What is the first‑line treatment for autosomal dominant polycystic kidney disease in an adult?

First-Line Treatment for Autosomal Dominant Polycystic Kidney Disease

Renin-angiotensin system inhibitors (ACE inhibitors or ARBs) are the first-line treatment for hypertension in adults with ADPKD, which is the primary therapeutic intervention for this disease. 1

Blood Pressure Management: The Cornerstone of ADPKD Treatment

First-Line Pharmacotherapy

• ACE inhibitors or ARBs must be used as the initial antihypertensive agent in all patients with ADPKD and hypertension, regardless of age or kidney function stage. 1, 2

• These agents have the largest evidence base for efficacy and safety in renal hypertension and provide superior proteinuria reduction compared to other antihypertensive classes. 1, 2

• The KDIGO 2025 guidelines explicitly recommend avoiding any combination of ACEi, ARB, and direct renin-inhibitor therapy due to lack of additional benefit and increased risk. 1

Blood Pressure Targets by Age and CKD Stage

For patients aged 18-49 years with CKD G1-G2:

• Target home BP ≤110/75 mm Hg if BP is >130/85 mm Hg and tolerated. 1
• This lower target is particularly important for patients at high risk of rapid progression (Mayo Class 1C-1E). 3

For patients aged ≥50 years and/or CKD G3-G5:

• Target mean systolic BP <120 mm Hg using standardized office measurement. 1

For children and adolescents:

• Target BP <50th percentile for age, sex, and height, or <110/70 mm Hg in adolescents, using ACEi or ARBs as first-line therapy. 1

Rationale for ACE Inhibitors/ARBs as First-Line

The preference for renin-angiotensin system blockade is based on several mechanisms:

• Activation of the renin-angiotensin-aldosterone system occurs due to cyst expansion and local renal ischemia, making RAAS inhibition pathophysiologically targeted. 4

• These agents reduce proteinuria more effectively than calcium channel blockers or other antihypertensives, which is critical since proteinuria is an established risk factor for CKD progression. 1, 5

• Long-term studies demonstrate that enalapril sustains decreased urinary albumin excretion over 5 years, whereas calcium channel blockers do not provide this benefit despite similar BP control. 5

Second-Line and Additional Considerations

• Second-line agents (calcium channel blockers, diuretics) should be added only after maximizing ACEi/ARB therapy to achieve target BP. 1

• Diuretics should be used cautiously as they may increase vasopressin levels and have deleterious effects on eGFR compared to ACE inhibitors in ADPKD. 1

• Resistant hypertension requiring ≥3 drugs warrants investigation for medication compliance and secondary causes of hypertension. 1

Disease-Modifying Therapy Beyond Blood Pressure Control

While ACE inhibitors/ARBs are first-line for hypertension management:

• Tolvaptan (vasopressin V2 receptor antagonist) should be considered for patients at high risk of rapid progression (Mayo Class 1C-1E or eGFR decline >3 mL/min/1.73 m² per year), as it reduces eGFR decline by 0.98-1.27 mL/min/1.73 m² annually. 2, 3

• However, tolvaptan is not considered "first-line" in the traditional sense—it is reserved for specific high-risk patients after establishing optimal BP control with ACEi/ARB. 2, 6

Common Pitfalls to Avoid

• Do not use dual RAAS blockade (ACEi + ARB combination), as this provides no additional benefit over monotherapy with optimal BP control and increases adverse event risk. 1

• Do not rely solely on office BP measurements—use home BP monitoring or 24-hour ambulatory BP monitoring to guide therapy, especially in younger patients with early CKD. 1

• Do not delay treatment in young patients with "borderline" hypertension—early aggressive BP control is critical for preserving kidney function and reducing left ventricular hypertrophy. 4, 6