Antenatally Diagnosed ADPKD
2018; Elsevier BV; Volume: 3; Issue: 5 Linguagem: Inglês
10.1016/j.ekir.2018.05.002
ISSN2468-0249
AutoresMelanie Aldridge, Chirag Patel, Andrew Mallett, Peter Trnka,
Tópico(s)Pediatric Urology and Nephrology Studies
ResumoAdvances in antenatal ultrasonography have substantially improved the counseling of pregnant women.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar With this advancement comes a diagnostic dilemma in the approach to antenatal diagnoses of cystic kidney disease. The differential diagnosis of enlarged cystic echogenic kidneys includes autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease, renal cysts and diabetes syndrome, and other syndromic disorders.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar ADPKD is the most commonly inherited renal disease, occurring in 1 in 400 to 1000 live births.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar Disease progression is marked by growth of renal cysts, nephromegaly, and advancing renal dysfunction, ultimately resulting in end-stage kidney disease in more than 50% of patients in the fifth to sixth decade of life.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 7Fencl F. Janda J. Blahova K. et al.Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease.Pediatr Nephrol. 2009; 24: 983-989Crossref PubMed Scopus (23) Google Scholar, 8Cornec-Le Gall E. Audrezet M.A. Rousseau A. et al.The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2015; 27: 942-951Crossref PubMed Scopus (180) Google Scholar, 9Fick-Brosnahan G. Tran Z. Johnson A. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Extrarenal manifestations include intracranial aneurysms, cardiac valvular defects, diverticular disease, and cysts in the liver, spleen, and pancreas.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 7Fencl F. Janda J. Blahova K. et al.Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease.Pediatr Nephrol. 2009; 24: 983-989Crossref PubMed Scopus (23) Google Scholar Mutations in 3 genes have been reported: PKD1 (16p13.3), responsible for 80% to 85% of cases; PKD2 (4q22.1), responsible for 10% to 15% of cases; and the recently identified GANAB (11q12.3).1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 8Cornec-Le Gall E. Audrezet M.A. Rousseau A. et al.The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2015; 27: 942-951Crossref PubMed Scopus (180) Google Scholar, 9Fick-Brosnahan G. Tran Z. Johnson A. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 13Tan Y.C. Blumenfeld J. Rennert H. Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs.Biochim Biophys Acta. 2011; 1812: 1202-1212Crossref PubMed Scopus (56) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Patients with PKD1 mutations have a poorer prognosis than patients with PKD2 mutations, on average reaching end-stage kidney disease at 55 versus 70 years, respectively.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 7Fencl F. Janda J. Blahova K. et al.Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease.Pediatr Nephrol. 2009; 24: 983-989Crossref PubMed Scopus (23) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar ADPKD is an autosomal dominant disorder with 100% penetrance and both intra- and interfamilial variability in disease presentation and phenotype.4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar A "2-hit" hypothesis postulates that a germline mutation inactivates one PKD1 allele whereas a subsequent somatic mutation inactivates the other allele, resulting in cyst formation.5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 13Tan Y.C. Blumenfeld J. Rennert H. Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs.Biochim Biophys Acta. 2011; 1812: 1202-1212Crossref PubMed Scopus (56) Google Scholar Because a second somatic mutation is not identified in all renal cysts, other genomic and nongenomic cystogenic impacts have been suggested.5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 13Tan Y.C. Blumenfeld J. Rennert H. Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs.Biochim Biophys Acta. 2011; 1812: 1202-1212Crossref PubMed Scopus (56) Google Scholar, 15Antignac C. Calvet J.P. Cermino G.G. et al.The future of polycystic kidney disease research—as seen by the 12 Kaplan Awardees.J Am Soc Nephrol. 2015; 26: 2081-2095Crossref PubMed Scopus (32) Google Scholar Historically, ADPKD has been recognized as an adult-onset disease; however, symptoms can manifest in early childhood.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar Since the first report of fetal cases in 1971, ADPKD has increasingly been diagnosed in utero.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar Early diagnosis allows the opportunity for close follow-up and monitoring of disease progression.