European Journal of Pediatrics

, Volume 167, Issue 5, pp 509–515 | Cite as

Hypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in Venezuela

  • Corina Gonzalez
  • G. Ariceta
  • C. B. Langman
  • P. Zibaoui
  • L. Escalona
  • L. F. Dominguez
  • M. A. Rosas
Original Paper

Abstract

Kidney involvement in children with Human Immunodeficiency Virus (HIV) infection is increasing in prevalence in parallel with the longer survival of HIV-infected patients and the side-effects of new antiretroviral drugs. However, there are only a few reports describing renal tubular disorders in HIV+ children. This is a cross-sectional, case series study evaluating kidney disease in 26 Venezuelan HIV-infected children. The study cohort consisted of 15 girls and 11 boys, with a median age of 5.9 years (25–75th percentile: 3.6–7.8), who had been treated with antiretrovirals for 2.8 ± 0.4 years, Overall, the patients were short for their age and gender (Z-height: −3.1; 25–75th percentile: −4.94 to −1.98), and 15 showed signs of mild to moderate malnutrition. All of the children had a normal estimated glomerular filtration rate (136 ± 22.6 ml/min/1.73 m2), and glomerular involvement was only observed in one patient with isolated proteinuria. None had nephromegaly. In contrast, tubular disorders were commonly found. Hypercalciuria was detected in 16 of the patients (UCa/Cr = 0.28; 25–75th percentile: 0.17–0.54 mg/mg), with five of these showing crystalluria. Eight children showed hyperchloremia, and three had frank metabolic acidosis. Kidney stones were absent in all, but one boy had bilateral medullary nephrocalcinosis. Conclusion, in Venezuelan children, HIV infection per se, or its specific treatment, was commonly associated with renal tubular dysfunction, especially hypercalciuria and acidosis, potentially leading to nephrocalcinosis and growth impairment. We recommend renal tubular evaluation during the follow-up of children with HIV infection.

