OpenLB
Open Library of Bioscience
Advanced Search
European journal of pediatrics
Dec, 2021;180 (12): 3477-3482.

Renal manifestations in children with neurofibromatosis type 1.

Binnaz Celik, Ozlem Yuksel Aksoy, Funda Bastug, Hatice Gamze Poyrazoglu
Author Information
  1. Binnaz Celik: Department of Pediatrics, Kayseri City Hospital, Kayseri, Turkey.
  2. Ozlem Yuksel Aksoy: Department of Pediatric Nephrology, Kayseri City Hospital, Kayseri, Turkey. ozlem_yurtsever@yahoo.com. ORCID
  3. Funda Bastug: Department of Pediatric Nephrology, Kayseri City Hospital, Kayseri, Turkey.
  4. Hatice Gamze Poyrazoglu: Faculty of Medicine, Department of Pediatric Neurology, Firat University, Elazig, Turkey.
PMID: 34091747 DOI: 10.1007/s00431-021-04144-6

Abstract

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neurocutaneous syndrome affecting various parts of the body, including the renovascular and urinary systems. We evaluated the renovascular, urinary, glomerular, and tubular functions of children with NF1. We compared blood pressures, urinary findings, and renal glomerular and tubular functions in children with NF1 with those of a healthy age- and gender-matched control group. We evaluated 46 NF1 patients and 33 healthy controls. The mean ages of the NF1 group (female/male: 20/26) and the control group (female/male: 15/18) were 10.1 ± 4.6 and 10.6 ± 4.3 years respectively. Six NF1 patients were hypertensive. The mean blood pressures of the NF1 group were significantly higher than those of the control group. Renal artery stenosis was detected in one NF1 patient. Urinary tract anomalies were evident in 21.7% of NF1 but only 9% of control subjects. The mean estimated glomerular filtration rate (eGFR) of the NF1 group was significantly lower than that of the control group. Six NF1 patients evidenced eGFRs < 90 mL/min. In the NF1 group, tubular phosphorus reabsorption was significantly lower and uric acid excretion significantly higher than in the control group.Conclusion: Hypertension, urinary tract anomalies, and impaired renal function were more common in NF1 patients than healthy controls. Regular blood pressure measurements and evaluation of urinary tract and kidney function are essential for NF1 patients. What is Known: • NF1 is most commonly associated with systemic hypertension due to renal artery vasculopathy and the development of a pheochromocytoma. • Hydronephrosis and bladder involvement have been documented in NF1. What is New: • Renal glomerular and tubular functions may be affected in NF1.

