Hematuria in the practice of a pediatric nephrologist: possible role of herpesvirus infection
F.I. RUSNAK, O.G. PAVLOVA
Domodedovo Central City Hospital, Domodedovo
Contact details:
Rusnak F.I. — MD, Professor, Head of the Consulting and Diagnostic Center
Address: 36A Kashirskoye shosse, Domodedovo, Russian Federation, 142005, tel.: +7 (496)-793-52-03, e-mail: fedor_rusnak@mail.ru
The purpose — to study the frequency of detection in the blood of antibodies to EBV, CMV and herpes type 6 among children turning to the outpatient unit for tubulointerstitial nephritis manifested by hematuria.
Material and methods. In the period from July 2018 to July 2019, 2183 patients, including 68 children with hematuria, turned to a nephrologist. Calcium excretion was assessed by the ratio of calcium/creatinine in daily urine. Blood levels of IgA, C3 and C4 complement fractions were determined in children with hematuria lasting more than 2 months. Only the level of antibodies in the blood to IgG(Nuclear Antigen) — CMV and EBV, as well as IgG antibodies to herpes type 6, was investigated by IFA.
Results. The frequency of children with hematuria was 3,1% (68 children). According to the number of red blood cells in the urine, microhematuria was detected in 50 children (73,5%), moderate hematuria — in 7 children (10,3%), severe hematuria — in 11 children (16,2%). Proteinuria was detected in 11 children (16,1%) and averaged 276 (47) mg/day. Calcium/creatinine ratio above 0,7 was detected only in 3 children (4,4%), indicating the presence of hypercalciuria. The level of IgA and Cȝ and C4 complement fractions in the blood was studied in 48 children (70,6%) with hematuria for more than 2 months: the majority of children (40 children, 83,3%) had normal indicators. The majority of children (66 children, 97,1%) had an increased level of antibodies in the blood to herpesvirus infection with a predominance of EBV infection in 70,5% of cases. CMV was detected in 32 children (47,1%). Herpes virus type 6 alone or in combination with other viruses in 30,9% of cases can be manifested as tubulointerstitial nephritis with hematuria.
Conclusion. Hematuria, accompanied in 19,1% of cases with long-term subfebrility, may be due to the development of postviraltubulointerstitial nephritis, due to the persistence and periodic reactivation of CMV, EBV or herpes type 6 viral infection. Tubulointestitial nephritis, manifested in most cases by wave-like microhematuria, has a possible herpesviral etiology and may be the initial manifestation of IgA nephropathy. These children should be observed to exclude progression and further development of chronic kidney disease.
Key words: tubulointerstitial nephritis, IgA nephropathy, Epstein-Barr virus, cytomegalovirus, herpes virus type 6, hematuria, calciuria, IgA, complement fractions C3 and C4.
(For citation: Rusnak F.I., Pavlova O.G. Hematuria in the practice of a pediatric nephrologist: possible role of herpesvirus infection. Practical Medicine. 2019. Vol. 17, № 5, P. 195-199)
REFERENCES
- Murakami M., Yamamoto H., Ueda Y. et al Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo. Pediatr Nephrol, 1991, vol. 5, pp. 50–53.
- Zainal D., , Mustaffa B.E. Screening proteinuria and hematuria in Malaysian children. Southeast Asian J. Trop Med Public Health, 1995, vol. 26, pp. 785–788.
- Yap H.K., Quek C.M., Shen O. et al. Role of urinary screening programmes in children in the prevention of chronic kidney diseases. Ann Acad Med Singapore, 2005, vol. 34, pp. 3–7.
- Lin C.Y., Hsiech C.C., Chen W.P. et al. The underlying diseases and follow-ap in Taiwanese Children sceening byurinanalisis. Pediatr Nephrol, 2001, vol. 16, pp. 232–237.
- Cho B.S., Kim S.D., Choi Y.M. et al. School urinanalysis screening in Korea: prevalence of chronic renal disease. Pediatr Nephrol, 2001, vol. 16, pp. 1126–1128.
- Yap H-K., Lau Y.W. Hematuria and proteinuria. Comprehensive Pediatric Nephrology, D.F. Geary, F. Schaefer. Mosby, 2008. Pp. 179–193.
- Papayan A.V., Savenkova N.D. Klinicheskaya nefrologiya detskogo vozrasta [Clinical nephrology of childhood]. Saint Petersburg: Levsha, 2008. 599 p.
