KDIGO 2025 ADPKD Guidelines: Evaluation and Management
The KDIGO 2025 Clinical Practice Guideline provides the first comprehensive global framework for diagnosing, risk-stratifying, and managing autosomal dominant polycystic kidney disease (ADPKD) through a multidisciplinary care pathway that emphasizes early diagnosis, prognostic assessment using the Mayo Imaging Classification, blood pressure control, and targeted therapy for rapid progressors. 1
Diagnosis and Screening
Adults with Positive Family History
Begin with abdominal ultrasound as the first-line imaging modality for screening adults at risk 1, 2
Apply age-specific ultrasound criteria to confirm or exclude ADPKD:
Proceed to MRI or CT if ultrasound results are equivocal or atypical features are present 1
For ages 16-40 years on MRI: >10 total cysts confirms diagnosis; <5 total cysts excludes ADPKD 1
Adults with Incidental Cysts (No Known Family History)
- If few cysts with normal kidney function/size and no extrarenal features: proceed to kidney MRI or CT 1
- If multiple cysts, discordant imaging/GFR, or atypical renal/extrarenal findings: proceed directly to genetic testing 1, 2
Genetic Testing Indications
Order comprehensive multigene cystic kidney disease panels (not just PKD1/PKD2) in the following scenarios: 2
- Few kidney cysts with suggestive clinical picture
- Variable intrafamilial disease severity or very-early-onset ADPKD
- Discordant imaging and glomerular filtration rate
- Negative or indeterminate family history
- Young (<30 years) living-related kidney donors at risk
- Family planning and preimplantation diagnosis considerations 1, 2
Prognostic Risk Stratification
Mayo Imaging Classification (MIC)
Use the Mayo Imaging Classification to predict future eGFR decline and timing of kidney failure once ADPKD is confirmed 1, 3, 4
- MIC stratifies patients into 5 risk groups (1A-1E) based on height-adjusted total kidney volume (htTKV) and age 3, 4
- Classes 1C-1E identify rapid progressors with accelerated eGFR loss and earlier kidney failure 3, 4
Important MIC Limitations
Do NOT apply MIC in the following situations: 3
- Atypical imaging patterns (Class 2 ADPKD) with unilateral, segmental, asymmetric, or lopsided cyst distributions 3
- Pathogenic variants in genes other than PKD1 or PKD2 3
- Prominent exophytic cysts that artificially inflate TKV measurements 3
Blood Pressure Management
Target Blood Pressure Goals
For patients aged 18-49 years with CKD G1-G2 and BP >130/85 mmHg: target 110/75 mmHg by home monitoring 5
For patients ≥50 years and/or CKD G3-G5: target systolic BP <120 mmHg measured in office 5, 4
Antihypertensive Therapy
- Use renin-angiotensin system inhibitors (ACE inhibitors or ARBs) as first-line therapy for hypertension in ADPKD 1, 5
- Never combine ACE inhibitors, ARBs, and direct renin inhibitors 5
- Measure BP using standardized office measurements, complemented by home or ambulatory monitoring 5
- Investigate resistant hypertension (requiring ≥3 medications) for medication non-adherence or secondary causes 5
Children and Adolescents with ADPKD
- Target BP <50th percentile for age, sex, and height, or <110/70 mmHg in adolescents 1
- Use renin-angiotensin system inhibitors as first-line therapy 1
- Perform echocardiography to exclude left ventricular hypertrophy in children with high BP 1
- Management should be by a pediatric nephrologist 1
Tolvaptan Therapy
Tolvaptan is indicated for patients with MIC 1C-1E or eGFR decline >3 mL/min/1.73 m² per year to slow disease progression and delay kidney failure 4
- Reduces annual rate of eGFR decline by 0.98-1.27 mL/min/1.73 m² 4
Critical Safety Warnings
- Can cause severe and potentially fatal liver injury—monitor liver function regularly 5
- Produces copious aquaresis with risk of dehydration and hypovolemia 5
- Contraindicated in patients who cannot perceive or respond to thirst 5
- Must discontinue before pregnancy (teratogenic) 5
Lifestyle and Dietary Management
Physical Activity
