Skip to main content
SpringerLink
Log in

The nephronophthisis complex

A clinicopathologic study in children

  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

The clinical and morphological findings are described in 27 children with nephronophthisis. Seventeen children were considered as sporadic cases. In 10 familial cases the presumed mode of inheritance was autosomal recessive. The clinical picture was rather uniform: polyuria-polydipsia, hyposthenuria, anemia, growth retardation, and azotemia with progressive renal failure. Six patients presented with tapeto-retinal degeneration. In a further seven children other ocular changes were detected. Two female siblings showed additional non-renal manifestations: mental retardation, pulmonary emphysema, skeletal anomalies, and congenital hepatic fibrosis.

Renal histology displayed a chronic sclerosing tubulo-interstitial nephropathy with extensive tubular atrophy and dedifferentiation. Medullary cysts were frequently found in end-stage kidneys. Immunofluorescence was either non-specific or completely negative. On electron microscopy, the tubular basement membrane changes predominated: thickening, lamellation, splitting, and deposition of microfibrils within the increased basement membrane substance. Detailed light- and electron microscopic findings were non-specific but the overall morphologic picture was characteristic and even diagnostic in conjunction with the clinical presentation.

A recurrence of nephronophthisis in transplanted kidneys has not been observed.

The pathogenesis of nephronophthisis is obscure but with respect to the morphologic findings a primary or secondary tubular basement membrane defect seems very likely.

Our experience suggests that nephronophthisis is a frequent cause of chronic renal failure in children and commonly associated with non-renal abnormalities. To avoid the separation of different syndromes presenting with a uniform renal disease but various non-renal manifestations, we suggest that the term “nephronopthisis complex” be used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Advisory Committee to the Renal Transplant Registry (1975) Renal transplantation in congenital and metabolic disease. A report from the ASC/NIH Renal Transplant Registry. JAM A 232:148–153

    Google Scholar 

  • Alexander F, Campbell S (1970) Familial uremic medullary cystic disease. Pediatrics 45:1024–1028

    Google Scholar 

  • André JL, Afflalo G, Duprez A, Kifffer B, Neimann N (1975) Néphropathie tubulo-interstitielle chronique et dégénérescence tapéto-rétinienne. Syndrome de Senior? Semaine Hôp 51:2995–3000

    Google Scholar 

  • Avasthi PS, Erickson DG, Gardner KD (1976) Hereditary renal-retinal dysplasia and the medullary cystic disease-nephronophthisis complex. Ann Intern Med 84:157–161

    Google Scholar 

  • Balen AT van, Collenburg JJM van (1976) Tapeto-retinal degeneration and familial juvenile nephronophthisis (FJN) J Pediatr Ophthalmol 13:329–335

    Google Scholar 

  • Bennett WM, Simon NM, Krill AE, Weinstein RF, Carone FA (1975) Cystic disease of the renal medulla associated with retinitis pigmentosa and imino acid abnormalities. Clin Nephrol 4:25–31

    Google Scholar 

  • Betts PR, Forrest-Hay I (1973) Juvenile nephronophthisis. Lancet 2:475–478

    Google Scholar 

  • Bodaghi E, Zaman T (1978) Familial nephropathy associated with bone anomaly, degenerative retinitis and congenital liver fibrosis. Abstract. 12th annual meeting of the European Society for Pediatric Nephrology, Israel

  • Bodaghi E, Zaman T, Kheradpir MH (1980) Familial nephropathy associated with congenital liver fibrosis, degenerative retinitis and cone-shaped epiphysis. Int. J Pediatr Nephrol 1:153–156

    Google Scholar 

  • Boichis H, Passwell J, David R, Miller H (1973) Congenital hepatic fibrosis and nephronophthisis. Q J Med 42:221–233

    Google Scholar 

  • Bois E, Royer P (1970) Association de néphropathie tubulo-interstitielle chronique et de dégénérescence tapéto-rétinienne. Etude génétique. Arch Fr Pédiatr 27:471–481

    Google Scholar 

  • Broberger O, Winberg J, Zetterström R (1960) Juvenile nephronophthisis. Part I. A genetically determined nephropathy with hypotonie polyuria and azotaemia. Acta Paediatr 49:470–479

    Google Scholar 

  • Brouhard BH, Srivastava RN, Travis LB, Kay MI, Beathard GA, Dodge WF, Lorentz WB jr. (1977) Nephronophthisis. Renal function and histologic studies in a family. Nephron 19:99–112

