• Amita Sharma
  • Jonathan PaolinoEmail author
Part of the Current Clinical Psychiatry book series (CCPSY)


The approach to the diagnosis and treatment of renal disorders in children and adults with autism spectrum disorder (ASD) is not unlike that of the general population. There are, however, some topics that need to be highlighted because patients with ASD may be at increased risk of these disorders. These include tuberous sclerosis complex, lithium toxicity, juvenile nephronophthisis, enuresis, and urinary tract infections. Because of the important role of the kidney both in the metabolism of commonly used medications and in the overall health of an individual, an understanding of these conditions is essential for both primary care and subspecialty healthcare providers caring for patients with ASD.


Autism spectrum disorder Tuberous sclerosis Angiomyolipoma (AML) Lithium toxicity Echogenic kidneys Enuresis UTIs 


  1. 1.
    van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science (New York, NY). 1997;277(5327):805–8.Google Scholar
  2. 2.
    Krueger DA, Northrup H. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):255–65.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Franz DN, Bissler JJ, McCormack FX. Tuberous sclerosis complex: neurological, renal and pulmonary manifestations. Neuropediatrics. 2010;41(5):199–208.PubMedGoogle Scholar
  4. 4.
    Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Human Genet. 2001;68(1):64–80.Google Scholar
  5. 5.
    O’Callaghan FJ, Noakes MJ, Martyn CN, Osborne JP. An epidemiological study of renal pathology in tuberous sclerosis complex. BJU Int. 2004;94(6):853–7.PubMedGoogle Scholar
  6. 6.
    Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355:1345.PubMedGoogle Scholar
  7. 7.
    Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9869):817–24.PubMedGoogle Scholar
  8. 8.
    Pirson Y. Tuberous sclerosis complex-associated kidney angiomyolipoma: from contemplation to action. Nephrol Dial Transplant. 2013;28(7):1680–5.PubMedGoogle Scholar
  9. 9.
    Murakami A, Gomi K, Tanaka M, Ohyama M, Itani Y, Ishikawa H, et al. Unilateral glomerulocystic kidney disease associated with tuberous sclerosis complex in a neonate. Pathol Int. 2012;62(3):209–15.PubMedGoogle Scholar
  10. 10.
    Srinivas V, Herr HW, Hajdu EO. Partial nephrectomy for a renal oncocytoma associated with tuberous sclerosis. J Urol. 1985;133(2):263–5.PubMedGoogle Scholar
  11. 11.
    Washecka R, Hanna M. Malignant renal tumors in tuberous sclerosis. Urology. 1991;37(4):340–3.PubMedGoogle Scholar
  12. 12.
    Paul E, Thiele EA, Shailam R, Rosales AM, Sadow PM. Case records of the Massachusetts General Hospital. Case 26-2011. A 7-year-old boy with a complex cyst in the kidney. N Engl J Med. 2011;365(8):743–51.PubMedGoogle Scholar
  13. 13.
    Matsui K, Tatsuguchi A, Valencia J, Yu Z, Bechtle J, Beasley MB, et al. Extrapulmonary lymphangioleiomyomatosis (LAM): clinicopathologic features in 22 cases. Hum Pathol. 2000;31(10):1242–8.PubMedGoogle Scholar
  14. 14.
    Flynn PM, Robinson MB, Stapleton FB, Roy S 3rd, Koh G, Tonkin IL. Coarctation of the aorta and renal artery stenosis in tuberous sclerosis. Pediatr Radiol. 1984;14(5):337–9.PubMedGoogle Scholar
  15. 15.
    Niemi AK, Northrup H, Hudgins L, Bernstein JA. Horseshoe kidney and a rare TSC2 variant in two unrelated individuals with tuberous sclerosis complex. Am J Med Genet A. 2011;155a(10):2534–7.PubMedGoogle Scholar
  16. 16.
