What is the best management approach for a patient with chronic kidney disease (CKD), diabetes mellitus (DM), and hypertension (HTN)?

Management of CKD, Diabetes, and Hypertension

Patients with CKD, diabetes, and hypertension require a multi-drug regimen centered on SGLT2 inhibitors (for type 2 diabetes), ACE inhibitors or ARBs (when albuminuria is present), and comprehensive cardiovascular risk reduction—this approach reduces mortality, slows kidney disease progression, and prevents cardiovascular events. 1

Core Pharmacologic Strategy

First-Line Therapy for Type 2 Diabetes with CKD

• Initiate an SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m², regardless of glycemic control status, as this class provides kidney protection, cardiovascular benefits, and reduces heart failure hospitalizations independent of glucose-lowering effects 1, 2
• Specific agents and doses: Canagliflozin 100 mg, Dapagliflozin 10 mg, or Empagliflozin 10 mg daily 2
• Continue SGLT2 inhibitors until dialysis or transplantation is initiated, even as eGFR declines, since kidney and cardiovascular benefits persist at lower eGFR levels 2

Metformin Use in CKD

• Add metformin when eGFR ≥30 mL/min/1.73 m² for additional glycemic control 1, 2
• Reduce metformin dose to 1000 mg daily when eGFR is 30-44 mL/min/1.73 m² 2
• Discontinue metformin when eGFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk 2

Hypertension Management with RAS Blockade

• Initiate an ACE inhibitor or ARB in all patients with diabetes, hypertension, AND albuminuria, titrating to the highest tolerated dose (this is a Grade 1B recommendation) 1
• For patients with diabetes and albuminuria but normal blood pressure, ACE inhibitor or ARB therapy may still be considered 1
• Monitor serum creatinine and potassium within 2-4 weeks after starting or increasing the dose 1
• Continue therapy unless creatinine rises >30% within 4 weeks—this degree of increase warrants evaluation for acute kidney injury, volume depletion, or renal artery stenosis 1
• Losartan specifically is FDA-approved for diabetic nephropathy with elevated creatinine and proteinuria (albumin-to-creatinine ratio ≥300 mg/g) in type 2 diabetes with hypertension 3

Blood Pressure Targets

• Target blood pressure <130/80 mmHg in patients with diabetes and CKD stages 1-4 1
• ACE inhibitors or ARBs should be first-line when albuminuria is present; otherwise, dihydropyridine calcium channel blockers or diuretics are acceptable alternatives 1
• Most patients require combination therapy with all three classes (ACE inhibitor/ARB, calcium channel blocker, and diuretic) to achieve blood pressure targets 1

Additional Risk-Based Therapies

GLP-1 Receptor Agonists

• Add a GLP-1 receptor agonist if glycemic targets are not met with metformin and SGLT2 inhibitors, or if these agents cannot be used 1, 2
• GLP-1 RAs are particularly beneficial for patients with obesity and CKD, promoting intentional weight loss 2
• GLP-1 RAs maintain glucose-lowering efficacy even when eGFR <20 mL/min/1.73 m², unlike SGLT2 inhibitors which have diminished glycemic effects at very low eGFR 2
• Avoid exenatide in severe CKD 2

Nonsteroidal Mineralocorticoid Receptor Antagonists

• Consider adding finerenone (a nonsteroidal MRA) for patients with type 2 diabetes who have persistent albuminuria ≥30 mg/g (≥3 mg/mmol) despite first-line therapy and normal potassium levels 1
• This provides additional kidney and cardiovascular protection for high-risk patients 1

Lipid Management

• Initiate statin therapy in all patients with type 1 or type 2 diabetes and CKD 1, 2
• Consider adding ezetimibe, PCSK9 inhibitors, or icosapent ethyl based on ASCVD risk and lipid levels 1

Antiplatelet Therapy

• Use aspirin lifelong for secondary prevention in patients with established cardiovascular disease 1
• Consider aspirin for primary prevention in high-risk individuals, balancing against bleeding risk (particularly relevant with thrombocytopathy at low eGFR) 1

