominence of topics such as diabetic nephropathy, non-insulin treatments, and lifestyle modifications highlighted ongoing research priorities in DKD and hemodialysis. Taiwan's dominance in publications suggested robust research activity in this field, while international collaboration underscored global interest and the potential for diverse research perspectives. The need for similar research development in Indonesia, leveraging big data and machine learning, indicates opportunities for advancing the understanding and management of DKD and hemodialysis within the region., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Aims: To estimate whether a mix of pre- and probiotics would strengthen the gut barrier and protect the kidneys in individuals with type 1 diabetes and albuminuria., Methods: Randomized, placebo-controlled, crossover study. Forty-one participants received synbiotic (pre- and probiotics) mix or placebo for 12 weeks with 6 weeks washout. Primary endpoint was change from baseline to end-of-period in UACR. Secondary endpoints were changes in endothelial glycocalyx thickness, inflammatory and intestinal barrier dysfunction markers, glomerular filtration rate (GFR) and ambulatory systolic blood pressure., Results: Thirty-five participants completed the study. Mean age was 58 (SD 10) years, 73 % (n = 30) were male, median UACR was 134 (IQR 63-293) mg/g, estimated GFR was 75 (30) ml/min/1.73m 2 . There was no significant difference in UACR with a mean relative change (CI 95 %) from baseline to end-of-treatment of -3.0 (-18.4; 15.5) % in the synbiotic group and -12.0 (-29.6; 9.6) % in the placebo group with no significant difference between treatment periods (9.37 (-25.2; 44.0) percentage points; p = 0.60). No significant beneficial difference in the secondary end points was demonstrated., Conclusion: Twelve weeks treatment with synbiotic mix had no effect on UACR or on any of the secondary endpoints in subjects with type 1 diabetes and albuminuria., Competing Interests: Declaration of competing interest EBS, NHT, SS, HS and ML have no conflicts of interest. RES and SV are employees of dsm-firmenich, Kaiseraugst, Switzerland. PHG has received lecture fees from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, PeerVoice, Sanofi, and Sciarc. He is an advisory board member for AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, and Sanofi. None of these entities participated in the design or interpretation of the study. FP has served as a consultant, on advisory boards or as educator for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Sanofi, Mundipharma, MSD, Novartis, Amgen and has received research grants to institution from Novo Nordisk, Boehringer Ingelheim, Amgen and AstraZeneca. PR has received consultancy and/or speaking fees (to SDCC) from AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Eli Lilly, MSD, Novo Nordisk and Sanofi Aventis, and research grants from Novo Nordisk Bayer and AstraZeneca. JS and TWH have shares in Novo Nordisk A/S., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To explore the trend of burden and care quality of chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) and their cross-country inequalities from 1990 to 2021., Materials and Methods: Data were from the Global Burden of Disease 2021 study. Disease burden and care quality were quantified using the disability-adjusted life years rate and the quality-of-care index (QCI). Trend analyses of the age-standardized disability-adjusted life years rate (ASDR) and age-standardized QCI from 1990 to 2021 were conducted using the estimated annual percentage change. The associations of disease burden and care quality with the socio-demographic index (SDI) were explored. Cross-country inequalities in disease burden and care quality were assessed using the slope index of inequality (SII) and concentration index., Results: From 1990 to 2021, the global ASDR for CKD-T2DM increased, while the age-standardized QCI slightly decreased, with an estimated annual percentage change of 0.81 [95% confidence interval (CI): 0.75, 0.87] and -0.08 (95% CI: -0.09, -0.07). The ASDR escalated with increasing SDI, reaching a peak at mid-level SDI, followed by a decrease. The age-standardized QCI was higher with increasing SDI. Globally, ASDR concentrated on countries/territories with a lower SDI. The SII of ASDR was -96.64 (95% CI: -136.94, -56.35) in 1990 and -118.15 (95% CI: -166.36, -69.94) in 2021,  with a concentration index of -0.1298 (95% CI: -0.1904, -0.0692) in 1990 and -0.1104 (95% CI: -0.1819, -0.0389) in 2021. In 1990 and 2021, countries/territories at higher SDI levels exhibited increased age-standardized QCI, indicated by an SII of 15.09 (95% CI: 10.74, 19.45) and 15.75 (95% CI: 10.92, 20.59), and a concentration index of 0.0393 (95% CI: 0.0283, 0.0503) and 0.0400 (95% CI: 0.0264, 0.0536)., Conclusions: Our study highlights considerable disparities in the burden and care quality of CKD-T2DM. Regions experiencing an increasing burden and a declining care quality simultaneously underscore the need for further research and tailored health interventions., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus (DM) and has become the main cause of end-stage renal disease worldwide. In recent years, with the increasing incidence of DM, the pathogenesis of DKD has received increasing attention. The pathogenesis of DKD is diverse and complex. Extracellular vesicles (EVs) contain cell-derived membrane proteins, nucleic acids (such as DNA and RNA) and other important cellular components and are involved in intercellular information and substance transmission. In recent years, an increasing number of studies have confirmed that EVs play an important role in the development of DKD. The purpose of this paper is to explain the potential diagnostic value of EVs in DKD, analyze the mechanism by which EVs participate in intercellular communication, and explore whether EVs may become drug carriers for targeted therapy to provide a reference for promoting the implementation and application of exosome therapy strategies in clinical practice.

