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Update On The Protective Renal Effects Of Metformin In Diabetic Nephropathy

Update On The Protective Renal Effects Of Metformin In Diabetic Nephropathy

Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy Author(s): Andreas Eisenreich* , Charite- Universitatsmedizin Berlin, Institut fur Klinische Pharmakologie und Toxikologie, Chariteplatz 1, 10117 Berlin, Germany Ulrike Leppert . Charite-Universitatsmedizin Berlin, Institut fur Physiologie, Chariteplatz 1, 10117 Berlin, Germany Journal Name: Current Medicinal Chemistry Background: Diabetic nephropathy is one of the most important complicationsin patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabeticnephropathy involve amongst others the modulation of cell signaling via AMP-activatedkinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation,and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. Theseprocesses mediate increased loss of renal cells, such as podocytes, which consequentiallyleads to renal damage and loss of renal functions, such as structural integrity and glomerularfiltration in diabetic nephropathy. The anti-diabetic drug metformin has been widelyused for pharmacotherapeutic treatment of patients with diabetes mellitus. Besides itsanti-diabetic actions, recent studies revealed additional nephroprotective effects of metforminin vitro and in vivo. Metformin was found to diminish apoptosis in different experimentalrenal settings. Moreover, it was shown to reduce albuminuria in diabetic ratsas well as in patients with type 2 diabetes mellitus. These effects were demonstrated to bemediated via the AMPK/mTOR signaling axis. These data indicate beneficial and renoprotectiveeffects of metformin in diabetic nephropathy. Objective: In this review, we will summarize the latest findings regarding the nephroprotectiveimpact of metformin in vitro and in vivo. Moreover, Continue reading >>

Recent Advances In Management Of Diabetic Nephropathy

Recent Advances In Management Of Diabetic Nephropathy

To view this video please enable JavaScript, and consider upgrading to a web browser that supports HTML5 video Recent advances in management of Diabetic Nephropathy Published by Robyn Perry Modified over 2 years ago Presentation on theme: "Recent advances in management of Diabetic Nephropathy" Presentation transcript: 1 Recent advances in management of Diabetic Nephropathy 4 Diabetic nephropathy Diabetic nephropathy is progressive kidney disease Most common cause of ESRD More likely to die than progress to ESRD Multi-risk factor intervention is critical Lowering blood pressure with RAAS blockade is critical Combinations of ACEi + ARB or MRA sensible No long term efficacy or safety data Prevent cardiovascular morbidity and mortality 6 Diabetes: The Most Common Cause of ESRD Primary Diagnosis for Patients Who Start Dialysis Diabetes 50.1% Hypertension 27% Glomerulonephritis 13% Other 10% No. of patients Projection 95% CI 700 600 500 No. of dialysis patients (thousands) 400 The pie chart shows that diabetes is currently the most common cause of ESRD. The lower graph reveals that the number of patients with ESRD maintained on dialysis is predicted to double over present levels by 2010, and the major contributor to this exponential increase is chronic renal failure associated with diabetes. 300 520,240 281,355 200 243,524 100 r2=99.8% 1984 1988 1992 1996 2000 2004 2008 United States Renal Data System. Annual data report United States Renal Data System. Annual data report Available at: Accessed April 25, 2001. 7 Cardiovascular Death is Major Cause of Mortality in ESRD 100 ESRD Population GP Male 10 GP Female GP Black 1 GP White Annual Cardiovascular Mortality (%) General Population Dialysis Male 0.1 Dialysis Female Dialysis Black 0.01 Key point: CVD mortality is 10-fold high Continue reading >>

