bubble_chart Overview

Polycystic kidney disease is a genetic disorder and a congenital abnormality of the kidneys. Both the cortex and medulla of the bilateral kidneys can be affected, though the extent may vary. It manifests in two inheritance patterns: autosomal dominant and autosomal recessive.

bubble_chart Etiology

In 90% of ADPKD patients, the abnormal gene is located on the short arm of chromosome 16, known as the ADPKD₁ gene, and its gene product remains unclear. Many coding genes in this region have been elucidated and cloned, and it is anticipated that the ADPKD₁ gene will be identified in the near future. In fewer than 10% of patients, the abnormal gene is located on the short arm of chromosome 4, termed the ADPKD₂ gene, and its encoded product is also unknown. The two groups differ in terms of disease onset, the emergence of hypertension, and the age at which they progress to renal failure.

The exact disease cause of this condition remains unclear. Although symptoms typically appear in adulthood, the disease begins to form during the fetal stage. Cysts originate from renal tubules, and the composition of the cyst fluid varies depending on the site of origin. If the cyst arises from the proximal tubule, the fluid contains components such as Na⁺, K⁺, Cl^-, H⁺, creatinine, and urea, similar to plasma. If it originates from the distal tubule, the concentrations of Na⁺ and K⁺ in the cyst fluid are lower, while those of Cl^-, H⁺, creatinine, and urea are higher.

Abnormal proliferation of cyst-lining epithelial cells is one of the hallmark features of ADPKD. These cells exist in an incompletely mature or redevelopmental state, strongly suggesting a disruption in the regulation of cellular maturation, which keeps the cells in an immature state and confers strong proliferative potential. Another prominent feature of ADPKD is abnormal cellular transport, manifested by alterations in the assembly, distribution, and activity expression of Na⁺

-K⁺-ATPase subunits, which are closely related to cellular transport, as well as abnormalities in cell signaling and ion transport channels. Excessive extracellular matrix proliferation is the third notable characteristic of ADPKD. Numerous studies have demonstrated that these abnormalities involve growth-related active factors. However, the key abnormal pathways and mechanisms remain unclear. In summary, altered cell growth and abnormal interstitial formation due to genetic defects constitute one of the important mechanisms of disease in this condition.

bubble_chart Pathological Changes

In the early stages of ADPKD, kidney size is normal, but in the late stage [third stage], the kidneys enlarge and exhibit morphological abnormalities, such as deformities of the renal pelvis and calyces, and the destruction of the intact structures of the renal papillae and pyramids. The cysts are spherical and vary in size. Initially, there may be only a few cysts in the kidneys, but as the disease progresses, their number gradually increases, eventually occupying the entire kidney, which can grow to the size of a football. Under light microscopy, intact renal structures can still be observed between the cysts, ranging from normal appearances to glomerulosclerosis, tubular atrophy, and interstitial fibrosis. These changes are all caused by renal ischemia due to cyst compression. Under electron microscopy, the cyst epithelial cells exhibit two morphologies: one resembling proximal tubular epithelial cells and the other similar to distal tubular cells. The cyst fluid is generally clear but may become purulent or bloody in cases of intracystic infection or hemorrhage.

In ARPKD, the volume and weight of both kidneys are significantly increased, approximately 10 times the normal size. The kidneys have a smooth surface, and cross-sections reveal fusiform or columnar cysts arranged in a radial pattern. The epithelial cells are columnar, consistent with those of the collecting ducts. The renal pelvis and calyces are compressed and narrowed by the expanded renal parenchyma. Liver lesions are confined to the portal areas, presenting as diffuse bile duct dilation accompanied by connective tissue proliferation, leading to periportal fibrosis. Over time, portal hypertension and hepatosplenomegaly develop.

bubble_chart Clinical Manifestations

1. Autosomal Dominant Polycystic Kidney Disease (ADPKD), previously known as adult-type polycystic kidney disease, is the most common form of polycystic kidney disease worldwide, affecting both genders equally with an incidence of approximately 1/200 to 1/1000. Its primary features include the formation, enlargement, and proliferation of renal cysts. Extracranial cysts are also common, particularly in the liver, with other affected organs including the pancreas, ovaries, gastrointestinal tract, and major blood vessels.

The disease has a prolonged and slow progression, often remaining asymptomatic before the age of 40. Clinical manifestations are divided into renal and extrarenal categories:

(1) Renal Manifestations: Diverse symptoms arise due to the growth and enlargement of renal cysts.