Zinc deficiency causes dysgeusia and dermatitis as well as anemia. As approximately half of dialysis patients have zinc deficiency, zinc supplementation should be considered in case of erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia. We report a case of a chronic dialysis patient with copper deficiency anemia caused by standard-dose zinc supplementation. The patient was a 70-year-old woman who had received maintenance hemodialysis for 8 years due to diabetic nephropathy. She had been treated with weekly administration of darbepoetin 30 μg for renal anemia, which resulted in Hb 12 to 14 g/dL. She had no dysgeusia. When zinc deficiency (44 μg/dL) had been identified 4 months earlier, 50 mg daily zinc acetate hydrate (Nobelzin®), which is the standard dose, was started. Unexpectedly, her anemia progressed slowly with macrocytosis together with granulocytopenia. Her platelet count did not decrease at that time. Laboratory tests revealed a marked decrease of serum copper (< 4 μg/dL) and ceruloplasmin (< 2 mg/dL), although serum zinc was within the normal limit (125 μg/dL). We discontinued zinc acetate and started copper supplementation including cocoa for 1 month. Her anemia and granulocytopenia were dramatically restored coincident with the increase in both serum copper and ceruloplasmin. Copper supplementation also improved her iron status as assessed by transferrin saturation and ferritin. Clinicians should monitor both zinc and copper status in anemic dialysis patients during zinc supplementation, as both are important to drive normal hematopoiesis., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interests. Ethical approval and consent to participate: The ethical committee of Kitano Hospital approved this case report. Consent for publication: Informed consent was obtained from the patient in this case report., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background and Aims: Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illustrated. To clarify the effect of MSC-Exo on NOD2 signaling pathway in podocytes under high glucose (HG) and DKD, we conduct this study., Methods: We co-cultured podocytes and MSCs-Exo under 30 mM HG and injected MSCs-Exo into DKD mice, then we detected the NOD2 signaling pathway by western blot, qRT-PCT, immunofluorescence, transmission electron microscopy and immunohistochemistry both in vitro and in vivo ., Results: In vitro , HG lead to the apoptosis, increased the ROS level and activated the NOD2 signaling pathway in podocytes, while MSCs-Exo protected podocytes from injury reduced the expression of inflammatory factors including TNF-α, IL-6, IL-1β, and IL-18 and alleviated the inflammatory response, inhibited the activation of NOD2 signaling pathway and the expression of it's downstream protein p-P65, p-RIP2, prevented apoptosis, increased cell viability in podocytes caused by HG. In vivo , MSCs-Exo alleviated renal injury in DKD mice, protected renal function, decreased urinary albumin excretion and inhibited the activation of NOD2 signaling pathway as well as the inflammation in renal tissue., Conclusion: MSCs-Exo protected the podocytes and DKD mice from inflammation by mediating NOD2 pathway, MSCs-Exo may provide a new target for the treatment of DKD.