My Site - Chapter 29: Chronic Kidney Disease In Diabetes

My Site - Chapter 29: Chronic Kidney Disease In Diabetes

Identification of chronic kidney disease in people with diabetes requires screening for proteinuria, as well as an assessment of serum creatinine converted into an estimated glomerular function rate (eGFR). All individuals with chronic kidney disease should be considered at high risk for cardiovascular events and should be treated to reduce these risks. The development and progression of renal damage in diabetes can be reduced and slowed through intensive glycemic control and optimization of blood pressure. Progression of chronic kidney disease in diabetes can also be slowed through the use of medications that disrupt the renin angiotensin aldosterone system. The earlier that the signs and symptoms of chronic kidney disease in diabetes are detected, the better, as it will reduce the chance of progression to advanced kidney disease and the need for dialysis or transplant. You should have your blood and urine tested annually for early signs of chronic kidney disease in diabetes. If you are found to have signs of chronic kidney disease, your health-care provider may recommend lifestyle or medication changes to help delay more damage to your kidneys. Management of Potassium and Creatinine During the Use of Angiotensin Converting Enzyme (ACE) inhibitor or Angiotensin II Receptor Blocker (ARB) or Direct Renin Inhibitor (DRI) Therapy Check serum potassium and creatinine at baseline and within 1 to 2 weeks of initiation or titration of therapy AND during times of acute illness. If potassium becomes elevated or creatinine increases by more than 30% from baseline, therapy should be reviewed and serum creatinine and potassium levels should be rechecked. If persistent, non-potassium-sparing diuretics and/or oral sodium bicarbonate (in those with a metabolic acidosis) should be con Continue reading >>

Current Challenges In Diabetic Nephropathy: Early Diagnosis And Ways To Improve Outcomes

Current Challenges In Diabetic Nephropathy: Early Diagnosis And Ways To Improve Outcomes

Current Challenges in Diabetic Nephropathy: Early Diagnosis and Ways to Improve Outcomes Sang Soo Kim , Jong Ho Kim , and In Joo Kim Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea. Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea. Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea. Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea. Corresponding author: In Joo Kim. Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea. Tel: +82-51-240-7224, Fax: +82-51-254-3127, [email protected] Received 2016 Apr 29; Revised 2016 May 4; Accepted 2016 May 13. Copyright 2016 Korean Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Diabetes is often associated with chronic kidney disease (CKD) and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burde Continue reading >>

Educate Physicians And Nurses On Practical Management Tips For Diabetes Control.

Educate Physicians And Nurses On Practical Management Tips For Diabetes Control.

Type 2 Diabetes Common in Hispanics, Native Americans and Pima Indians Incidence of ESRD is lower, but the disease is more frequent – thus it is the most common cause of renal failure United Kingdom Prospective Diabetes Study UKPDS – large British study, (predominantly Caucasians) Adler, AI, Stevens, RJ, Manley, SE, Bilous, RW, Cull, CA & Holman, RR: Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int, 63:225-32, 2003. Incidence of microalbuminuria 25% but incidence of ESRD only 0.8% Microlbuminuria patients spent an average of 11 years before progressing to overt proteinuria Only 2.3% progress from macroalbuminuria to ESRD 1. Hypertension in people with Type 2 diabetes: knowledge-based diabetes-specific guidelines. Diabet Med, 20:972-87, 2003. 2. Abbott, KC & Bakris, GL: What have we learned from the current trials? Med Clin North Am, 88:189-207, 2004. 3. Anderson, PW, McGill, JB & Tuttle, KR: Protein kinase C beta inhibition: the promise for treatment of diabetic nephropathy. Curr Opin Nephrol Hypertens, 16:397-402, 2007. 4. Baghdasarian, SB, Jneid, H & Hoogwerf, BJ: Association of dyslipidemia and effects of statins on nonmacrovascular diseases. Clin Ther, 26:337-51, 2004. 5. Bakris, GL, Weir, MR, Shanifar, S, Zhang, Z, Douglas, J, van Dijk, DJ & Brenner, BM: Effects of blood pressure level on progression of diabetic nephropathy: results from the RENAAL study. Arch Intern Med, 163:1555-65, 2003. 6. Bando, Y, Ushiogi, Y, Okafuji, K, Toya, D, Tanaka, N & Miura, S: Non-autoimmune primary hypothyroidism in diabetic and non-diabetic chronic renal dysfunction. Exp Clin Endocrinol Diabetes, 110:408-15, 2002. 7. Berl, T, Hunsicker, LG, Lewis, JB, Pfeffer, MA, Porush, JG, Rouleau, JL Continue reading >>

Classification And Differential Diagnosis Of Diabetic Nephropathy

Classification And Differential Diagnosis Of Diabetic Nephropathy

Copyright © 2017 Chenyang Qi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review. 1. Introduction Diabetic nephropathy (DN) caused by diabetes mellitus is one of the major causes of end-stage renal failure worldwide [1]. Clinically, microalbuminuria is an important index to assess the progression of DN [2]. However, it is not accurate to evaluate the severity or prognosis simply based on the degree of proteinuria. It is now well recognized that not all diabetic patients who develop renal function failure have massive albuminuria [3]. Therefore, nephrologists and endocrinologists should be aware of the significance of pathological c Continue reading >>