    Google Scholar 

  • Chakera TMH (1975) Peripheral dysostosis associated with juvenile nephronophthisis. Br J Radiol 48:765–766

    Google Scholar 

  • Chamberlin BC, Hagge WW, Stickler GB (1977) Juvenile nephronopthisis and medullary cystic disease. Mayo Clin Proc 52:485–491

    Google Scholar 

  • Chipail A, Haimovici M, Scumpu G, Leibovici M, Georgescu T (1973) La néphronophtise juvénile familiale. Pédiatrie 28:321–329

    Google Scholar 

  • Coles GA, Branch RA (1976) Familial interstitial nephritis. Clin Nephrol 6:513–517

    Google Scholar 

  • Collan Y, Sipponen P, Haapanen E, Lindahl J, Jokinen EJ, Hhelt L (1977) Herditary nephronophthisis with a life span of three decades. Virch Arch [Pathol Anat] 376:195–208

    Google Scholar 

  • Delaney V, Mullaney J, Bourke E (1978) Juvenile nephronophtisis, congenital hepatic fibrosis and retinal hypoplasia in twins. Q J Med 47:281–290

    Google Scholar 

  • Dieterich E, Straub E (1978) Hepatozerebelläre Variante der familiären juvenilen Nephronophthise. Therapiewoche 28:4252–4256

    Google Scholar 

  • Dietrich E, Straub E (1980) Familial juvenile nephronophthisis with hepatic fibrosis and neurocutaneous dysplasia. Helv Paediatr Acta 35:261–267

    Google Scholar 

  • Dunnill MS, Millard PR, Oliver D (1977) Aquired cystic disease of the kidneys: a harzard of long-term intermittent maintenance hemodialysis. J Clin Pathol 30:868–877

    Google Scholar 

  • Fanconi G, Hanhart E, Albertini A von, Uehlinger E, Dolivo G, Prader A (1951) Die familiäre juvenile Nephronopthise (die idiopathische parenchymatöse Schrumpfniere). Helv Paediatr Acta 6:1–49

    Google Scholar 

  • Fillastre JP, Gruenel J, Riberi P, Marx P, Whitworth JA, Kuhn MJ (1976) Senior-Loken syndrome (nephronophthisis and tapeto-retinal degeneration): a study of 8 cases from 5 families. Clin Nephrol 5:14–19

    Google Scholar 

  • Fontaine JL, Boulesteix J, Saraux H, Lasfargues G, Grenet P, Dung N, Dhermy P, Roy C, Laplane R (1970) Néphropathie tubulo-interstitielle de l'enfant avec dégénérescence tapétorétinienne. Arch Fr Pédiatr 27:459–470

    Google Scholar 

  • Freycon MTH, Ravussin JJ, Gilly J, Freycon F (1977) Néphrite tubulo-interstitielle avec fibrose hépatique. Pédiatrie 32:685–689

    Google Scholar 

  • Gardner KD jr (1971) Evolution of clinical signs in adult-onset cystic disease of the renal medulla. Ann Intern Med 74:47–54

    Google Scholar 

  • Gardner KD jr (1976) In: Gardner KD jr (ed) Cystic disease of the kidney. Juvenile nephronophthisis and renal medullary cyxtic disease. John Wiley & Sons, New York-London-Sydney-Toronto. pp 173–185

    Google Scholar 

  • Giangiacomo J, Monteleone PL, Witzleben CL (1975) Medullary cystic disease vs nephronophthisis. A valid distinction? JAMA 232:629–631

    Google Scholar 

  • Giedion A (1979) Phalangeal cone shaped epiphysis of the hands (PhCSEH) and chronic renal disease — the conorenal syndromes. Pediatr Radiol 8:32–38

    Google Scholar 

  • Giselson N, Heinegard D, Holmberg C-G, Lindberg L-G, Lindstedt E, Lindstedt G, Schersten B (1970) Renal medullary cystic disease or familial juvenile nephronophthisis: a renal tubular disease. Biochemical findings in two siblings. Am J Med 48:174–184

    Google Scholar 

  • Goldman SH, Walker SR, Merigan TC jr, Gardner KD, Bull JMC (1966) Hereditary occurrence of cystic disease of the renal medulla. N Engl J Med 274:984–992

    Google Scholar 

  • Grüttner R, Lenz W (1957) Zur Kenntnis und zur Differentialdiagnose der familiären Nephronophthise im Kindesalter. Arch Kinderheilkunde 155:271–284