Objective: To study the effects of acupuncture combined with the formula of Yi Qi Yang Yin and blood activating (A-YBF) on blood glucose levels and renal function in patients with early diabetic nephropathy., Methods: 96 patients with early diabetic nephropathy treated in our hospital from April 2021 to April 2022 were included in the study and divided into the control group (conventional medical treatment) and the study group (A-YBF), with 48 cases in each group. The efficacy and adverse effects were recorded by comparing the Chinese medicine symptom points, blood glucose level, renal function, and inflammatory factor level between the two groups before and after the treatment., Results: The clinical efficacy of the study group was significantly higher than that of the control group (P < .05). Before treatment, no difference was found between the primary and secondary symptom scores of the two groups (P > .05); after treatment, the primary and secondary symptom scores of the study group were lower than those of the control group (P < .05). Before treatment, there was no difference in fasting blood glucose (FPG) and 2h postprandial glucose (2hPG) levels; 24h urine protein quantification, cystatin C (Cys-C), urinary albumin excretion rate (UAER), and estimated glomerular filtration rate (eGFR) levels; and growth differentiation factor-15 (GDF-15), interleukin-1β (IL-1β), interleukin-17 (IL-17), and serum amyloid A (SAA) levels between the two groups (P > .05). After treatment, FPG and 2hPG levels; 24h urine protein quantification, Cys-C and UAER levels; and GDF-15, IL-1β, IL-17, and SAA levels were lower in the study group than in the control group, while eGFR levels were higher than those in the control group (P < .05)., Conclusion: A-YBF can effectively reduce blood glucose levels and improve renal function in patients with early diabetic nephropathy and can be promoted in clinical application.

The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m 2 ) is poorly studied. We examined this association in patients with advanced CKD in Japan. We used the Rapid Assessment of Physical Activity to assess baseline physical activity and classify patients as active or inactive. CKD progression was defined as 40% decline in eGFR, eGFR < 10, or requiring dialysis or transplantation. Among the 1,808 eligible patients, after adjusting for possible confounders, hazard ratios (HRs) for poor renal outcome in the active group were 0.68 (95% CI, 0.44-1.04), 1.09 (0.86-1.38), and 1.01 (0.82-1.25) in CKD stage G3b, G4, and G5, respectively, suggesting a renal benefit of exercise in CKD stage G3b. Adjusted HRs for death were 0.79 (0.40-1.57), 0.55 (0.38-0.80), and 0.75 (0.44-1.26) in stage G3b, G4, and G5, respectively. While the adjusted HRs of death were 0.84 (0.52-1.38) and 0.60 (0.43-0.83) in diabetic and non-diabetic patients, suggesting that exercise may reduce mortality in non-diabetic patients. Our study suggests that exercise is associated with better survival in non-diabetic patients with CKD stage G3b-5, and better renal outcome in diabetic and non-diabetic CKD stage G3b., (© 2024. The Author(s).)