Recent Advances In Managing And Understanding Diabetic Nephropathy

Recent Advances In Managing And Understanding Diabetic Nephropathy

Recent advances in managing and understanding diabetic nephropathy 1Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong 1Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong 1Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong 2Nephrology Department, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong 1Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong 2Nephrology Department, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options. This review article focuses on available data from landmark studies on the main therapeutic approaches and highlights some novel management strategies. Keywords: Diabetic nephropathy, glycemia control Diabetic nephropathy (DN) affects approximately one-third of individuals with diabetes mellitus (DM) and carries with it considerable cardiovascular morbidity and mortality. Despite modern management of DM, the Continue reading >>

Management Of Diabetic Nephropathy

Management Of Diabetic Nephropathy

Lukas Foggensteiner , BM MRCP, Sharon Mulroy , DM MRCP, and John Firth , DM FRCP Dialysis Centre, Box 118 Addenbrooke's Hospital, Cambridge CB2 2QQ, UK Correspondence to: Dr Lukas Foggensteiner E-mail: [email protected] Copyright 2001, The Royal Society of Medicine This article has been cited by other articles in PMC. Diabetic nephropathy is the single most common cause of end-stage renal disease in the western world and is associated with greatly increased cardiovascular morbidity and mortality. With the rising prevalence of type 2 disease it has come to pose a heavy burden on healthcare systems worldwide. Investment in fundamental and clinical research has yielded strategies that can reduce the risk of diabetic renal disease and slow its progression. Type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes are aetiologically and epidemiologically distinct conditions affecting different segments of the population. Nevertheless, no major difference has been identified between the nephropathies seen in these conditions, either pathophysiologically or in terms of management. They can thus be conveniently considered together. It should be remembered, however, that patients with type 2 diabetes tend to be older and more hypertensive, and thus more likely to have concomitant hypertensive and renovascular disease. The association of proteinuria with diabetes was first recognized in the eighteenth century but it was Kimmelstiel and Wilson 1 in 1936 who defined the condition by describing the lesions of nodular glomerulosclerosis and the association with proteinuria and hypertension in type 2 diabetes. These features represent a late stage in the progression of the condition. Subsequent work, mainly on type 1 diabetes, led to the definition of sever Continue reading >>

Diabetic Nephropathy

Diabetic Nephropathy

Author: Vecihi Batuman, MD, FASN; Chief Editor: Romesh Khardori, MD, PhD, FACP more... Diabetic nephropathy is a clinical syndrome characterized by the following [ 1 ] : Persistent albuminuria (>300 mg/d or >200 g/min) that is confirmed on at least 2 occasions 3-6 months apart Progressive decline in the glomerular filtration rate (GFR) Elevated arterial blood pressure (see Workup) Proteinuria was first recognized in diabetes mellitus in the late 18th century. In the 1930s, Kimmelstiel and Wilson described the classic lesions of nodular glomerulosclerosis in diabetes associated with proteinuria and hypertension. (See Pathophysiology.) By the 1950s, kidney disease was clearly recognized as a common complication of diabetes, with as many as 50% of patients with diabetes of more than 20 years having this complication. (See Epidemiology.) Currently, diabetic nephropathy is the leading cause of chronic kidney disease in the United States and other Western societies. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes. Diabetes is responsible for 30-40% of all end-stage renal disease (ESRD) cases in the United States. (See Prognosis.) Generally, diabetic nephropathy is considered after a routine urinalysis and screening for microalbuminuria in the setting of diabetes. Patients may have physical findings associated with long-standing diabetes mellitus. (See Clinical Presentation.) Good evidence suggests that early treatment delays or prevents the onset of diabetic nephropathy or diabetic kidney disease. This has consistently been shown in both type1 and type 2 diabetes mellitus. (See Treatment and Management). Regular outpatient follow-up is key in managing diabetic nephropathy successfully. ( Continue reading >>