    Wills BK, Mycyk MB, Mazor S, Zell-Kanter M, Brace L, Erickson T. Factitious lithium toxicity secondary to lithium heparin-containing blood tubes. J Med Toxicol. 2006;2(2):61–3.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Fenves AZ, Emmett M, White MG. Lithium intoxication associated with acute renal failure. South Med J. 1984;77(11):1472–4.PubMedGoogle Scholar
  18. 18.
    Clendeninn NJ, Pond SM, Kaysen G, Barraza JJ, Farrell T, Becker CE. Potential pitfalls in the evaluation of the usefulness of hemodialysis for the removal of lithium. J Toxicol Clin Toxicol. 1982;19(4):341–52.PubMedGoogle Scholar
  19. 19.
    Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med. 1994;97(4):383–9.PubMedGoogle Scholar
  20. 20.
    Lavonas EJ, Buchanan J. Hemodialysis for lithium poisoning. Cochrane Database Syst Rev. 2015;(9):Cd007951.Google Scholar
  21. 21.
    Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis. 1987;10(5):329–45.PubMedGoogle Scholar
  22. 22.
    Trepiccione F, Christensen BM. Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental findings. J Nephrol. 2010;23(Suppl 16):S43–8.PubMedGoogle Scholar
  23. 23.
    Christensen BM, Kim YH, Kwon TH, Nielsen S. Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct. Am J Physiol Renal Physiol. 2006;291(1):F39–48.PubMedGoogle Scholar
  24. 24.
    Batlle DC, von Riotte AB, Gaviria M, Grupp M. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med. 1985;312(7):408–14.PubMedGoogle Scholar
  25. 25.
    Sinke AP, Kortenoeven ML, de Groot T, Baumgarten R, Devuyst O, Wetzels JF, et al. Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus independently of the sodium-chloride cotransporter. Am J Physiol Renal Physiol. 2014;306(5):F525–33.PubMedGoogle Scholar
  26. 26.
    Markowitz GS, Radhakrishnan J, Kambham N, Valeri AM, Hines WH, D’Agati VD. Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol: JASN. 2000;11(8):1439–48.PubMedGoogle Scholar
  27. 27.
    Aiff H, Attman PO, Aurell M, Bendz H, Schon S, Svedlund J. End-stage renal disease associated with prophylactic lithium treatment. Eur Neuropsychopharmacol: J Eur Coll Neuropsychopharmacol. 2014;24(4):540–4.Google Scholar
  28. 28.
    Farres MT, Ronco P, Saadoun D, Remy P, Vincent F, Khalil A, et al. Chronic lithium nephropathy: MR imaging for diagnosis. Radiology. 2003;229(2):570–4.PubMedGoogle Scholar
  29. 29.
    Presne C, Fakhouri F, Noel LH, Stengel B, Even C, Kreis H, et al. Lithium-induced nephropathy: rate of progression and prognostic factors. Kidney Int. 2003;64(2):585–92.PubMedGoogle Scholar
  30. 30.
    Wood IK, Parmelee DX, Foreman JW. Lithium-induced nephrotic syndrome. Am J Psychiatry. 1989;146(1):84–7.PubMedGoogle Scholar
  31. 31.
    Santella RN, Rimmer JM, MacPherson BR. Focal segmental glomerulosclerosis in patients receiving lithium carbonate. Am J Med. 1988;84(5):951–4.PubMedGoogle Scholar
  32. 32.
    Vivante A, Kohl S, Hwang DY, Dworschak GC, Hildebrandt F. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Pediatr Nephrol (Berlin Germany). 2014;29(4):695–704.Google Scholar
  33. 33.
    Thomas R, Sanna-Cherchi S, Warady BA, Furth SL, Kaskel FJ, Gharavi AG. HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr Nephrol (Berlin Germany). 2011;26(6):897–903.Google Scholar
  34. 34.
    Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM, Adam MP, et al. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet. 2010;87(5):618–30.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Clissold RL, Shaw-Smith C, Turnpenny P, Bunce B, Bockenhauer D, Kerecuk L, et al. Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int. 2016;90(1):203–11.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Sanna-Cherchi S, Kiryluk K, Burgess KE, Bodria M, Sampson MG, Hadley D, et al. Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet. 2012;91(6):987–97.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Arts HH, Knoers NVAM. Current insights into renal ciliopathies: what can genetics teach us? Pediatr Nephrol. 2013;28(6):863–74.PubMedGoogle Scholar
  38. 38.
    Hildebrandt F, Otto E, Rensing C, Nothwang HG, Vollmer M, Adolphs J, et al. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat Genet. 1997;17(2):149–53.PubMedGoogle Scholar
  39. 39.
    Yasuda Y, Hashimoto R, Fukai R, Okamoto N, Hiraki Y, Yamamori H, et al. Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series. Ann General Psychiatry. 2014;13:22.Google Scholar
  40. 40.
    Roberts JL, Hovanes K, Dasouki M, Manzardo AM, Butler MG. Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services. Gene. 2014;535(1):70–8.PubMedGoogle Scholar
  41. 41.
    Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, et al. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management – a KDIGO consensus report. Kidney Int. 2015;88(4):676–83.PubMedGoogle Scholar
  42. 42.
    Curtin C, Jojic M, Bandini LG. Obesity in children with autism spectrum disorder. Harv Rev Psychiatry. 2014;22(2):93–103.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Neveus T, Eggert P, Evans J, Macedo A, Rittig S, Tekgul S, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children’s Continence Society. J Urol. 2010;183(2):441–7.PubMedGoogle Scholar
  44. 44.
    Forsythe WI, Redmond A. Enuresis and spontaneous cure rate. Study of 1129 enuretis. Arch Dis Child. 1974;49(4):259–63.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Hunskaar S, Arnold EP, Burgio K, Diokno AC, Herzog AR, Mallett VT. Epidemiology and natural history of urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2000;11(5):301–19.PubMedGoogle Scholar
  46. 46.
    von Gontard A. Urinary incontinence in children with special needs. Nat Rev Urol. 2013;10(11):667–74.Google Scholar
  47. 47.
    Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008;47(8):921–9.PubMedGoogle Scholar
  48. 48.
    von Gontard A, Pirrung M, Niemczyk J, Equit M. Incontinence in children with autism spectrum disorder. J Pediatr Urol. 2015;11(5):264.e1-7.Google Scholar
  49. 49.
    Kroeger K, Sorensen R. A parent training model for toilet training children with autism. J Intellect Disabil Res: JIDR. 2010;54(6):556–67.PubMedGoogle Scholar
  50. 50.
    Zaffanello M, Giacomello L, Brugnara M, Fanos V. Therapeutic options in childhood nocturnal enuresis. Minerva Urol Nefrol = Ital J Urol Nephrol. 2007;59(2):199–205.Google Scholar
  51. 51.
    Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J. 2008;27(4):302–8.PubMedGoogle Scholar
  52. 52.
    Rosen NJ, Yoshida CK, Croen LA. Infection in the first 2 years of life and autism spectrum disorders. Pediatrics. 2007;119(1):e61–9.PubMedGoogle Scholar
  53. 53.
    Pang KH, Croaker GD. Constipation in children with autism and autistic spectrum disorder. Pediatr Surg Int. 2011;27(4):353–8.PubMedGoogle Scholar
  54. 54.
    Loening-Baucke V. Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood. Pediatrics. 1997;100(2 Pt 1):228–32.PubMedGoogle Scholar
  55. 55.
    Hellerstein S, Linebarger JS. Voiding dysfunction in pediatric patients. Clin Pediatr. 2003;42(1):43–9.Google Scholar
  56. 56.
    Jones E, Dimmock PW, Spencer SA. A randomised controlled trial to compare methods of milk expression after preterm delivery. Arch Dis Child Fetal Neonatal Ed. 2001;85(2):F91–5.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Jahnukainen T, Chen M, Celsi G. Mechanisms of renal damage owing to infection. Pediatr Nephrol (Berlin Germany). 2005;20(8):1043–53.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Massachusetts General HospitalBostonUSA

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