Automated insulin delivery (AID) in people with type 1 diabetes (pwT1D) and end-stage kidney disease (ESKD) on haemodialysis (HD) has not been reported previously. We describe practical considerations and our findings in four pwT1D on HD for ESKD where AID was safely implemented, with significant improvements in time in range., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SH Honoraria from Medtronic, Abbot \Dexcom, Insulet and Tandem None for JK, TJ, BH, KC and SP.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end‑stage renal disease, and is characterized by persistent proteinuria and decreased glomerular filtration rate. Despite extensive efforts, the increasing incidence highlights the urgent need for more effective treatments. Histone methylation is a crucial epigenetic modification, and its alteration can destabilize chromatin structure, thereby regulating the transcriptional activity of specific genes. Histone methylation serves a substantial role in the onset and progression of various diseases. In patients with DKD, changes in histone methylation are pivotal in mediating the interactions between genetic and environmental factors. Targeting these modifications shows promise in ameliorating renal histological manifestations, tissue fibrosis and proteinuria, and represents a novel therapeutic frontier with the potential to halt DKD progression. The present review focuses on the alterations in histone methylation during the development of DKD, systematically summarizes its impact on various renal parenchymal cells and underscores the potential of targeted histone methylation modifications in improving DKD outcomes.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost-effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high-risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Patients with diabetes on dialysis experience wide variations in glucose levels and an increased risk of hypoglycaemia. Due to the inaccuracies of HbA1c in dialysis patients, JBDS-IP and KDIGO recommend the use of continuous glucose monitoring (CGM). We conducted a systematic review to examine the current evidence for CGM use and its impact on clinical outcomes in patients with diabetes on dialysis., Methods: A search of MEDLINE(R) ALL, Ovid Emcare, Journals@Ovid Full Text and Embase databases were conducted. Clinical or observational trials in adults with Type 1(T1D) or Type 2 (T2D) diabetes on dialysis and CGM intervention reporting on glycaemic outcomes were included., Results: Of the 936 citations identified, 49 duplicates were removed. 887 citations were screened by title and abstract. 9 full texts were reviewed and a further 7 excluded due to duplications or failure to meet to selection criteria. Data was extracted for 2 studies, both prospective before-and-after interventional studies with no control group. Joubert et al. (2015) showed results for 15 participants with T1D. Mean CGM glucose level decreased from 8.37mmol/L at baseline to 7.7mmol/L at the end of the CGM period (p < 0.05) while HbA1c decreased from 6.9 to 6.5% (p < 0.05) during the same period. Mean CGM was lower on dialysis days (7.68mmol/L vs. 7.8mmol/L, p < 0.05). Képénékian et al. (2014) reported on data from 29 T2D patients. Following a 3 month CGM-adapted insulin regimen, HbA1c decreased from 8.4% at baseline to 7.6% (p < 0.01) by the end of study. Mean CGM values decreased from 9.9mmol/L to 8.9mmol/L (p = 0.05) and the frequency of glucose values > 10mmol/L decreased from 41 to 30% (p < 0.05), without a significant increase in hypoglycaemia frequency. Both studies were deemed to be of 'good' quality., Conclusion: Evidence demonstrating the benefits of CGM in patients with diabetes receiving dialysis is lacking. There is a need for well-designed randomised controlled trials to ascertain the benefits of this technology in this patient group., Trail Registration: PROSPERO registration number: CRD42023371635, https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=371635 ., (© 2024. The Author(s).)

Aims: Diabetic nephropathy, vision loss and diabetic retinopathy (DR) are frequent comorbidities among individuals with type 2 diabetes (T2D). The Retinopathy in People Currently On Renal Dialysis (RiPCORD) study sought to examine the epidemiology and risk of vision impairment (VI) and DR among a cohort of Indigenous and non-Indigenous Australians with T2D currently receiving haemodialysis for end-stage renal failure (ESRF)., Methods: A total of 106 Indigenous and 109 non-Indigenous Australians were recruited in RiPCORD across five haemodialysis centres in urban and remote settings. Clinical assessments, questionnaires and medical record data determined the rates of ocular complications and risk factor profiles., Results: Prevalence rates include unilateral VI, 23.5 %; bilateral VI, 11.7 %; unilateral blindness, 14.2 %; and bilateral blindness, 3.7 %, with no significant differences between sub-cohorts (p=0.30). DR prevalence rates were 78.0 % among non-Indigenous Australians and 93.1 % among Indigenous Australians (p=<0.001). Non-Indigenous ethnicity (OR: 0.28) and pre-dialysis diastolic blood pressure (OR: 0.84 per 10-mmHg) were protective, while peripheral vascular disease (OR: 2.79) increased DR risk., Conclusions: Ocular complications among individuals with T2D and ESRF are disproportionately high, especially for Indigenous Australians, and beyond what can be accounted for by risk factor variation. Findings suggest a need to improve screening and preventative efforts within this high-risk population group., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (MSC-sEV) provide a pragmatic solution as a cell-free therapy for patients with diabetic kidney disease (DKD). However, the underlying protective mechanisms of MSC-sEV remain largely unknown in DKD. Invivo and in vitro analyses demonstrated that MSC-sEV attenuated renal fibrosis and inflammation of DKD. The underlying mechanism of the MSC-sEV-induced therapeutic effect was explored by high-throughput sequencing, which identified the unique enrichment of a set of miRNAs in MSC-sEV compared with human skin fibroblasts-sEV (HSF-sEV). Vitro experiments demonstrated that the protective potential was primarily attributed to miR-23a-3p, one of the most abundant miRNAs in MSC-sEV. Further, overexpression or knockdown analyses revealed that miR-23a-3p, and its target Krüppel-like factor 3 (KLF3) suppressed the STAT3 signaling pathway in high glucose (HG) induced HK-2 cells were essential for the renal-protective property of MSC-sEV. Moreover, we found that miR-23a-3p was packaged into MSC-sEV by RNA Binding Motif Protein X-Linked (RBMX) and transmitted to HG-induced HK-2 cells. Finally, inhibiting miR-23a-3p could mitigate the protective effects of MSC-sEV in db/db mice. These findings suggest that a systemic administration of sEV derived from MSC, have the capacity to incorporate into kidney where they can exert renal-protective potential against HG-induced injury through delivery of miR-23a-3p., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), which severely affects the quality of patients' lives. However, the current therapeutic approaches can only postpone its progression to ESRD. It is therefore imperative to develop a novel therapeutic strategy for renal injury in DKD, with the objective of restoring renal function and reversing the process of ESRD. In recent years, the potential of mesenchymal stem cell (MSC) therapy for DKD has garnered increasing attention within the scientific community. Preclinical research on MSC therapy has yielded promising results, and the safety of MSC treatment in vivo has been substantiated in clinical studies. An increasing body of evidence suggests that MSC therapy has significant potential for the treatment of DKD. This article reviews the existing research on MSCs and their derived exosomes in treating DKD and analyzes the underlying mechanism of MSC-based therapy for DKD. Additionally, we discuss the potential of combining MSC therapy with conventional pharmacological treatments, along with the constraints and prospects of MSC therapy for DKD. We hope this review can provide a precise and comprehensive understanding of MSCs for the treatment of DKD.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus (DM). With the increasing prevalence of DM worldwide, the incidence of DKD remains high. If DKD is not well controlled, it can develop into chronic kidney disease or end-stage renal disease (ESRD), which places considerable economic pressure on society. Traditional therapies, including glycemic control, blood pressure control, blood lipid control, the use of renin-angiotensin system blockers and novel drugs, such as sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor inhibitors and glucagon-like peptide-1 receptor agonists, have been used in DKD patients. Although the above treatment strategies can delay the progression of DKD, most DKD patients still ultimately progress to ESRD. Therefore, new and multimodal treatment methods need to be explored. In recent years, researchers have continuously developed new treatment methods and targets to delay the progression of DKD, including miRNA therapy, stem cell therapy, gene therapy, gut microbiota-targeted therapy and lifestyle intervention. These new molecular therapy methods constitute opportunities to better understand and treat DKD. In this review, we summarize the progress of molecular therapeutics for DKD, leading to new treatment strategies.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement., Methods: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission., Results: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions., Conclusions: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis., (© 2024. The Author(s).)

