What is the treatment for nephropathy (kidney disease)?

From the Guidelines

The treatment of nephropathy should prioritize renin-angiotensin system (RAS) inhibition, lifestyle modification, and optimization of blood pressure control to slow disease progression and reduce cardiovascular risk, as recommended by the most recent guidelines 1. The mainstay of treatment for diabetic nephropathy includes tight glycemic control with a target HbA1c of less than 7%, along with blood pressure management using ACE inhibitors or ARBs, which not only control hypertension but also reduce proteinuria and slow disease progression 1. Key aspects of treatment include:

• RAS inhibition with ACE inhibitors or ARBs, titrated to the maximal tolerated dose, with close monitoring of serum potassium and serum creatinine levels 1
• Lifestyle modifications, such as smoking cessation, sodium restriction to less than 2g daily, protein limitation to 0.8g/kg/day, and potassium restriction in advanced disease 1
• Optimization of blood pressure control, with a goal of reducing cardiovascular risk and slowing CKD progression 1
• Consideration of SGLT2 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes and CKD, as they may have benefits in reducing cardiovascular risk and slowing CKD progression 1
• Regular monitoring of kidney function and proteinuria, as well as management of complications like anemia, metabolic acidosis, and mineral bone disorders, are crucial in patients with nephropathy 1.

From the FDA Drug Label

The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial (CREDENCE) was a multinational, randomized, double-blind, placebo-controlled trial comparing canagliflozin with placebo in adult patients with type 2 diabetes mellitus, an eGFR ≥ 30 to < 90 mL/min/1. 73 m 2and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g) who were receiving standard of care including a maximum-tolerated, labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) The primary objective of CREDENCE was to assess the efficacy of canagliflozin relative to placebo in reducing the composite endpoint of end stage kidney disease (ESKD), doubling of serum creatinine, and renal or CV death. Canagliflozin 100 mg significantly reduced the risk of the primary composite endpoint based on a time-to-event analysis [HR: 0.70; 95% CI: 0.59,0.82; p<0. 0001]

Treatment of Nephropathy: Canagliflozin 100 mg is effective in reducing the risk of end stage kidney disease (ESKD), doubling of serum creatinine, and renal or CV death in adult patients with type 2 diabetes mellitus and nephropathy.

• The primary composite endpoint was reduced by 30% with canagliflozin compared to placebo.
• Canagliflozin also significantly reduced the risk of hospitalization for heart failure [HR: 0.61; 95% CI: 0.47 to 0.80; p<0. 001] 2

From the Research

Treatment of Nephropathy

• The treatment of nephropathy involves the use of various therapeutic strategies to reduce albuminuria, control blood pressure, and delay progression to end-stage renal disease (ESRD) 3.
• Renin-angiotensin-aldosterone (RAAS) blockers, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are crucial in reducing cardiovascular and renal outcomes 3, 4.
• Achieving blood pressure targets, particularly a blood pressure goal of < 130 mmHg, is essential in reducing albuminuria and delaying progression of nephropathy 3.
• Patients with hypertensive proteinuric nephropathy require aggressive blood pressure-lowering with multiple agents, including RAAS blockers, calcium antagonists, and diuretics 3.
• ACE inhibitors and ARBs have been shown to delay the progression to microalbuminuria and clinical albuminuria in patients with diabetic nephropathy 4, 5.
• Combination therapy with ACE inhibitors and ARBs may slow the progression of microalbuminuria to clinical albuminuria 4.

Diabetic Nephropathy

• Diabetic nephropathy affects 30-40% of people with diabetes and is the leading cause of end-stage kidney disease 6.
• The current treatment paradigm for diabetic nephropathy relies on early detection, glycaemic control, and tight blood pressure management with preferential use of renin-angiotensin system blockade 6.
• Antihypertensive therapy, particularly with ACE inhibitors or ARBs, is essential in preventing or delaying the onset of nephropathy in patients with type 2 diabetes and hypertension 5.

Underuse of ACE Inhibitors and ARBs

• Despite the recommended use of ACE inhibitors or ARBs in patients with diabetic nephropathy, there is a significant underuse of these agents, with only 50% of patients receiving the recommended treatment 7.
• Predictors of ACE inhibitor or ARB use include the presence of coronary artery disease or congestive heart failure 7.