1. - **Back or Abdominal Pain**: The most common symptom, presenting as flank, lumbar, or abdominal pain. It may be persistent or intermittent, typically mild and characterized by distending pain. Severe pain may indicate cyst rupture or renal colic due to kidney stones.
2. - **Urinary Abnormalities**: Primarily hematuria or proteinuria, which are among the earliest symptoms. Hematuria, either microscopic or gross, occurs in over 50% of patients, more frequently in those with enlarged kidneys or hypertension. Proteinuria is present in nearly all cases, mostly grade I and persistent. Urinary tract infections may lead to leukocytes or pus cells in the urine.
3. - **Impaired Renal Concentration**: Manifests as polyuria and nocturia, usually mild and detectable early. Advanced stages may exhibit salt-wasting nephritis, while dilution and acidification functions generally remain intact.
4. - **Hypertension**: Occurs in 50–60% of patients during the disease course, often preceding renal function decline and accelerating its progression. Studies suggest ADPKD-related hypertension is linked to hyperactivity of the renin-angiotensin (R-A) system, with aldosterone levels higher than expected for the R-A system activity.
5. - **Renal Impairment**: Approximately 50% of patients develop renal failure, with incidence increasing with age. Data indicate that ADPKD ₁ gene carriers, early clinical presentation, male gender, hypertension, hematuria, and larger kidneys predispose patients to renal decline and progression to uremia.

(2) **Extrarenal Manifestations**: ADPKD is a systemic disorder affecting multiple organs. Liver cysts are the most common (∼50%), increasing in number and size with age. These cysts are typically spherical and unilocular. Liver fibrosis may occur near the hilum, but hepatic dysfunction is rare. Women are more susceptible. Some patients experience abdominal pain or dyspnea due to massive hepatomegaly, and liver cyst infections are occasional. Pancreatic cysts occur in ∼10% of cases, while splenic, thyroid, ovarian, and epididymal cysts are also observed. **Stirred pulse** aneurysms (e.g., intracranial, thoracic, or aortic) are significant extrarenal features. Other manifestations include:

1. - **Cardiac Valve Abnormalities**: Mitral or tricuspid valve prolapse, aortic regurgitation, etc.
2. - **Hernias**: Hiatal hernia, intestinal diverticula, or inguinal hernia.

Due to abnormal erythropoietin production within cysts, polycythemia may occur. Alternatively, end-stage ADPKD patients exhibit milder anemia compared to other causes of end-stage renal failure.

II. Autosomal recessive polycystic kidney disease (ARPKD), also known as infantile or childhood polycystic kidney disease, is a rare condition. 75% of affected infants die within hours to days after birth. For patients who survive the neonatal period, the 15-year survival rate is 50-80%. It is often accompanied by liver abnormalities. The {|###|} pathogenesis of this disease is unclear, and recent studies have identified the abnormal gene on chromosome 6.

Newborns and those with symptoms during the perinatal period primarily exhibit renal manifestations, while those with symptoms in infancy or childhood mainly show hepatic manifestations. Cases in older children and adults are rare. The main clinical manifestations include abdominal masses, urinary tract infections, decreased urine concentration, and impaired acidification function. 90% of affected children have hypertension and growth retardation. When renal failure occurs, symptoms of uremia such as anemia and renal osteodystrophy may appear. Hepatic manifestations include hepatomegaly, hypersplenism, esophageal varices, and rupture bleeding due to portal hypertension. Affected children often have a history of hypamnion and difficult delivery. Severe cases may present with respiratory distress at birth.

bubble_chart Diagnosis

ADPKD: Diagnosis is difficult in the early stages when renal cysts are small and asymptomatic. A definitive diagnosis is established when the following manifestations are present: imaging reveals numerous cysts of varying sizes throughout the renal cortex and medulla in both kidneys; there is a clear family history of the disease; or extrarenal manifestations such as liver cysts, intracranial aneurysms, or pancreatic cysts are present. For patients with inconspicuous extrarenal manifestations, unclear family history, or only unilateral renal cysts or a limited number of cysts, regular imaging follow-ups—including ultrasound, CT, and MRI—are recommended. The diagnosis can be confirmed if cyst enlargement, increased cyst numbers, or contralateral kidney involvement is observed. Genetic linkage analysis can provide diagnostic reference for individuals who have not yet developed cysts, but it is costly and technically demanding.