Keywords

Children Neurofibromatosis type 1 Renal manifestations eGFR

References

Hirbe AC, Gutmann DH (2014) Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 13:834–843. https://doi.org/10.1016/S1474-4422(14)70063-8 [DOI: 10.1016/S1474-4422(14)70063-8]
Weiss B, Bollag G, Shannon K (1999) Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet 89:14–22 [DOI: 10.1002/(SICI)1096-8628(19990326)89]
Ly KI, Blakeley JO (2019) The diagnosis and management of neurofibromatosis type 1. Med Clin North Am 103:1035–1054. https://doi.org/10.1016/j.mcna.2019.07.004 [DOI: 10.1016/j.mcna.2019.07.004]
Friedman JM, Arbiser J, Epstein JA, Gutmann DH, Huot SJ, Lin AE, Mcmanus B, Korf BR (2002) Cardiovascular disease in neurofibromatosis 1: report of the NF1 cardiovascuar task force. Genet Med 4:105–111 [DOI: 10.1097/00125817-200205000-00002]
Oderich GS, Sullivan TM, Bower TC, Gloviczki P, Miller DV, Babovic-Vuksanovic D, Macedo TA, Stanson A (2007) Vascular abnormalities in patients with neurofibromatosis syndrome type 1: clinical spectrum, management and results. J Vasc Surg 46:475–484 [DOI: 10.1016/j.jvs.2007.03.055]
Norton KK, Xu J, Guttman DH (1995) Expression of the neurofibromatosis 1 gene product, neurofibromin, in blood vessel endothelial cells and smooth muscle. Neurobiol Dis 2:13–21 [DOI: 10.1006/nbdi.1995.0002]
Jouhilahti EM, Peltonen S, Heape AM, Peltonen J (2011) The pathoetiology of neurofibromatosis 1. Am J Pathol 178:1932–1939 [DOI: 10.1016/j.ajpath.2010.12.056]
Pycha A, Klingler CH, Reiter WJ, Schroth B, Haitel A, Latal D (2001) Von Recklinghausen neurofibromatosis with urinary bladder involvement. Urology 58:106 [DOI: 10.1016/S0090-4295(01)01083-4]
Kaefer M, Adams MC, Rink RC, Keating MA (1997) Principles in management of complex pediatric genitourinary plexiform neurofibroma. Urology 49:936–940 [DOI: 10.1016/S0090-4295(97)00098-8]
Kaas B, Huisman TA, Tekes A et al (2013) Spectrum and prevalence of vasculopathy in pediatric neurofibromatosis type 1. J Child Neurol 28:561–569 [DOI: 10.1177/0883073812448531]
Kokubo T, Hiki Y, Horii A, Kobayashi Y (1993) Recklinghausen’s neurofibromatosis associated with membranous nephropathy. Nephron 1993 65:486. https://doi.org/10.1159/000187543 [DOI: 10.1159/000187543]
Lin F, Zhang D, Chang J, Tang X, Guan W, Jiang G, Zhu C, Bian F (2018) THSD7A-associated membranous nephropathy in a patient with neurofibromatosis type 1. Eur J Med Genet 61:84–88. https://doi.org/10.1016/j.ejmg.2017.10.014 [DOI: 10.1016/j.ejmg.2017.10.014]
Tóth T, Trinn C, Simon L, Nagy J (1996) A case of membranous glomerulonephritis associated with Recklinghausen’s neurofibromatosis. Clin Nephrol 45:271–272 [PMID: 9156954]
Wani MM, Reshi AR, Banday KA, Najar MS (2006) von Recklinghausen’s neurofibromatosis associated with membranous glomerulonephritis. Saudi Med J 27:534–535 [PMID: 16598334]
Taniguchi Y, Yorioka N, Kanbe M, Okushin S, Oda H, Nishida Y, Kushihata S&;, Murakami I, Yamakido M (1997) Parent and child cases of IgA nephropathy associated with von Recklinghausen’s disease. Nephron 75:113–114. https://doi.org/10.1159/000189515
Van-Gils J, Harambat J, Jubert C et al (2014) Atypical hematologic and renal manifestations in neurofibromatosis type I: coincidence or pathophysiological link? Eur J Med Genet 57:639–642. https://doi.org/10.1016/j.ejmg.2014.09.001 [DOI: 10.1016/j.ejmg.2014.09.001]
Tarrass F (2008) Focal and segmental glomerulosclerosis and von Recklinghausen’s neurofibromatosis: coincidental or associated? Saudi J Kidney Dis Transpl 19:453–454 [PMID: 18445911]