    Google Scholar 

  • Habib R (1974) Nephronophthisis and medullary cystic disease. In: Strauss J (ed) Pediatric nephrology. Vol. 1 Stratton Intercontinental Medical Book Corporation, New York, pp 393–401

    Google Scholar 

  • Hall PhW, Dammin GJ (1978) Balkan nephropathy. Nephron 22:282–300

    Google Scholar 

  • Herdman RC, Good RA, Vernier RL (1967) Medullary cystic disease in two siblings. Am J Med 43:335–344

    Google Scholar 

  • Hooft C, Roels H, Herpol J (1959) A case of Fanconi's familial juvenile nephronophthisis. Helv Paediatr Acta 14:217–233

    Google Scholar 

  • Kerr DNS, Harrison CV, Sherlock S, Walker RM (1961) Congenital hepatic fibrosis. Q J Med 30:91–117

    Google Scholar 

  • Kerr DNS, Warrick CK, Hart-Mercer J (1962) A lesion resembling medullary sponge kidney in patients with congenital hepatic fibrosis. Clin Radiol 13:85–91

    Google Scholar 

  • Kleinknecht C, Habib R (1979) Nephronophthisis. Arbeitsgemeinschaft für Pädiatrische Nephrologie, Heidelberg, 13.-14.10.1979

  • Kliger AS, Scheer RL (1976) Familial disease of the renal medulla. A study of progeny in a family with medullary cystic disease. Ann Intern Med 85:190–194

    Google Scholar 

  • Landing HB, Wells TR, Claireaux AE (1981) Morphometric analysis of liver lesions in cystic diseases of childhood. Hum Pathol 11:549–560

    Google Scholar 

  • Lennert Th, Schärer K, Brandis M (1978) Ocular abnormalities in nephronophthisis. Abstract, 12th meeting of the Eur. Soc Pediatr. Nephrology, Israel

  • Lindstedt E, Lindstedt G (1973) Tubular proteinuria early in nephronophthisis. Lancet 2:1215–1216

    Google Scholar 

  • Løken AC, Hanssen O, Halvorsen S, Jølster NJ (1961) Hereditary renal dysplasia and blindness. Acta Paediatr 50:177–184

    Google Scholar 

  • Mainzer F, Saldino RM, Ozonoff MB, Minagi H (1970) Familial nephropathy associated with retinitis pigmentosa, cerebellar ataxia and skeletal abnormalities. Am J Med 49:556–562

    Google Scholar 

  • Mangos JA, Opitz JM, Lobeck CC, Cookson DU (1964) Familial juvenile nephronophthisis: an unrecognized renal disease in the United States. Pediatrics 34:337–345

    Google Scholar 

  • Meier DA, Hess JW (1965) Familial nephropathy with retinitis pigmentosa. A new oculorenal syndrome in adults. Am J Med 39:58–69

    Google Scholar 

  • Mongeau JG, Worthen HG (1967) Nephronophthisis and medullary cystic disease. Arn J Med 43:345–355

    Google Scholar 

  • Pedreira FA, Marmer EL, Bergstrom WH (1968) Familial juvenile nephronophthisis and medullary cystic disease. J Pediatr 73:77–83

    Google Scholar 

  • Popovic-Rolović M, Čalić-Peri šić N, Bunje-Rački G, Negovanović D (1976) Juvenile nephronoph-Thisis associated with retinal pigmentary dystrophy, cerebellar ataxia. and skeletal abnormalities. Arch Dis Child 51:801–803

    Google Scholar 

  • Price JDE, Pratt-Johnson JA (1970) Medullary cystic disease with degeneration. Can Med Assoc J 102:165–167

    Google Scholar 

  • Proesmans W, Damme B van, Macken J (1975) Nephronophthisis and tapetoretinal degeneration associated with liver fibrosis. Clin Nephrol 3:160–164

    Google Scholar 

  • Rayfield EJ, McDonald FD (1972) Red and blonde hair in renal medullary cystic disease. Arch Intern Med 130:72–75

    Google Scholar 

  • Robins DG, French TA, Chakera TMH (1976) Juvenile nephronophthisis associated with skeletal abnormalities and hepatic fibrosis. Arch Dis Child 51:799–801

    Google Scholar 

  • Saldino R, Mainzer F (1971) Cone-shaped epiphyses (SCE) in siblings with hereditary renal disease and retinitis pigmentosa. Radiology 98:39–45