Objective: Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men., Research Design and Methods: Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure < 130/80 mmHg, HbA1c < 7%, LDL < 100 mg/dL, and total cholesterol < 175 mg/dL) on cardiovascular and mortality risk in patients with type 2 diabetes. In this post-hoc analysis, we stratified patients by sex to compare the occurrence of MACEs (primary endpoint) and all-cause death (secondary endpoint) between women (104 MT and 105 UC) and men (103 MT and 83 UC)., Results: Achievement of therapeutic goals was similar by sex, with 44% and 47% of women and men in MT achieving at least 3 targets vs. 16% and 20% of women and men in UC. During a median follow-up of 13.0 years, we recorded 262 MACE (48.5% in women) and 189 deaths (53.6% in women). Compared to the UC group, the risk of MACE in the MT group was reduced by 52% in women and by 44% in men (P = 0.11). Conversely, the reduction in mortality risk by MT was greater in women (44% versus 12%, P = 0.019)., Conclusions: MT similarly reduces the risk of MACEs in either sex. This therapeutic approach is associated with a survival advantage in women as compared with men and it may represent an important rationale to motivate physicians in overcoming their therapeutic inertia often encountered in female patients as well as to encourage patients of both sexes at improving their adherence to multidrug therapy., (© 2024. The Author(s).)

