What is the best management approach for a patient with hypertension (HTN) and diabetes mellitus (DM), currently on hydrochlorothiazide (HCTZ), with severely impaired kidney function, indicated by a glomerular filtration rate (GFR) of 19, and no current antidiabetic medications?

Management of Hypertension and Diabetes with Severe CKD (GFR 19)

This patient requires immediate discontinuation of hydrochlorothiazide and initiation of an ACE inhibitor or ARB as first-line therapy, combined with a loop diuretic for volume control, plus an SGLT2 inhibitor for both glycemic control and renoprotection. 1, 2, 3

Immediate Antihypertensive Management

Discontinue Hydrochlorothiazide

• Hydrochlorothiazide must be stopped immediately because thiazide diuretics lose substantial efficacy at GFR <30 mL/min/1.73m² and this patient has GFR 19, representing stage 4-5 CKD 4, 5
• While recent evidence suggests thiazides retain some blood pressure-lowering effect even at low GFR, loop diuretics are superior for volume control at this level of kidney function 4, 5, 6

Initiate ACE Inhibitor or ARB

• Start lisinopril 10 mg daily or losartan 50 mg daily as mandatory first-line therapy because RAS blockade is the cornerstone for patients with diabetes, hypertension, and CKD 1, 2, 3
• ACE inhibitors/ARBs reduce intraglomerular pressure, decrease proteinuria, and slow diabetic kidney disease progression independent of blood pressure effects 1, 2, 3
• Titrate to maximum tolerated dose (lisinopril up to 40 mg daily or losartan up to 100 mg daily) over 4-8 weeks 2, 3

Add Loop Diuretic for Volume Control

• Add furosemide 40-80 mg daily because loop diuretics are the only effective diuretic class for volume management at GFR <30 mL/min/1.73m² 4, 5, 6
• Loop diuretics control volume overload more rapidly than thiazides in advanced CKD and are essential for blood pressure control in this sodium-sensitive state 4, 7, 6

Blood Pressure Target

• Target blood pressure <130/80 mmHg as recommended for patients with diabetes and CKD 1, 2, 3
• Most patients with diabetes and stage 4-5 CKD require 3-4 antihypertensive medications to achieve this target 2

Glycemic Management

Initiate SGLT2 Inhibitor

• Start canagliflozin 100 mg daily, empagliflozin 10 mg daily, or dapagliflozin 10 mg daily because SGLT2 inhibitors provide both glycemic control and renoprotection even at GFR as low as 20 mL/min/1.73m² 1, 3
• The CREDENCE trial demonstrated that canagliflozin reduced the primary renal outcome by 30% in patients with eGFR 30-90 mL/min/1.73m² and can be used with benefit down to eGFR 30 mL/min/1.73m² 1
• SGLT2 inhibitors are Class I, Level A recommendation for reducing progression of diabetic kidney disease 1

Consider Metformin

• Metformin is contraindicated at GFR 19 mL/min/1.73m² because it should only be used if eGFR ≥30 mL/min/1.73m² 1, 3
• Do not initiate metformin in this patient 1

Alternative Glycemic Agents

• Consider GLP-1 receptor agonist (liraglutide or semaglutide) if additional glycemic control is needed, as these agents are associated with lower risk of renal endpoints and can be used if eGFR >30 mL/min/1.73m² 1
• However, at GFR 19, this patient is below the threshold for GLP-1 RA use 1
• Insulin therapy may be necessary for glycemic control at this stage of CKD 1

Glycemic Target

• Target HbA1c <7.0% (53 mmol/mol) to decrease microvascular complications 1, 3

Critical Monitoring Requirements

Renal Function and Electrolytes

• Monitor serum creatinine and potassium within 7-14 days after initiating ACE inhibitor/ARB and loop diuretic 2, 3
• Accept creatinine increases up to 30% from baseline after RAS blocker initiation, as this reflects beneficial reduction in intraglomerular pressure 2
• Discontinue or reduce ACE inhibitor/ARB dose if potassium >5.5 mEq/L or if creatinine increases >30% 2

Blood Pressure Monitoring

• Follow-up within 2-4 weeks after medication changes to titrate toward target BP <130/80 mmHg 2, 3
• Goal is to achieve blood pressure target within 3 months 2

Albuminuria Assessment

• Measure urinary albumin-to-creatinine ratio to assess baseline proteinuria and monitor response to therapy 1, 3
• Therapeutic reductions in albuminuria are associated with renoprotection 1

Additional Management Considerations

Lifestyle Modifications

• Sodium restriction to <2,000-2,300 mg/day to optimize effectiveness of antihypertensive medications and reduce volume overload 2, 3
• Weight loss if BMI >25 kg/m², moderate-intensity aerobic exercise ≥150 minutes/week, smoking cessation, and alcohol limitation 2, 3

Cardiovascular Risk Reduction

• Initiate statin therapy (atorvastatin 40-80 mg daily) for ASCVD risk reduction 2, 3
• Consider aspirin 75-162 mg daily if 10-year ASCVD risk >10% 2

Nephrology Referral

• Immediate referral to nephrology is mandatory for GFR 19 mL/min/1.73m², as this represents stage 4-5 CKD requiring preparation for renal replacement therapy 3

Important Caveats

Never Combine ACE Inhibitor with ARB

• Do not combine ACE inhibitors with ARBs, as this increases adverse effects (hyperkalemia, acute kidney injury) without additional cardiovascular or renal benefit 2, 3

Avoid Nephrotoxins

• Patients with CKD on ACE inhibitor/ARB therapy are particularly susceptible to acute kidney injury with exposure to NSAIDs, aminoglycosides, amphotericin B, and radiocontrast 1
• When contrast exposure is necessary, consider temporarily reducing or holding ACE inhibitor/ARB with intravenous fluid administration 1

Pregnancy Considerations

• ACE inhibitors and ARBs are contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential not using reliable contraception 2