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar Given the increasing diagnosis of ADPKD in utero, it is desirable to form an approach so as to better inform clinical practice and to counsel affected families. The aim of our study was to review our antenatally diagnosed cases of ADPKD and to describe their phenotype during a short-term follow-up. Full methods are included as supplemental material (Supplementary Methods). An overview of our ADPKD cohort is shown in Table 1.Table 1Clinical characteristics of children with antenatally diagnosed ADPKDClinical featuresCase 1Case 2Case 3Case 4Case 5Case 6SexFMFMMMAt diagnosisAt last follow- upAt diagnosisAt last follow-upAt diagnosisAt last follow- upAt diagnosisAt last follow-upAt diagnosisAt last follow- upAt diagnosisAt last follow-upAge20 wk GA30 mo20 wk GA4 mo20 wk GA4 mo20 wk GA13 mo33+2 wk GA2 mo33+5 wk GA2 moUltrasound findings Cystic kidneys–+++–+++–+++ Number of cystsN/A>3>3>3>3>3>3>3N/A>31>3 Echogenic kidneys++++++++++++ Other anomalies––––––––––––Kidney length Left (centile)85>95>95>95>95>9570>9550>9550>95 Right (centile)>95>95>95>95>95>9585>9550>9550>95Genetic testing+N/AN/AN/AN/AN/AUrological complications–––++–Systemic features––+aSplenic cyst.–––HypertensionN/A–N/A–N/A–N/A–N/A–N/A–Creatinine (μmol/l)N/A<30N/A<30N/A<30N/A<30N/A<30N/A 3 cysts bilaterally) at last follow up. Mean age at last follow-up was 10.6 months (range, 2.5–30 months). One child had pyelonephritis at 4 months of age requiring i.v. antibiotics. One child had a splenic cyst noted at 4 months of age. One subject had no known family history of ADPKD (1/6). Parents of this subject had normal renal ultrasound results before the age of 40 years, and thus ADPKD could not be confidently excluded. Genetic testing identified two PKD1 variants: a de novo pathogenic mutation (p.Lys2529Asn) and a paternally inherited "variant of uncertain significance" (VOUS) (p.Ser225Leu). With increasing awareness of ADPKD and advancements in imaging technology, more cases of ADPKD are being diagnosed antenatally.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar We have experienced an increase in referrals of antenatally diagnosed cases in recent years. Antenatal cystic kidneys are identified by ultrasound imaging.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Although the differential for echogenic or cystic kidneys in utero remains broad, a focused family history is able to delineate these.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar In the absence of a positive family history, the distinction of ADPKD from autosomal recessive polycystic kidney disease may be difficult.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Involvement of a multidisciplinary team is essential for antenatal counseling and for guiding postnatal management.12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 17Gimpel C. Avni F. Bergmann C. et al.Perinatal diagnosis, management, and follow up of cystic renal diseases: a clinical practice recommendation with systematic literature reviews.JAMA. 2018; 172: 74-86Google Scholar Furthermore, early detection of affected individuals facilitates timely implementation of an anticipatory approach, particularly important with potential emerging disease-modifying therapies.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar All children included in this report were appropriately referred to a tertiary center and received timely multidisciplinary team review. The current pediatric approach to the management of cystic kidneys includes annual clinical reviews and intermittent ultrasonography.2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Once renal function declines, irreversible structural damage has already been established.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Regular screening of affected individuals allows early diagnosis and treatment of hypertension, review for potential systemic complications, and enrollment into potential future clinical trials of disease-modifying treatments.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar Gimpel et al. published recommendations on the diagnosis, management, and follow-up of perinatal cystic kidneys. They recommended phenotype-specific timing of renal ultrasounds postnatally, and a referral to clinical genetics for diagnostic counseling and possible genetic testing.17Gimpel C. Avni F. Bergmann C. et al.Perinatal diagnosis, management, and follow up of cystic renal diseases: a clinical practice recommendation with systematic literature reviews.JAMA. 2018; 172: 74-86Google Scholar They found that fetuses with bilateral hyperechogenic cystic kidneys, such as in our cohort, have a good prognosis but significant risk of long-term renal disease.17Gimpel C. Avni F. Bergmann C. et al.Perinatal diagnosis, management, and follow up of cystic renal diseases: a clinical practice recommendation with systematic literature reviews.JAMA. 2018; 172: 74-86Google Scholar To add further to the recommendations from Gimpel et al., our approach is to refer the parents of affected children to an adult nephrologist (Figure 1). The natural history of ADPKD is characterized by a slow growth of the kidney cysts with few renal or systemic complications until adulthood.