Is Nitroglycerin (NTG) better for treating hypertensive emergencies in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) or fibromuscular dysplasia?

Nitroglycerin is NOT the Preferred Agent for Hypertensive Emergencies in ADPKD or Fibromuscular Dysplasia

For patients with ADPKD or fibromuscular dysplasia presenting with hypertensive emergencies, nitroglycerin should not be considered a first-line agent; instead, nicardipine, labetalol, or clevidipine are preferred based on current guidelines, with ACE inhibitors or ARBs as the foundation for chronic blood pressure management in ADPKD. 1

Why Nitroglycerin is Not Optimal

Limited Role in Hypertensive Emergencies

• Nitroglycerin is specifically recommended only for acute coronary syndromes and acute pulmonary edema in the context of hypertensive emergencies. 1
• The 2017 ACC/AHA guidelines explicitly state that nitroglycerin should be used "only in patients with acute coronary syndrome and/or acute pulmonary edema" and "do not use in volume-depleted patients." 1
• Research evidence from 2008 indicates that nitroglycerin "should not be considered first-line therapy in the management of hypertensive crises because these agents are associated with significant toxicities and/or adverse effects." 2

Inferior Performance Compared to Alternatives

• A 2022 study directly comparing nicardipine versus nitroglycerin in hypertensive acute heart failure syndrome demonstrated that nicardipine achieved faster blood pressure control (1.0 vs 2.0 hours), shorter duration of continuous infusion (2.0 vs 3.0 days), less frequent need for additional agents (3.1% vs 42.3%), and shorter hospital stays (9.0 vs 17.5 days). 3

Preferred Agents for Hypertensive Emergencies

First-Line Intravenous Options

• Nicardipine is preferred as it provides potent arteriolar vasodilation with predictable, titratable blood pressure control. 1
• Labetalol offers combined alpha and beta blockade with more predictable responses than nitroglycerin. 1
• Clevidipine is a newer agent that may hold considerable advantages in managing hypertensive crises. 2
• The 2017 ACC/AHA guidelines note that "2 trials have demonstrated that nicardipine may be better than labetalol in achieving the short-term BP target." 1

Agents to Avoid

• Sodium nitroprusside should be avoided as it is "an extremely toxic drug" with risk of cyanide toxicity, particularly problematic in patients with renal disease like ADPKD. 2

Specific Considerations for ADPKD

Chronic Blood Pressure Management Foundation

• ACE inhibitors and ARBs are the first-line agents for chronic hypertension management in ADPKD patients. 1, 4
• The 2019 international consensus statement emphasizes that "ACE inhibitors and ARBs have the largest evidence base for efficacy and safety in paediatric patients and in patients with renal hypertension." 1
• KDIGO guidelines recommend renin-angiotensin system inhibitors as first-line treatment for hypertension in ADPKD. 4

Pathophysiology Rationale

• Hypertension in ADPKD is driven by activation of the renin-angiotensin-aldosterone system due to bilateral cyst expansion and intrarenal ischemia, making RAAS blockade particularly logical. 5, 6, 7
• Cardiovascular involvement starts very early in ADPKD, with endothelial dysfunction and left ventricular hypertrophy present even in young normotensive patients with preserved renal function. 5, 6

Agents to Use with Caution in ADPKD

• Diuretics should be used cautiously as they may increase vasopressin levels and have deleterious effects on estimated GFR compared to ACE inhibitors in ADPKD. 1
• Calcium channel blockers have mixed evidence: animal models showed they promoted cyst growth, though human studies are inconsistent. 1

Blood Pressure Targets in ADPKD

Evidence-Based Goals

• For adults with ADPKD and CKD, target blood pressure is <130/80 mmHg according to ACC recommendations. 4
• KDIGO guidelines recommend more aggressive targets for younger patients: ≤110/75 mmHg if tolerated for patients aged 18-49 years with CKD G1-G2. 4
• The HALT-PKD Study A demonstrated significant benefits of lower blood pressure goals (95/60 to 110/75 mmHg) versus standard targets in terms of total kidney volume, left ventricular mass index, and albuminuria in adults with ADPKD and early CKD. 1

Considerations for Fibromuscular Dysplasia

While the provided evidence does not specifically address fibromuscular dysplasia in detail, the general principles for hypertensive emergencies apply:

• Use titratable intravenous agents like nicardipine or labetalol rather than nitroglycerin. 1
• The European Society of Cardiology position document supports nicardipine or labetalol as preferred agents for most hypertensive emergencies. 1

Critical Monitoring Parameters

During Acute Management

• Avoid excessive blood pressure reduction: the goal in hypertensive emergencies is typically to reduce mean arterial pressure by no more than 25% in the first hour. 1
• Continuous infusion of short-acting titratable agents is preferable to prevent further target organ damage, as autoregulation of tissue perfusion is disturbed. 1

Long-Term Follow-Up in ADPKD

• Follow-up every 6-8 weeks after initiating or adjusting antihypertensive medications until blood pressure goal is safely achieved. 4
• Once target blood pressure is achieved, laboratory monitoring and clinic follow-up every 3-6 months is recommended. 4
• Monitor for isolated nighttime hypertension with normal daytime blood pressure, which occurs in 16-18% of children with ADPKD. 4