    Google Scholar 

  • Schärer K, Chantler C, Brunner FP, Gurland JH, Jacob C, Selwood NH, Spies G, Wing AJ (1976) Combined report on regular dialysis and transplantation of children in Europe, 1975. Proc EDTA 13:59–105

    Google Scholar 

  • Schimke RN (1969) Hereditary renal-retinal dysplasia. Ann Intern Med 70:735–744

    Google Scholar 

  • Senior B, Friedman AI, Braudo JL (1961) Juvenile familial nephropathy with tapetoretinal degeneration. Amer J Ophthalmol 52:625–633

    Google Scholar 

  • Senior B (1973) Familial renal-retinal dystrophy. Am J Dis Child 125:442–447

    Google Scholar 

  • Sherman FE, Studnicki FM, Fetterman GH (1971) Renal lesions of familial juvenile nephronoph-thisis examined by microdissection. Am J Clin Path 55:391–400

    Google Scholar 

  • Smith CH, Graham JB (1945) Congenital medullary cysts of the kidneys with severe refractory anemia. Am J Dis Child 69:369–377

    Google Scholar 

  • Spicer RD, Ogg CS, Saxton HM, Cameron JS (1969) Renal medullary cystic disease. Br Med J 1:824–825

    Google Scholar 

  • Steele BT, Lirenman DS, Battie CW (1980) Nephronophthisis. Am J Med 68:531–538

    Google Scholar 

  • Strauss MB, Sommers SC (1967) Medullary cystic disease and familial juvenile nephronopthisis. Clinical and pathological identity. N Engl J Med 277:863–864

    Google Scholar 

  • Sworn MU, Eisinger AJ (1972) Medullary cystic disease and juvenile nephrophthisis in separate members of the same family. Arch Dis Child 47:278–281

    Google Scholar 

  • Sydow G von, Ranström S (1962) Familial juvenile nephronophthisis. Acta Paediatr 51:561–574

    Google Scholar 

  • Victorin L, Ljungqvist A, Winberg J, Åkesson HO (1970) Nephronophthisis. A uremie disease with hypotonie urine. Acta Med Scand 188:145–156

    Google Scholar 

  • Waldherr R, Lennert T, Weber H-O, Födisch H-J, Michalk D, Müller-Wiefei D, Schärer K (1981 in press) The nephronophthisis complex. A clinico-pathologic study. In: Bulla M (ed) Renal insufficiency in children. Springer, Berlin-Heidelberg-New York

    Google Scholar 

  • Weber H-P, Becker M, Rotthauwe HW, Födisch HJ, Waldherr R (1979) Familiäre Nephronophthise mit periportaler Leberfibrose. (Abstract) Nieren u. Hochdruckkrkh 8:89

    Google Scholar 

  • Wrigley KA, Sherman RL, Ennis FA, Becker EL (1973) Progressive hereditary nephropathy. A variant of medullary cystic disease? Arch Intern Med 131:240–244

    Google Scholar 

  • Zimmermann H-D, Boseck S (1975) Licht-, elektronenmikroskopische und beugungsanalytische Untersuchungen an intraepithelialen Filamentbündeln in der Niere des erwachsenen Menschen. Virchows Arch [Pathol Anat] 366:27–49

    Google Scholar 

  • Zollinger HU, Mihatsch MJ, Edefonti A, Gaboardi F, Imbasciati E, Lennert T (1980) Nephronophthisis (medullary cystic disease of the kidney). A study using electron microscopy, immuno-fluorescence, and a review of the morphological findings. Helv Paediatr Acta 35:509–530

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology and Pediatrics, University of Heidelberg, Germany

    R. Waldherr, T. Lennert, H. -P. Weber, H. J. Födisch & K. Schärer

  2. Department of Pediatrics, University of Berlin, Germany

    R. Waldherr, T. Lennert, H. -P. Weber, H. J. Födisch & K. Schärer

  3. Departments of Pediatrics and Pediatric Pathology, University of Bonn, Germany

    R. Waldherr, T. Lennert, H. -P. Weber, H. J. Födisch & K. Schärer

Authors
  1. R. Waldherr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Lennert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. -P. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. J. Födisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Schärer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waldherr, R., Lennert, T., Weber, H.P. et al. The nephronophthisis complex. Virchows Arch. A Path. Anat. and Histol. 394, 235–254 (1982). https://doi.org/10.1007/BF00430668

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00430668

Key words

Search

Navigation