Polycystic kidney disease - causes, symptoms, diagnosis, treatment, pathology

Summary

Polycystic kidney disease (PKD) is a genetic disorder where the kidneys develop numerous fluid-filled cysts, leading to enlarged kidneys and eventual kidney failure. There are two types: autosomal dominant (ADPKD), typically presenting in adulthood, and autosomal recessive (ARPKD), which appears in infancy. ADPKD involves mutations in the PKD1 and PKD2 genes, while ARPKD is linked to mutations in the PKHD1 gene. Complications include hypertension, kidney stones, and liver cysts. Diagnosis can be prenatal, and treatments focus on managing symptoms, with options like dialysis or organ transplants for severe cases.

Takeaways

• 🧬 Polycystic Kidney Disease (PKD) is a genetic disorder where kidneys develop fluid-filled cysts, causing them to enlarge and lose function over time.
• 🔬 The cysts in PKD form in both the outer (cortex) and inner (medulla) layers of the kidneys, compressing surrounding tissues and reducing kidney function.
• 🩸 Poorly perfused kidneys activate the renin-angiotensin-aldosterone system (RAAS), leading to fluid retention and high blood pressure.
• 💧 Expanding cysts can block the urinary system, causing urinary stasis and increasing the risk of kidney stones.
• ⚠️ As PKD progresses, it can cause symptoms like flank pain, hematuria (blood in urine), and eventually kidney failure due to nephron destruction.
• 🧬 Autosomal Dominant PKD (ADPKD) is linked to mutations in the PKD1 and PKD2 genes, leading to varying severity and age of onset.
• ⚙️ Cyst growth in ADPKD is caused by abnormal cellular signaling due to mutations in the PKD genes, leading to fluid buildup in cysts.
• 🧠 ADPKD can also affect other organs, potentially causing liver cysts, heart issues like aortic root dilation, and brain aneurysms.
• 👶 Autosomal Recessive PKD (ARPKD) typically presents in infancy and can cause kidney failure before birth, leading to complications like Potter sequence and lung underdevelopment.
• 🏥 PKD treatment focuses on managing symptoms such as hypertension with medication, and in severe cases, dialysis or organ transplants may be needed.

Q & A

What is Polycystic Kidney Disease (PKD)?

PKD is a genetic disorder in which the kidneys develop hundreds of cysts, or fluid-filled sacs, causing them to become larger than normal and lose function over time.

Where do the cysts develop in PKD?

The cysts develop in both the cortex (outer layer) and medulla (inner layer) of the kidneys.

How does PKD affect kidney function over time?

As the cysts grow, they compress blood vessels feeding healthy nephrons, leading to reduced oxygen supply. This activates the renin-angiotensin-aldosterone system, leading to fluid retention and hypertension, ultimately resulting in renal insufficiency and failure.

What are the two types of PKD, and how do they differ?

The two types are Autosomal Dominant PKD (ADPKD) and Autosomal Recessive PKD (ARPKD). ADPKD usually manifests in adulthood, while ARPKD appears in infancy or even before birth. ADPKD is associated with mutations in PKD1 and PKD2 genes, while ARPKD involves mutations in the PKD1 gene affecting fibrocystin.

What is the role of polycystin 1 and polycystin 2 in ADPKD?

Polycystin 1 and 2 are proteins that help regulate calcium influx in cells. In ADPKD, mutations in PKD1 or PKD2 prevent proper signaling, leading to abnormal cell growth and cyst formation.

How does the 'second hit' phenomenon contribute to cyst formation in ADPKD?

While individuals with ADPKD inherit one mutated gene, a second random mutation in the remaining good copy of the gene in some tubular cells triggers the formation of cysts, impairing normal signaling and promoting abnormal cell proliferation.

What are the extra-renal complications associated with ADPKD?

Patients may develop cysts in the liver, seminal vesicles, and pancreas. Vascular issues like aortic root dilation and cerebral artery aneurysms, particularly in the Circle of Willis, can also occur, potentially leading to heart failure and subarachnoid hemorrhage.

How does ARPKD affect fetal development?

In ARPKD, cyst formation can lead to renal failure before birth, resulting in oligohydramnios (low amniotic fluid), which can cause Potter sequence—a set of physical abnormalities including club feet and a flattened nose, as well as pulmonary hypoplasia (underdeveloped lungs), which can be fatal after birth.

What are the liver complications associated with ARPKD?

ARPKD can cause congenital hepatic fibrosis, leading to portal hypertension, esophageal varices, upper GI bleeds, hemorrhoids, and splenomegaly due to blood flow issues. Additionally, defects in bile ducts can lead to cholestasis and ascending cholangitis.

What are some treatment options for PKD?

Treatments are symptom-specific and include medications like ACE inhibitors or ARBs for hypertension, ursodiol for cholestasis, and dialysis or kidney transplants in cases of renal failure. In severe liver complications, a portal-caval shunt or liver transplant may be needed.