Keywords

Acidosis HIV Nephropathy Hypercalciuria Kidney stones Tubular disorders 

References

  1. 1.
    Abitbol CL, Strauss J, Zilleruelo G, Montane B, Rodriguez E (1996) Validity of random urines to quantitate proteinuria in children with human deficiency virus nephropathy. Pediatr Nephrol 10:598–601PubMedCrossRefGoogle Scholar
  2. 2.
    Ahuja TS, Abbott KC, Pack L, Kuo YF (2004). HIV associated nephropathy and end stage renal disease in children in the United States. Pediatr Nephrol 19:808–811PubMedCrossRefGoogle Scholar
  3. 3.
    Batlle D, Hizon M, Cohen E, Gutterman C, Guptan R (1988) The use of urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Eng J Med 318:594–599CrossRefGoogle Scholar
  4. 4.
    Bhandari A, Menon M (2004). Reducing the risk of kidney stone recurrence. Patient Care 38:26–32Google Scholar
  5. 5.
    Birkus G, Hitchcock M, Cihlar T (2002) Assessment of mitochondrial therapy toxicity in human cells treated with Tenofovir: comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother 46:716–723PubMedCrossRefGoogle Scholar
  6. 6.
    Boubaker K, Sudre P, Bally F, Vogel G, Meuwly JY, Glauser MP, Telenti A (1998). Changes in renal function associated with indinavir. AIDS 12:F249–F254PubMedCrossRefGoogle Scholar
  7. 7.
    Carter RW, Singh J, Archambault C, Arrieta A (2004) Severe lactic acidosis in association with reverse transcriptase inhibitors with potential response to L-Carnitine in a pediatric HIV-positive patient. Aids Patient Care STD 18:131–134CrossRefGoogle Scholar
  8. 8.
    Centers for Disease Control and Prevention: USPHS Task Force Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States (2002). MMWR 51(RR-18):1–38Google Scholar
  9. 9.
    Chakraborty R, Uy CS, Oleske JM, Coen PG, McSherry GD (2003) Persistent non-gastrointestinal metabolic acidosis in pediatric HIV-1 infection. AIDS 17: 673–677PubMedCrossRefGoogle Scholar
  10. 10.
    Coe FL (1977) Treated and untreated recurrent calcium nephrolithiasis in patients with idiopathic hypercalciuria, hyperuricosuria or no metabolic disorder. Ann Intern Med 87:404–410PubMedGoogle Scholar
  11. 11.
    Cohen A (1997) HIV-Associated nephropathy pathology and current thoughts on pathogenesis. In: Coral Gables (ed) Pediatric nephrology: continuing challenges. Current concepts in diagnosis and management. University of Miami Press, Miami, pp 155–167Google Scholar
  12. 12.
    D’Agati V, Appel GB (1998) Renal pathology in human immunodeficiency virus infection. Semin Nephrol 18:406–421PubMedGoogle Scholar
  13. 13.
    D’Agati V, Appel GB (1997) HIV infection and the kidney. J Am Soc Nephrol 18:138–152Google Scholar
  14. 14.
    Daly J, Ertingshausen G (1972) Direct method for determining inorganic phosphate in serum with the “Centrifichem”. Clin Chemistry 18:263–265Google Scholar
  15. 15.
    Detwiler RK, Falk RJ, Hogan SL, Jennette JC (1994) Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 45:1416–1424PubMedCrossRefGoogle Scholar
  16. 16.
    Dieleman JP, van Rossum AMC, Stricker BCH, Sturkenboom MCJM, de Groot R, Telgt D, Blok WL, Burger DM, Blijenberg BG, Zietse R, Gyssens IC (2003) Persistent Leukocyturia and loss of renal function in a prospectively monitored cohort of HIV-infected patients treated with Indinavir. JAIDS 32:135–142PubMedGoogle Scholar
  17. 17.
    Domachowske JB (1996) Pediatric human immunodeficiency virus infection. Clin Microbiol Rev 9:448–468PubMedGoogle Scholar
  18. 18.
    Doran TI, Jenson HB (1996) Acquired immunodeficiency syndrome (AIDS). In: Pediatrics infection diseases: principles and practice. Appleton and Lange, Norwalk, pp 577–627Google Scholar
  19. 19.
    Earle KE, Seneviratne T, Shaker J, Shoback D (2004) Fanconi’s syndrome in HIV + adults: report of three cases and literature review. J Bone Miner Res 19:714–721PubMedCrossRefGoogle Scholar
  20. 20.
    Engeler DS, John H, Rentsch KM, Ruef C, Oertle D, Suter S (2002) Nelfinavir urinary stones. J Urol 167:1384–1385PubMedCrossRefGoogle Scholar
  21. 21.
    Friedman EA, Rao TKS (1983) Why does uremia in heroin abusers occur predominantly among blacks? JAMA 250:2965–2966PubMedCrossRefGoogle Scholar
  22. 22.
    Fundacion Centro de Estudio sobre Crecimiento y Desarrollo de la Poblacion Venezolana (1993). Ministerio Salud y Desarrollo Social, Republica Bolivariana de Venezuela. Available at: http://www.fundacredesa.org. Proyecto Venezuela (1981–1987), Division de Investigaciones Biológicas, Departamento de Auxología, Percentiles Ajustados por Spline Cubico
  23. 23.
