Abstract
Autosomal dominant polycystic kidney disease (ADPKD) in children is sometimes considered to be a benign condition, with morbidity manifesting in adulthood. Therefore, diagnostic screening of children at risk is controversial. The aim of our study was to to compare the manifestations of ADPKD in children diagnosed by postnatal ultrasound (US) screening versus those presenting with symptoms. This was a retrospective chart review of children with ADPKD assessed in a single centre between 1987 and 2007. Age and reason for diagnosis were noted, and children were separated into two groups: (1) those diagnosed on the basis of family-based screening; (2) those presenting with a symptom. The two groups were compared for renal size, number of cysts, estimated glomerular filtration rate (eGFR), the presence of hypertension and microalbuminuria. In the 47 children with ADPKD (21 females) from 33 families who satisfied the enrollment criteria, mean (standard deviation) age at referral and last follow-up was 7.2 (4.4) and 12.9 (5.1) years, respectively, and the mean follow-up duration was 5.7 (3.6) years. Diagnosis was based on postnatal US screening in 31 children, whereas 16 were diagnosed after presenting with symptoms. The proportions of children with nephromegaly, hypertension, microalbuminuria and decreased eGFR, respectively, were similar in both groups. Based on these results, we conclude that renal-related morbidities, including hypertension and microalbuminia, do occur in children with ADPKD and at a similar frequency in those diagnosed after presenting with symptoms and those diagnosed upon postnatal screening. We suggest that at-risk children should have regular checks to detect hypertension. Moreover, affected children may benefit from novel therapies to minimise cystic disease progression.
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References
Torres VE, Harris PC (2009) Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 76(2):149–168
Ecder T, Schrier RW (2009) Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol 5(4):221–228
Kelleher CL, McFann KK, Johnson AM, Schrier RW (2004) Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population. Am J Hypertens 17(11 Pt 1):1029–1034
Fick GM, Johnson AM, Hammond WS, Gabow PA (1995) Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 5(12):2048–2056
Chang MY, Ong AC (2008) Autosomal dominant polycystic kidney disease: recent advances in pathogenesis and treatment. Nephron Physiol 108(1):1–7
MacDermot KD, Saggar-Malik AK, Economides DL, Jeffery S (1998) Prenatal diagnosis of autosomal dominant polycystic kidney disease (PKD1) presenting in utero and prognosis for very early onset disease. J Med Genet 35(1):13–16
Boyer O, Gagnadoux MF, Guest G, Biebuyck N, Charbit M, Salomon R, Niaudet P (2007) Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth. Pediatr Nephrol 22(3):380–388
Fick GM, Johnson AM, Strain JD, Kimberling WJ, Kumar S, Manco-Johnson ML, Duley IT, Gabow PA (1993) Characteristics of very early onset autosomal dominant polycystic kidney disease. J Am Soc Nephrol 3(12):1863–1870
Consugar MB, Wong WC, Lundquist PA, Rossetti S, Kubly VJ, Walker DL, Rangel LJ, Aspinwall R, Niaudet WP, Ozen S, David A, Velinov M, Bergstralh EJ, Bae KT, Chapman AB, Guay-Woodford LM, Grantham JJ, Torres VE, Sampson JR, Dawson BD, Harris PC (2008) Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1/TSC2 contiguous gene syndrome. Kidney Int 74(11):1468–1479
Denamur E, Delezoide AL, Alberti C, Bourillon A, Gubler MC, Bouvier R, Pascaud O, Elion J, Grandchamp B, Michel-Calemard L, Missy P, Zaccaria I, Le Nagard H, Gerard B, Loirat C, de Foetopathologie Société Française, Barbet J, Beaufrère AM, Berchel C, Bessières B, Boudjemaa S, Buenerd A, Carles D, Clemenson A, Dechelotte P, Devisme L, Dijoud F, Espérandieu O, Fallet C, Gonzalès M, Hillion Y, Jacob B, Joubert M, Kermanach P, Lallemand A, Laquerrière A, Laurent N, Liprandi A, Loeuillet L, Loget P, Martinovic J, Ménez F, Narcy F, Roux JJ, Rouleauto-Dubois C, Sinico M, Tantau J, Wann AR (2010) Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease. Kidney Int 77(4):350–358
Feather SA, Winyard PJ, Dodd S, Woolf AS (1997) Oral-facial-digital syndrome type 1 is another dominant polycystic kidney disease: clinical, radiological and histopathological features of a new kindred. Nephrol Dial Transplant 12(7):1354–1361
Coward RJ, Risdon RA, Bingham C, Hattersley AT, Woolf AS (2001) Kidney disease in hypomelanosis of Ito. Nephrol Dial Transplant 16(6):1267–1269
Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van’t Hoff W, Marks SD, Trompeter RS, Tullus K, Winyard PJ, Cansick J, Mushtaq I, Dhillon HK, Bingham C, Edghill EL, Shroff R, Stanescu H, Ryffel GU, Ellard S, Bockenhauer D (2009) HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 20(5):1123–1131
Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, Parfrey P, Cramer B, Coto E, Torra R, San Millan JL, Gibson R, Breuning M, Peters D, Ravine D (2009) Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol 20(1):205–212
