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Diabetic Nephropathy

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1. Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Diabetic Nephropathy: A Review of Clinical Effectiveness

Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Diabetic Nephropathy: A Review of Clinical Effectiveness Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Diabetic Nephropathy: A Review of Clinical Effectiveness | CADTH.ca Find the information you need Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Diabetic Nephropathy: A Review of Clinical Effectiveness Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Diabetic Nephropathy: A Review (...) of Clinical Effectiveness Last updated: September 20, 2019 Project Number: RC1184-000 Product Line: Research Type: Drug Report Type: Summary with Critical Appraisal Result type: Report Question What is the clinical effectiveness of sodium glucose cotransporter 2 inhibitor for the treatment of diabetic nephropathy? Key Message Four systematic reviews and five randomized controlled trials on the clinical effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors for treatment of adult patients

2019 Canadian Agency for Drugs and Technologies in Health - Rapid Review

3. Hypertension management and renin-angiotensin-aldosterone system blockade in patients with diabetes, nephropathy and/or chronic kidney disease

Hypertension management and renin-angiotensin-aldosterone system blockade in patients with diabetes, nephropathy and/or chronic kidney disease Hypertension management and renin-angiotensin-aldosterone system blockade in patients with diabetes, nephropathy and/or chronic kidney disease Indranil Dasgupta DM FRCP , Debasish Banerjee MD FRCP , Tahseen A Chowdhury MD FRCP , Parijat De MD FRCP , Mona Wahba MA FRCP , Stephen Bain MD FRCP , Andrew Frankel MD FRCP , Damian Fogarty MD FRCP , Ana Pokrajac (...) blockade in patients with type 2 diabetes, nephropathy and/or early chronic kidney disease (stages 1–3) 13 Recommendations 14 Audit standards 14 Areas that require further research 15 Introduction 15 The renin-angiotensin-aldosterone system 16 Hypertension in patients with type 2 diabetes 16 The role of home and ambulatory blood pressure measurement 16 Lifestyle modification and impact on blood pressure 17 Blood pressure lowering agents 18 RAAS blockade in patients with type 2 diabetes without

2017 Association of British Clinical Diabetologists

4. Association of British Clinical Diabetologists - Renal Association (ABCD-RA) Clinical Practice Guidelines for Management of Lipids in Adults with Diabetes Mellitus and Nephropathy and/or Chronic Kidney Disease

Association of British Clinical Diabetologists - Renal Association (ABCD-RA) Clinical Practice Guidelines for Management of Lipids in Adults with Diabetes Mellitus and Nephropathy and/or Chronic Kidney Disease ABCD-RA Clinical Practice Guidelines – Lipid management in DN &/or DM CKD. Online June 2017 © ABCD-RA 2017 1 CONTENTS Introduction ……………………………………. 2 Rationale for guidelines 22-24 ………… 14 Methodology…………………………………… 2 Rationale for guidelines 25-28 ……….. 15 Why do we need these guidelines (...) for diabetic patients with concomitant renal disease. Herein a detailed rationale is presented in association with the guidelines, as well as recommendations for clinical audit and outstanding questions for further research. Box 1. Differentiating renal disease in diabetes Diabetic Nephropathy (DN) Damage to glomerular capillaries in patients with diabetes mellitus resulting in albuminuria in the absence of other causes of albuminuria. Diabetes Mellitus Chronic Kidney Disease (DM CKD) Presence

2017 Association of British Clinical Diabetologists

5. Urine proteomic analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension

Urine proteomic analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension 1 Translation of the executive summary of the final report Proteomanalyse im Urin zur Erkennung einer diabetischen Nephropathie bei Patientinnen und Patienten mit Diabetes mellitus und arteriellem Hypertonus (Version 1.0; Status: 17 September 2015). Please note: This translation is provided as a service by IQWiG to English-language readers. However, solely the German (...) original text is absolutely authoritative and legally binding. Executive Summary IQWiG Reports – Commission No. D13-01 Urinary proteome analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension 1 Executive summary of final report D13-01 Version 1.0 Proteome analysis for detection of DN 17 September 2015 Institute for Quality and Efficiency in Health Care (IQWiG) - i - Publishing details Publisher: Institute for Quality and Efficiency in Health Care