    Galetto G, Morrow CT (1995) Noninfectious manifestations of human immunodeficiency virus infection. Emerg Med Clin North Am 13:105–131PubMedGoogle Scholar
  24. 24.
    Gerstoft J, Kirk O, Obel N, Pedersen C, Mathiesen L, Nielsen H, Katzenstein T, Lundgren J (2003) Low efficacy and high frequency of adverse events in a randomized trial of triple nucleoside regimen abacavir, stavudine and didanosine. AIDS 17:2045–2052PubMedCrossRefGoogle Scholar
  25. 25.
    Ghazali A, Fuentes V, Desaint C, Bataille P, Westeel A, Brazier M, Prin L, Fournier A (1997) Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria. J Clin Endocrinol Metab 82:32–38PubMedCrossRefGoogle Scholar
  26. 26.
    Hermieu J, Prevot M, Ravery V (1999) Urolithiasis and protease inhibitor indinavir. Eur Urol 35:239–241PubMedCrossRefGoogle Scholar
  27. 27.
    Humphreys MC (1995) Human immunodeficiency virus-associated glomerulosclerosis. Kidney Int 48:311–320PubMedCrossRefGoogle Scholar
  28. 28.
    Iwasaki I, Utsumi S, Ozawa T (1952) New colorimetric determination of chloride using mercuric thiocyanate and ferric ion. Bull Chem Soc Jpn 25:226CrossRefGoogle Scholar
  29. 29.
    Kruse K, Kracht U, Kruse U (1984) Reference values for urinary calcium excretion and screening for hypercalciuria in children and adolescents. Eur J Pediatr 143:25–31PubMedCrossRefGoogle Scholar
  30. 30.
    Laufer J, Boichis H (1989) Urolithiasis in children: current medical management. Pediatr Nephrol 3:317–331PubMedCrossRefGoogle Scholar
  31. 31.
    Liu X-H, Achim A, Xu L, Wellstein A, Ray PE (2001) Up-regulation of a fibroblast growth factor binding protein in children with renal diseases. Kidney Int 59:1850–1858PubMedCrossRefGoogle Scholar
  32. 32.
    Lopez MM, Castillo LA, Chavez JB, Ramones C (1999) Hypercalciuria and recurrent urinary tract infection in Venezuelan children. Pediatr Nephrol 13:433–437PubMedCrossRefGoogle Scholar
  33. 33.
    Meraviglia P, Angeli E, Del Sorbo F, Rombola G, Vigano P, Orlando G, Cordier l, Faggion I, Cargnel A (2002) Risk factors for indinavir-related renal colic HIV patients: predictive value of indinavir dose/body mass index. AIDS 16:2089–2093PubMedCrossRefGoogle Scholar
  34. 34.
    Moley G, Datta D, Mandalia S, Moriese J, Asboe D, Gazzard B (2002) Hyperlactataemia and lactic acidosis during antiretroviral therapy: prevalence, reproducibility and possible risk factors. AIDS 16:1341–1349CrossRefGoogle Scholar
  35. 35.
    Morin LG (1974) Direct colorimetric determination of serum calcium with o-cresolphthalein complexone. Am J Clin Pathol 61:114–117PubMedGoogle Scholar
  36. 36.
    Murphy JM, Griswold WR, Reznik VM, Mendoza SA (1999) TMP-SMZ-induced RTA. Child Nephrol Urol 10:49–50Google Scholar
  37. 37.
    Nadler RB, Rubenstein JN, Eggener SE, Loor MM, Smith ND (2003) The etiology of urolithiasis in HIV infected patients. J Urol 169:475–477PubMedCrossRefGoogle Scholar
  38. 38.
    Nochy D, Glotz D, Dosquet P, Pruna A, Lemoine R, Guettier C, Weiss L, Hinglais N, Idatte JM, Mery JP (1993) Renal lesions associated with human immunodeficiency virus infection (North America vs. European experience). Adv Nephrol Necker Hosp 22:269–286PubMedGoogle Scholar
  39. 39.
    Osorio AV, Alon US (1997) The relationship between urinary calcium, sodium, and potassium excretion and the role of potassium in treating idiopathic hypercalciuria. Pediatrics 100:675–681PubMedCrossRefGoogle Scholar
  40. 40.
    Pacifici R (1997) Idiopathic hypercalciuria and osteoporosis. Distint clinical manifestations of increased cytokine-induced bone resorption? J Clin Endocrinol Metab 82:29–31PubMedCrossRefGoogle Scholar
  41. 41.
    Palmieri GM, Pitcock JA (1995) Osteoporosis and hypercalciuria secondary to salt ingestion. J Lab Clin Med 126:503PubMedGoogle Scholar
  42. 42.
    Pardo V, Aldana M, Colton RM, Fischl MA, Jaffe D, Moskowitz L, Hensley T, Bourgoignie JJ (1984) Glomerular lesions in the acquired immunodeficiency syndrome. Ann Intern Med 101:429–434PubMedGoogle Scholar
  43. 43.
    Pardo V, Meneses R, Ossa L, Jaffe DJ, Strauss J, Roth D, Bourgoignie JJ (1987) AIDS-related glomerulopathy: occurrence in specific risk groups. Kidney Int 31:1167–1173PubMedCrossRefGoogle Scholar
  44. 44.
    Pardo V, Strauss J, Abitol C (1995) Renal disease in children with HIV infection, renal and urologic aspects of HIV Infection. Churchill Livingstone, New York, pp 135–153Google Scholar
  45. 45.
    Parekh DJ, Pope JC 4th, Adams MC, Brock JW 3rd (2002) The association of an increased urinary calcium-to-creatinine ratio, and asymptomatic gross and microscopic hematuria in children. J Urol 167:272–274PubMedCrossRefGoogle Scholar
  46. 46.
