What is the management approach for Polycystic Kidney Disease (PKD)?

Polycystic Kidney Disease (ADPKD): Management Summary

ADPKD is a systemic genetic disorder requiring aggressive blood pressure control, lifestyle modifications, and in select high-risk patients, tolvaptan therapy, with management guided by progression risk stratification using total kidney volume and Mayo imaging classification. 1

Diagnosis and Risk Stratification

Diagnostic Approach

• Imaging-based diagnosis is standard for patients with positive family history using ultrasound, CT, or MRI 1, 2
• Genetic testing is recommended for very-early-onset disease (before 18 months), rapidly progressive disease with negative family history, or atypical presentations 1
• Use multigene panels including PKD1, PKD2, PKHD1, DZIP1L, HNF1B rather than single-gene testing due to phenotypic overlap 1
• Do not perform genetic testing for single cysts with no extrarenal findings and negative family history 1

Progression Risk Assessment

• Mayo Imaging Classification (MIC) stratifies patients by height-adjusted total kidney volume and age (classes 1A-1E) to predict disease progression 3, 4
• Additional risk factors include PKD genotype, eGFR trajectory, early-onset hypertension, and early urologic complications 4, 2

Blood Pressure Management

Target Blood Pressure

For patients 18-49 years with CKD G1-G2 and BP >130/85 mmHg: Target 110/75 mmHg by home monitoring 1, 3

For patients ≥50 years or CKD G3-G5: Target systolic BP <120 mmHg by office measurement 1, 3

Monitoring and Treatment

• Annual standardized office BP measurement for all ADPKD patients regardless of kidney function 1
• First-line therapy: ACE inhibitors or ARBs 1, 3
• Never combine ACE inhibitors, ARBs, and direct renin inhibitors 3
• Supplement with home BP monitoring or 24-hour ambulatory monitoring 1, 3
• Investigate resistant hypertension (requiring ≥3 drugs) for medication non-adherence or secondary causes 3

Pediatric BP Management

• Annual office BP measurement for all children and adolescents with ADPKD 1
• Annual 24-hour ambulatory BP monitoring for children >5 years (height >120 cm) with very-early-onset or early-onset ADPKD, or those with BP >75th percentile 1
• Target BP <50th percentile for age, sex, and height, or <110/70 mmHg in adolescents 1
• Perform echocardiography to exclude left ventricular hypertrophy in children with high BP 1
• Use ACE inhibitors or ARBs as first-line therapy 1

Disease-Modifying Therapy: Tolvaptan

FDA Warnings and Contraindications

Tolvaptan is CONTRAINDICATED in standard formulations for ADPKD outside FDA-approved REMS due to hepatotoxicity risk 5

Additional contraindications include: 5

• Inability to sense or respond to thirst
• Hypovolemic hyponatremia
• Concomitant strong CYP3A inhibitors
• Anuria

Key Safety Considerations

• Can cause severe and potentially fatal liver injury - requires regular hepatic function monitoring 3, 5
• Produces copious aquaresis with risk of dehydration and hypovolemia 3, 5
• Must be initiated and re-initiated in hospital with close serum sodium monitoring 5
• Avoid rapid sodium correction (>12 mEq/L/24 hours) to prevent osmotic demyelination 5

Clinical Benefits

• Reduces kidney stone incidence in ADPKD patients 6
• Slows disease progression in high-risk patients 4, 2

Management of Complications

Kidney Pain

Sequential approach: 1, 3

1. First: Non-pharmacologic, non-invasive interventions
2. Second: Pharmacologic treatment if no relief
3. Third: Cyst aspiration or aspiration sclerotherapy for pain from dominant cysts
4. Fourth: Celiac plexus block or percutaneous renal denervation for refractory chronic visceral pain
5. Last resort: Nephrectomy for intractable severe pain, typically in advanced disease

• Refer to multidisciplinary pain management teams for refractory cases 1, 3
• Refer to centers of expertise before considering invasive interventions 1

Nephrolithiasis

• Medical management follows general population guidelines 1, 3, 6
• Obstructing stones MUST be managed at centers of expertise due to technical complexity with enlarged polycystic kidneys 1, 6
• Investigate additional risk factors when stones are identified 6
• Interrupt tolvaptan during stone episodes if volume depletion risk exists 6

Hematuria

• Discuss gross hematuria possibility at diagnosis to avoid unnecessary worry when it occurs 1, 3
• Recurrent gross hematuria before age 30-35 years associates with worse renal survival 6

