Abstract
Chronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM), contributing substantially to morbidity, mortality, and health care burden. Progressive decline in kidney function, often accompanied by albuminuria, increases the risk of cardiovascular disease and end-stage kidney disease. Pharmacological interventions have transformed nephroprotection, offering opportunities to delay progression and improve outcomes. This article synthesizes current evidence and provides practical guidance for diabetes care and education specialists (DCESs) and the multidisciplinary care team.1-3 (Table 1).
Guideline-Recommended Therapies for Nephroprotection in People With T2DM and CKD
Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; GLP-1 RA, glucagon-like peptide-1 receptor agonist; NS-MRA, nonsteroidal mineralocorticoid receptor antagonist; RAAS, renin angiotensin aldosterone system; SGLT2, sodium-glucose cotransporter 2; T2DM, type 2 diabetes mellitus.
Epidemiology
Approximately 40% of individuals with T2DM develop CKD, making diabetes the leading cause of kidney failure worldwide. 2 CKD in T2DM is associated with poor prognosis due to its relationship with hypertension, dyslipidemia, and cardiovascular disease. 3 Early detection and intervention, including routine estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio screening, are critical. 4
Pathophysiology
Diabetes-related kidney disease results from interactions between metabolic and hemodynamic factors. Chronic hyperglycemia promotes glomerular hyperfiltration, advanced glycation end-product accumulation, and oxidative stress. Hypertension and renin angiotensin aldosterone system (RAAS) activation further exacerbate glomerular injury.5,6 These processes lead to albuminuria, eGFR decline, and kidney failure. 7
Pharmacological Nephroprotection Strategies
RAAS Inhibitors
RAAS inhibitors (RAASi), including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), reduce intraglomerular pressure and albuminuria and slow CKD progression.4,6,7 Dual RAAS blockade is not recommended due to hyperkalemia and acute kidney injury risk. 7 DCESs support patients by providing education about taking their medications consistently and monitoring for signs of hyperkalemia, a possible side effect of these medications.
A similar class of medication is utilized in those with diabetes and CKD who also have congestive heart failure: angiotensin receptor-neprilysin inhibitor. Technically not considered an RAASi, it does include an ARB (valsartan) and is a medication that DCESs will also provide patient education regarding the importance of taking the medicaton as prescribed and the need to monitor for signs/symptoms of hyperkalemia.
Sodium-Glucose Cotransporter 2 Inhibitors
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce CKD progression, heart failure hospitalization, and cardiovascular mortality.3,8-11 Benefits extend across moderate CKD. 10 DCESs play an integral role in patient success by counseling on hydration, monitoring volume status, and encouraging consistent medication use. As part of this support, DCESs educate patients on the importance of taking medications as prescribed and recognizing signs and symptoms of adverse effects, such as those related to possible dehydration, hypotension, or genitourinary tract infection, that can be complications of SGLT2 inhibitor therapy.8-11
Nonsteroidal Mineralocorticoid Receptor Antagonists
Nonsteroidal mineralocorticoid receptor antagonists (NS-MRA), such as finerenone, block mineralocorticoid receptors in the kidneys, heart, and blood vessels. This results in reduced risk of CKD progression and cardiovascular events in those with T2DM.1,4,6,12-14 Studies are ongoing to investigate their efficacy of use. The recently completed Phase 2 CONFIDENCE study highlights that concomitant finerenone use with SGLT2 inhibitors, such as empagliflozin, is superior to monotherapy, particularly in the reduction of urine albumin levels. 15 NS-MRA also provide additive protection with RAASi. Given their selectivity, there are fewer side effects seen in NS-MRA compared to their steroidal-MRA counterparts. 14 Potassium monitoring remains essential; DCESs educate patients about the importance of taking medications as prescribed and recognizing the risk and signs of hyperkalemia. 13
Glucagon-Like Peptide-1 Receptor Agonists
Glucagon-like peptide-1 receptor agonists improve glycemic management and reduce cardiovascular risk, with emerging kidney protective effects.3,8 DCESs play a key role in optimizing medication use and supporting consistent medication use by providing education on proper injection techniques, strategies to manage gastrointestinal side effects, and the importance of implementing sustainable lifestyle modifications.
Lifestyle and Meal Planning Interventions
Lifestyle interventions complement pharmacologic therapy and are critical for long-term nephroprotection. DCESs educate patients on nutrition, exercise, smoking cessation, and weight optimization.
A key component of the nutrition education provided by DCESs includes guidance on balancing protein intake between plant and animal sources. Both observational studies and randomized trials have demonstrated that diets higher in plant-based relative to animal-based protein are associated with slower eGFR decline and reduced all-cause mortality risk. 16 Additionally, the lower dietary acid load associated with plant-based protein sources may confer protective effects against kidney injury. 17 Given the complexity of dietary management in patients with diabetes and chronic kidney disease, DCESs should also consider referral for medical nutrition therapy (MNT) with a registered dietitian nutritionist specializing in renal nutrition. Importantly, MNT is a covered Medicare benefit for individuals with diabetes and kidney disease and is provided without patient cost-sharing, supporting its use as an accessible, evidencebased intervention. 18 Key lifestyle and dietary interventions are summarized in Table 2.
Lifestyle and Dietary Interventions for Nephroprotection in Patients With T2DM and CKD
Abbreviations: BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; T2DM, type 2 diabetes mellitus.
Role of the Diabetes Care Team
DCESs, dietitians, pharmacists, primary care providers, endocrinologists, and nephrologists collaborate to implement evidence-based interventions.3,4,19 DCESs provide education, self-management support, and guidance on consistent medication use and lifestyle behaviors. Tools such as electronic health record reminders, teach-back methods, and shared decision-making aid enhance engagement.
Underutilization of nephroprotective therapies persists due to therapeutic inertia, side effect concerns, cost, and limited awareness. 19 DCESs mitigate barriers through education, counseling, and coordinated care support while assisting providers with guideline-based monitoring.
Future Directions
Emerging therapies targeting endothelin receptor pathways, anti-inflammatory agents, and gene-based interventions may offer additional kidney protection.6,13,20 Advances in precision medicine and biomarker-guided care allow earlier detection and individualized therapy, with DCESs guiding patient education and engagement.
Conclusion
Pharmacologic nephroprotection in CKD patients with T2DM has advanced significantly. RAASi, SGLT2 inhibitors, NS-MRAs, and GLP-1 RAs form the foundation of therapy, providing kidney and cardiovascular benefits. A multidisciplinary approach, with DCESs leading patient education and self-management support, is essential for translating evidence into improved patient outcomes.1-6 ,19 ■
Footnotes
Author Contributions
Brian Burroughs served as the primary and senior author, conceptualized the manuscript, and contributed content related to background, nephroprotection, and interdisciplinary care. Craig Schapekahm provided expert input, assisted with conceptualization, and contributed to sections addressing pharmacologic management. Becky M. Ness provided expert input and contributed content related to both pharmacologic and lifestyle management. All authors reviewed, edited, and approved the final manuscript.
Declaration of Conflicting Interests
None.
Funding
None.
Guarantor Statement
Brian Burroughs serves as the guarantor of this work and takes responsibility for the integrity of the content, including the accuracy of the data and analysis presented.
