Novel avenues for treating diabetic nephropathy: new investigational drugs (original) (raw)

Novel Therapies for Diabetic Kidney Disease: Storied Past and Forward Paths

Diabetes Spectrum, 2015

IN BRIEF Current therapeutic approaches are only moderately efficacious at preventing the progression of diabetic kidney disease (DKD). As the number of people with DKD continues to rise worldwide, there is an urgent need for novel therapies. A better understanding of the root causes and molecular mechanisms of DKD pathogenesis has enabled the identification of numerous new therapeutic targets, including advanced glycation end products, reactive oxygen species, protein kinase C, and serum amyloid A. Although experimental studies have illustrated the potential of such approaches, challenges in clinical translation remain a barrier in therapeutic development. Advances in preclinical safety and efficacy evaluations and improved delivery systems may aid in clinical translation of novel DKD therapies.

Potential New Therapeutic Agents for Diabetic Kidney Disease

American Journal of Kidney Diseases, 2010

Diabetic nephropathy is the leading cause of end-stage renal disease, and both the incidence and prevalence of diabetic nephropathy continue to increase. Currently, various treatment regimens and combinations of therapies provide only partial renoprotection. It is obvious that new approaches are desperately needed to retard the progression of diabetic nephropathy. Recently, a number of new agents have been described that have the potential to delay the progression of diabetic kidney disease and minimize the growing burden of end-stage renal disease. These include inhibitors and breakers of advanced glycation end products, receptor antagonists for advanced glycation end products, protein kinase C inhibitors, NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase inhibitors, glycosaminoglycans, endothelin receptor antagonists, antifibrotic agents, and growth factor inhibitors. This review addresses these promising new therapeutic agents for delaying the progression of diabetic kidney disease. Am J Kidney Dis 55:928-940.

Drug Therapy Targets for Diabetic Nephropathy: An Overview

International Journal of Pharmaceutical Sciences Review and Research

Diabetic nephropathy is a leading cause of chronic kidney disease and end stage renal disease and accounts for significant morbidity and mortality in diabetic patients. Hyperglycemia may lead to end stage renal damage through both metabolic and non metabolic pathways. The non-enzymatic glycation of proteins with irreversible formation and deposition of reactive advanced glycation end products (AGE) have been noted to play a major role in the pathogenesis of diabetic nephropathy. Further, diabetic nephropathy is associated with hyperactivity of sorbitol aldose reductase pathway, hyperactivity of hexosamine biosynthetic pathway, activation of protein kinase C and MAPK and overexpression of growth factors and cytokines i.e. transforming growth factor-β, vascular endothelial growth factor, platelet-derived growth factor and insulin-like growth factor. Moreover, high glucose concentration in diabetes has been noted to induce oxidative and nitrosative stress, activate intracellular RAAS and release endothelin-1 and prostaglandins to deteriorate the function of kidney. In addition, up-regulation of transforming growth factor-β (TGF-β) and consequent overproduction of extracellular matrix molecules have been implicated in the progression of diabetic nephropathy. The present review study the various drug targets and drug therapy in diabetic nephropathy.

New pharmacological treatments for improving renal outcomes in diabetes

Nature reviews. Nephrology, 2010

Diabetic nephropathy is the most common and most rapidly growing cause of end-stage renal failure in developed countries. Diabetic nephropathy results from complex interactions between genetic, metabolic and hemodynamic factors. Improvements in our understanding of the pathogenesis of fibrosis associated with diabetic kidney disease have led to the identification of several novel targets for the treatment of diabetic nephropathy. Albuminuria is a useful clinical marker of diabetic nephropathy, as it can be used to predict a decline in renal function. A reduction in albuminuria might not, however, be reflective of a protective effect of therapies focused on ameliorating renal fibrosis. Although new strategies for slowing down the progression of several types of renal disease have emerged, the challenge of arresting the relentless progression of diabetic nephropathy remains. In this Review, we discuss novel pharmacological approaches that aim to improve the renal outcomes of diabetic ...

Therapeutic Modalities in Diabetic Nephropathy: <i>Future Approaches</i&gt

Open journal of nephrology, 2012

Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Several therapeutic interventions for the treatment of diabetic nephropathy have been developed and implemented over the past few decades with some degree of success. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are therefore urgently needed. Recently, several novel therapeutic strategies have been explored in treating DN patients including Islet cell transplant, Aldose reductase inhibitors, Sulodexide (GAC), Protein Kinase C (PKC) inhibitors, Connective tissue growth factor (CTGF) inhibitors, Transforming growth factor-beta (TGF-β) inhibitors and bardoxolone. The benefits and risks of these agents are still under investigation. This review aims to summarize the utility of these novel therapeutic approaches.

Novel effective drugs for diabetic kidney disease? or not

Introduction: Diabetes mellitus is increasingly common worldwide and is expected to affect 592 million people by 2035. The kidney is often involved. A key goal in treating diabetes is to reduce the risk of development of kidney disease and, if kidney disease is already present, to delay the progression to end-stage renal disease (ESRD). This represents a social and ethical issue, as a significant proportion of patients reaching ESRD in developing countries do not have access to renal replacement therapy. Areas covered: The present review focuses on novel therapeutic approaches for diabetic nephropathy (DN), implemented on the basis of recent insights on its pathophysiology, which might complement the effects of single inhibition of the renin-angiotensin-aldosterone system (RAAS), the cornerstone of renoprotective interventions in diabetes, along with glycemic and blood pressure control. Expert opinion: Although a plethora of new treatment options has arisen from experimental studies, the number of novel renoprotective molecules successfully implemented in clinical practice over the last two decades is disappointingly low. Thus, new investigational strategies and diagnostic tools -- including the appropriate choice of relevant renal end points and the study of urinary proteome of patients -- will be as important as new therapeutic interventions to fight DN. Finally, in spite of huge financial interests in replacing the less expensive ACE inhibitors and angiotensin II receptor blockers with newer drugs, any future therapeutic approach has to be tested on top of -- rather than instead of -- optimal RAAS blockade.

Slowing Diabetic Kidney Disease Progression: Where Do We Stand Today?

ADA Clinical Compendia

This article aims to provide an overview of the major clinical trials conducted within the past 20 years, addressing this critical clinical need. Specifically, we will review several therapeutic drug classes that have demonstrated renoprotective potential by halting the progression of DKD.

Overview: Combating Diabetic Nephropathy

Journal of the American Society of Nephrology, 2003

Much has been said in the scientific and lay media about the growing epidemic of diabetes around the globe, but individuals and societies should never lose sight of the immeasurable human suffering and the enormous healthcare costs that this epidemic exacts. With the growing population of type 2 diabetes, the prevalence of diabetic nephropathy is on the rise, and there is an urgent need to define the pathophysiologic mechanisms for this devastating disorder. Genetic factors conspire with metabolic and hemodynamic insults to induce renal injury in susceptible individuals. In the current issue of the Journal of the American Society of Nephrology, four authoritative papers provide a balanced overview of the pathogenesis of the disease along with a comprehensive update on the clinical aspects and current management of diabetic nephropathy. Only by translating the new understanding of diabetic nephropathy into medical practice and implementing widespread clinical guidelines will we ever ensure that all at-risk patients receive the ideal care to stem the epidemic and stop nephropathy in its tracks.