- Dlin V.V., Ignatova M.S. Nefropatii s sindromom gematurii u detey [Nephropathy with hematuria syndrome in children]. Moscow: Overley, 2016. 119 p.
- Safina A.I., Mal’tsev S.V., Makarova T.P. New data on kidney diseases in children. Mediko-farmatsevticheskiy vestnik Tatarstana, 2004, no. 43 (175), p. 9 (in Russ.).
- Sumi T. Epstein-Barr virus infections in children. Curr Probl Pediatr, 1987, vol. 17, pp. 677–745.
- Schuster V., Kreth H.W. Epstein-Barr virus infection and associated disease in children. Pathogenesis, epidemiology and clinical aspects. Eur J Pediatr, 1992, vol. 151, pp. 718–725.
- Norwood V.F., Strugill D. Unexplained acute renal failure in a toddler: a rare complication of Epstein-Barr virus. Nephrol, 2002, vol. 17, pp. 628–632.
- Mayer H.B., Wanke C.A., Williams M. et al. Epstein-Barr virus-induced infectious mononucleosis complicated by acute renal failure: case report and review. Clin Infect Dis, 1996, vol. 22, p. 1018.
- Sumi T. Epstein-Barr virus infections in children. Curr Probl Pediatr, 1987, vol. 17, pp. 677–745.
- Schwarz A., Krause P.H., Kunzendorf U. et al. The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis. Clin Nephrol, 2000, vol. 54, pp. 179–190.
- Matsukura H., Itoh Y., Kanegane H. et al. Acute tubulointerstitial nephritis: possible association with cytomegalovirus infection. Pediatr Nephrol, 2006, vol. 21, pp. 442–443.
- Kaminska A., Roszkowska-Blaim M., Weglarska J. et al. Rare causes of interstitial nephritis in two children. Wiad Lek, 2005, vol. 1, pp. 93–97.
- Birk P.E., Chavers B.M. Does cytomegalovirus cause glomerular injury in renal allograft recipients? J Am Soc Nephrol, 1997, vol. 8, pp. 1801–1808.
- Cameron J., Rigby R.J., van Deth A.G., Petrie J.J. Severe tubulo-interstitial disease in a renal allograft due to cytomegalovirus infection. Clin Nephrol, 1982, vol. 18, pp. 321–325.
- Shaver M.J., Bonsib S.M., Abul-Ezz S., Barri Y.M. Renal allograft dysfunction associated with cytomegalovirus infection. Am J Kidney Dis, 1999, vol. 34, pp. 942–946.
- Wenderfer S.E. Viral-associated glomerulopathies in children. Pediatr Nephrol, 2015, vol. 30, pp. 1929–1938.
- Schwarz A., Krause P.H., Kunzendorf U. et al. The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis. Clin Nephrol, 2000, vol. 54, pp. 179–190.
- Tanaka H., Suzuki K., Nakahata T., Waga S. Long-term outcome of acute tubulointerstitial nephritis: report of a case. Clin Nephrol, 2003, vol. 59, pp. 65–67.
- Spivacow F.R., del Valle E.E., Rey P.G. Metabolic risk factors in children with asymptomatic hematuria. Pediatr Nephrol, 2016, vol. 31, pp. 1101–1106.
- Vehaskari V.M., Rapola J., Koskimies O., Savilahti E., Vilska J., Hallman N. Microscopic hematuria in school children: epidemiology and clinicopathologic evaluation. J Pediatr, 1979, vol. 95, pp. 676–684.
- Dodge W.F., West E.F., Smith E.H., Bunce H. Proteinuria and hematuriain school children: epidemiology and early natural history. J Pediatr, 1976, vol. 88, pp. 327–347.
- Park Y.H., Choi J.C., Chung H.S.et al. Hematuria and proteinuria in a mass school urine screening test. Pediatr Nephrol, 2005, vol. 20, pp. 1126–1130.
- Shaw N.J., Weeldon J., Brocklehurst J.T. Indices of intact serum parathyroid hormone and renal excretion of calcium, phosphate and magnesium. Arch Dis Child, 1990, vol. 65, pp. 1208–1212.
- Alon U.S. Pediatric Tubulointerstitial Nephritis. E.D. Avner et al. (eds.). Pediatric Nephrology-Springer-Verlag, 2016. Pp. 1407–1428.
- Koukourgianni F., Pichaut V., Liutkus A. et.al. HIV 6 infection in a pediatric kidney transplant patients. Pediatric Nephrol, 2009, vol. 24, p. 2445.