What is the primary management approach for patients with polycystic kidney disease (PKD)?

Primary Management of Polycystic Kidney Disease

The primary management approach for PKD centers on aggressive blood pressure control using ACE inhibitors or ARBs as first-line therapy, combined with lifestyle modifications including salt restriction, maintenance of normal weight, and adequate hydration, with tolvaptan reserved for high-risk patients likely to progress to end-stage renal disease.

Blood Pressure Management

Target Blood Pressure Goals

• For patients 18-49 years with early disease (CKD G1-G2) and BP >130/85 mmHg: Target 110/75 mmHg measured by home monitoring 1
• For patients ≥50 years and/or CKD G3-G5: Target systolic BP <120 mmHg measured in office 1
• During pregnancy: Target ≤130/85 mmHg 1

First-Line Antihypertensive Therapy

• ACE inhibitors or ARBs are the recommended first-line agents for hypertension in ADPKD, particularly when proteinuria is present 2, 3
• These agents have the largest evidence base for efficacy and safety in renal hypertension and provide superior renoprotection 2
• Avoid any combination of ACE inhibitors, ARBs, and direct renin inhibitors 1
• Use diuretics with caution as they may increase vasopressin levels and have deleterious effects on eGFR compared to ACE inhibitors 2

Monitoring Proteinuria

• Monitor proteinuria/albuminuria regularly as it is an established risk factor for CKD progression 2
• Measure albumin-to-creatinine ratio (ACR) in laboratory rather than dipstick testing for greater sensitivity 2
• ACE inhibitors or ARBs should be used as primary treatment when proteinuria is present 2

Lifestyle Modifications

Essential Interventions

• Physical activity: At least 150 minutes per week of moderate-intensity activity plus strength training ≥2 sessions weekly 1
• Maintain normal weight: Obesity is an independent predictor of faster renal function loss 2
• Salt restriction: Achieve recommended low dietary salt intake, as high salt intake is associated with higher blood pressure, proteinuria, and progression to ESRD 2
• Adequate hydration: Encourage drinking to satisfy thirst and avoid dehydration, though high water intake benefits remain speculative 2
• Avoid excessive protein intake: May be beneficial in slowing progression, but unnecessary restriction should be avoided to prevent malnutrition 2
• Tobacco cessation and limit alcohol: Avoid tobacco products, limit alcohol to ≤1 drink/day for women and ≤2 drinks/day for men 1

Disease-Modifying Pharmacotherapy

Tolvaptan (Vasopressin V2-Receptor Antagonist)

• Licensed for adults with ADPKD at high risk of progression to ESRD 2, 4
• Delays cyst enlargement and decline in renal function 4, 5
• Critical warnings: Can cause severe and potentially fatal liver injury requiring regular hepatic monitoring; produces copious aquaresis with risk of dehydration and hypovolemia; contraindicated in patients unable to perceive or respond to thirst 1
• Not routinely recommended for children and adolescents: Off-label use can be considered at clinician discretion in children at high risk based on large total kidney volume, rapid kidney growth, or family history 2
• Side effects include substantial polyuria affecting sleep and daily activities, impacting quality of life 2

Agents NOT Recommended

• mTOR inhibitors should NOT be used in classical ADPKD as prospective RCTs found no eGFR benefit and important adverse effects including worsening proteinuria, hyperlipidemia, and cytopenias 2
• Somatostatin analogues should NOT be used due to insufficient evidence supporting their use 2
• Vasopressin analogues (e.g., desmopressin) should be used with caution in children with ADPKD and enuresis due to potential negative effects on cyst growth 2

Statins in Children

• One RCT in children aged 8-22 years showed pravastatin plus lisinopril resulted in slower increase in height-adjusted total kidney volume compared to placebo 2
• However, no consensus was reached on routine statin use to slow disease progression in children with ADPKD 2

Management of Complications

Renal Pain

• Investigate to determine if pain is kidney-related 1
• Treatment sequence: (1) Non-pharmacological/non-invasive interventions first; (2) Pharmacological treatment if no relief; (3) Aspiration or scleroterapy for dominant cysts; (4) Celiac plexus block or percutaneous renal denervation for refractory visceral pain; (5) Nephrectomy reserved for intractable severe pain, typically in advanced disease 1

Urinary Tract Infections

• Do NOT treat asymptomatic bacteriuria 1
• Obtain urine culture before initiating antibiotics 1
• Use first-line therapy (nitrofurantoin, trimethoprim-sulfamethoxazol, fosfomycin) for uncomplicated symptomatic UTIs 1
• Treat acute cystitis with shortest reasonable antibiotic duration (generally ≤7 days) 1

Nephrolithiasis and Hematuria

• Treat kidney stones medically as in the general population 1
• Manage obstructive stones at specialized centers 1
• Discuss possibility, causes, and natural history of macroscopic hematuria with patients at diagnosis 1

Risk Stratification and Monitoring

Imaging for Prognosis

• Total kidney volume (TKV) is the most important predictive factor for loss of renal function 4, 5
• Kidney volume measurement is recommended as soon as diagnosis is made 4
• Mayo Imaging Classification (MIC) stratifies patients by height-adjusted kidney volume and age (classes 1A-1E) for predicting disease progression 1, 6
• Patients <30 years with combined kidney volume >1500 mL and eGFR <90 mL/min are at high risk of needing kidney replacement therapy within 20 years 4

Routine Monitoring in Asymptomatic Children

• Do NOT perform routine monitoring of cyst growth too frequently in asymptomatic children as ultrasonography findings are unlikely to influence clinical management and create psychological burden 2
• Regular blood pressure and proteinuria screening should be performed at recommended intervals 2

Special Populations

Pregnancy

• Follow with multidisciplinary team 1
• Discontinue ACE inhibitors/ARBs, tolvaptan, and other teratogenic drugs before pregnancy 1
• Low-dose aspirin from week 12 to 36 for preeclampsia prevention 1

Screening for Extrarenal Manifestations

• Consider intracranial aneurysm screening in patients with family history of aneurysms or subarachnoid hemorrhage 1
• Consider echocardiography in patients with severe/uncontrolled hypertension, cardiac murmur, or family history of thoracic aortic aneurysm 1
• Consider impact of hormonal contraceptives in women with liver cysts 1