From the Guidelines
Polycystic kidney disease (PKD) management should prioritize the use of tolvaptan, a vasopressin-2 receptor antagonist, to slow disease progression in selected patients, as it has been shown to reduce the decline in eGFR and total kidney volume growth, according to the most recent guideline from Kidney International (2025) 1. The type of PKD can be either autosomal dominant (ADPKD) or autosomal recessive (ARPKD), with ADPKD being the most common form, typically presenting in adulthood due to mutations in the PKD1 or PKD2 genes. Pathophysiologically, the genetic defects in PKD cause dysfunction in primary cilia of kidney tubular epithelial cells, leading to increased cell proliferation, fluid secretion, and cyst formation, as described in the kdigo 2025 clinical practice guideline for the evaluation, management, and treatment of ADPKD 1. Some key signs and symptoms of PKD include:
- Hypertension
- Flank pain
- Hematuria
- Urinary tract infections
- Kidney stones
- Eventually, chronic kidney disease Management of PKD should focus on:
- Blood pressure control
- Pain management
- Treating complications
- The use of tolvaptan, which has been shown to have a net difference in eGFR decline of 1.3 ml/min per 1.73 m2 per year and in total kidney volume growth of 2.7%, both favoring tolvaptan use, as reported in the Kidney International study (2025) 1. Tolvaptan treatment should be initiated with a daily dose of 45 mg upon waking, and of 15 mg 8 hours later, and titrated gradually by the treating physician to permit adequate hydration and minimize the risk of volume depletion 1. Patients should be counseled to drink liquids without sugar or fat, and to adopt a low-sodium intake, because low osmolar intake reduces polyuria, and to have a “sick-day plan” to skip doses of tolvaptan in situations in which they are at risk of volume depletion, such as those with limited access to water, those with increased fluid losses, and activities in warm weather, as recommended in the kdigo 2025 guideline 1.
From the Research
Type of Polycystic Kidney Disease
- Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of the disease, accounting for approximately 90% of cases 2, 3, 4, 5.
- Autosomal recessive polycystic kidney disease (ARPKD) is a less common form of the disease, often diagnosed in infancy or childhood 2, 6.
Cause of Polycystic Kidney Disease
- Mutations in the PKD1 or PKD2 genes, which encode polycystin 1 and polycystin 2, are the underlying cause of ADPKD 6.
- The exact cause of ARPKD is not fully understood, but it is believed to be related to mutations in the PKHD1 gene 2.
Pathophysiology of Polycystic Kidney Disease
- The disease is characterized by the formation of fluid-filled cysts in the kidneys, leading to renal enlargement and insufficiency 2, 6.
- The molecular mechanisms underlying cyst formation are not fully understood, but are believed to involve abnormalities in epithelial cell proliferation, fluid secretion, extracellular matrix, and differentiation 6.
Signs and Symptoms of Polycystic Kidney Disease
- The disease often presents with symptoms such as abdominal pain, hematuria, and hypertension 3, 5.
- Other signs and symptoms may include kidney stones, urinary tract infections, and kidney failure 4, 6.
Management of Polycystic Kidney Disease
- Current treatments mainly focus on symptom relief and slowing disease progression, without offering a cure 2, 3.
- Pharmacological interventions, such as tolvaptan, have shown promise in slowing disease progression and preserving kidney function 3, 4, 5.
- Lifestyle modifications, such as optimizing blood pressure control and reducing protein intake, may also help slow disease progression 3, 4.
- Gene therapy, including CRISPR-Cas9 and miR-17 antisense oligonucleotides, has shown potential in animal models and early clinical trials 2.