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 6Helal I. Reed B. McFann K. et al.Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.Clin J Am Soc Nephrol. 2011; 6: 2439-2443Crossref PubMed Scopus (60) Google Scholar, 9Fick-Brosnahan G. Tran Z. Johnson A. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Kidney function and blood pressure usually remain normal during childhood and adolescence,1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 2Sweeney W. Avner E. Diagnosis and management of childhood polycystic kidney disease.Pediatr Nephrol. 2011; 26: 675-692Crossref PubMed Scopus (84) Google Scholar, 3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 5Rizk D. Chapman A. Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD.Pediatr Nephrol. 2008; 23: 1029-1036Crossref PubMed Scopus (25) Google Scholar, 10Mai J. Lee V. Lopez-Vargas P. Vladica P. KHA-CARI autosomal dominant polycystic kidney disease guideline: imaging approaches for diagnosis.Semin Nephrol. 2015; 35: 538-544Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar as in the case of our cohort. Previous studies have documented that patients detected with ADPKD in utero or less than 18 months of age have earlier progression to end-stage kidney disease.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar, 9Fick-Brosnahan G. Tran Z. Johnson A. et al.Progression of autosomal-dominant polycystic kidney disease in children.Kidney Int. 2001; 59: 1654-1662Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar On the other hand, Boyer et al. observed a favorable long-term prognosis in prenatally diagnosed ADPKD cases, at least until adolescence.1Boyer O. Gagnadoux M. Guest G. et al.Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth.Pediatr Nephrol. 2007; 22: 380-388Crossref PubMed Scopus (58) Google Scholar Long-term follow-up of our cohort is required to determine outcomes. Given the degree of phenotypic variability of ADPKD, counseling of patients and parents can present challenges.4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 13Tan Y.C. Blumenfeld J. Rennert H. Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs.Biochim Biophys Acta. 2011; 1812: 1202-1212Crossref PubMed Scopus (56) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Genetic testing is not routinely performed. It is costly, time consuming, and not universally available.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 7Fencl F. Janda J. Blahova K. et al.Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease.Pediatr Nephrol. 2009; 24: 983-989Crossref PubMed Scopus (23) Google Scholar, 11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Furthermore, legal and regulatory frameworks guiding the use of genetic information for insurance and employment remain undefined in some jurisdictions.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 7Fencl F. Janda J. Blahova K. et al.Genotype-phenotype correlation in children with autosomal dominant polycystic kidney disease.Pediatr Nephrol. 2009; 24: 983-989Crossref PubMed Scopus (23) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar De Rechter et al. reported that 37.1% of nephrologists advise against genetic testing in childhood because of the adult onset of ADPKD complications, fear of psychological stress, and the lack of effective treatment.11De Rechter S. Kringen J. Janssens P. et al.Clinician's attitude towards family planning and timing of diagnosis in autosomal dominant polycystic kidney disease.PLoS One. 2017; 12: e0185779Crossref PubMed Scopus (19) Google Scholar However, genetic testing can assist in pediatric ADPKD cases with no family history.4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar A confirmed genetic diagnosis can allow more targeted management and accurate genetic counseling for parents and other relatives.4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar One of our subjects presented without a family history of ADPKD, prompting diagnostic genetic testing. This identified a de novo pathogenic mutation and a paternally inherited VOUS in PKD1 gene.18US National Library of Medicine. Safety pharmacokinetics, tolerability and efficacy of tolvaptan in children and adolescents with ADPKD (autosomal dominant polycystic kidney disease). Available at: https://clinicaltrials.gov/ct2/show/NCT02964273. Accessed January 2, 2018.Google Scholar The VOUS has been classified as such due to the following: conflicting in silico predictions; a case report of an ADPKD case stating it as "likely pathogenic"19Polycystic Kidney Disease Foundation. ADPKD Mutation Database. Available at: http://pkdb.pkdcure.org. Accessed October 28, 2017.Google Scholar, 20Cornec-Le Gall E. Audrezet M.P. Chen J.M. et al.Type of PKD1 mutation influences renal outcome in ADPKD.J Am Soc Nephrol. 