Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches (original) (raw)

Diabetic nephropathy: Clinical presentation, course, and novel treatment possibilities

Opsta medicina

Diabetic kidney disease (DBD) is one of the major complications of diabetes (DM) and the leading cause of chronic kidney disease (CKD) worldwide. About 10% of patients with DBD progress to terminal HBB, and the rest die mostly due to cardiovascular disorders and infection even before they need treatment for kidney replacement. The main strategies to prevent the development and alleviate the progression of DBB in recent decades have been intensive glycemic control and blockade of the renin-angiotensin-aldosterone system. However, this approach did not achieve optimal results. Taking into account the increase in patients with DBB, high spending from the health care budget and the development of new therapeutic possibilities with significant kidney protection, the International Society of Nephrology issued in 2020. (Kidney Disease: Improving Global Outcomes (KDIGO) Guideline) is the first guide to treating patients with DBB. This review paper aims to point out phenotypic variability an...

Diabetic nephropathy: Pathophysiology, Staging, Prevalence, and Management

IP International Journal of Comprehensive and Advanced Pharmacology

Diabetes mellitus (DM) has become a significant economic burden because of high healthcare costs for the treatment and its related complications. Chronic hyperglycemia, affect severely our organ systems mainly, cardiovascular, nervous, and renal system. These diabetic complications can progress into morbidity and mortality. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) which affects 20-30% diabetic patients, characterized by sustained reduction in end glomerular filtration rate (GFR)and persistently high urinary albumin-to-creatinine ratio. Elevated glucose levels, high blood pressure long duration of diabetes, obesity, and dyslipidemia can increase the progression of DN. The pathophysiology of DN is mainly due to result of interactions between metabolic and hemodynamic pathways, which are often disrupted in diabetes. Pharmacological approaches for DN mainly include regulation of BP, control of blood sugar level, use of hypolipidemic agents, quitting smoking, diet control, and use of vitamin D receptor agonists. Hence, strategies of treatment like BP control and dyslipidemia control etc. are required to decrease the burden of DN and prevent its progression to end stage renal disease (ESRD).

Prevention and treatment of diabetic nephropathy

Diabetes Research and Clinical Practice, 2005

Increasing number of diabetic patients develop different stages of renal failure. However, often an inappropriate parameter, the serum creatinine is measured as a marker of glomerular function. Calculated glomerular filtration rate or endogenous creatinine clearance are suggested to be used for the estimation of the glomerular function. Important structures preventing proteinuria in the kidney are glomerular basement membrane, podocytes and proximal tubular cells. In diabetes mellitus loss of nephrin of podocytes can play a role in the development of microalbuminuria, and podocyte desquamation may result in the progression to proteinuria. In diabetes mellitus there is an increased formation of advanced glycation endproducts (AGE), of which the only elimination organ is the kidney. The AGE induce proteinuria and atherosclerosis. Therefore, in diabetes mellitus a vicious circle develops due to proteinuria, nephron loss and accumulation of AGE, which play a role in the initiation and progression of diabetic nephropathy and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers having antiproteinuric effect may decrease the risk of diabetic nephropathy and atherosclerosis. Improvement of carbohydrate metabolism with a consequential decrease in the formation of AGE is an important contributor to the prevention and treatment of diabetic nephropathy and atherosclerosis.

Renal Disease in Diabetes Mellitus: Recent Studies and Potential Therapies

Journal of Diabetes & Metabolism, 2013

Diabetic kidney disease is the predominant cause of end stage kidney disease in North America, estimated to be 152 per million population in 2010. New guidelines published by KDIGO on Chronic Kidney Disease classification are discussed. In light of recent clinical trials, better insight has been gained on how improve management of diabetic patients to prevent renal disease and its progression, especially with regards to metabolic and blood pressure control. Unfortunately, studies of newer therapies such as endothelin 1 antagonists and bardoxolone methyl have been disappointing, but several other possible therapeutic agents are under investigation and may provide hope for patients with diabetes mellitus in the future.

Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression

Diabetes Care

Management of diabetic kidney disease (DKD) has evolved in parallel with our growing understanding of the multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD. Since its initial discovery, the blockade of the renin-angiotensin system has remained a cornerstone of DKD management, leaving a large component of residual risk to be dealt with. The advent of sodium–glucose cotransporter 2 inhibitors followed by nonsteroidal mineralocorticoid receptor antagonists and, to some extent, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has ushered in a resounding paradigm shift that supports a pillared approach in maximizing treatment to reduce outcomes. This pillared approach is like that derived from the approach to heart failure treatment. The approach mandates that all agents that have been shown in clinical trials to reduce cardiovascular...

Therapeutic approaches to slowing the progression of diabetic nephropathy – is less best?

Drugs in Context, 2013

Objective: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin-angiotensinaldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI), to monotherapy.

New modalities for treatment of diabetic nephropathy: a mini review

International journal of epidemiologic research, 2015

Background and aims: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure which could increase the risk of cardiovascular disease and morbidity and mortality in patients. The aim of this study was to investigate new modalities for treatment of diabetic nephropathy. Methods:This study was a mini-review research to investigate drugs that are used for DN treatment. Results: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptors blocker (ARB) are the bases of DN treatment during recent decades. Due to some of adverse reactions of these drugs like hyperkalemia and chronic cough, other drugs such as non dihydropridin Ca channel blockers, uric acid lowering drugs, renin antagonists, lipid lowering agents, oral hypoglycemic agents such as Thiazolidinediones, Vitamin D and selective endothelin receptor antagonists have been used in some studies for decreasing proteinuria and slowing progression of DN. The results of these studies are different and ...

Diabetic Nephropathy: Diagnosis, Prevention, and Treatment

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ϳ40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE Ͼ20 g/min and Յ199 g/min) and macroalbuminuria (UAE Ն200 g/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro-and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c Ͻ7%), treating hypertension (Ͻ130/80 mmHg or Ͻ125/75 mmHg if proteinuria Ͼ1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the reninangiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol Ͻ100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes. Abbreviations: ARB, angiotensin II type 1 receptor blocker; DCCT, Diabetes Control and Complications Trial; GFR, glomerular filtration rate; RAS, renin-angiotensin system; UAE, urinary albumin excretion; UKPDS, U.K. Prospective Diabetes Study.

Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment

BioMed Research International, 2021

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are the main risk factors for the development of DN. In general, screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis and annually thereafter in type 2 diabetes. Standard therapy is blood glucose and blood pressure control using the renin-angiotensin system blockade, targeting A 1 c < 7 % , and <130/80 mmHg. Regression of albuminuria remains an important therapeutic goal. However, there are problems in diagnosis and treatment of nonproteinuric DN (NP-DN), which does not follow the classic pattern of DN. In fact, the prevalence of DN continues to increase, and additional therapy is needed to prevent or ameliorate the condition. In addition to conventional therapies, vitamin D receptor activators, incretin-related drugs, and therapies that target inflammation may also be pro...