Fick GM, Duley IT, Johnson AM, Strain JD, Manco-Johnson ML, Gabow PA (1994) The spectrum of autosomal dominant polycystic kidney disease in children. J Am Soc Nephrol 4(9):1654–1660
Reed B, McFann K, Kimberling WJ, Pei Y, Gabow PA, Christopher K, Petersen E, Kelleher C, Fain PR, Johnson A, Schrier RW (2008) Presence of de novo mutations in autosomal dominant polycystic kidney disease patients without family history. Am J Kidney Dis 52(6):1042–1050
Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34(3):571–590
Gonzalez Celedon C, Bitsori M, Tullus K (2007) Progression of chronic renal failure in children with dysplastic kidneys. Pediatr Nephrol 22(7):1014–1020
Stevens LA, Levey AS (2009) Current status and future perspectives for CKD testing. Am J Kidney Dis 53[3 Suppl 3]:S17–S26
Han BK, Babcock DS (1985) Sonographic measurements and appearance of normal kidneys in children. AJR Am J Roentgenol 145(3):611–616
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114[2 Suppl 4th Rep]:555–576
Rademacher ER, Sinaiko AR (2009) Albuminuria in children. Curr Opin Nephrol Hypertens 18(3):246–251
Grantham JJ (2008) Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 359(14):1477–1485
Grootendorst DC, Jager KJ, Zoccali C, Dekker FW (2009) Screening: why, when, and how. Kidney Int 76(7):694–699
Schrier RW (2009) Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 20(9):1888–1893
Loghman-Adham M, Soto CE, Inagami T, Cassis L (2004) The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Renal Physiol 287(4):F775–F788
Torres VE, Donovan KA, Scicli G, Holley KE, Thibodeau SN, Carretero OA, Inagami T, McAteer JA, Johnson CM (1992) Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Kidney Int 42(2):364–373
Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW (2009) Prospective change in renal volume and function in children with ADPKD. Clin J Am Soc Nephrol 4(4):820–829
Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW (2008) Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int 74(9):1192–1196
Chapman AB, Guay-Woodford LM (2009) Renal volume in children with ADPKD: size matters. Clin J Am Soc Nephrol 4(4):698–699
Tee JB, Acott PD, McLellan DH, Crocker JF (2004) Phenotypic heterogeneity in pediatric autosomal dominant polycystic kidney disease at first presentation: a single-center, 20-year review. Am J Kidney Dis 43(2):296–303
Fencl F, Janda J, Blahova K, Hribal Z, Stekrova J, Puchmajerova A, Seeman T (2009) Genotype–phenotype correlation in children with autosomal dominant polycystic kidney disease. Pediatr Nephrol 24(5):983–989
Azurmendi PJ, Fraga AR, Galan FM, Kotliar C, Arrizurieta EE, Valdez MG, Forcada PJ, Stefan JS, Martin RS (2009) Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function. Nephrol Dial Transplant 24(8):2458–2463
Shamshirsaz AA, Reza Bekheirnia M, Kamgar M, Johnson AM, McFann K, Cadnapaphornchai M, Nobakhthaghighi N, Schrier RW (2005) Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int 68(5):2218–2224
Ecder T, Chapman AB, Brosnahan GM, Edelstein CL, Johnson AM, Schrier RW (2000) Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis 35(3):427–432
Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr, Wetzel LH, Baumgarten DA, Kenney PJ, Harris PC, Klahr S, Bennett WM, Hirschman GN, Meyers CM, Zhang X, Zhu F, Miller JP, Investigators CRISP (2006) Volume progression in polycystic kidney disease. N Engl J Med 354(20):2122–2130
Grantham JJ, Chapman AB, Torres VE (2006) Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol 1(1):148–157
Chapman AB (2008) Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. Clin J Am Soc Nephrol 3(4):1197–1204
Cowley BD Jr (2008) Introduction: new insights, treatments, and management strategies for ADPKD. Clin J Am Soc Nephrol 3(4):1195–1196
Rizk D, Chapman A (2008) Treatment of autosomal dominant polycystic kidney disease (ADPKD): the new horizon for children with ADPKD. Pediatr Nephrol 23(7):1029–1036
van Keimpema LV, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM, de Man RA, Drenth JP (2009) Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 137(5):1661–1668
Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA (2001) Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int 59(5):1654–1662
Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20(3):629–637
Zerres K, Rudnik-Schöneborn S, Deget F (1993) Childhood onset autosomal dominant polycystic kidney disease in sibs: clinical picture and recurrence risk. German Working Group on Paediatric Nephrology (Arbeitsgemeinschaft für Pädiatrische Nephrologie). J Med Genet 30(7):583–588
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Our research is supported by Great Ormond Street Hospital Special Trustees. A.S.W’s research is supported by the Manchester Biomedical Research Centre and the University of Manchester.
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Mekahli, D., Woolf, A.S. & Bockenhauer, D. Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms. Pediatr Nephrol 25, 2275–2282 (2010). https://doi.org/10.1007/s00467-010-1617-8
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DOI: https://doi.org/10.1007/s00467-010-1617-8