Gersch MS, Talor Z (2006) Focal segmental glomerular sclerosis in a patient with neurofibromatosis type I. Am J Kidney Dis 47:e17–e19. https://doi.org/10.1053/j.ajkd.2005.09.017 [DOI: 10.1053/j.ajkd.2005.09.017]
Orera A, Lacarra S, Fernández L, Gómez N, Slon MF, Manrique J (2019) Síndrome nefrótico secundario en neurofibromatosis tipo 1. A propósito de dos casos [Secondary glomerulonephritis in neurofibromatosis type 1. Two case reports]. An Sist Sanit Navar 42:345–349. https://doi.org/10.23938/ASSN.0720 [DOI: 10.23938/ASSN.0720]
Khan U, Razdan R, Perazella MA (2013) Anuric acute kidney injury in neurofibromatosis 1. Am J Kidney Dis 61:519–522. https://doi.org/10.1053/j.ajkd.2012.08.044 [DOI: 10.1053/j.ajkd.2012.08.044]
Yılmaz K, Dusunsel R, Dursun I, Coskun A, Erten S, Kucukaydın M, Yel S, Gunduz Z (2013) Neurofibromas of the bladder in a child with neurofibromatosis type 1 causing chronic renal disease. Ren Fail 35:1005–1007. https://doi.org/10.3109/0886022X.2013.809004 [DOI: 10.3109/0886022X.2013.809004]
DeBella K, Szudek J, Friedman JM (2000) Use of the national institutes of health criteria for diagnosis of neurofibromatosis1 in children. Pediatrics 105:608–614 [DOI: 10.1542/peds.105.3.608]
Flynn JT, Kaelber DC, Baker-Smith CM et al (2017) Subcommittee on screening and management of high blood pressure in children. Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatrics. 140:e20173035 [DOI: 10.1542/peds.2017-1904]
Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263 [PMID: 951142]
Patel PA, Cahill AM (2021) Renovascular hypertension in children. CVIR Endovasc 7(4):10. https://doi.org/10.1186/s42155-020-00176-5 [DOI: 10.1186/s42155-020-00176-5]
Estepa R, Gallego N, Orte L, Puras E, Aracil E, Ortuño J (2001) Renovascular hypertension in children. Scand J Urol Nephrol 35:388–392. https://doi.org/10.1080/003655901753224459 [DOI: 10.1080/003655901753224459]
Dubov T, Alhadef HT, Chernin G, Constantini S, Cleper R, Shachar SB (2016) High prevalence of elevated blood pressure among children with neurofibromatosis type 1. Pediatr Nephrol 31:131–136 [DOI: 10.1007/s00467-015-3191-6]
Duan L, Feng K, Tong A, Liang Z (2014) Renal artery stenosis due to neurofibromatosis type 1: case report and literature review. Eur J Med Res 28(19):17. https://doi.org/10.1186/2047-783X-19-17 [DOI: 10.1186/2047-783X-19-17]
Stabouli S, Vargiami E, Maliachova et al (2018) Arterial stiffness in a toddler with neurofibromatosis type 1 and refractory hypertension. Case Rep Pediatr 31:5957987–5957984. https://doi.org/10.1155/2018/5957987 [DOI: 10.1155/2018/5957987]
Lee ML, Chang TM, Yang RC, Yang AD, Chen M (2019) Systemic hypertension followed by insidious stroke in a 12-year-old boy with childhood neurofibromatosis type 1 presenting with renal and cerebral artery vasculopathy. Turk J Pediatr 61:629–634. https://doi.org/10.24953/turkjped.2019.04.026 [DOI: 10.24953/turkjped.2019.04.026]
Fossali E, Signorini E, İntermite RC et al (2000) Renovascular disease and hypertension in children with neurofibromatosis. Pediatr Nephrol 14:806–810 [DOI: 10.1007/s004679900260]
Leppӓvirta J, Kallionpӓӓ RA, Uusitalo E et al (2018) Congenital anomalies in neurofibromatosis 1: a retrospective register-based total population study. Orphanet J Rare Dis 13:5 [DOI: 10.1186/s13023-017-0756-4]
Senel S, Erkek N, Karacan CD (2010) Neurofibromatosis type 1 with idiopathic hypercalciuria, nephrolithiasis and horshoe kidney. Pediatr Nephrol 25:1575–1576 [DOI: 10.1007/s00467-010-1480-7]
