What is Autosomal Dominant Polycystic Kidney Disease (ADPKD)?

From the Guidelines

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development of fluid-filled cysts in both kidneys, leading to kidney enlargement and progressive decline in kidney function, as outlined in the KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of ADPKD 1.

Key Characteristics of ADPKD

• Affects millions of people worldwide, making it the fourth most common global cause for kidney replacement therapy
• Caused by mutations in either the PKD1 gene or the PKD2 gene, with an autosomal dominant inheritance pattern
• Symptoms typically begin to appear between the ages of 30 and 40, including high blood pressure, back or side pain, blood in the urine, kidney stones, and urinary tract infections
• Can affect other organs, causing liver cysts, heart valve abnormalities, brain aneurysms, and diverticular disease

Management and Treatment of ADPKD

• Focuses on controlling blood pressure, maintaining a healthy lifestyle, and treating complications
• Tolvaptan (Jynarque) is the only FDA-approved medication specifically for ADPKD that can slow disease progression in appropriate candidates, as recommended by the KDIGO 2025 guideline 1
• Regular monitoring with blood tests, urine tests, and imaging studies is essential for tracking disease progression and managing complications effectively

Importance of Guideline-Based Management

• The KDIGO 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of ADPKD provides graded recommendations and ungraded practice points to help guide clinical practice and aid in decision-making 1
• The guideline considers disparities in available resources and possible cultural differences in different parts of the world, making it a valuable resource for healthcare providers worldwide.

From the Research

Definition and Overview of ADPKD

• Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage kidney disease 2.
• ADPKD is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and increased kidney volume that eventually leads to end-stage renal disease 3.
• It is considered the fourth leading cause of end-stage renal disease in the United States and globally 3.

Clinical Manifestations and Complications

• ADPKD is associated with multiple clinical manifestations, such as enlarged kidneys filled with growing cysts, hypertension, and multiple extrarenal complications, including liver cysts, intracranial aneurysms, and cardiac valvular disease 2.
• The development of cysts is accompanied by destruction of the renal parenchyma, interstitial fibrosis, cellular infiltration, and loss of functional nephrons 4.
• ADPKD is not only a kidney disease but also a systemic disorder associated with intracranial arterial aneurysms, cardiac valvular defects, colonic diverticulosis, and cyst formation in other organs such as the liver, spleen, and pancreas 4.

Pathogenesis and Molecular Basis

• The identification of PKD1 and PKD2, and the drive to elucidate the functions of their encoded proteins, polycystin-1 (PC1) and polycystin-2 (PC2), has led to an explosion of clinical and scientific interest in this common disorder 4.
• Both polycystins function together in a nonredundant fashion, through a common pathway, and produce cellular responses that regulate proliferation, migration, differentiation, and kidney morphogenesis 5.
• Loss of function of either protein due to gene mutations results in the tubular cells reverting to a less differentiated state, which is more prone to proliferation, leading to cyst formation 5.

Risk Factors and Disease Progression

• Age at diagnosis after 30 years, baseline serum creatinine levels, and cyst infection are independent risk factors for kidney failure in patients with ADPKD 6.
• Early diagnosis and close observation for the onset of cyst infection are crucial to delay the advance of ADPKD to end-stage renal disease 6.
• By the age of 65 years, 45% to 70% of patients with ADPKD reach end-stage renal disease (ESRD) 6.