Diabetic Nephropathytreatment & Management

Diabetic Nephropathytreatment & Management

Diabetic NephropathyTreatment & Management Author: Vecihi Batuman, MD, FASN; Chief Editor: Romesh Khardori, MD, PhD, FACP more... Several issues are key in the medical care of patients with diabetic nephropathy. [ 20 , 21 ] These include glycemic control, management of hypertension, and reducing dietary salt intake and phosphorus and potassium restriction in advanced cases. A meta-analysis from the Cochrane Database shows a large fall in blood pressure with salt restriction, similar to that of single-drug therapy. [ 22 ] All diabetic patientsshould consider reducing salt intake at least to less than 5-6 g/d, in keeping with current recommendations for the general population, and may benefit from lowering salt intake to even lower levels. Reducing dietary salt intake may help slow progression of diabetic kidney disease. Renal replacement therapy may be necessary in patients with end-stage renal disease (ESRD). A 2012 post-hoc analysis of the data merged from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial and the Irbesartan Diabetic Nephropathy Trial (IDNT) in 1177 patients demonstrated that a low-sodium diet (24-h urinary sodium/creatinine ratio (mmol/g) < 121) enhanced the renoprotective and cardioprotective effect of angiotensin receptor blockers (losartan or irbesartan) in type 2 diabetic patients with nephropathy. Compared with higher sodium intake groups, the patients in the low-sodium group had better renal (by 43%) and cardiovascular (by 37%) outcomes. These improved outcomes in the low-sodium group underscore the importance of recent calls for population-wide intervention to reduce dietary salt intake, particularly in patients with diabetes and nephropathy treated with angiotensin receptor blockers. [ 23 ] In perso Continue reading >>

Ppt Diabetic Nephropathy Powerpoint Presentation | Free To Download - Id: 1cc35f-ntq0n

Ppt Diabetic Nephropathy Powerpoint Presentation | Free To Download - Id: 1cc35f-ntq0n

PPT Diabetic Nephropathy PowerPoint presentation | free to download - id: 1cc35f-NTQ0N The Adobe Flash plugin is needed to view this content In 2001, 41,312 people with diabetes began treatment for end-stage renal disease. ... Wastes, excess water, and salt are removed from blood using a dialyzer ... PowerPoint PPT presentation Over 40 of new cases of end-stage renal disease In 2001, 41,312 people with diabetes began In 2001, it cost 22.8 billion in public and private funds to treat patients with kidney Minorities experience higher than average rates Stage 1 Hyperfiltration, or an increase in glomerular filtration rate (GFR) occurs. Kidneys increase in size. Stage 2 Glomeruli begin to show damage and microalbuminurea occurs. Stage 3 Albumin excretion rate (AER) exceeds 200 micrograms/minute, and blood levels of creatinine and urea-nitrogen rise. Blood pressure may rise Stage 4 GFR decreases to less than 75 ml/min, large amounts of protein pass into the urine, and high blood pressure almost always occurs. Levels of creatinine and urea-nitrogen in the blood rise further. Stage 5 Kidney failure, or end stage renal disease (ESRD). GFR is less than 10 ml/min. The average length of time to progress from Stage 1 to Stage 4 kidney disease is 17 years for a person with type 1 diabetes. The average length of time to progress to Stage 5, kidney failure, Bethesda, MD National Institute of Diabetes and PowerShow.com is a leading presentation/slideshow sharing website. Whether your application is business, how-to, education, medicine, school, church, sales, marketing, online training or just for fun, PowerShow.com is a great resource. And, best of all, most of its cool features are free and easy to use. You can use PowerShow.com to find and download example online PowerPoint ppt pre Continue reading >>

Albumin Antioxidant Response To Stress In Diabetic Nephropathy Progression

Albumin Antioxidant Response To Stress In Diabetic Nephropathy Progression

Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression Affiliation Department of Experimental Metabolism, Center for Biomedical Research of Michoacn (CIBIMI-IMSS), Morelia, Michoacn, Mxico Affiliation Department of Nephrology, General Regional Hospital N 1, IMSS, Morelia, Michoacn, Mexico Affiliation Department of Nephrology, General Regional Hospital N 1, IMSS, Morelia, Michoacn, Mexico Affiliation Biochemistry Medical Research Unit, National Medical Center, IMSS, Mxico City, Mxico Affiliation Biochemistry Medical Research Unit, National Medical Center, IMSS, Mxico City, Mxico Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage. Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively co Continue reading >>