ARPKD: The diagnosis is established based on the age of onset, the aforementioned clinical manifestations, and a typical family history.

bubble_chart Treatment Measures

Currently, there is no method to target the formation and development of cysts in ADPKD. The primary approach involves symptomatic management, preventing and addressing complications, preserving renal function, and treating renal function decline.

Asymptomatic early-stage patients generally do not require treatment and can be closely monitored. Vigorous exercise may cause renal cyst rupture leading to kidney damage and should be avoided as much as possible. Back and abdominal pain are common symptoms, ranging from dull aches to sharp pains. The causes include enlarged cysts causing tension, intracystic bleeding, stones, or even renal malignancies, and should be managed accordingly. Measures include bed rest, analgesics, or even surgical interventions such as cyst puncture and drainage, decompression, or nephrectomy. Urinary tract infections, kidney stones, and obstructions require prompt treatment. Hypertension must be strictly controlled, with ACE inhibitors (ACEIs) being the first-line drugs. While these drugs are highly effective, caution is needed in patients with massive kidneys, as ACEIs may cause severe renal bleeding and rapid deterioration of renal function. Calcium channel blockers are also effective and can be considered. For refractory hypertension, β₂-blockers may be added as appropriate. Patients with confirmed intracranial or other stirred pulse aneurysms require close monitoring, and larger stirred pulse aneurysms should be surgically removed to prevent rupture and bleeding. Regular renal function tests are necessary, and if renal function declines, the management principles are the same as for renal insufficiency due to other causes.

Nephrectomy is generally not considered unless in the following cases: intolerable pain, uncontrolled urinary or cyst infections, severe compression symptoms due to massive kidneys, recurrent hematuria, severe kidney stones, or suspected malignancy.

Due to the strong genetic predisposition of this disease, confirmed cases should prompt routine screening and follow-up of blood relatives to identify early-stage cases, allowing for proactive prevention and management to preserve and prolong renal function.

There is no specific treatment for ARPKD. Management is primarily symptomatic. The most critical issue in the neonatal period is respiratory distress leading to respiratory failure, requiring comprehensive rescue measures, including artificial ventilation. Once this critical stage is overcome, the prognosis for the child generally improves. Other treatments include managing hypertension, renal failure, and liver failure, as well as aggressive control of urinary tract infections. For grade I children, attention should be paid to their growth and development.

bubble_chart Complications

Among the complications of ADPKD, urinary tract infections are the most common, mostly involving the lower urinary tract. Pyelonephritis and cyst infections can also occur. Other complications include urinary tract stones and obstructions; rupture and bleeding of stirred pulse aneurysms, particularly intracranial stirred pulse aneurysms, which account for 7–13% of deaths in ADPKD patients. In rare cases, malignant tumors may develop in both kidneys.

bubble_chart Differentiation

ADPKD primarily requires differentiation from multilocular simple renal cysts, with key points summarized in Table 19-30. Other differential diagnoses to consider include ARPKD, acquired renal cysts, and multicystic renal dysplasia.

Table 19-39 Differential Diagnosis Between Early ADPKD and Multilocular Simple Renal Cysts

Feature	Multilocular Simple Renal Cyst	ADPKD
Family History	Absent	Approximately 60% present
Other family members confirmed by ultrasound to have cysts	Absent	Approximately 90% present
Age	More common in adults	More common in children
Gender	Male > Female	Male = Female
Kidney Size	Normal	Normal to grade I enlargement
Kidney Involvement	Usually unilateral, may be bilateral	Usually bilateral, may be unilateral in early stages
Cyst Distribution	Cortex	Cortex and medulla
Cyst Size	Usually <2cm, occasionally larger	Early stage <2cm
Intracystic Hemorrhage	Rare	Common
Liver Cysts	Absent	40–60% present, may increase with age
Intracranial Aneurysm	Absent	10–40% present
Hypertension	Rare	60% present

For ARPKD, considerations include bilateral Wilms tumor, nephroblastomatosis, and ADPKD. Examination of family members, liver evaluations such as ultrasound and liver biopsy, can aid in differential diagnosis. Recent studies suggest that maternal blood or amniotic fluid α-fetoprotein testing may serve as an indicator for prenatal diagnosis.