2013; 24: 1006-1013Crossref PubMed Scopus (318) Google Scholar; and the variant co-occurring with another pathogenic mutation in another patient. Therefore, the VOUS could be a benign finding or could suggest that the father is also at risk for developing ADPKD. If this is a functionally significant variant, it may explain the more severe and earlier onset phenotype in the child due to a 2-mutation hypothesis.12Patel C. Tchan M. Savige J. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetics and genetic counselling.Semin Nephrol. 2015; 35: 550-556Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 13Tan Y.C. Blumenfeld J. Rennert H. Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs.Biochim Biophys Acta. 2011; 1812: 1202-1212Crossref PubMed Scopus (56) Google Scholar, 14Tchan M. Savig J. Patel C. et al.KHA-CARI autosomal dominant polycystic kidney disease guideline: genetic testing for diagnosis.Semin Nephrol. 2015; 35: 545-549Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Pharmacological management of ADPKD is rapidly evolving. Phase III clinical trials on the long-term safety of tolvaptan in children with ADPKD have commenced. Adult studies have demonstrated delayed decline of kidney function in patients with rapidly progressing ADPKD on tolvaptan.8Cornec-Le Gall E. Audrezet M.A. Rousseau A. et al.The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2015; 27: 942-951Crossref PubMed Scopus (180) Google Scholar, 18US National Library of Medicine. Safety pharmacokinetics, tolerability and efficacy of tolvaptan in children and adolescents with ADPKD (autosomal dominant polycystic kidney disease). Available at: https://clinicaltrials.gov/ct2/show/NCT02964273. Accessed January 2, 2018.Google Scholar Early treatment with angiotensin inhibitors to control hypertension might minimize cardiovascular morbidity in ADPKD patients.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar These emerging treatments may offer early intervention to pediatric high-risk cases or those found to have early disease progression.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 8Cornec-Le Gall E. Audrezet M.A. Rousseau A. et al.The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2015; 27: 942-951Crossref PubMed Scopus (180) Google Scholar Furthermore, they may alter the approach to antenatally diagnosed ADPKD and improve the prognosis of affected families.3Mekahli D. Woolf A. Bockenhauer D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.Pediatr Nephrol. 2010; 22: 2275-2282Crossref Scopus (25) Google Scholar, 4Rangan G. Alexander S. Campbell K. KHA-CARI guideline recommendations for the diagnosis and management of autosomal dominant polycystic kidney disease.Nephrology. 2016; 21: 705-716Crossref PubMed Scopus (21) Google Scholar, 8Cornec-Le Gall E. Audrezet M.A. Rousseau A. et al.The PROPKD score: a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease.J Am Soc Nephrol. 2015; 27: 942-951Crossref PubMed Scopus (180) Google Scholar In conclusion, ADPKD has become acknowledged as a pediatric condition, with advancements in ultrasonography resulting in increased diagnosis. With this early recognition, clinicians and families alike are faced with an uncertain future and prognosis, requiring regular reviews for disease progression. Psychosocial outcomes including significant treatment burden, fear of end-stage kidney disease, and variable familial presentation are all realistic concerns that affected individuals and families face. Here we have presented a multidisciplinary approach to and clinical progress of a cohort of antenatally diagnosed cases of ADPKD. Emerging disease-modifying medications may improve the prognosis for these individuals and ultimately reduce the disease burden in adulthood. AM has been a member of the tolvaptan Medical Advisory Board for Otsuka Australia Pharmaceutical Pty Ltd. All the other authors declared no competing interests. Download .docx (.06 MB) Help with docx files Supplementary Methods
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