A 17-year-old boy is seen in the office with mild abdominal pain and blood in his urine noticed after playing football with his friends. Exam is significant only for left flank tenderness and his vital signs, including blood pressure, are normal. His urine tests positive for blood (3+) and 1+ protein; microscopic urinalysis reveals numerous red blood cells but no white blood cells or casts. On further questioning, his mother reports that the boy’s father and paternal aunt have some type of “kidney problem” but she and his father have been divorced for many years and he rarely sees his father. An ultrasound reveals bilateral enlarged kidneys with multiple cysts and a calculus in the left kidney. A CT scan confirms the diagnoses (Figure 66-1).

Polycystic kidney disease (PKD) is a manifestation of a group of inherited disorders resulting in renal cyst development. In the most common form, autosomal-dominant polycystic kidney disease (ADPKD), extensive epithelial-lined cysts develop in the kidney; in some cases, abnormalities also occur in the liver, pancreas, brain, arterial blood vessels, or a combination of these sites. In autosomal recessive polycystic disease (ARPKD), the disease primarily causes enlarged cystic kidneys and hepatic fibrosis and usually presents in infancy. The cysts in ARPKD form only in the collecting tubule and are smaller and typically not visible on gross examination.

• 
  

  Most common tubular disorder of the kidney, affecting 1 in 300 individuals.

  
  
• 
  

  Autosomal dominant in 90 percent of cases.¹ The majority of cases of ADPKD are diagnosed in adults but can be diagnosed at any age.² In a German population study, the overall prevalence of ADPKD was 32.7/100,000 reaching a maximum of 57.3/100,000 in the 6th decade of life.³

  
  
• 
  

  Sporadic mutation in approximately 1:1000 individuals.

  
  
• 
  

  ADPKD accounts for approximately 5 to 10 percent of cases of end-stage renal disease (ESRD) in the US.

  
  
• 
  

  ADPKD is most frequently seen in the third and fourth decades of life, but can be diagnosed at any age.

  
  
• 
  

  ARPKD is estimated to occur in 1:10,000 to 1:40,000 live births, although this may be an underestimate as severely affected neonates do not survive beyond the first few days of life and may not be correctly diagnosed.²

  
  
• 
  

  Both diseases are seen in all races and ethnicities and affect males and females equally.

• 
  

  ADPKD results from mutations in either of 2 genes that encode plasma membrane–spanning polycystin 1 (PKD1) and polycystin 2 (PKD2).⁴ Polycystins regulate tubular and vascular development in the kidneys and other organs (liver, brain, heart, and pancreas). PKD1 and PKD2 are colocalized in primary cilia and appear to mediate Ca²⁺ signaling as a mechanosensor, essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract.⁵

  
  
• 
  

  In ADPKD, few (1% to 5%) nephrons actually develop cysts. The remaining renal parenchyma shows varying degrees of tubular atrophy, interstitial fibrosis, and nephrosclerosis.

  
  
• 
  

  ADPKD can also be a component of tuberous sclerosis.²

  
  
• 
  

  In ADPKD, cysts are also found in other organs such as liver (Figure 66-2), spleen, pancreas, and ovaries; liver cysts are found in up to 80 percent of patients with ADPKD.³ There is also an increased incidence of intracranial aneurysms (5% to 12%).

  
  
• 
  

  ARPKD, previously thought to be the neonatal form of PKD, is caused by genetic mutations in PKHD1 (polycystic kidney hepatic disease 1). This gene encodes the protein, fibrocystin/polyductin, that is localized to cilia/basal body and complexes with PKD2. This large, receptor-like protein is thought to be involved in the tubulogenesis and/or maintenance of duct-lumen architecture of epithelium.

  
  
• 
  

  ARPKD can be associated with pulmonary hypoplasia, generally as a result of the oligohydramnios (Potter’s) sequence.²

  
  
• 
  

  In one study of young patients (mean age 16 years) with ADPKD, serum log(10) vascular endothelial growth factor was negatively correlated with creatinine clearance indicating a possible role for angiogenesis in the early progression of renal disease in these patients.⁶

  
  
• 
  

  Rare syndromic forms of PKD include defects of the eye, central nervous system, digits, and/or neural tube.⁵

  
  
• 
  

  A variant of PKD is glomerulocystic kidney (GCK), which refers to a kidney with greater than 5 percent cystic glomeruli.⁷ This condition is usually diagnosed in young patients. Although PKD-associated gene mutations have been excluded in many cases, there is a familial form of GCK presenting with cystic kidneys, hyperuricemia, and isosthenuria (concentration similar to plasma).⁷

Family history is a useful tool for diagnosing early ADPKD.

Clinical Features

• 
  

  ADPKD is usually asymptomatic in children, diagnosed incidentally on imaging studies done for other reasons.²

  
  
• 
  

  Chronic flank pain as a result of the mass effect of enlarged kidneys.