    Peyriere H, Reynes J, Rouanet I, Daniel N, de Boever CM, Mauboussin JM, Leary H, Moachon L, Vincent D, Salmon-Ceron D (2004). Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr 35:269–273PubMedCrossRefGoogle Scholar
  47. 47.
    Prencipe L, Fossati P, Vanzetti G (1978) Enzymatic determination of uric acid in serum with the Trider Reaction. Quad Sclavo Diagn 15:382–394PubMedGoogle Scholar
  48. 48.
    Rao TK, Filippone EJ, Nicastri AD, Landesman SH, Frank S, Chen CK, Friedman EA (1984) Associated focal and segmental glomerulosclerosis in acquired immunodeficiency syndrome. N Engl J Med 310:669–673PubMedCrossRefGoogle Scholar
  49. 49.
    Ray PE, Bruggeman L, Weeks B, Kopp J, Bryant J, Owens, Notkins A, Klotman PE (1994) Role of bFGF and its low affinity receptors in the pathogenesis of HIV-associated nephropathy in transgenic mice. Kidney Int 46:759–772PubMedCrossRefGoogle Scholar
  50. 50.
    Ray PE, Xu L, Rakusan T, Liu X-H (2004) A 20-year history of childhood HIV-associated nephropathy. Pediatr Nephrol 19:1075–1092PubMedCrossRefGoogle Scholar
  51. 51.
    Ray PE, Rakusan T, Loechelt BJ, Selby DM, Liu X-H, Chandra RS (1998) Human Immunodeficiency Virus (HIV)-Associated Nephropathy in children from the Washington, D.C. area: 12 years’ experience. Semin Nephrol 18:396–405PubMedGoogle Scholar
  52. 52.
    Santos F, García Nieto V (2001) Exploración basal de la función renal. In: Santos F, Garcia Nieto V (eds) Nefrología Pediátrica. Aula Medica SL, Madrid, pp 15–26Google Scholar
  53. 53.
    Sapan Ch, Lundblad R, Price N (1999) Review: colorimetric protein assay techniques. Biotechnol Appl Biochem 29:99–108PubMedGoogle Scholar
  54. 54.
    Schaffer RM, Schwartz GE, Becker JA, Rao TK, Shih YH (1984) Renal ultrasound in acquired immune deficiency syndrome. Radiology 153:511–513PubMedGoogle Scholar
  55. 55.
    Schiller D (2004) Identification, management, and prevention of adverse effects associated with HIV antiretroviral therapy. Am J Health-Syst Pharm 61:2507–2522PubMedGoogle Scholar
  56. 56.
    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 58:259–263PubMedGoogle Scholar
  57. 57.
    Seaton B, Ali A (1984) Simplified manual high performance clinical chemistry methods for developing countries. Med Lab Sci 41:327–336PubMedGoogle Scholar
  58. 58.
    Simpson D, Estanislao L Scott E, McArthur J, Marcus K, Truffa M, Lucey B, Naismith R, Lonergan J, Clifford D and the HIV neuromuscular syndrome study group (2004) HIV-associated neuromuscular weakness syndrome. AIDS 18:1403–1412CrossRefGoogle Scholar
  59. 59.
    Stapleton FB, Miller LA (1989) Renal function in children with idiopathic hypercalciuria. Pediatr Nephrol 2:229–235CrossRefGoogle Scholar
  60. 60.
    Strauss J, Abitol C, Zilleruelo G, Scott G, Paredes A, Malaga S, Montane B, Mitchell C, Parks W, Pardo V (1989) Renal disease in children with acquired immunodeficiency syndrome. N Engl J Med 321:625–630PubMedCrossRefGoogle Scholar
  61. 61.
    Talke H, Schubert GE (1965) Enzymatische harnstoffbestimmung in blut und serem in optischen test nach warburg. Klin Wochenschr 41:174–178CrossRefGoogle Scholar
  62. 62.
    Tolaymat A, al-Mousily F, Sleasman J, Paryani S, Neiberger R (1995) Hyponatremia in pediatric patients with HIV-1 infection. South Med J 88:1039–1042PubMedGoogle Scholar
  63. 63.
    van Rossum AMC, Dieleman JP, Fraaji PLA, Cransberg K, Harwig NG, Burger DM, Gyssens IC, de Groot R (2002) Persistent sterile leukocyturia is associated with impaired renal function in Human Immunodeficiency Virus type 1-infected children treated with indinavir. Pediatrics 1101–7CrossRefGoogle Scholar
  64. 64.
    van Rossum A, Dieleman JP, Fraaij P, Cransberg K, Hartwig NG, Gyssens IG, de Groot R (2001) Indinavir-associated asymptomatic nephrolithiasis and renal cortex atrophy in two HIV-1 infected children. AIDS 15:1745–1747PubMedCrossRefGoogle Scholar
  65. 65.
    Waterlow JC (1972) Classification and definition of protein calorie malnutrition. Br Med J 3:566–569PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Corina Gonzalez
    • 1
  • G. Ariceta
    • 2
    • 3
  • C. B. Langman
    • 2
  • P. Zibaoui
    • 1
  • L. Escalona
    • 1
  • L. F. Dominguez
    • 1
  • M. A. Rosas
    • 1
  1. 1.Departments of Pediatric Infectology and Pediatric Nephrology, Hospital Doctor Enrique TejeraUniversity of CaraboboValenciaVenezuela
  2. 2.Division of Kidney Diseases, Children’s Memorial Hospital, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  3. 3.Children’s Memorial Hospital, Division of Kidney DiseasesChicagoUSA

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