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: Atherosclerotic disease of the forearm arteries can impede the maturation of distal fistulas in diabetic patients. The goal of this study was to look at the maturity of diabetic hemodialysis patients' distal forearm (radiocephalic snuffbox or distal forearm) arteriovenous fistulas., Materials and Methods: Patients with chronic renal failure who were candidates for distal forearm radiocephalic arteriovenous fistula implantation were evaluated in this cross-sectional study. Patients' demographic details, underlying disorders, laboratory measurements, vital signs, and information on their surgery were all noted. Patients were checked for fistula development 1 week, 1 month, 2 months, and then monthly until 6 months after surgery. Arteriovenous fistula maturation characterized by optimal blood flow, vessel dilation, and structural adaptations., Results: Among 343 patients (56% male, 44% female, mean age: 57.32 ± 12.48 years), hypertension prevailed (81.9%), followed by hyperlipidemia (42.3%) and coronary artery disease history (25.9%). AVFs achieved 58.3% maturation in 64.98 ± 11.05 days; higher BP during creation correlated with successful maturation (17.02 ± 1.46 mmHg vs 13.90 ± 1.93 mmHg, P < .05). No significant statistical difference found in distal forearm arteriovenous fistula maturation between males (57.8%) and females (58.9%) ( P > .005). However, 41.7% of AVFs failed in 18.83 ± 17.89 days. Failed AVFs exhibited lower BP during operation and failure (11.75 ± 1.86 mmHg). Kaplan-Meier analysis depicted maturation probabilities over 90 days post-surgery., Conclusion: Diabetes and patient sex did not affect the maturation time of distal forearm AVFs in hemodialysis patients. Increased blood pressure during and after surgery correlated with shorter maturation time., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN., Methods: A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC + Irb). MSCs (2 × 10 6 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging., Results: The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys., Conclusions: Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells., (© 2024. The Author(s).)

Background: Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored., Purpose: This study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement., Methods: A cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE)., Results: Among 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m 2 . GLP-1RAs' new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE., Conclusion: Given to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis., (© 2024. The Author(s).)

Background: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis., Methods: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves., Results: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds., Conclusions: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis., (© 2024. The Author(s).)

Albuminuria is a marker of diabetic kidney disease. Raised albuminuria in children and young people with diabetes is associated with an increased risk of microvascular and macrovascular complications. This review provides guidance for paediatricians caring for children and young people with type 1 and type 2 diabetes on screening, investigations and treatments for albuminuria in line with relevant national and international recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Prolonged hyperglycemia in diabetes mellitus can result in the development of diabetic nephropathy (DN) and increase the susceptibility to kidney failure. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive modality that has demonstrated effective tissue repair capabilities. The objective of this study was to showcase the reparative potential of LIPUS on renal injury at both animal and cellular levels, while also determining the optimal pulse length (PL)., Research Design and Methods: We established a rat model of DN, and subsequently subjected the rats' kidneys to ultrasound irradiation (PL=0.2 ms, 10 ms, 20 ms). Subsequently, we assessed the structural and functional changes in the kidneys. Additionally, we induced podocyte apoptosis and evaluated its occurrence following ultrasound irradiation., Results: Following irradiation, DN rats exhibited improved mesangial expansion and basement membrane thickening. Uric acid expression increased while urinary microalbumin, podocalyxin in urine, blood urea nitrogen, and serum creatinine levels decreased (p<0.05). These results suggest that the optimal PL was 0.2 ms. Using the optimal PL further demonstrated the reparative effect of LIPUS on DN, it was found that LIPUS could reduce podococyte apoptosis and alleviate kidney injury. Metabolomics revealed differences in metabolites including octanoic acid and seven others and western blot results showed a significant decrease in key enzymes related to lipolysis (p<0.05). Additionally, after irradiating podocytes with different PLs, we observed suppressed apoptosis (p<0.05), confirming the optimal PL as 0.2 ms., Conclusions: LIPUS has been demonstrated to effectively restore renal structure and function in DN rats, with an optimal PL of 0.2 ms. The mechanism underlying the alleviation of DN by LIPUS is attributed to its ability to improve lipid metabolism disorder. These findings suggest that LIPUS may provide a novel perspective for future research in this field., Competing Interests: Competing interests: The authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetes mellitus (DM) significantly impacts renal and hepatic function, necessitating comprehensive understanding and management strategies. Renal involvement, namely diabetic kidney disease (DKD), presents a global challenge, with increasing prevalence paralleling DM rates. Lifestyle modifications and pharmacotherapy targeting hypertension and glycemic control have pivotal roles in DKD management. Concurrently, hepatic involvement in DM, characterized by metabolic dysfunction-associated steatotic liver disease (MASLD), presents a bidirectional relationship. DM exacerbates MASLD progression, while MASLD predisposes to DM development and worsens glycemic control. Screening for MASLD in DM patients is of high importance, utilizing non-invasive methods like ultrasound and fibrosis scores. Lifestyle modifications, such as weight loss and a Mediterranean diet, mitigate MASLD progression. Promising pharmacotherapies, like SGLT2 inhibitors and GLP-1 agonists, demonstrate efficacy in both DM and MASLD management. Special populations, such as diabetic individuals undergoing hemodialysis or kidney transplant recipients, demand special care due to unique clinical features. Similarly, DM exacerbates complications in MASLD patients, elevating the risks of hepatic decompensation and hepatocellular carcinoma. Recognizing the interconnectedness of DM, renal, and hepatic diseases underscores the need for multidisciplinary approaches for optimal patient outcomes. The present review aims to present the main characteristics and crucial points not to be overlooked regarding the renal and hepatic involvement in DM patients focusing on the inter-relationships between the renal and the hepatic involvements.

