Management Of Diabetic Kidney Disease Research Articles

Advancements in diabetic kidney disease management: integrating innovative therapies and targeted drug development.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and affects approximately 40% of individuals with diabetes . Cases of DKD continue to rise globally as the prevalence of diabetes mellitus increases, with an estimated 415 million people living with diabetes in 2015 and a projected 642 million by 2040. DKD is associated with significant morbidity and mortality, representing 34% and 36% of all chronic kidney disease deaths in men and women, respectively. Common comorbidities including hypertension and ageing-related nephron loss further complicate disease diagnosis and progression. The progression of DKD involves several mechanisms including glomerular endothelial cell dysfunction, inflammation, and fibrosis. Targeting these mechanisms has formed the basis of several therapeutic agents. Renin-angiotensin-aldosterone system (RAAS) blockers, specifically angiotensin receptor blockers (ARBs), demonstrate significant reductions in macroalbuminuria. Sodium-glucose transporter type 2 (SGLT-2) inhibitors demonstrate kidney protection independent of diabetes control while also decreasing the incidence of cardiovascular events. Emerging agents including glucagon-like peptide 1 (GLP-1) agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, lixudebart, and tozorakimab; mesenchymal stem/stromal cell infusion; and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.

Aberrant expression of NEDD4L disrupts mitochondrial homeostasis by downregulating CaMKKβ in diabetic kidney disease

Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKβ/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKβ in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKβ. Moreover, deletion of NEDD4L under high glucose conditions prevented rapid CaMKKβ protein degradation. In vitro studies revealed that the aberrant expression of NEDD4L negatively influences the protein stability of CaMKKβ. This study also explored the role of NEDD4L in DKD by using AAV-shNedd4L in db/db mice. These findings confirmed that NEDD4L inhibition leads to a decrease in urine protein excretion, tubulointerstitial fibrosis, and oxidative stress, and mitochondrial dysfunction. Further in vitro studies demonstrated that si-Nedd4L suppressed mitochondrial fission and reactive oxygen species (ROS) production, effects antagonized by si-CaMKKβ. In summary, the findings provided herein provide strong evidence that dysregulated NEDD4L disturbs mitochondrial homeostasis by negatively modulating CaMKKβ in the context of DKD. This evidence underscores the potential of therapeutic interventions targeting NEDD4L and CaMKKβ to safeguard renal tubular function in the management of DKD.

Chinese Healthcare Workers' Knowledge, Attitudes, and Practices in Diabetic Kidney Management: A Multi-Centered Cross-Sectional Study.

Given the importance of diabetic kidney disease (DKD) management, this study aims to explore the knowledge, attitudes, and practices in disease management demonstrated by healthcare workers from the nephrology department. This study is a multi-centered cross-sectional study, and adopts snowball sampling, with 530 healthcare workers being recruited to complete a questionnaire covering areas such as demographic characteristics, knowledge, attitude, and practices (KAP) of DKD management. This data was analyzed using descriptive statistics and binary logistics analysis. In this study, 530 healthcare workers were studied, including 94 doctors and 436 nurses. The participants were mainly from general tertiary hospitals in 14 provinces. For Chinese nurse, the results indicate that both poor knowledge level (Odds Ratio (OR) =0.63, 95% Confidence Interval (CI): 0.42-0.94) and having experience in further medical training in nephrology (OR=1.92, 95% CI: 1.20-3.08) are associated with the practice levels. For Chinese doctors, having not experience in further medical training in nephrology (OR=0.36, 95% CI: 0.15-0.83) are associated with their practice levels. In summary, Chinese doctors and nurses in this study showed positive attitudes towards DKD management, but their knowledge and practical skills were lacking. This underscores a notable gap in achieving optimal DKD care. Notably, nurses' knowledge influenced their management practices, and additional nephrology training correlated with better engagement. To improve patient care, enhancing nephrology healthcare professional training and addressing knowledge-practice disparities are recommended.

Lipid metabolism disorder in diabetic kidney disease.

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.

Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a substantial complication of type 2 diabetes (T2D), presenting challenges in chronic kidney disease (CKD) management. In addition to traditional and recent therapies, including angiotensin, converting enzyme (ACE) inhibitors, angiotensin receptor blockers, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists, the evolution of antihyperglycemic treatments has introduced a promising agent, glucagon-like peptide-1 receptor agonist (GLP-1RA) for the management of DKD. GLP-1RAs enhance insulin release and reduce glucagon release, offering a novel approach to DKD management. This review analyzes the molecular pathways through which GLP1-RAs confer renal protection in T2D and DKD, which are complex and multifaceted. They include modulation of renal hemodynamics, antioxidative and anti-inflammatory actions, metabolic regulation, and direct cellular effects. These mechanisms highlight GLP1-RA's potential as a therapeutic option for glycemic control and direct or indirect renal function protection in diabetic patients, emphasizing the potentiality of GLP-1RAs for dual therapy, with cardiovascular and renal protection as a holistic approach. Clinical evidence supports GLP-1RAs in reducing albuminuria and enhancing kidney outcomes, highlighting their value in a comprehensive DKD management strategy.

Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression.

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), a promising class of agents, possess the potential to act as renal protectors, effectively slowing the progression of DKD. Other agents, including pentoxifylline (PTF), selonsertib, and baricitinib hold great promise as potential therapies for DKD due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, encompassing lifestyle modifications and drug therapy, can effectively decelerate the progression of DKD. Based on the treatment of heart failure, it is recommended to use multiple drugs in combination rather than a single-use drug for the treatment of DKD. Unearthing the mechanisms underlying DKD is urgent to optimize the management of DKD. Inflammatory and fibrotic factors (including IL-1, MCP-1, MMP-9, CTGF, TNF-a and TGF-β1), along with lncRNAs, not only serve as diagnostic biomarkers, but also hold promise as therapeutic targets. In this review, we delve into the potential mechanisms and the current therapies of DKD. We also explore the additional value of combing these therapies to develop novel treatment strategies. Drawing from the current understanding of DKD pathogenesis, we propose HIF inhibitors, AGE inhibitors, and epigenetic modifications as promising therapeutic targets for the future.

PGC1-α in diabetic kidney disease: unraveling renoprotection and molecular mechanisms.

Mitochondrial dysfunction represents a pivotal aspect of the pathogenesis and progression of diabetic kidney disease (DKD). Central to the orchestration of mitochondrial biogenesis is the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α), a master regulator with a profound impact on mitochondrial function. In the context of DKD, PGC1-α exhibits significant downregulation within intrinsic renal cells, precipitating a cascade of deleterious events. This includes a reduction in mitochondrial biogenesis, heightened levels of mitochondrial oxidative stress, perturbed mitochondrial dynamics, and dysregulated mitophagy. Concurrently, structural and functional abnormalities within the mitochondrial network ensue. In stark contrast, the sustained expression of PGC1-α emerges as a beacon of hope in maintaining mitochondrial homeostasis within intrinsic renal cells, ultimately demonstrating an impressive renoprotective potential in animal models afflicted with DKD. This comprehensive review aims to delve into the recent advancements in our understanding of the renoprotective properties wielded by PGC1-α. Specifically, it elucidates the potential molecular mechanisms underlying PGC1-α's protective effects within renal tubular epithelial cells, podocytes, glomerular endothelial cells, and mesangial cells in the context of DKD. By shedding light on these intricate mechanisms, we aspire to provide valuable insights that may pave the way for innovative therapeutic interventions in the management of DKD.

Synopsis of the Korean Society of Nephrology 2023 Practical Recommendations for the Management of Diabetic Kidney Disease

Korea has one of the highest rates of end-stage kidney disease (ESKD) worldwide and nearly half of all new cases are attributed to diabetes. Diabetes represents a critical aspect of chronic kidney disease (CKD)-related mortality that entails substantial treatment costs. Given the profound impact of ESKD, it is imperative to initiate robust initiatives to formulate and implement effective preventive and therapeutic strategies. These strategies should target the prevention of CKD development in individuals with diabetes and decelerate the progression of diabetic kidney disease. Recognizing this challenge, the Korean Society of Nephrology (KSN) has introduced the kidney health plan 2033, a comprehensive endeavor designed to alleviate the burdens associated with CKD and ESKD in Korea. As part of this initiative, KSN has undertaken the development of the KSN 2023 practical recommendations for the management of diabetic kidney disease. The hope is that implementation of this guideline will delay the onset of kidney-related complications in diabetic patients throughout the country.

The Role of Autophagy in Type 2 Diabetic Kidney Disease Management.

