What are the treatment options for a patient with chronic kidney disease (CKD), hypertension, and diabetes?

Treatment of Chronic Kidney Disease with Hypertension and Diabetes

Start an SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m², regardless of current glycemic control, as this provides kidney protection, reduces cardiovascular events, and slows CKD progression independent of glucose-lowering effects. 1

Core Pharmacologic Strategy

SGLT2 Inhibitors (First Priority)

• Initiate SGLT2 inhibitors as the foundational therapy for all patients with type 2 diabetes and CKD when eGFR ≥20 mL/min/1.73 m². 2, 1
• These agents reduce the risk of kidney failure, dialysis, or renal death by 30-40% even when added to maximum ACE inhibitor/ARB therapy. 3
• SGLT2 inhibitors reduce intraglomerular pressure, albuminuria, oxidative stress, and slow GFR loss through mechanisms independent of glycemia. 2
• Continue SGLT2 inhibitors even if HbA1c is at target, as the renal and cardiovascular benefits are not mediated through glucose lowering. 1

Renin-Angiotensin System Blockade (Second Priority)

• Initiate ACE inhibitors or ARBs in all patients with diabetes, hypertension, AND albuminuria (UACR ≥30 mg/g creatinine). 2, 1
• Titrate to the highest approved dose that is tolerated before considering additional agents. 2, 1
• For UACR ≥300 mg/g creatinine and/or eGFR <60 mL/min/1.73 m², ACE inhibitor or ARB therapy is strongly recommended. 3
• Monitor serum creatinine and potassium within 2-4 weeks after starting or increasing dose. 1
• Never combine ACE inhibitors with ARBs—this increases harm despite theoretical benefits. 1, 4

GLP-1 Receptor Agonists (Third Priority)

• Consider GLP-1 receptor agonists for patients with type 2 diabetes and CKD, as they have demonstrated renoprotective effects independent of glycemic control. 2, 3
• These agents improve kidney outcomes and provide additional cardiovascular benefits. 2

Blood Pressure Management

Target Blood Pressure

• Target blood pressure <130/80 mmHg for all patients with diabetes and CKD to reduce cardiovascular mortality and slow CKD progression. 2, 1, 3
• Consider lower targets (e.g., <130/80 mmHg) in patients with severely elevated albuminuria (≥300 mg/g creatinine). 2, 1

Antihypertensive Selection

• ACE inhibitors or ARBs are preferred first-line agents for patients with diabetes, hypertension, eGFR <60 mL/min/1.73 m², and UACR ≥300 mg/g creatinine. 2
• If additional blood pressure control is needed beyond maximally dosed ACE inhibitor/ARB, add a calcium channel blocker rather than a thiazide diuretic in patients with eGFR <45 mL/min/1.73 m². 3
• Dihydropyridine calcium channel blockers should not be used as monotherapy in proteinuric CKD patients but always in combination with a RAAS blocker. 5

Glycemic Control

HbA1c Targets

• Target HbA1c between 6.5-8.0%, individualized based on hypoglycemia risk, life expectancy, comorbidities, and patient preferences. 1
• Intensive glucose control (HbA1c ~7%) delays onset and progression of albuminuria and reduces eGFR decline. 1, 3
• There is a lag time of at least 2 years in type 2 diabetes to over 10 years in type 1 diabetes for the effects of intensive glucose control to manifest as improved eGFR outcomes. 2

Metformin Dosing in CKD

• Metformin is contraindicated when eGFR falls below certain thresholds per FDA guidance. 2
• Medication dosing may require modification when eGFR <60 mL/min/1.73 m². 2

Cardiovascular Risk Reduction

Statin Therapy

• Initiate statin therapy in all patients with type 1 or type 2 diabetes and CKD, regardless of baseline lipid levels, to reduce cardiovascular events and mortality. 1, 4
• High-intensity statin therapy is recommended for all patients ≥50 years with CKD, regardless of GFR. 4

Cardiovascular Disease Management

• Ensure level of care for ischemic heart disease is not prejudiced by CKD, as patients with CKD are more likely to have cardiovascular events than progress to end-stage renal disease. 1

Lifestyle Interventions

Dietary Modifications

• Limit protein intake to 0.8 g/kg/day for patients with diabetes and CKD not on dialysis. 1, 3, 4
• Restrict sodium intake to <2 g/day (<90 mmol/day or <5 g sodium chloride/day). 1, 4
• A Mediterranean-style diet reduces cardiovascular risk. 4

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

• Advise all patients with diabetes and CKD who use tobacco to quit using tobacco products. 2

Monitoring and Follow-Up

Screening and Monitoring Frequency

• Screen annually with spot urinary albumin-to-creatinine ratio and estimated GFR in all patients with type 2 diabetes regardless of duration, and in type 1 diabetes patients with disease duration ≥5 years. 1
• Monitoring frequency should be 1-4 times per year based on CKD stage. 2, 1
• Reassess every 3-6 months all cardiovascular and metabolic risk factors, monitoring kidney function, electrolytes, and adjusting medications as CKD progresses. 2, 1

HbA1c Monitoring

• Check HbA1c every 3 months when therapy changes or targets are not met, and at least twice yearly in stable patients. 1

Albuminuria as Treatment Target

• A reduction of 30% or greater in urinary albumin (mg/g creatinine) slows CKD progression. 3
• Continue monitoring urinary albumin-to-creatinine ratio in patients treated with ACE inhibitor/ARB/SGLT2 inhibitor to assess response to treatment and progression. 3

Referral to Nephrology

Indications for Referral

• Consider earlier referral for complex cases requiring multidisciplinary management involving nephrologists, endocrinologists, cardiologists, and dietitians. 1
• Refer when eGFR <30 mL/min/1.73 m² for discussion of renal replacement therapy. 3, 4
• Promptly refer for rapidly progressing kidney disease, uncertainty about kidney disease etiology, resistant hypertension, or significant albuminuria increases despite good BP control. 3, 4

Multidisciplinary Team Care

• Diabetes and CKD management is ideal when the health care system model includes a multidisciplinary team involving the patient, physician, nephrologists, endocrinologists, cardiologists, and dietitians. 2
• Education for patients and an integrated approach to treatment is effective for both patients and clinicians. 2
• Avoid therapeutic inertia—most patients with diabetes and CKD have high residual risks despite treatment, and increasing treatment options are available. 2

Common Pitfalls to Avoid

• Never combine ACE inhibitors with ARBs, as this increases harm. 1
• Do not overlook cardiovascular disease management, as cardiovascular events are more likely than progression to end-stage renal disease. 1
• Do not delay SGLT2 inhibitor initiation until glycemic control worsens—start immediately for renal protection. 1, 3
• Monitor for acute kidney injury, as all people with CKD are at increased risk. 1