Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression (original) (raw)
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Nephron extra, 2012
Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been glycemic control and blood pressure lowering using agents blocking the renin-angiotensin system. Clinical trials are currently under way using novel agents for the treatment of patients with diabetic nephropathy. Promising agents emerging from some of the completed trials include pirfenidone and bardoxolone methyl, which have been shown in two recent randomized controlled trials in patients with diabetic nephropathy to result in an improved estimated glomerular filtration rate compared to placebo. Also, paricalcitol has been shown to decrease the urinary albumin-to-creatinine ratio, whereas sulodexide failed to do so in a large randomized double-blind placebo-controlled trial. Of note, pyridoxamine has also shown promise in the treatment of diabetic nephropathy if started early in the disease course. These preliminary trials have shown significant promise for managing patients with diabetic nephropathy, sparking active research in this field and providing the rationale for further clinical testing in long-term, hard-outcomes trials.
Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches
Journal of General Internal Medicine, 2011
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. Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, proteinuria/albuminuria reduction, interruption of the renin-angiotensin-aldosterone system through the use of angiotensin converting enzyme inhibitors and angiotensin type-1 receptor blockers, along with dietary modification and cholesterol lowering agents. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are urgently needed. This review highlights the available standard therapeutic approaches to manage progressive diabetic nephropathy, including markers for early diagnosis of diabetic nephropathy. Furthermore, we will discuss emerging strategies such as PPAR-gamma agonists, Endothelin blockers, vitamin D activation and inflammation modulation. Finally, we will summarize the recommendations of these interventions for the primary care practitioner.
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...
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.
Blockade of the renin–angiotensin system for the primary prevention of diabetic nephropathy
Diabetes management, 2012
The prevention of chronic kidney disease is a primary goal for diabetes management. Lowering blood pressure can reduce the incidence of microalbuminuria in Type 1 or Type 2 diabetes, especially in patients with hypertension. Blockade of the renin-angiotensin system (RAS) is an effective strategy to reduce blood pressure in diabetic patients, but no more so than other antihypertensive strategies. RAS blockers have a more favorable side-effects profile compared to other antihypertensive agents, meaning that generally patients are more likely to take them. Any 'independent' effect of RAS blockade for the primary prevention of diabetic nephropathy, beyond blood-pressure control, remains to be clearly established. New combination strategies using renin inhibitors or aldosterone antagonists, to achieve a more complete RAS blockade, have the potential to improve renal outcomes in patients with diabetes. Summary There is clear evidence for the pathogenic role of the renin-angiotensin system (RAS) in the progression of diabetic kidney. Treatment with either an a ngiotensin-converting enzyme inhibitor or angiotensin receptor blocker have been shown to reduce proteinuria and preserve renal function in patients with diabetes and chronic kidney disease. While such data provide a strong rationale for early and sustained blockade of the RAS for the primary prevention of kidney disease, clinical trial evidence to support this goal is limited and inconsistent. By contrast, data from observational and clinical trials clearly demonstrate the primacy of blood-pressure control in the development of diabetic kidney disease, especially in hypertensive patients. Whether RAS blockade offers additional benefits for primary prevention, over-and-above blood-pressure control, remains contentious. At best, any 'independent effects' on primary prevention are modest, and certainly not the panacea envisaged by many practitioners. However, the better tolerability, efficacy and side-effects profile of RAS blockers, and other actions on retinopathy and cardiovascular disease, means that most patients with diabetes currently receive RAS blockers as first line antihypertensive agents. The future development of more effective 'escape-proof' regimens currently offers the best way forward to realize the hope that RAS blockade will ultimately prevent diabetic kidney disease in the clinic as effectively as it does in animal models.
A narrative review of new treatment options for chronic kidney disease in type 2 diabetes
Annals of Translational Medicine, 2021
Diabetic kidney disease is a frequent and costly complication to type 2 diabetes. After many years with a lack of successful trials there are now significant developments that will change treatment, guidelines and future outcome. Since the last two decades blockade of the renin-angiotensin system (RAS) is standard treatment, but new antidiabetic treatments have shown potential for kidney protection. After cardiovascular outcome studies with glucagon-like peptide (GLP-1) receptor agonists it is evident that drugs like liraglutide, semaglutide and dulaglutide can reduce albuminuria levels and progression to macroalbuminuria. At present, a renal outcome trial with semaglutide is ongoing which will provide more evidence on the drug class in the future. The sodium glucose co-transporter 2 (SGLT2) inhibitor class has also demonstrated effects beyond glucose-lowering, as the drugs can reduce blood pressure, albuminuria and loss of renal function. In the first renal outcome study the SGLT2 inhibitor canagliflozin was found to reduce the risk of hard renal outcome with 30%. SGLT2 inhibition is now recommended in type 2 diabetes with chronic kidney disease. Renal outcome studies testing additional SGLT2 inhibitors and the GLP-1 receptor agonist semaglutide will report in the coming future potentially providing more and much needed options for treatment.