Urinary Tract Infections

Do NOT treat asymptomatic bacteriuria 1, 3

For uncomplicated symptomatic UTIs: 1, 3

• Use first-line therapy: nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin based on local susceptibility
• Obtain urine culture before starting antibiotics
• Treat acute cystitis with shortest reasonable duration (generally ≤7 days)
• Investigate recurrent UTIs for underlying predisposition

For suspected kidney cyst infection: 1

• Obtain blood cultures if upper UTI or cyst infection suspected
• Diagnostic features: CRP ≥50 mg/L or WBC >11 × 10⁹/L
• Consider 18F-FDG PET-CT for confirmation if needed
• Treat with 4-6 weeks of antibiotic therapy 1

Proteinuria

• High-grade proteinuria should be investigated for coexisting kidney disease 1

Gout

• Do NOT routinely treat asymptomatic hyperuricemia 1
• Gout is not more common in ADPKD than other CKD causes 1
• Evaluate and treat gout according to kidney function level 1
• Genetic testing for autosomal dominant tubulointerstitial kidney disease if gout onset in childhood/adolescence 1

Lifestyle Modifications

Physical Activity

• Moderate-intensity activity ≥150 minutes per week 1, 3
• Strength training ≥2 sessions per week 1, 3
• Advise patients with large kidneys/liver about direct injury risk during physical activity 1
• Expert consultation needed for those with cardiovascular disease, frailty, bone disease, or on dialysis/post-transplant 1

Substance Use

• Avoid all tobacco products 1, 3
• Limit alcohol: ≤1 drink/day for women, ≤2 drinks/day for men 1, 3
• Avoid excessive caffeine intake, particularly during pregnancy 1, 3
• Refrain from cannabis products (risk of acute kidney injury from contamination), recreational drugs, and anabolic steroids 1

Dietary Recommendations

• Sodium restriction is beneficial 4, 2
• Maintain healthy weight 4

Pregnancy and Reproductive Issues

Preconception Counseling

• Stop ACE inhibitors, ARBs, tolvaptan, and teratogenic drugs before pregnancy and do not restart until breastfeeding complete 1, 3
• Offer counseling about reproductive options including preimplantation genetic testing 1
• Multidisciplinary team counseling at ADPKD referral center when possible 1

Pregnancy Management

• Follow with multidisciplinary team at expert center 1, 3
• BP target: ≤130/85 mmHg 1, 3
• Use labetalol, long-release nifedipine, hydralazine, clonidine, or methyldopa for BP control 1
• Low-dose aspirin from week 12 to week 36 to prevent preeclampsia 1, 3
• Monitor soluble fms-like tyrosine kinase 1-to-placental growth factor ratio from 24 weeks gestation 1
• Increased risk of preeclampsia and preterm delivery 1
• Postpartum nephrology review at 6 weeks and within 6 months 1
• Offer pelvic-floor physical therapy for bladder instability or urinary incontinence after delivery 1

Contraception

• Women with ADPKD and liver cysts should be educated about contraceptive choices as estrogen exposure may increase polycystic liver disease progression 1
• Perform liver imaging before considering hormone therapy 1
• Progestin-only intrauterine devices likely safe for moderately severe polycystic liver disease (low systemic exposure) 1, 3
• Non-hormonal methods safest for severe polycystic liver disease 1
• Do not restrict contraception in adolescents or young adults with ADPKD 1

Extrarenal Manifestations

Intracranial Aneurysms

• Consider screening in patients with family history of aneurysms or subarachnoid hemorrhage 3

Cardiac Evaluation

• Consider echocardiography in patients with severe or uncontrolled hypertension, cardiac murmur, or family history of thoracic aortic aneurysm 3

Polycystic Liver Disease

• Consider impact of hormonal contraceptives in women with liver cysts 3

Follow-Up and Care Coordination

Monitoring Strategy

• Comprehensive, multidisciplinary, holistic care pathway 1
• Regular monitoring of BP, kidney function, and associated complications 3
• Detailed imaging and progression risk scoring 1
• Annual follow-up with nephrology or shared primary care 1
• Re-referral conditions: complications or eGFR <60 mL/min/1.73 m² 1

Patient Support

• Encourage participation in registries, cohort studies, and clinical trials 1
• Implement self-management programs 1
• Inform about patient organizations and support services 1
• Screen for and assess psychosocial issues periodically 1
• Discuss financial impacts and help avoid unnecessary medical expenses 1