The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work., (© The Author(s) 2024. Published by Oxford University Press.)

Diabetes mellitus (DM) is a disease syndrome characterized by chronic hyperglycaemia. A long-term high-glucose environment leads to reactive oxygen species (ROS) production and nuclear DNA damage. Human umbilical cord mesenchymal stem cell (HUcMSC) infusion induces significant antidiabetic effects in type 2 diabetes mellitus (T2DM) rats. Insulin-like growth factor 1 (IGF1) receptor (IGF1R) is important in promoting glucose metabolism in diabetes; however, the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear. In this study, a DM rat model was induced with high-fat diet feeding and streptozotocin (STZ) administration and rats were infused four times with HUcMSC. Blood glucose, interleukin-6 (IL-6), IL-10, glomerular basement membrane, and renal function were examined. Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays. The expression of IGF1R, phosphorylated checkpoint kinase 2 (p-CHK2), and phosphorylated protein 53 (p-p53) was examined using immunohistochemistry (IHC) and western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of 8-hydroxydeoxyguanosine (8-OHdG). Flow cytometry experiments were used to detect the surface markers of HUcMSC. The identification of the morphology and phenotype of HUcMSC was performed by way of oil red "O" staining and Alizarin red staining. DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane, increased the expression of IGF1 and IGF1R. IGF1R interacted with CHK2, and the expression of p-CHK2 was significantly decreased in IGF1R -knockdown cells. When cisplatin was used to induce DNA damage, the expression of p-CHK2 was higher than that in the IGF1R -knockdown group without cisplatin treatment. HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats. The expression of IGF1, IGF1R, p-CHK2, and p-p53, and the level of 8-OHdG in the DM group increased significantly compared with those in the control group, and decreased after HUcMSC treatment. Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage. HUcMSC infusion protected against kidney injury in DM rats. The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

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., (© 2024. The Author(s).)

Background: Ischaemic mononeuropathy (IMN) is a rarely reported type of peripheral neuropathy secondary to an ischaemic injury, due to a complication of haemodialysis access. Although underreported, this phenomenon typically occurs in diabetic patients and may reflect the predisposition to neuropathic injury on a background of chronic deleterious changes in the microvasculature in diabetes. It is characterised by mononeuropathic features such as paraesthesia, pain and motor weakness and usually is reported as a rare complication of brachiocephalic fistula. We report a case of IMN which occurred in a patient with end-stage diabetic nephropathy following polytetrafluoroethylene (PTFE) graft placement in the groin as vascular access for haemodialysis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diabetic nephropathy (DN), defined as continuously elevated urinary albumin and a diminished estimated glomerular filtration rate, is a serious complication of both type 1 diabetes and type 2 diabetes and is the main cause of end-stage kidney disease. Patients with end-stage renal disease require chronic kidney dialysis and/or a kidney transplantation. Research highlights the role of diet in modulating specific signaling pathways that are instrumental in the progression of DN. Nutrient-sensitive pathways, affected by nutritional compounds and dietary components, offer a novel perspective on the management of DN by influencing inflammation, oxidative stress, and nutrient metabolism. Animal models have identified signaling pathways related to glucose metabolism, inflammation responses, autophagy, and lipid metabolism, while human population studies have contributed to the clinical significance of designing medical and nutritional therapies to attenuate DN progression. Here, we will update recent progress in research into the renoprotective or therapeutic effects of nutritional compounds, and potential nutrition-modulated pathways.