- Undertake moderate-intensity physical activity for at least 150 minutes per week 1, 5
- Perform strength training at least 2 sessions per week 1, 5
- Advise patients with large kidneys/liver about risk of direct injury during physical activity 1
Dietary Recommendations
- Follow general healthy diet consistent with WHO and CKD guidelines 1
- Restrict dietary sodium to <2000 mg/day 4
- Maintain adequate hydration (>2.5 L daily) 4
- Consider estimated weight of cystic kidneys when calculating body mass index 1
- Refer patients with CKD G4-G5, high stone risk, obesity (BMI >30), or malnutrition to registered dietitians 1
Substance Use Counseling
- Avoid all tobacco products 1, 5
- Limit alcohol to ≤1 drink/day for females, ≤2 drinks/day for males 1, 5
- Avoid excessive caffeine intake, particularly during pregnancy 1, 5
- Counsel about dangers of cannabis products (risk of acute kidney injury from contamination/synthetic versions) 1
- Advise refraining from recreational drugs and anabolic steroids 1
Management of Complications
Renal Pain
Use a stepwise approach for pain management: 5
- First-line: Non-pharmacological and non-invasive interventions 5
- Second-line: Pharmacological treatment if no relief 5
- Third-line: For pain from dominant cysts—cyst aspiration or aspiration sclerotherapy 5
- Fourth-line: For chronic refractory visceral pain—celiac plexus block or percutaneous renal denervation 5
- Last resort: Nephrectomy reserved for severe intractable pain, typically in advanced kidney disease 5
Urinary Tract Infections
- Do NOT treat asymptomatic bacteriuria 5
- Obtain urine culture before starting antibiotics 5
- Use first-line therapy (nitrofurantoin, trimethoprim-sulfamethoxazole, fosfomycin) for uncomplicated symptomatic UTIs 5
- Treat acute cystitis with shortest reasonable antibiotic duration (generally ≤7 days) 5
- Investigate recurrent UTIs for underlying predisposition 5
Nephrolithiasis
- Treat kidney stones in ADPKD the same as general population 5
- Manage obstructive kidney stones at specialized centers 5
- Discuss possibility, causes, and natural history of gross hematuria with patients at diagnosis 5
Intracranial Aneurysms
- Consider screening for intracranial aneurysms in patients with family history of aneurysms or subarachnoid hemorrhage 5
- Rupture rate is 0.57 per 1000 patient-years 4
- Approximately 9-14% of ADPKD patients develop intracranial aneurysms 4
Polycystic Liver Disease
- Liver cysts present in >80% of patients by age 30 years 1
- Consider impact of hormonal contraceptives in women with liver cysts 5
- Symptomatic polycystic liver disease affects <5%, predominantly females 1
Cardiac Manifestations
- Consider echocardiography in patients with: 5
- Severe or uncontrolled hypertension
- Cardiac murmur
- Family history of thoracic aortic aneurysm
Pregnancy Management
- Pregnant women with ADPKD should be followed by a multidisciplinary team 5
- Target BP ≤130/85 mmHg during pregnancy 5
- Discontinue ACE inhibitors/ARBs, tolvaptan, and other teratogenic drugs before pregnancy 5
- Administer low-dose aspirin from week 12 to week 36 to prevent preeclampsia 5
Care Coordination and Follow-Up
Comprehensive Care Pathway
- Implement a comprehensive, multidisciplinary, holistic care pathway for monitoring kidney disease progression 1
- Provide care coordination and/or patient navigation along care pathways 1
- Annual follow-up in nephrology or primary care/shared care 1
- Re-referral conditions include complications or eGFR <60 mL/min/1.73 m² 1
Patient Education and Support
- Screen for and periodically assess psychosocial issues (physical stressors, social concerns, family-related issues, inherited disease burden) 1
- Implement self-management education programs providing comprehensive information to patients and families 1
- Inform patients about PKD patient organizations, kidney disease support groups, and other advice services 1
- Encourage participation in registries, cohort studies, and clinical trials 1