Jat KR, Marwaha RK, Panigrahi I, Gupta V (2008) Neurofibromatosis type 1 with intracranial hemorrhage and horseshoe kidney. Pediatr Neurol 2008 39:295–297. https://doi.org/10.1016/j.pediatrneurol.2008.07.009 [DOI: 10.1016/j.pediatrneurol.2008.07.009]
Chen MH, Chen KS, Hou JW, Lee CC, Huang JS (2002) Coexistence of autosomal dominant polycystic kidney disease and neurofibromatosis: report of a family. Am J Nephrol 22:376–380. https://doi.org/10.1159/000065231 [DOI: 10.1159/000065231]
Peces R, Mena R, Martín Y, Hernández C, Peces C, Tellería D, Cuesta E, Selgas R, Lapunzina P, Nevado J (2020) Co-occurrence of neurofibromatosis type 1 and optic nerve gliomas with autosomal dominant polycystic kidney disease type 2. Mol Genet Genomic Med 8:e1321. https://doi.org/10.1002/mgg3.1321 [DOI: 10.1002/mgg3.1321]
Varyani UT, Shah NM, Shah PR, Kute VB, Balwani MR, Trivedi HL (2019) C1q nephropathy in a patient of neurofibromatosis type 1: a rare case report. Indian J Nephrol 29:125–127. https://doi.org/10.4103/ijn.IJN_353_17 [DOI: 10.4103/ijn.IJN_353_17]
Ali US (2011) Joubert syndrome with nephronophthisis in neurofibromatosis type 1. Saudi J Kidney Dis Transpl 22:788–791 [PMID: 21743231]
Bouty A, Dobremez E, Harper L, Harambat J, Bouteiller C, Zaghet B, Wolkenstein P, Ducassou S, Lefevre Y (2018) Bladder dysfunction in children with neurofibromatosis type I: report of four cases and review of the literature. Urol Int 100:339–345. https://doi.org/10.1159/000487193 [DOI: 10.1159/000487193]
Diplomatico M, Marzuillo P, La Manna A, Apicella A, Guarino S, Piccolo V (2020) From skin to kidneys: cutaneous clues of renal disease in children. Dermatol Pract Concept 26:e2020095. https://doi.org/10.5826/dpc.1004a95 [DOI: 10.5826/dpc.1004a95]
Stay EJ, Vawter G (1977) The relationship between nephroblastoma and neurofibromatosis (Von Recklinghausen’s disease). Cancer 39:2550–2555. https://doi.org/10.1002/1097-0142(197706)39:6<2550::aid-cncr2820390636>3.0.co;2-y [DOI: 10.1002/1097-0142(197706)39]
Stone NN, Atlas I, Kim US, Kwan D, Leventhal I, Waxman JS (1993) Renal angiomyolipoma associated with neurofibromatosis and primary carcinoid of mesentery. Urology 41:66–71. https://doi.org/10.1016/0090-4295(93)90249-a [DOI: 10.1016/0090-4295(93)90249-a]
Nguyen KT, Chiu M (2008) Segmental neurofibromatosis associated with renal angiomyolipomas. Cutis 82:65–68 [PMID: 18712027]
Iarrobino G, Capasso L, Buonincontro S, Alderisio A, Sciano D, Calabrese R, Borsi E (2008) Chirurgia conservativa del parenchima renale per angiomiolipoma emorragico: due casi clinici [Preservative surgery of the kidney for haemorrhagic angiomyolipoma: a report of two cases]. Chir Ital 60:587–593 [PMID: 18837263]
Korkiamäki T, Ylä-Outinen H, Leinonen P, Koivunen J, Peltonen J (2005) The effect of extracellular calcium concentration on calcium-mediated cell signaling in NF1 tumor suppressor-deficient keratinocytes. Arch Dermatol Res 296:465–472. https://doi.org/10.1007/s00403-004-0538-4 [DOI: 10.1007/s00403-004-0538-4]
Wang Y, Brittain JM, Wilson SM, Hingtgen CM, Khanna R (2010) Altered calcium currents and axonal growth in NF1 haploinsufficient mice. Transl Neurosci 1:106–114. https://doi.org/10.2478/v10134-010-0025-8 [DOI: 10.2478/v10134-010-0025-8]

MeSH Term

Adolescent
Child
Child, Preschool
Female
Glomerular Filtration Rate
Humans
Hypertension
Kidney
Male
Neurofibromatosis 1
Journal Article

Word Cloud

Similar Articles

Cited By