For ADPKD in Children, New Guidelines Speak to Ethical Issues

Autosomal dominant polycystic kidney disease (ADPKD) is typically thought of as a disease of adulthood. Although cyst development begins early in life, many of those affected will remain asymptomatic and not require treatment for decades. There are, however, a considerable number of children and adolescents who will have early treatable disease manifestations.

A recently published international consensus statement developed on behalf of the Network for Early Onset Cystic Kidney Disease is intended to provide guidance on diagnosing, monitoring, and providing counsel for children and youth with – or at risk for – ADPKD while addressing attendant ethical quandaries. 

How is your knowledge of ADPKD in children and adolescents? Try these 6 short questions based on the new guideline on diagnosis and management to find out. 

1. What proportion of children with ADPKD-causing mutations will have early onset or rapidly progressive disease?

A. 1%

B. 3%

C. 11%

D. 23%

Please click here for answer and next question.

(Image composite ©Crystal Light/Shutterstock.com [kidney];
©Vinicius Tupanaba/adobe.stock.com [baby])

Answer: B. 3%.  ADPKD is the most common hereditary kidney disease in adults, with a prevalence of 1 in 500 to 1 in 2,500. Cyst development, however, can begin at an early age and while substantial impact of the disease isn’t usually seen until adulthood, about 3% of children with ADPKD-causing mutations have disease of very early onset or that is uncommonly rapid in its progression.

2. How common is symptomatic childhood ADPKD compared to other severe pediatric kidney disorders?

Pick the order that best represents the absolute incidence, from highest to lowest, of: recessive polycystic kidney disease(ARPKD),nephrotic syndrome (NS),hemolytic uremic syndrome(HUS), and ADPKD:

A. ADPKD, ARPKD, NS, HUS

B. ARPKD, ADPKD, NS, HUS

C. ARPKD, NS, ADPKD, HUS

D. ARPKD, NS, HUS, ADPKD

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Answer: A. ADPKD, ARPKD, NS, HUS.  Because about 3% of children with ADPKD-related mutations have disease with very early onset or that is rapidly progressive, the absolute incidence is thought to be higher than that of other serious pediatric kidney diseases. That means that symptomatic childhood ADPKD incidence tops that of: ARPKD (~1 out of 20 000) -- NS (~1 out of 50 000) -- and, HUS (~1 out of 100 000).

3. The consensus recommendation on the role of vasopressin antagonist therapy in children with ADPKD is:

A. Use routinely in children with high risk of early progression

B. Consider use in select children with high risk for early progression

C. Avoid due to potential negative impact on cyst growth

D. Avoid due to risk of side effects such as aminotransferase elevations

E. No recommendation at this time due to lack of data in younger patients

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Answer: B. Consider use in select children at high risk of early progression.  The vasopressin antagonist tolvaptan is the first pharmacologic treatment to be licensed in the United States, Europe, and Japan for slowing ADPKD progression in adults. There are currently no data to support use of the drug in children and adolescents nor are there safety studies in this population. There is one international, double-blind, placebo-controlled trial of tolvaptan in teenagers underway.

For now, the consensus group recommends against use of vasopressin antagonists in younger patients, with the caveat that clinicians might consider off-label use in children with family history, large total renal volume, rapid kidney growth, or other factors that confer high risk of early progression.

4. Which of the following treatments is recommended by consensus statement authors to slow disease progression in children and youth with ADPKD?

A. Vasopressin analogues

B. mTOR inhibitors

C. Somatostatin analogues

D. Statins

E. None of the above

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Answer: E. None of the above. None of these options was fully, if at all, endorsed, by guideline authors as treatment for ADPKD in young patients.

Although vasopressin analogues (eg, desmopressin) are a treatment option for nocturnal enuresis in school-aged children, potential for negative effects on cyst growth suggest that they be used only with caution in children with ADPKD. 

The guidelines state that mTOR inhibitors and somatostatin analoguesshould not be used in children and adolescents with ADPKD.

While there are some encouraging data on statin use from one controlled pediatric study in ADPKD, conflicting evidence on statin benefits on renal outcomes in adults with ADPKD prevented guideline panelists from reaching consensus on the role of statins to slow ADPKD progression in children.

5. According to the expert consensus, which of the following interventions might slow progression of renal failure in children with ADPKD?

A. Drinking lots of water and avoiding excessive protein

B. Following a low-osmolar diet (low sodium, low protein, adjusted water intake)

C. Following a low-protein diet

D. Following a ketogenic diet (low carbohydrate, moderate protein)

Please click here for answer and last question.

Answer: A. Drinking lots of water and avoiding excessive protein. Although the current level of evidence is weak, guideline authors cite research that suggests high water intake and avoiding excessive protein may help slow progression of renal failure in these children.

By contrast, a low-osmolar diet reduced levels of a surrogate vasopressin marker in a study of adults with ADPKD, but the long-term effects of this intervention on cyst growth are unclear.

A low-protein diet did not have a positive impact on decline in GFR in children with chronic kidney disease; moreover, unnecessary protein restriction should be avoided in children with ADPKD to reduce risk of malnutrition.

6. The recommended target blood pressure for a 17-year-old with ADPKD-related hypertension is:

A. <95/60 mm Hg

B. <120/70 mm Hg

C. <125/72 mm Hg

D. <130/80 mm Hg

Please click here for answer.

Answer: C. <125/72 mm Hg. Hypertension is one of the most common complications of childhood ADPKD, with a prevalence of about 20%, according to consensus statement authors. Based on current evidence, the authors recommend a target blood pressure that is below the 75th percentile, or <125/72 mm Hg for young patients older than age 16 years.

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The evidence-based guideline, International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people, reflects the consensus of experts in pediatric and adult nephrology, human genetics, pediatric radiology, and ethics, along with patient representatives. It was published online in Nature Reviews Nephrology on May 22, 2019.

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Andrew D. Bowser is a medical writer living in Pennsylvania and a regular contributing author to Patient Care Online.