How to manage hypertension in a patient with impaired renal function, on multiple antihypertensives, considering the addition of a diuretic?

Management of Hypertension with Impaired Renal Function on Multiple Antihypertensives

Yes, add a diuretic to this patient's regimen—combination therapy including loop diuretics is usually required to achieve blood pressure control in patients with renal dysfunction, and this patient's creatinine of 120 μmol/L (estimated GFR ~50-60 mL/min) indicates stage 3 CKD where diuretics are both necessary and beneficial. 1

Blood Pressure Target

• Target BP should be <130/80 mmHg in patients with chronic kidney disease and impaired renal function. 1
• This strict blood pressure control is one of two main requirements for protecting against progression of renal dysfunction, alongside lowering proteinuria. 1
• Even lower targets (<130/80 mmHg) may be considered if proteinuria exceeds 1 g/day. 1

Diuretic Selection Based on Renal Function

With a creatinine of 120 μmol/L (approximately 1.4 mg/dL), this patient has moderate renal impairment (estimated GFR 50-60 mL/min) and requires a loop diuretic rather than a thiazide. 1

• Loop diuretics (furosemide, torsemide, bumetanide) should be used when estimated GFR is <30 mL/min or in the presence of significant renal impairment. 1
• While this patient's GFR is above 30 mL/min, the creatinine of 120 μmol/L indicates sufficient impairment to warrant loop diuretic consideration, particularly if volume overload is present. 1
• Thiazide or thiazide-type diuretics are less effective in lowering blood pressure once renal function declines below GFR 30-40 mL/min. 1

Combination Therapy Strategy

Most hypertensive patients with renal dysfunction require combination therapy of several antihypertensive agents (including a diuretic) to achieve blood pressure goals. 1

Recommended Medication Framework:

• Continue or ensure ACE inhibitor or ARB therapy as the foundation, since these agents reduce proteinuria and slow progression of kidney disease. 1
• Add a loop diuretic (starting with furosemide 20-40 mg daily or equivalent) to the existing regimen. 1
• Diuretics potentiate the beneficial effects of ACE inhibitors and ARBs in hypertensive patients with diabetic and non-diabetic kidney disease. 1
• Between 60-90% of patients in hypertension treatment studies for kidney disease used either thiazide-type or loop diuretics in addition to ACE inhibitors or ARBs. 1

Additional Agents if Needed:

• Calcium channel blockers (particularly non-dihydropyridine types like diltiazem or verapamil) can be added as they have antiproteinuric effects. 1
• Aldosterone receptor antagonists (spironolactone 25-50 mg or eplerenone) may be considered for resistant hypertension, but require careful monitoring. 1

Critical Monitoring Parameters

Electrolytes and Renal Function:

• Monitor serum potassium closely when combining diuretics with ACE inhibitors or ARBs, as hyperkalemia risk increases. 2
• Check serum creatinine and potassium within 1-2 weeks after initiating or increasing diuretic dose. 2
• Mild increases in creatinine (up to 30% from baseline) are acceptable and do not necessarily indicate harm when achieving adequate blood pressure control. 1, 3
• The patient's current potassium of 3.5 mmol/L is at the lower end of normal, which actually provides some buffer against hyperkalemia when adding a diuretic to an ACE inhibitor. 2

Sodium and Chloride:

• The patient's sodium of 135 mmol/L and chloride of 100 mmol/L are both at the lower end of normal. 1
• Hypochloremia and metabolic alkalosis can antagonize loop diuretic effects, so monitor these parameters. 1
• Avoid severe sodium restriction (<2,300 mg daily) as this can impair diuretic efficacy and worsen outcomes. 4

Common Pitfalls to Avoid

Do not withhold or reduce diuretics prematurely due to mild increases in creatinine or BUN. 3

• The goal is to eliminate clinical evidence of fluid retention, even if this results in mild or moderate decreases in blood pressure or increases in creatinine. 3
• Excessive concern about azotemia often leads to underutilization of diuretics and persistent volume overload, which worsens outcomes. 3
• Focus on the patient's clinical status and symptoms of hypoperfusion rather than laboratory numbers alone. 3

Avoid combining two diuretics initially (such as furosemide plus metolazone or hydrochlorothiazide), as this markedly enhances electrolyte depletion and can precipitate pre-renal azotemia. 4, 5

• The CLOROTIC trial showed that adding hydrochlorothiazide to furosemide increased weight loss but also increased rates of impaired kidney function. 1
• Sequential nephron blockade with multiple diuretics should be reserved for refractory cases with careful monitoring. 1

Do not discontinue ACE inhibitors or ARBs due to small creatinine increases. 2, 6, 7

• Increases in blood urea nitrogen and serum creatinine are usually minor, transient, and reversible. 2
• These increases are more likely when diuretics are used concomitantly, but this combination is often necessary. 2
• Dose reduction of the ACE inhibitor, diuretic, or both may be required rather than complete discontinuation. 2

Dosing Considerations with Renal Impairment

ACE inhibitor doses should be adjusted for renal function. 2, 6, 7

• With creatinine of 120 μmol/L (approximately 1.4 mg/dL), moderate dose reduction of ACE inhibitors may be appropriate. 6, 7
• Start with lower doses and titrate gradually while monitoring renal function. 6, 7
• Studies show effective blood pressure control can be achieved with dose-adjusted ACE inhibitors in patients with GFR as low as 10-60 mL/min. 6

Loop diuretic dosing: Start with furosemide 20-40 mg daily (or equivalent torsemide 10-20 mg daily) and titrate based on response. 1

Long-term Renal Outcomes

Effective blood pressure control predicts better renal outcomes, even when initial creatinine is elevated. 8

• Studies of patients with malignant hypertension and renal impairment show that the quality of blood pressure control achieved at follow-up predicts outcome, not the severity of initial renal impairment. 8
• Renal function can remain stable or even improve in some patients with aggressive blood pressure management, despite initial creatinine elevations. 8
• Careful monitoring of renal function and effective blood pressure treatment is mandatory. 8