  
  
• 
  

  Acute pain with infection, obstruction, or hemorrhage into a cyst.

  
  
• 
  

  Enlarged liver.

  
  
• 
  

  Hypertension is common in adults (75%) and is present in 10 to 30 percent of children. Left ventricular hypertrophy can be seen in adolescents/young adults even before overt hypertension is present.²

  
  
• 
  

  Mitral valve prolapse (MVP) occurs in up to 15 percent of children and adults with ADPKD.²

  
  
• 
  

  Gross hematuria or urinary tract infection; the former can effect up to 40 percent of patients.² Because renal cysts can be disconnected from the urinary tract, infection can result in abscess; persistent fever and flank pain should raise suspicion even if the urine culture is negative.²

  
  
• 
  

  Kidney stones (calcium oxalate and uric acid) develop in 15 to 20 percent of affected individuals because of urinary stasis from distortion of the collecting system, low urine pH, and low urinary citrate. Kidney stones are uncommon in children, but have been reported in children as young as age 11 years.⁸

  
  
• 
  

  Nocturia can also be present from impaired renal concentrating ability.

  
  
• 
  

  In a Danish study, low birth weight was a risk factor for earlier onset of ESRD in patients with ADPKD as was male gender and increased mean arterial pressure.⁹

  
  
• 
  

  Up to half the cases of ARPKD are diagnosed prenatally, usually with evidence of its sequelae (e.g., oligohydramnios, pulmonary hypoplasia).² Neonates and infants can present with palpable flank masses, hepatomegaly, hypertension, or respiratory distress due to pulmonary hypoplasia.²

  
  
• 
  

  The diagnosis of children with ARPKD is clinical, based on the presence of enlarged, echogenic kidneys and one or more of the following: absence of renal cysts in both parents; history of a previously affected sibling; parental consanguinity; or clinical, laboratory, or pathologic features of hepatic fibrosis.²

  
  
• 
  

  A small subset of patients with ARPKD present as older children or young adults with hepatic (portal hypertension, hepatomegaly) and/or renal disease.²

  
  
• 
  

  In a case series of Brazilian patients with ARPKD (N = 25), median age at diagnosis was 61 months, half had arterial hypertension, 40 percent had urinary tract infections, almost 1/3 had portal hypertension, and about 1/4 had chronic kidney disease stage ≥2.¹⁰

Laboratory Testing

• 
  

  Gross or microscopic hematuria (60% with ADPKD).⁴ Obtain a urinalysis to document hematuria and a complete blood count or hemoglobin to identify anemia.

  
  
• 
  

  Genetic testing is available for both disorders but is unnecessary in patients with a family history and typical appearance of bilateral renal cysts. Screening asymptomatic children with a family history of ADPKD is not recommended due to financial and psychosocial concerns and lack of disease-specific treatment; annual monitoring of blood pressure and urine (hematuria, proteinuria) should be considered, with additional evaluation as needed.² In one retrospective study, renal outcomes were similar between children with ADPKD diagnosed by screening or presenting with symptoms.¹¹

Imaging

• 
  

  Diagnosis is often made with ultrasound. More than 80 percent of patients with ADPKD have cysts present by age 20 years and 100 percent by age 30 years. In one study, the sensitivity of ultrasound in at-risk individuals younger than age 30 years was 70 to 95 percent, depending on the type of PKD present.¹² For younger patients or those with small cysts, CT scan (Figures 66-1 and 66-2) or MRI can be helpful. Authors of one case series found MRI satisfactory for following total kidney and cyst volume in children with ADPKD.¹³

  
  
• 
  

  In the neonatal period, ultrasound of patients with ARPKD shows markedly enlarged echogenic kidneys, indicating the presence of numerous microscopic cysts not discernible by ultrasound (Figure 66-3).² Larger cysts, more typical of ADPKD, are usually absent in neonates.

  
  
• 
  

  Over time, the appearance of the kidneys in patients with ARPKD looks similar to ADPKD.²

  
  
• 
  

  Children with ADPKD can have asymmetric involvement or even isolated unilateral cysts.² Because simple cysts are rare in children, the finding of a single cyst in a patient at-risk for ADPKD is considered diagnostic by some authors.

  
  
• 
  

  If an infected cyst is suspected, positron emission tomography has been reported to be the optimal test.¹⁴

  
  
• 
  

  In patients with ADPKD, cysts are commonly found in the liver (50% to 80%) (Figure 66-2), spleen, pancreas, and ovaries.

  
  
• 
  

  Age-dependent ultrasound criteria have been established for both diagnosis and disease exclusion in subjects at risk of PKD1 (the more severe disorder),¹⁵ but criteria for at-risk children have not been established.²

  
  
• 
  

  Transient elastography can be useful in detecting liver fibrosis in cystic kidney diseases.¹⁶