2015 Institute for Quality and Efficiency in Healthcare (IQWiG)

6. NLRX1 does not play a role in diabetes nor the development of diabetic nephropathy induced by multiple low doses of streptozotocin. Full Text available with Trip Pro

NLRX1 does not play a role in diabetes nor the development of diabetic nephropathy induced by multiple low doses of streptozotocin. Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus that results in both tubular and glomerular injury. Low-grade inflammation and oxidative stress are two mechanisms known to drive the progression of DN. Nucleotide-binding leucine-rich repeat containing family member X1 (NLRX1) is an innate immune receptor, uniquely located (...) the development of streptozotocin-induced diabetes and diabetic-induced nephropathy in mice after multiple low doses of streptozotocin. This data implies that, while NLRX1 can be triggered by cellular stress, its regulatory and functional effects may be dependent on the specific physiological conditions. In the case of DN, NLRX1 may be neither helpful nor harmful, but rather a marker of metabolic stress.

2019 PLoS ONE

7. HbA<sub>1c</sub> level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study. Full Text available with Trip Pro

HbA1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study. To evaluate if the lowest target level for glycated haemoglobin (HbA1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults with type 1 diabetes.Population based cohort study.Swedish National Diabetes Registry, 1 January 1998 to 31 December 2017.10 398 children and adults (...) with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017.Relative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA1c.Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA1c <6.5% (<48 mmol/mol) compared

2019 BMJ

8. Efficacy and safety of mineralocorticoid receptor antagonists with ACEI/ARB treatment for diabetic nephropathy: A meta-analysis (Abstract)

Efficacy and safety of mineralocorticoid receptor antagonists with ACEI/ARB treatment for diabetic nephropathy: A meta-analysis To explore the efficacy and safety of adding mineralocorticoid receptor antagonists (MRAs) to the treatment in diabetic nephropathy (DN) with ACEI/ARB.We systematically searched the PubMed, Embase and Cochrane Library databases for randomised controlled trials up to November 1st 2018 that evaluated the effects of MRAs with ACEI/ARB treatment.The combination treatment

2019 EvidenceUpdates

9. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. Full Text available with Trip Pro

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic (...) had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture.In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

2019 NEJM Controlled trial quality: predicted high

10. [Urine proteomic analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension]

[Urine proteomic analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension] Proteomanalyse im urin zur erkennung einer diabetischen nephropathie bei patientinnen und patienten mit diabetes mellitus und arteriellem hypertonus [Urine proteomic analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension] Proteomanalyse im urin zur erkennung einer diabetischen nephropathie bei patientinnen und (...) patienten mit diabetes mellitus und arteriellem hypertonus [Urine proteomic analysis for detection of diabetic nephropathy in patients with diabetes mellitus and arterial hypertension] IQWiG Record Status This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database. Citation IQWiG. Proteomanalyse im urin zur erkennung einer diabetischen nephropathie bei patientinnen und patienten mit

2016 Health Technology Assessment (HTA) Database.

11. Effect of PF-04634817, an Oral CCR2/5 Chemokine Receptor Antagonist, on Albuminuria in Adults with Overt Diabetic Nephropathy Full Text available with Trip Pro

Effect of PF-04634817, an Oral CCR2/5 Chemokine Receptor Antagonist, on Albuminuria in Adults with Overt Diabetic Nephropathy Inflammatory cell recruitment, which is potentially mediated by the monocyte chemoattractant protein 1/C-C chemokine receptor type 2 (CCR2) system and by C-C chemokine receptor type 5 (CCR5) activity, may play a role in the development and progression of diabetic nephropathy. PF-04634817 is a dual chemokine CCR2/5 receptor antagonist that is being developed (...) for the treatment of diabetic nephropathy.We evaluated the efficacy of PF-04634817 compared with matching placebo for reduction of albuminuria after 12 weeks of treatment in subjects with type 2 diabetes who received standard of care (SOC; angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy), in a randomized, double-blind, placebo-controlled, parallel-group phase 2 study.A total of 226 subjects who received SOC with baseline estimated glomerular filtration rates between 20 and 75 ml

