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Nephronophthisis and Medullary Cystic Kidney Disease in Children

Pediatric Nephrology

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Abstract

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that constitutes one of the most frequent genetic causes for end-stage kidney disease (ESKD) in the first three decades of life (Hildebrandt and Otto, Nat Rev Genet, 2005; Smith and Graham, Am J Dis Child 69:369–377, 1945; Fanconi et al., Helv Pediatr Acta 6:1–49, 1951; Hildebrandt and Zhou, J Am Soc Nephrol 18(6):1855–1871, 2007). Three clinical forms of NPHP have been distinguished by age of onset of ESKD: infantile (Gagnadoux et al., Pediatr Nephrol 3(1):50–55, 1989; Otto et al., Nat Genet 34(4):413–420, 2003), juvenile (Hildebrandt et al., Clin Investig 70(9):802–808, 1992), and adolescent NPHP (Omran et al., Am J Hum Genet 66(1):118–127, 2000), which manifest with ESKD at median ages of 1 year, 13 years, and 15 years, respectively. Initial symptoms are relatively mild with the exception of infantile NPHP type 2. They consist of polyuria, polydipsia with regular fluid intake at nighttime, secondary enuresis, and anemia (Omran et al., Am J Hum Genet 66(1):118–127, 2000). A slightly raised serum creatinine is noted at an average age of 9 years, before ESKD invariably develops within a few years (Fig. 1). Renal ultrasound reveals increased echogenicity (Fig. 2). Beyond the age of 9 years, cysts appear at the corticomedullary junction within the kidneys of normal or slightly reduced size (Fig. 2) (Blowey et al., Pediatr Nephrol 10(1):22–24, 1996). Renal histology reveals a characteristic triad of tubular basement membrane disruption, tubulointerstitial nephropathy, and cysts (Fig. 3) (Waldherr et al., Virchows Arch A Pathol Anat Histol 394(3):235–254, 1982; Zollinger et al., Helv Paediatr Acta 35(6):509–530, 1980). In nephronophthisis cysts arise from the corticomedullary junction of the kidneys (Fig. 2). Because kidney size is normal or slightly reduced, cysts seem to develop e vacuo through loss of normal tissue. This is in contrast to polycystic kidney disease, where cysts are distributed evenly and lead to gross enlargement of the kidneys (Hildebrandt F (1999) Juvenile nephronophthisis. In: Harmon WE (ed) Pediatric nephrology. Williams & Wilkins, Baltimore). NPHP is part of a broad spectrum of renal cystic/degenerative diseases that often include extrarenal manifestations. Over 80 recessive single-gene causes have been identified. Because the related gene products localize to primary cilia and centrosomes, the term “NPHP-related ciliopathies (NPHP-RC)” is now used for these disorders.

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  1. Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Friedhelm Hildebrandt

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  1. Friedhelm Hildebrandt
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  1. Children's Hospital of Wisconsin Children's Research Institute, Milwaukee, Wisconsin, USA

    Ellis D. Avner

  2. Harvard Medical School Children's Hospital Boston, Boston, Massachusetts, USA

    William E. Harmon

  3. Hôpital Necker Enfants Malades Dept. Néphrologie Pédiatrique, Paris, France

    Patrick Niaudet

  4. Wakayama Medical University Dept. Pediatrics, Wakayama City, Japan

    Norishige Yoshikawa

  5. Department of Nephrology and Urology Division of Nephrology, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy

    Francesco Emma

  6. Division of Nephrology and Hypertension The Heart Institute, University of Cincinnati Cincinnati Children’s Hospital Medical C, Cincinnati, Ohio, USA

    Stuart Goldstein

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Hildebrandt, F. (2014). Nephronophthisis and Medullary Cystic Kidney Disease in Children. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N., Emma, F., Goldstein, S. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27843-3_31-1

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    Nephronophthisis–Medullary Cystic Kidney Disease in Children
    Published:
    13 May 2015

    DOI: https://doi.org/10.1007/978-3-642-27843-3_31-2

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    Nephronophthisis and Medullary Cystic Kidney Disease in Children
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    DOI: https://doi.org/10.1007/978-3-642-27843-3_31-1

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