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.
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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 10:598–601
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 19:808–811
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 318:594–599
Bhandari A, Menon M (2004). Reducing the risk of kidney stone recurrence. Patient Care 38:26–32
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 46:716–723
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–F254
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 18:131–134
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):1–38
Chakraborty R, Uy CS, Oleske JM, Coen PG, McSherry GD (2003) Persistent non-gastrointestinal metabolic acidosis in pediatric HIV-1 infection. AIDS 17: 673–677
Coe FL (1977) Treated and untreated recurrent calcium nephrolithiasis in patients with idiopathic hypercalciuria, hyperuricosuria or no metabolic disorder. Ann Intern Med 87:404–410
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 155–167
D’Agati V, Appel GB (1998) Renal pathology in human immunodeficiency virus infection. Semin Nephrol 18:406–421
D’Agati V, Appel GB (1997) HIV infection and the kidney. J Am Soc Nephrol 18:138–152
Daly J, Ertingshausen G (1972) Direct method for determining inorganic phosphate in serum with the “Centrifichem”. Clin Chemistry 18:263–265
Detwiler RK, Falk RJ, Hogan SL, Jennette JC (1994) Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 45:1416–1424
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 32:135–142
Domachowske JB (1996) Pediatric human immunodeficiency virus infection. Clin Microbiol Rev 9:448–468
Doran TI, Jenson HB (1996) Acquired immunodeficiency syndrome (AIDS). In: Pediatrics infection diseases: principles and practice. Appleton and Lange, Norwalk, pp 577–627
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 19:714–721
Engeler DS, John H, Rentsch KM, Ruef C, Oertle D, Suter S (2002) Nelfinavir urinary stones. J Urol 167:1384–1385
Friedman EA, Rao TKS (1983) Why does uremia in heroin abusers occur predominantly among blacks? JAMA 250:2965–2966
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
Galetto G, Morrow CT (1995) Noninfectious manifestations of human immunodeficiency virus infection. Emerg Med Clin North Am 13:105–131
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 17:2045–2052
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 82:32–38
Hermieu J, Prevot M, Ravery V (1999) Urolithiasis and protease inhibitor indinavir. Eur Urol 35:239–241
Humphreys MC (1995) Human immunodeficiency virus-associated glomerulosclerosis. Kidney Int 48:311–320
Iwasaki I, Utsumi S, Ozawa T (1952) New colorimetric determination of chloride using mercuric thiocyanate and ferric ion. Bull Chem Soc Jpn 25:226
Kruse K, Kracht U, Kruse U (1984) Reference values for urinary calcium excretion and screening for hypercalciuria in children and adolescents. Eur J Pediatr 143:25–31
Laufer J, Boichis H (1989) Urolithiasis in children: current medical management. Pediatr Nephrol 3:317–331
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 59:1850–1858
Lopez MM, Castillo LA, Chavez JB, Ramones C (1999) Hypercalciuria and recurrent urinary tract infection in Venezuelan children. Pediatr Nephrol 13:433–437
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 16:2089–2093
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 16:1341–1349
Morin LG (1974) Direct colorimetric determination of serum calcium with o-cresolphthalein complexone. Am J Clin Pathol 61:114–117
Murphy JM, Griswold WR, Reznik VM, Mendoza SA (1999) TMP-SMZ-induced RTA. Child Nephrol Urol 10:49–50
Nadler RB, Rubenstein JN, Eggener SE, Loor MM, Smith ND (2003) The etiology of urolithiasis in HIV infected patients. J Urol 169:475–477
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 22:269–286
Osorio AV, Alon US (1997) The relationship between urinary calcium, sodium, and potassium excretion and the role of potassium in treating idiopathic hypercalciuria. Pediatrics 100:675–681
Pacifici R (1997) Idiopathic hypercalciuria and osteoporosis. Distint clinical manifestations of increased cytokine-induced bone resorption? J Clin Endocrinol Metab 82:29–31
Palmieri GM, Pitcock JA (1995) Osteoporosis and hypercalciuria secondary to salt ingestion. J Lab Clin Med 126:503
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 101:429–434
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 31:1167–1173
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 135–153
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 167:272–274
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 35:269–273
Prencipe L, Fossati P, Vanzetti G (1978) Enzymatic determination of uric acid in serum with the Trider Reaction. Quad Sclavo Diagn 15:382–394
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 310:669–673
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 46:759–772
Ray PE, Xu L, Rakusan T, Liu X-H (2004) A 20-year history of childhood HIV-associated nephropathy. Pediatr Nephrol 19:1075–1092
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 18:396–405
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 15–26
Sapan Ch, Lundblad R, Price N (1999) Review: colorimetric protein assay techniques. Biotechnol Appl Biochem 29:99–108
Schaffer RM, Schwartz GE, Becker JA, Rao TK, Shih YH (1984) Renal ultrasound in acquired immune deficiency syndrome. Radiology 153:511–513
Schiller D (2004) Identification, management, and prevention of adverse effects associated with HIV antiretroviral therapy. Am J Health-Syst Pharm 61:2507–2522
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
Seaton B, Ali A (1984) Simplified manual high performance clinical chemistry methods for developing countries. Med Lab Sci 41:327–336
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 18:1403–1412
Stapleton FB, Miller LA (1989) Renal function in children with idiopathic hypercalciuria. Pediatr Nephrol 2:229–235
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 321:625–630
Talke H, Schubert GE (1965) Enzymatische harnstoffbestimmung in blut und serem in optischen test nach warburg. Klin Wochenschr 41:174–178
Tolaymat A, al-Mousily F, Sleasman J, Paryani S, Neiberger R (1995) Hyponatremia in pediatric patients with HIV-1 infection. South Med J 88:1039–1042
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 1101–7
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 15:1745–1747
Waterlow JC (1972) Classification and definition of protein calorie malnutrition. Br Med J 3:566–569
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Gonzalez, C., Ariceta, G., Langman, C.B. et al. Hypercalciuria is the main renal abnormality finding in Human Immunodeficiency Virus-infected children in Venezuela. Eur J Pediatr 167, 509–515 (2008). https://doi.org/10.1007/s00431-007-0538-4
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DOI: https://doi.org/10.1007/s00431-007-0538-4