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Table of Contents
The American Diabetes Association (ADA) and Kidney Disease Improving global Outcomes (KDIGO) have updated their guidelines for managing chronic kidney disease (CKD) in patients with type 2 diabetes (T2D).These guidelines highlight promising therapies like sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs).
the goal is to optimize glycemic control, reducing the risk of CKD progression and cardiovascular events. Pharmacists, being accessible healthcare professionals, need to understand these updates to guide optimal treatment approaches.
The Growing Concern of Diabetes and CKD
Diabetes prevalence is rising in the US, with approximately 38.4 million people (11.6%) affected in 2021, according to the ADA. Chronic hyperglycemia and insulin resistance can lead to macrovascular complications (heart disease, stroke) and microvascular complications (retinopathy, nephropathy, neuropathy). Sustained high blood sugar damages renal microvasculature, leading to CKD. It’s estimated that 1 in 3 people with diabetes will develop CKD.
CKD diagnosis involves assessing estimated glomerular filtration rate (eGFR) and albuminuria. Uncontrolled CKD can progress to kidney failure or require a transplant. Guidelines recommend optimizing glucose management to slow CKD progression. emerging data supports using SGLT2 inhibitors and GLP-1 agonists to reduce CKD progression and cardiovascular events. Nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs) like finerenone also show promise.
2025 ADA Guidelines: A Holistic Approach
The 2025 ADA guidelines advocate a comprehensive approach for T2D and CKD. After lifestyle modifications, SGLT2 inhibitors are recommended for individuals with eGFR ≥20 mL/min/1.73 m2 and T2D, independent of glucose management. GLP-1 agonists with demonstrated CV and kidney benefits are also recommended. For individuals with CKD (eGFR ≥ 25 mL/min/1.73 m2) and albuminuria, ns-MRAs can reduce CV events and CKD progression, with potassium monitoring. Renin-angiotensin system inhibitors (RASi) are first-line for non-pregnant individuals with hypertension and a urinary albumin-to-creatinine ratio (UACR) of 30-299 mg/g, titrated to the maximum tolerated dose. The goal is to slow CKD progression, evidenced by a ≥30% reduction in urinary albumin.
2024 KDIGO Guidelines: Treatment and Risk Modification
The 2024 KDIGO guidelines focus on delaying CKD progression and managing complications. Similar to the ADA, KDIGO emphasizes lifestyle modifications followed by SGLT2 inhibitors as first-line therapy. KDIGO aims for systolic blood pressure <120 mmHg with an RASi and targeted therapies for complications. SGLT2 inhibitors are recommended for people with T2D,CKD,and an eGFR ≥ 20 mL/min/1.73 m2. Trials like EMPA-KIDNEY, DAPA-CKD, and CREDENCE have shown SGLT2 inhibitors reduce the risk of kidney failure, CV mortality, and heart failure (HF) in people with CKD. Once initiated, SGLT2 inhibitors can be continued even if eGFR falls below 20 mL/min/1.73 m2 unless not tolerated or kidney replacement therapy is initiated. ACE inhibitors or ARBs are strongly recommended for people with CKD and moderately to severely increased albuminuria with or without diabetes. Finerenone is suggested for adults with T2D, an eGFR >25 mL/min/1.73 m2, normal serum potassium, and albuminuria (>30 mg/g) despite maximum tolerated RASi dose. A long-acting GLP-1 agonist is recommended for adults with T2D and CKD who haven’t achieved glycemic targets despite metformin and SGLT2 inhibitors or cannot use those medications.
Spotlight on Emerging Therapies
Non-steroidal mineralocorticoid receptor antagonist (MRA)
FERERENONE (KERENDIA)
Finerenone blocks MR-mediated sodium reabsorption and MR overactivation. It’s the only ns-MRA with proven kidney and CV benefits,demonstrated by FIDELIO-DKD and FIGARO-DKD trials. It’s dosed at 10 mg or 20 mg once daily based on eGFR and potassium levels. Common side effects include hyperkalemia, hypotension, and hyponatremia.
FIDELIO-DKD showed a considerably lower incidence of kidney failure, sustained eGFR decrease of ≥40%, or death from renal causes with finerenone compared to placebo. The finerenone group also had a significantly lower risk of death from CV causes, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization from heart failure (HHF).
FIGARO-DKD demonstrated that finerenone significantly lowered the incidence of death from CV causes, nonfatal MI, nonfatal stroke, or HHF compared to placebo.
SGLT2 inhibitors
SGLT2 inhibitors reduce glucose reabsorption in the kidney, increasing glucose excretion in the urine. Empagliflozin and dapagliflozin are FDA approved for HF and T