Glycemic Monitoring and Targets

• Use HbA1c to monitor glycemic control, checking every 3 months when therapy changes or targets are not met, and at least twice yearly in stable patients 1
• Target HbA1c between <6.5% and <8.0%, individualized based on hypoglycemia risk, life expectancy, comorbidities, and patient preferences 1
• Be aware that HbA1c accuracy decreases in advanced CKD 2

Critical Monitoring and Safety Considerations

Hyperkalemia Management with ACE Inhibitors/ARBs

• Do not immediately discontinue ACE inhibitors or ARBs for hyperkalemia—first attempt to manage potassium levels through dietary modification, diuretics, sodium bicarbonate, or GI cation exchangers 1
• Review concurrent medications that raise potassium (potassium-sparing diuretics, NSAIDs, potassium supplements) 1, 3
• Reducing or stopping the ACE inhibitor/ARB should be a last resort 1

Hypoglycemia Risk in Advanced CKD

• Assess hypoglycemia risk before initiating SGLT2 inhibitors, particularly if the patient is on insulin or sulfonylureas 2
• Consider reducing insulin or sulfonylurea doses when starting SGLT2 inhibitors 2
• Patients on insulin may require dose reductions of 25% or more when eGFR <45 mL/min/1.73 m² due to decreased insulin clearance and impaired renal gluconeogenesis 2
• Avoid first-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide) entirely in CKD; if sulfonylureas are necessary, use glipizide as it lacks active metabolites 2

SGLT2 Inhibitor-Specific Precautions

• Evaluate volume depletion risk, especially with concurrent diuretic use, and consider reducing diuretic doses if needed 2
• Educate patients about genital infections, euglycemic diabetic ketoacidosis risk (particularly during illness or perioperative periods), and potential foot ulcer concerns 2
• Monitor for euglycemic ketoacidosis, which can occur even with normal blood glucose levels 2

Drug Interactions and Contraindications

• Avoid dual RAS blockade (combining ACE inhibitors with ARBs or aliskiren) as this increases risks of hypotension, hyperkalemia, and acute kidney injury without additional benefit 3
• The VA NEPHRON-D trial demonstrated that combining losartan with lisinopril provided no benefit over monotherapy but increased hyperkalemia and acute kidney injury 3
• Do not coadminister aliskiren with ARBs in patients with diabetes, and avoid in patients with eGFR <60 mL/min/1.73 m² 3
• Monitor renal function when NSAIDs are used with ACE inhibitors/ARBs, as this combination can cause acute renal failure, especially in elderly or volume-depleted patients 3
• Monitor lithium levels if coadministered with ARBs due to toxicity risk 3

Pregnancy Considerations

• Advise contraception in women receiving ACE inhibitors or ARBs and discontinue these agents in women considering pregnancy or who become pregnant 1

Lifestyle Interventions

Dietary Recommendations

• Limit protein intake to 0.8 g/kg/day for patients with diabetes and CKD not on dialysis 1
• Restrict sodium intake to <2 g/day (<90 mmol/day or <5 g sodium chloride/day) 1
• Emphasize a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts; lower in processed meats, refined carbohydrates, and sweetened beverages 1

Physical Activity

• Advise moderate-intensity physical activity for at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance 1

Smoking Cessation

• Strongly recommend tobacco cessation for all patients who use tobacco products 1

Monitoring for Complications

• Perform comprehensive foot examinations annually with Semmes-Weinstein monofilament testing, 128-Hz tuning fork for vibratory sensation, and pedal pulse evaluation 1
• Visual foot inspection should occur at every healthcare visit 1
• Screen regularly for retinopathy, cardiovascular disease, anemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, and secondary hyperparathyroidism 4

Common Pitfalls to Avoid

• Do not withhold SGLT2 inhibitors based solely on glycemic control needs—their primary benefit in CKD is kidney and cardiovascular protection, not glucose lowering 2
• Do not stop ACE inhibitors/ARBs prematurely for mild creatinine elevations (<30% increase) or manageable hyperkalemia—these are often the most important medications for kidney protection 1
• Do not delay SGLT2 inhibitor initiation until later stages of CKD—earlier initiation provides greater cumulative benefit 2
• Do not use metformin when eGFR <30 mL/min/1.73 m² despite its benefits at higher eGFR levels 2