What is the treatment for an elderly patient with established Autosomal Dominant Polycystic Kidney Disease (ADPKD) and numerous bilateral renal cysts?

Treatment of Established ADPKD

For patients with established ADPKD, tolvaptan is the cornerstone pharmacologic therapy for those at risk of rapid progression, combined with blood pressure control targeting systolic <120 mm Hg (or <110/75 mm Hg for high-risk younger patients), increased water intake of 2-3 liters daily, dietary sodium restriction, and preparation for kidney replacement therapy when kidney failure approaches. 1

Disease-Modifying Pharmacotherapy

Tolvaptan (Vasopressin V2 Receptor Antagonist)

Tolvaptan is the only FDA-approved disease-modifying treatment for ADPKD and should be considered for patients at risk of rapid progression. 1

• Reduces eGFR decline by 1.3 mL/min/1.73 m² per year (95% CI: 1.0-1.7) and total kidney volume growth by 2.7% (95% CI: -3.3% to -2.1%) 1
• Significantly reduces incidence of UTI, kidney stones, hematuria, and kidney pain 1
• Requires adequate water intake to replace urinary losses for long-term tolerability 1
• Patients must have a "sick-day plan" to skip doses during volume depletion risk (limited water access, increased fluid losses, warm weather activities) 1
• Monitor liver enzymes closely due to risk of hepatotoxicity 1
• Common side effects include thirst, dry mouth, hyperuricemia, and rarely gout 1

Water Intake Strategy (Without Tolvaptan)

• Adapt water intake spread throughout the day to achieve at least 2-3 liters per day in patients with eGFR ≥30 mL/min/1.73 m² 1
• Contraindications include medications increasing hyponatremia risk (serotonin reuptake inhibitors, tricyclic antidepressants, thiazide diuretics) 1

Therapies NOT Recommended

The following interventions should NOT be used to slow ADPKD progression: 1

• mTOR inhibitors (mammalian target of rapamycin inhibitors) - not recommended 1
• Metformin (in non-diabetic patients) - not recommended 1
• Statins specifically for kidney disease progression - not recommended 1
• SGLT2 inhibitors or GLP-1 receptor agonists - insufficient evidence, not advised at this time 1
• Ketogenic interventions - insufficient long-term evidence 1
• Somatostatin analogues - should not be prescribed solely for slowing eGFR decline, but can be considered for severe symptoms from massively enlarged kidneys when no better options exist 1

Blood Pressure Management

Strict blood pressure control is essential and should target systolic <120 mm Hg for most patients. 2

• ACE inhibitors or ARBs are first-line agents 2
• For high-risk patients (Mayo Class 1C-1E, eGFR >60 mL/min/1.73 m², age <50 years), target even lower at <110/75 mm Hg 2
• ACEi significantly reduces diastolic blood pressure (MD -4.96 mm Hg, 95% CI -8.88 to -1.04) 3

General CKD Management

Management of CKD complications in ADPKD follows standard CKD guidelines with specific modifications: 1

Anemia Management

• Patients with ADPKD tend to have higher hemoglobin levels compared to other CKD patients due to regional hypoxia driving erythropoietin production 1
• Erythrocytosis (hematocrit >51% or hemoglobin >17 g/dL) may occur, especially post-transplant 1
• Therapeutic phlebotomy indicated when ACEi/ARB contraindicated or ineffective at maximal dose 1

Diabetes Management

• Use metformin when eGFR ≥30 mL/min/1.73 m² 1
• Use GLP-1 receptor agonist when eGFR <30 mL/min/1.73 m², when metformin not tolerated, or when metformin alone insufficient 1
• SGLT2 inhibitors not advised due to lack of evidence in ADPKD 1

Cardiovascular Risk Management

• Initiate lipid-lowering therapy per KDIGO Lipid Management guidelines 1

Dietary Modifications

• Sodium restriction <2000 mg/day 2
• Weight management 2

Management of Complications

Kidney Cyst Infections

• Use lipid-soluble antibiotics (trimethoprim-sulfamethoxazole or fluoroquinolone) for better cyst penetration 1
• Caution with fluoroquinolones due to increased risk of tendinopathies and aortic aneurysms/dissections 1

Polycystic Liver Disease (PLD)

Most patients do not develop clinically symptomatic PLD, but when symptoms occur due to mass effect, treatment options include: 1

• Aspiration sclerotherapy for one or few large dominant cysts (symptomatic improvement 72-100%, mortality <1.0%) 1
• Laparoscopic cyst fenestration for large symptomatic anterior/caudal cysts (complications 29%, mortality 2.3%) 1
• Liver transplantation for massive PLD with high symptom burden when other options fail (postoperative complications 46%, mortality 9%) 1
• Combined kidney-liver transplantation when liver transplant indicated AND eGFR <30 mL/min/1.73 m² 1

Kidney Replacement Therapy

Kidney Transplantation

Kidney transplantation, preferably preemptive living-donor transplantation, is the preferred treatment for kidney failure in ADPKD. 1

• Perform imaging within 1 year prior to anticipated transplant timing to rule out solid or complex cystic lesions 1
• Immunosuppressive protocols same as other transplant recipients 1

Native nephrectomy should be performed ONLY for specific indications: 1

• Severe symptoms from massively enlarged kidneys
• Recurrent or severe kidney infection or bleeding
• Complicated nephrolithiasis
• Intractable pain
• Suspicion of renal cell carcinoma
• Insufficient space for kidney graft
• Severe ventral hernia

Timing: nephrectomy should occur at time of or AFTER transplantation, NOT before (due to transfusion risk, preventing preemptive transplant, increased complications) 1

Technique: hand-operated laparoscopic nephrectomy preferred over open nephrectomy 1

Post-transplant monitoring for ADPKD-specific complications: new-onset diabetes, erythrocytosis, worsening valvular regurgitation, aortic root dilatation, subarachnoid hemorrhage, thromboembolic events, skin cancers, cyst infections, and diverticulitis 1

Dialysis

• Shared decision-making and hemodialysis prescription same as non-ADPKD patients 1
• Peritoneal dialysis is a viable option, but use caution with massive kidney/liver enlargement or abdominal wall hernias 1

Special Considerations for Elderly Patients

For elderly patients with established ADPKD (as in this case): 4

• PKD2 mutations result in milder, later disease with CKD stage 3 around age 55 and kidney failure in the 70s, making this genotype particularly relevant 4
• Approximately 50% of ADPKD patients require kidney replacement therapy by age 62 2
• Tolvaptan eligibility depends on progression risk, not age alone - assess Mayo Imaging Classification and eGFR decline rate 2
• Focus on blood pressure control, symptom management, and preparation for kidney replacement therapy 1