Diabetic kidney disease (DKD), or diabetic nephropathy (DN), is one of the most prevalent complications of type 2 diabetes mellitus (T2DM) and causes severe burden on the general welfare of T2DM patients around the world. While several new agents have shown promise in treating this condition and potentially halting the progression of the disease, more work is needed to understand the complex regulatory network involved in the disorder. Recent studies have provided new insights into the connection between autophagy, a physiological metabolic process known to maintain cellular homeostasis, and the pathophysiological pathways of DKD. Typically, autophagic activity plays a role in DKD progression mainly by promoting an inflammatory response to tissue damage, while both overactivated and downregulated autophagy worsen disease outcomes in different stages of DKD. This correlation demonstrates the potential of autophagy as a novel therapeutic target for the disease, and also highlights new possibilities for utilizing already available DN-related medications. In this review, we summarize findings on the relationship between autophagy and DKD, and the impact of these results on clinical management strategies.

Diabetic kidney disease

Diabetes is the leading cause of chronic kidney disease and end stage renal disease (ESRD) globally. Diabetic kidney disease, previously known as diabetic nephropathy, is a general term used for deterioration of kidney function in patients with diabetes. It is important to diagnose and manage diabetic kidney disease early, so as to reduce the incidence of ESRD and the cardiovascular complications of diabetes. This article looks at the epidemiology, presentation and management of diabetic kidney disease.

Earlier Intervention in Diabetic Kidney Disease Management Using the In Vitro Diagnostic Test PromarkerD Shows Economic Health Benefits over Current Standard of Care

Earlier Intervention in Diabetic Kidney Disease Management Using the In Vitro Diagnostic Test PromarkerD Shows Economic Health Benefits over Current Standard of Care

LncRNA H19: a novel player in the regulation of diabetic kidney disease.

Diabetic kidney disease (DKD), one of the most severe complications of diabetes mellitus (DM), has received considerable attention owing to its increasing prevalence and contribution to chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, the use of drugs targeting DKD remains limited. Recent data suggest that long non-coding RNAs (lncRNAs) play a vital role in the development of DKD. The lncRNA H19 is the first imprinted gene, which is expressed in the embryo and down-regulated at birth, and its role in tumors has long been a subject of controversy, however, in recent years, it has received increasing attention in kidney disease. The LncRNA H19 is engaged in the pathological progression of DKD, including glomerulosclerosis and tubulointerstitial fibrosis via the induction of inflammatory responses, apoptosis, ferroptosis, pyroptosis, autophagy, and oxidative damage. In this review, we highlight the most recent research on the molecular mechanism and regulatory forms of lncRNA H19 in DKD, including epigenetic, post-transcriptional, and post-translational regulation, providing a new predictive marker and therapeutic target for the management of DKD.

Identifying key genes for diabetic kidney disease by bioinformatics analysis

BackgroundThere are no reliable molecular targets for early diagnosis and effective treatment in the clinical management of diabetic kidney disease (DKD). To identify novel gene factors underlying the progression of DKD.MethodsThe public transcriptomic datasets of the alloxan-induced DKD model and the streptozotocin-induced DKD model were retrieved to perform an integrative bioinformatic analysis of differentially expressed genes (DEGs) shared by two experimental animal models. The dominant biological processes and pathways associated with DEGs were identified through enrichment analysis. The expression changes of the key DEGs were validated in the classic db/db DKD mouse model.ResultsThe downregulated and upregulated genes in DKD models were uncovered from GSE139317 and GSE131221 microarray datasets. Enrichment analysis revealed that metabolic process, extracellular exosomes, and hydrolase activity are shared biological processes and molecular activity is altered in the DEGs. Importantly, Hmgcs2, angptl4, and Slco1a1 displayed a consistent expression pattern across the two DKD models. In the classic db/db DKD mice, Hmgcs2 and angptl4 were also found to be upregulated while Slco1a1 was downregulated in comparison to the control animals.ConclusionsIn summary, we identified the common biological processes and molecular activity being altered in two DKD experimental models, as well as the novel gene factors (Hmgcs2, Angptl4, and Slco1a1) which may be implicated in DKD. Future works are warranted to decipher the biological role of these genes in the pathogenesis of DKD.

Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms.

Diabetic kidney disease (DKD) is a serious complication of diabetes that can lead to end-stage kidney disease. Despite its significant impact, most research has concentrated on the glomerulus, with little attention paid to the tubulointerstitial region, which accounts for the majority of the kidney volume. DKD's tubulointerstitial lesions are characterized by inflammation, fibrosis, and loss of kidney function, and recent studies indicate that these lesions may occur earlier than glomerular lesions. Evidence has shown that inflammatory mechanisms in the tubulointerstitium play a critical role in the development and progression of these lesions. Apart from the renin-angiotensin-aldosterone blockade, Sodium-Glucose Linked Transporter-2(SGLT-2) inhibitors and new types of mineralocorticoid receptor antagonists have emerged as effective ways to treat DKD. Moreover, researchers have proposed potential targeted therapies, such as inhibiting pro-inflammatory cytokines and modulating T cells and macrophages, among others. These therapies have demonstrated promising results in preclinical studies and clinical trials, suggesting their potential to treat DKD-induced tubulointerstitial lesions effectively. Understanding the immune-inflammatory mechanisms underlying DKD-induced tubulointerstitial lesions and developing targeted therapies could significantly improve the treatment and management of DKD. This review summarizes the latest advances in this field, highlighting the importance of focusing on tubulointerstitial inflammation mechanisms to improve DKD outcomes.

Downregulation of ARNTL in renal tubules of diabetic db/db mice reduces kidney injury by inhibiting ferroptosis

BackgroundThe prevalence of ferroptosis in diabetic kidney tubules has been documented, yet the underlying mechanism remains elusive. The aim of this study was to ascertain the pivotal gene linked to ferroptosis and establish a novel target for the prevention and management of diabetic kidney disease (DKD). MethodsTranscriptomics data (GSE184836) from DKD mice (C57BLKS/J) were retrieved from the GEO database and intersected with ferroptosis-related genes from FerrDb. Then, differentially expressed genes associated with ferroptosis in the glomeruli and tubules were screened. Gene ontology analysis and protein-protein interaction network construction were used to identify key genes. Western blotting and real-time quantitative polymerase chain reaction were employed to validate the expression in the same model. Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) expression in patients and mice with DKD was assessed using immunohistochemistry staining. ARNTL knockdown in C57BLKS/J mice was established and plasma malonaldehyde, superoxide dismutase, and renal pathology were analyzed. The efficacy of ARNTL knockdown was evaluated using proteomics analysis. Mitochondrial morphology was observed using transmission electron microscopy. ResultsARNTL was screened by bioinformatics analysis and its overexpression verified in patients and mice with DKD. ARNTL knockdown reduced oxidative stress in plasma. Kidney proteomics revealed that ferroptosis was inhibited. The reduction of the classic alteration in mitochondrial morphology associated with ferroptosis was also observed. Gene set enrichment analysis demonstrated that the downregulation of the TGFβ pathway coincided with a decrease in collagen protein and TGFβ1 levels. ConclusionsThe ferroptosis-associated gene ARNTL is a potential target for treating DKD.

Noninvasive Assessment of Diabetic Kidney Disease With MRI: Hype or Hope?

Owing to the increasing prevalence of diabetic mellitus, diabetic kidney disease (DKD) is presently the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early identification and disease interception is of paramount clinical importance for DKD management. However, current diagnostic, disease monitoring and prognostic tools are not satisfactory, due to their low sensitivity, low specificity, or invasiveness. Magnetic resonance imaging (MRI) is noninvasive and offers a host of contrast mechanisms that are sensitive to pathophysiological changes and risk factors associated with DKD. MRI tissue characterization involves structural and functional information including renal morphology (kidney volume (TKV) and parenchyma thickness using T1- or T2-weighted MRI), renal microstructure (diffusion weighted imaging, DWI), renal tissue oxygenation (blood oxygenation level dependent MRI, BOLD), renal hemodynamics (arterial spin labeling and phase contrast MRI), fibrosis (DWI) and abdominal or perirenal fat fraction (Dixon MRI). Recent (pre)clinical studies demonstrated the feasibility and potential value of DKD evaluation with MRI. Recognizing this opportunity, this review outlines key concepts and current trends in renal MRI technology for furthering our understanding of the mechanisms underlying DKD and for supplementing clinical decision-making in DKD. Progress in preclinical MRI of DKD is surveyed, and challenges for clinical translation of renal MRI are discussed. Future directions of DKD assessment and renal tissue characterization with (multi)parametric MRI are explored. Opportunities for discovery and clinical break-through are discussed including biological validation of the MRI findings, large-scale population studies, standardization of DKD protocols, the synergistic connection with data science to advance comprehensive texture analysis, and the development of smart and automatic data analysis and data visualization tools to further the concepts of virtual biopsy and personalized DKD precision medicine. We hope that this review will convey this vision and inspire the reader to become pioneers in noninvasive assessment and management of DKD with MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.

To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care. A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation. Of the 2.3 million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90 mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58 mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5 mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97). There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.

#5431 THE VALUE OF MANAGING DIABETIC KIDNEY DISEASE: CONTRASTING FINDINGS FROM THE INDIVIDUAL PATIENT AND POPULATION LEVEL PERSPECTIVES

Abstract Background and Aims The management of diabetic kidney disease (DKD) is associated with considerable resource utilisation. Within the context of the broader healthcare system, understanding the health economic implications of adopting strategies to ameliorate the progression of DKD is imperative for fully informed decision-making. The objective of this study was to estimate the UK whole healthcare system economic value, from the individual patient and population perspectives, associated with modifying the progression of DKD through attenuating the decline in eGFR by values consistent with those observed in recent randomised clinical outcome trials. Method Since type 2 diabetes (T2D) is the commonest single cause of chronic kidney disease (CKD), we developed a deterministic model utilising published estimates of disease progression stratified by stages: stage 1/2, stage 3a, stage 3b and stage 4/5. Patient characteristics and mean annual decline in eGFR were aligned to the placebo arm of DECLARE-TIMI 58 (-2.44 ml/min/1.732). We explored scenarios where a sustained attenuation in the rate of eGFR decline by 1 and 2ml/min/1.732 per year was realised. T2D specific and all-cause mortality were captured using UKPDS risk equations. CKD stage specific costs and changes in health utility were drawn from NICE guidelines (NG203). Per-patient and population level costs (indexed to 2022) and quality adjusted life years (QALYs) were estimated, and both discounted at 3.5%. Results We estimated there were 3.2M, 0.6M, 0.2M and 0.04M DKD patients in stages 1/2, 3a, 3b and 4/5 respectively. Declining kidney function was associated with increasing per-patient lifetime costs and decreasing QALYs: stage 1/2 £36,714, 8.1 QALYs; stage 3a £90,666, 6.5 QALYs; stage 3b £126,931, 5.2 QALYs; stage 4/5 £168,604, 3.7 QALYs. A sustained attenuation in the rate of eGFR decline by 1 and 2ml/min/1.732 per year had the greatest impact in those in stage 3b: with cost savings of £23,690 and £47,463 and gains in QALYs of 0.68 and 1.46 for 1 and 2ml/min/1.732 respectively. At the population level, however, total lifetime cost for DKD was greatest in those in stage 1/2 £30.3Bn; followed by stage 3a, £19.2Bn; stage 3b £9.5Bn; stage 4/5 £146M. A sustained attenuation in eGFR resulted in the largest cost savings in those in stage 1/2: £16.9 Bn and £22.3Bn for 1 and 2ml/min/1.732 respectively, and the greatest gains in QALYs of 0.8M and 1.1M for 1 and 2ml/min/1.732 respectively. In contrast, population level stage 4 cost savings and QALY gains were modest at £70.7M and £281.6M and 0.02M and 0.4M for 1 and 2ml/min/1.732 respectively. Conclusion The notion of value in healthcare is influenced by stakeholder perspective. From the clinician's and patient's perspective the greatest value in attenuating the progression of DKD is in those with more advanced disease. However, from the health care provider perspective, at the population level, modest cost-savings and QALY gains are realised in such patients. By contrast, those at an earlier disease stage deliver much greater population level return on investment consequent upon larger numbers of such individuals. This study illustrates that attenuating DKD progression provides value at both the individual and public health levels, irrespective of disease stage.

#4674 CLINICAL PROFILE OF PATIENTS WITH DIABETIC KIDNEY DISEASE ATTENDING NEPHROLOGY CLINICS IN A LOW-MIDDLE INCOME COUNTRY

Abstract Background and Aims Chronic kidney disease secondary to diabetes is a significant contributor to the global burden of disease, both financially and through a marked deterioration in the quality of life. Diabetic kidney disease (DKD) increases the likelihood of adverse outcomes such as infirmity, cardiovascular events, progressive multi-organ damage, impaired quality of life and reduced life expectancy. Pakistan, a low-middle income country, is ranked among the top 10 countries for absolute diabetes prevalence. Over 19 million Pakistani adults have diabetes, which amounts to 17.1% of the adult population in the country. There is a dearth of literature examining the quality of care of diabetic kidney disease (DKD) patients in Pakistan. The aim of the current study is to evaluate the clinical profile and the quality of care delivered to patients with DKD attending nephrology clinics at a large tertiary care hospital in Karachi, Pakistan. Method It was a cross-sectional observational study at Aga Khan University Hospital (AKUH), a private tertiary-care facility located in Karachi, Pakistan. The data used in the study was acquired from the Diabetic Kidney Disease outpatient-database, a registry of patients managed by AKUH. It was used to identify a cohort of patients, with DKD presenting to the nephrology clinic at AKUH from December 2018-January 2021 (n = 553). Results Mean age of the study participants was 61.7 + 11.0 years and 60.9% of the study participants were male. 80.5% (n = 445) were non-smokers and over three-quarters (n = 400) had a body mass index (BMI) &amp;gt; 25 which according to the Asian-Pacific BMI cut-offs classified them as obese. These patients had been living with diabetes for an average of 15 years (median IQR = 10-21) and 99% had type 2 diabetes mellitus. A total of 519 study participants (93.9%) had hypertension while 34.2% and 30.9% had dyslipidemia and ischemic heart disease (IHD), respectively. Almost two third of the participants (68.4%) had advanced CKD (stages 3b, 4and 5) at the time of presentation. Less than half of the study population (43.6%) had HbA1c &amp;lt; 7.0 percentage and only 34.9% attained systolic blood pressure (BP) target &amp;lt;130mm Hg while optimal diastolic BP (&amp;lt;80 mmHg) targets were achieved in 72.7%. Almost 70% of the study population were on insulin while 49.7% were receiving oral anti-diabetics. The most prescribed oral anti-diabetic was DPP4 followed by metformin and two thirds were on statins. Calcium channel blockers and beta-blockers were the most used antihypertensive drugs 53.5% and 52.6% respectively; half of the population was on diuretics, while 47.4% were taking Renin-angiotensin system (RAAS) blockers. Those who had eGFR&amp;gt; 60, only 60% of them were receiving RAAS blockade therapy. Women were more likely to be obese and to have higher systolic BP compared to men. Diastolic BP and HbA1c were similar in men and women. The use of statins was higher in men and use of calcium channel blockers and RAAS blockers was significantly higher in women. Conclusion The basis for DKD management is multifactorial risk factor reduction which is achieved by optimizing care through modifiable risk factors. In our study we identified potential gaps in the quality of care related to risk factor control, optimal glycemic and/or blood pressure targets and pharmacotherapy to delay the progression of DKD and minimize cardiovascular events. This highlights a major treatment gap in DKD prevention and management calling for greater quality improvement effort in Pakistan, which now has the third highest number of people living with diabetes in the world.

Mitigation of renal microvascular injury in diabetic kidney disease model mice by electroacupuncture: 电针改善糖尿病肾病模型小鼠肾微血管损伤

ObjectiveRenal microvascular injury, as the result of diabetic toxicity, plays a vital role in the pathogenesis of diabetic kidney disease (DKD) during diabetes progression. Here, we investigated whether electroacupuncture (EA) could ameliorate renal microvascular impairment to prevent DKD and its underlying mechanism. MethodsThe male db/db mice with Leprdb mutation were used as the model of type 2 diabetes mellitus-induced DKD and treated with EA at “Zusanli (ST36)” and “Weiwanxiashu (EX-B3)” acupoints for 4 weeks. Age-matched wild-type mice were used as control group. Renal protection of EA was evaluated by mouse urine production, water consumption, renal index and tubules dilation. Two-photon microscope imaging was applied to visualize renal microvascular blood flow in vivo. Immunostaining and western blot analysis were used to detect the glomerular alternations and inflammatory signaling. ResultsEA significantly attenuated renal dysfunction in db/db mice. The protective effect of EA on renal microvascular recovery was observed both in function and structure analysis. Firstly, EA restored the renal microvascular blood flow in db/db mice. Then, glomerular hypertrophy and glomerular barrier destruction were suppressed after EA, as respectively demonstrated by the reduction of glomerular dilation, Collagen Ⅳ and Claudin-1 deposits. In mechanism, EA suppressed the diabetes-induced inflammatory response in renal microvessels, presenting as the downregulation of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) activation, and macrophage infiltration after EA treatment. ConclusionThese findings indicated the benefits of EA against renal microvascular impairment and DKD progression, which was associated with the action of anti-inflammation, and supported EA as a promising modality for DKD management.