The Pathogenesis Of Diabetic Nephropathy

The Pathogenesis Of Diabetic Nephropathy

Held PJ et al. (1991) The United States Renal Data Systems 1991 annual data report: an introduction. Am J Kidney Dis 18: 1-16 Makino H et al. (1996) Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. Diabetes 45: 488-495 Mauer SM et al. (1984) Structural-functional relationships in diabetic nephropathy. J Clin Invest 74: 1143-1155 Nielsen S et al. (1997) The clinical course of renal function in NIDDM patients with normo- and microalbuminuria. J Intern Med 241: 133-141 Raile K et al. (2007) Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care 30: 2523-2528 Remuzzi G et al. (2002) Clinical practice. Nephropathy in patients with type 2 diabetes. N Engl J Med 346: 1145-1151 Steinke JM et al. (2005) The early natural history of nephropathy in type 1 diabetes: III. Predictors of 5-year urinary albumin excretion rate patterns in initially normoalbuminuric patients. Diabetes 54:2164-2171 Ziyadeh FN (2004) Mediators of diabetic renal disease: the case for TGF- as the major mediator. J Am Soc Nephrol 15 (Suppl 1): S55-S57 Ichinose K et al. (2007) Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy. Am J Nephrol 27: 554-564 Raptis AE and Viberti G (2001) Pathogenesis of diabetic nephropathy. Exp Clin Endocrinol Diabetes 109 (Suppl 2): S424-S437 Singh DK et al. (2008) Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol 4: 216-226 Ziyadeh FN and Wolf G (2008) Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 4: 39-45 Wolf G and Ziyadeh FN (1999) Molecular me Continue reading >>

Diabetic Nephropathy

Diabetic Nephropathy

Nephropathy means kidney disease or damage. Diabetic nephropathy is damage to your kidneys caused by diabetes. In severe cases it can lead to kidney failure. But not everyone with diabetes has kidney damage. The kidneys have many tiny blood vessels that filter waste from your blood. High blood sugar from diabetes can destroy these blood vessels. Over time, the kidney isn't able to do its job as well. Later it may stop working completely. This is called kidney failure. Diabetic nephropathy is treated with medicines that lower blood pressure and protect the kidneys. These medicines may slow down kidney damage and are started as soon as any amount of protein is found in the urine. The use of these medicines before nephropathy occurs may also help prevent nephropathy in people who have normal blood pressure. If you have high blood pressure, two or more medicines may be needed to lower your blood pressure enough to protect the kidneys. Medicines are added one at a time as needed. The estimate of the actual number of diabetics in India is around 40 million. The prevalence of IGT is thought to be around 8.7 per cent in urban areas and 7.9 per cent in rural areas, although this estimate may be too high. It is thought that around 35 per cent of IGT sufferers go on to develop type 2 diabetes, so India is genuinely facing a healthcare crisis. Inhibition of the renin-angiotensin system is important to reduce intra glomerular pressure but other classes of antihypertensive agent may also be needed to gain adequate control of systemic blood pressure. Such measures can at least half the rate of progression of nephropathy and cardiovascular disease. Continue reading >>

Sglt-2 Inhibition: A Potential New Treatment For Diabetic Kidney Disease?

Sglt-2 Inhibition: A Potential New Treatment For Diabetic Kidney Disease?

Abstract Diabetic nephropathy is the leading cause of kidney failure. Treatments with drugs that block the renin-angiotensin system have proven beneficial in slowing kidney disease progression among those with diabetes; their benefit is limited and they do not stop disease progression. Despite multiple clinical trials of various interventions including dual blockade of the renin-angiotensin system over the past 15 years, no new therapies have emerged to slow kidney disease progression in diabetes. SGLT-2 inhibitors are a new class of antiglycemic drugs that have been shown to lower blood glucose by inhibition of the sodium-glucose transporter 2 in the proximal tubule of the kidney. Several of these inhibitors have been marketed for treatment of hyperglycemia in patients with type 2 diabetes mellitus. In a recent double-blind randomized and placebo-controlled trial of cardiovascular outcomes, an SGLT-2 inhibitor-based intervention using empagliflozin was shown to be superior to placebo-based regimen for reducing the risk of major cardiovascular events among people with type 2 diabetes and established cardiovascular disease. In a pre-specified secondary analysis of renal outcomes from this trial, Wanner et al. [N Engl J Med 2016;375:323-334] recently reported that empagliflozin administration was also associated with significant reductions in the progression of kidney disease including the rate of decline in estimated glomerular filtration rate (eGFR), progression of albuminuria and initiation of renal replacement therapy. While the results of this trial are striking and impressive, the majority of those enrolled in the trial did not have evidence of diabetic kidney disease as assessed by eGFR or albuminuria. Thus, whether or not they represent a breakthrough in the treat Continue reading >>

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