2018 Kidney international reports Controlled trial quality: predicted high

12. Long‐term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin‐converting enzymes/angiotensin receptor blockers: results from AMETHYST‐DN Full Text available with Trip Pro

Long‐term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin‐converting enzymes/angiotensin receptor blockers: results from AMETHYST‐DN Chronic kidney disease (CKD) in heart failure (HF) increases the risk of hyperkalaemia (HK), limiting angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) use. Patiromer is a sodium-free, non-absorbed potassium binder approved for HK treatment. We (...) retrospectively evaluated patiromer's long-term safety and efficacy in HF patients from AMETHYST-DN.Patients with Type 2 diabetes, CKD, and HK [baseline serum potassium >5.0-5.5 mmol/L (mild) or >5.5-<6.0 mmol/L (moderate)], with or without HF (New York Heart Association Class I and II, by investigator judgement), on ACE-I/ARB, were randomized to patiromer 8.4-33.6 g to start, divided twice daily. Overall, 105/304 (35%) patients had HF (75%, Class II). Mean (standard deviation) ejection fraction (EF) was 44.9

2018 ESC heart failure Controlled trial quality: uncertain

13. Proteomic and bioinformatic discovery of biomarkers for diabetic nephropathy Full Text available with Trip Pro

Proteomic and bioinformatic discovery of biomarkers for diabetic nephropathy Diabetes is associated with numerous metabolic and vascular risk factors that contribute to a high rate of micro-vascular and macro-vascular disorders leading to mortality and morbidity from diabetic complications. In this case, the major cause of death in overall diabetic patients results from diabetic nephropathy (DN) or renal failure. The risk factors and mechanisms that correspond to the development of DN (...) are not fully understood and so far, no specific and sufficient diagnostic biomarkers are currently available other than micro- or macroalbuminuria. Therefore, this review describes current and novel protein biomarkers in the context of DN as well as probable proteins biomarkers associated with pathological processes for the early stage of DN via proteomics data together with bioinformatics. In addition, the mechanisms involved in early development of diabetic vascular disorders and complications resulting

2018 EXCLI journal

14. Rationale and protocol of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial: A clinical trial design novel to diabetic nephropathy. Full Text available with Trip Pro

Rationale and protocol of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial: A clinical trial design novel to diabetic nephropathy. Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR (...) ), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit.SONAR is a randomized, double-blind, placebo-controlled trial with approximately 3500 participants who have stage 2-4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin-angiotensin system inhibitor.After 6 weeks

2018 obesity & metabolism Controlled trial quality: predicted high

15. A variant within the FTO confers susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes. Full Text available with Trip Pro

A variant within the FTO confers susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes. To explore novel genetic loci for diabetic nephropathy, we performed genome-wide association studies (GWAS) for diabetic nephropathy in Japanese patients with type 2 diabetes. We analyzed the association of 5,768,242 single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes, 2,380 nephropathy cases and 5,234 controls. We further performed GWAS for diabetic (...) nephropathy using independent Japanese patients with type 2 diabetes, 429 cases and 358 controls and the results of these two GWAS were combined with an inverse variance meta-analysis (stage-1), followed by a de novo genotyping for the candidate SNP loci (p < 1.0 × 10-4) in an independent case-control study (Stage-2; 1,213 cases and 1,298 controls). After integrating stage-1 and stage-2 data, we identified one SNP locus, significantly associated with diabetic nephropathy; rs56094641 in FTO, P = 7.74 × 10

2018 PLoS ONE

16. Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes Full Text available with Trip Pro

Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes Diabetic nephropathy (DN) is a form of progressive kidney disease that often leads to end-stage renal disease (ESRD). It is initiated by microvascular complications due to diabetes. Although microalbuminuria (MA) is the earliest clinical indication of DN among patients with type 1 diabetes (T1D), it lacks the sensitivity and specificity to detect the early onset of DN (...) . Recently, microRNAs (miRNAs) have emerged as critical regulators in diabetes as well as various forms of kidney disease, including renal fibrosis, acute kidney injury, and progressive kidney disease. Additionally, circulating extracellular miRNAs, especially miRNAs packaged in extracellular vesicles (EVs), have garnered significant attention as potential noninvasive biomarkers for various diseases and health conditions.As part of the University of Pittsburgh Epidemiology of Diabetes Complications (EDC

2017 Kidney international reports

17. Socioeconomic differences among community-dwelling diabetic adults screened for diabetic retinopathy and nephropathy: The 2015 Korean Community Health Survey. Full Text available with Trip Pro

Socioeconomic differences among community-dwelling diabetic adults screened for diabetic retinopathy and nephropathy: The 2015 Korean Community Health Survey. We investigated the association between socioeconomic status (SES) and screening for diabetic retinopathy (DR) and diabetic nephropathy (DN) in community-dwelling diabetics. We analyzed data from 22,134 people with diabetes aged ≥19 years at the time of the nationwide 2015 Korean Community Health Survey. Multiple logistic regression (...) analysis was used to explore the relationship between SES and screening for DR and DN both before and after adjustment for health behaviors, comorbidities, and educational level. Of all diabetic subjects, 33.9% and 38.1% underwent DR and DN screening, respectively. In the fully adjusted model, the extent of the DR and DN screening trended significantly lower as the educational level fell. Monthly household income was positively associated with DR screening, but a lower odds ratio (OR) for DN screening

2018 PLoS ONE

18. Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy Full Text available with Trip Pro

Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease.In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses (...) acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts.In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes

2017 Kidney international reports

19. Serum levels of CTRP3 in diabetic nephropathy and its relationship with insulin resistance and kidney function. Full Text available with Trip Pro

Serum levels of CTRP3 in diabetic nephropathy and its relationship with insulin resistance and kidney function. C1q TNF related protein 3 (CTRP3) is an adipokine secreted from adipose tissue. Previous studies have suggested that CTRP3 improves insulin sensitivity and reduces inflammation. Human studies have evaluated circulating levels of this adipokine in patients with diabetes mellitus (DM), diabetic retinopathy, metabolic syndrome, and coronary artery diseases. However, circulating levels (...) of this adipokine in patients with diabetic nephropathy have not been evaluated. The present study aimed to assess serum levels of CTRP3 in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (T2DM-NP) and its relationship with metabolic and inflammatory markers.This cross-sectional study was performed on 55 controls, 54 patients with T2DM, and 55 patients with T2DM-NP. Serum levels of CTRP3, adiponectin, TNF-α, and IL-6 were measured by ELISA technique.Serum levels of CTRP3 were

2019 PLoS ONE

20. Involvement of Elf3 on Smad3 activation-dependent injuries in podocytes and excretion of urinary exosome in diabetic nephropathy. Full Text available with Trip Pro

Involvement of Elf3 on Smad3 activation-dependent injuries in podocytes and excretion of urinary exosome in diabetic nephropathy. Diabetic nephropathy (DN) is among the most serious complications of diabetes mellitus, and often leads to end-stage renal disease ultimately requiring dialysis or renal transplantation. The loss of podocytes has been reported to have a role in the onset and progression of DN. Here, we addressed the activation mechanism of Smad3 signaling in podocytes. Expression (...) of RII and activation of Smad3 were induced by AGE exposure (P<0.05). Reduction of the activation of RII-Smad3 signaling ameliorated podocyte injuries in Smad3-knockout diabetic mice. The bone morphogenetic protein 4 (BMP4) significantly regulated activation of RII-Smad3 signalings (P<0.05). Moreover, the epithelium-specific transcription factor, Elf3was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Smad3

2019 PLoS ONE

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