Skip to main content

Advertisement

SpringerLink
Log in

Tubular dysfunction in extremely low birth weight survivors

  • Original article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

Extremely low birth weight (ELBW) survivors may develop glomerulosclerosis due to low nephron number, whereas their tubular function remains unknown except for hypercalciuria and phosphaturia.

Methods

Fifty-three subjects (30 boys and 23 girls, aged 7 months-19 years, median 36 months) were studied retrospectively. The median gestational age and birth weight were 26 weeks (range 22–32) and 745 g (range 316–999), respectively. Urine calcium-to-creatinine ratio (Ca/Cr), N-acetyl-β-d-glucosaminidase-to-creatinine ratio (NAG/Cr), β2 microglobulin-to-creatinine ratio (β2m/Cr), uric acid-to-creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin-to-creatinine ratio (malb/Cr) were examined. We also assessed the association between urine parameters and current age, gestational age, birth weight, and predictors of renal injury. Follow-up data were analyzed in 43 subjects 4–6 years later.

Results

Ninety percent of subjects had at least one tubular dysfunction. Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, β2m/Cr 38.2%, malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr, suggesting tubular function maturation. Urine β2M/Cr and glu/Cr were negatively correlated with the gestational age. There were significant associations between elevated glu/Cr and asphyxia or neonatal acute kidney injury, and elevated NAG/Cr and indomethacin use, although these were not confirmed by multivariate analysis. At follow-up, the frequency of elevated NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr, IgG/Cr, and β2m/Cr remained similar or increased.

Conclusion

Tubular dysfunction is common in ELBW survivors. Some abnormalities resolved with age while some remained persistent or even increased.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ELBW:

Extremely low birth weight

Ca:

Calcium

Cr:

Creatinine

NAG:

N-acetyl-β-d-glucosaminidase

β2m:

β2 microglobulin

UA:

Uric acid

glu:

Glucose

malb:

Microalbumin

LBW:

Low birth weight

IUGR:

Intrauterine growth restriction

AKI:

Acute renal injury

CLD:

Chronic lung disease

MBD:

Mineral bone disorder

SCr:

Serum creatinine

eGFR:

Estimated glomerular filtration rate

References

  1. Kwinta P, Klimek M, