Chronic Kidney Disease Treatment in Patients with Hypertension and/or Diabetes
All patients with chronic kidney disease, hypertension, and diabetes require a multi-drug regimen centered on SGLT2 inhibitors (initiated when eGFR ≥20 mL/min/1.73 m²), ACE inhibitors or ARBs (titrated to maximum tolerated dose when albuminuria is present), and high-intensity statin therapy, combined with strict blood pressure control to <130/80 mmHg. 1
Foundation: Lifestyle Modifications (All Patients)
- Dietary sodium restriction to <2 g/day (<5 g sodium chloride/day) for blood pressure control and reduced CKD progression 2, 3
- Protein restriction to 0.8 g/kg/day to slow kidney disease progression 2, 3
- Moderate-intensity physical activity for ≥150 minutes per week, adjusted to cardiovascular tolerance 1, 3
- Tobacco cessation for all patients who use tobacco products 3
- Weight reduction if overweight or obese 4
First-Line Pharmacologic Therapy
For Type 2 Diabetes with CKD:
Glycemic Control:
- Start SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m² and continue until dialysis or transplantation, regardless of glucose levels—this provides kidney and cardiovascular protection independent of glucose-lowering effects 1, 5, 3
- Add metformin when eGFR ≥30 mL/min/1.73 m², with dose reduction to maximum 1000 mg daily when eGFR is 30-44 mL/min/1.73 m² 1, 3
- Discontinue metformin when eGFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk 3
Critical SGLT2 Inhibitor Safety Monitoring:
- Reduce insulin or sulfonylurea doses by 10-20% when initiating SGLT2 inhibitors to prevent hypoglycemia 5, 3
- Counsel patients on euglycemic ketoacidosis risk (nausea, vomiting, abdominal pain, fatigue even with normal glucose) and to discontinue during acute illness 5
- Monitor for genital mycotic infections (6% incidence) 5
For Type 1 Diabetes with CKD:
- Insulin remains the foundation for glycemic control 1
- SGLT2 inhibitors are NOT recommended for type 1 diabetes in standard practice 1
Blood Pressure Management
When Albuminuria is Present (with or without hypertension):
- Initiate ACE inhibitor (e.g., lisinopril 10 mg daily) or ARB (e.g., losartan 50 mg daily) immediately 1, 2, 3
- Titrate to maximum approved tolerated dose (e.g., telmisartan 80 mg daily, losartan 100 mg daily) for optimal kidney and cardiovascular protection 1, 2
- Target blood pressure <130/80 mmHg when albuminuria is present 1, 2
When Albuminuria is Absent:
- Target blood pressure <140/90 mmHg 4
- ACE inhibitor/ARB may still be considered but is not mandatory 1
- Dihydropyridine calcium channel blockers or diuretics can be first-line alternatives 1
Additional Antihypertensives (Often Needed):
- Add dihydropyridine calcium channel blocker (e.g., amlodipine) and/or thiazide-like diuretic (or loop diuretic if eGFR <30 mL/min/1.73 m²) to achieve blood pressure targets 1, 2
ACE Inhibitor/ARB Monitoring Protocol:
Within 2-4 weeks of initiation or dose increase, check: 1, 3
- Serum creatinine
- Serum potassium
- Blood pressure
Continue therapy unless: 1
- Creatinine rises >30% within 4 weeks (evaluate for acute kidney injury, volume depletion, renal artery stenosis, or nephrotoxic medications like NSAIDs)
- Symptomatic hypotension occurs
- Uncontrolled hyperkalemia persists despite management
For hyperkalemia, DO NOT immediately discontinue ACE inhibitor/ARB—first attempt: 1, 3
- Dietary potassium restriction
- Diuretics (thiazide or loop)
- Sodium bicarbonate (if metabolic acidosis present)
- GI cation exchangers (e.g., patiromer, sodium zirconium cyclosilicate)
- Only reduce dose or discontinue as last resort
Critical contraindication: Discontinue ACE inhibitor/ARB in women considering pregnancy or who become pregnant 1
Additional Risk-Based Therapies
Cardiovascular and Kidney Protection:
Statin Therapy (ALL patients):
- Initiate high-intensity statin immediately (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) for all patients with type 1 or type 2 diabetes and CKD, regardless of baseline LDL-cholesterol 1, 2, 5, 3
GLP-1 Receptor Agonist:
- Add if glycemic targets not met with metformin and SGLT2 inhibitor, or if these agents cannot be used 1, 3
- Provides additional cardiovascular and kidney benefits 1
Nonsteroidal Mineralocorticoid Receptor Antagonist (Finerenone):
- Consider adding for type 2 diabetes patients with persistent albuminuria ≥30 mg/g (≥3 mg/mmol) despite first-line therapy and normal potassium levels 1, 3
- Provides additional kidney and cardiovascular protection beyond RAS blockade 1
Antiplatelet Therapy:
- Aspirin for lifelong secondary prevention in patients with established cardiovascular disease 1
- May consider for primary prevention in high-risk patients with atherosclerotic cardiovascular disease 1
Glycemic Targets and Monitoring
- Target HbA1c between 7.0-8.0% in patients with CKD, multiple comorbidities, and high hypoglycemia risk 5
- Check HbA1c every 3 months when therapy changes or targets not met, then at least twice yearly when stable 5, 3
- Monitor eGFR and urine albumin-to-creatinine ratio every 3 months to assess CKD progression 5
Common Pitfalls to Avoid
Do not discontinue metformin prematurely: It can be safely used with dose reduction until eGFR falls below 30 mL/min/1.73 m² 1, 3
Do not stop SGLT2 inhibitors as eGFR declines: Continue until dialysis or transplantation, as kidney and cardiovascular benefits persist even at eGFR 20-30 mL/min/1.73 m² 1, 3
Do not reflexively stop ACE inhibitor/ARB for mild hyperkalemia or creatinine rise <30%: Attempt medical management first, as these agents provide critical kidney protection 1, 3
Avoid nephrotoxins: NSAIDs, aminoglycosides, and contrast agents should be avoided or used with extreme caution 6, 7
Adjust drug dosing: Many antibiotics, oral hypoglycemic agents, and other medications require dose adjustment based on eGFR 6
High-Risk Patients Requiring Nephrology Referral
Refer promptly when: 6
- eGFR <30 mL/min/1.73 m²
- Albuminuria ≥300 mg per 24 hours
- Rapid decline in eGFR (>5 mL/min/1.73 m² per year)
- Uncontrolled hypertension despite multiple agents
- Persistent hyperkalemia or metabolic acidosis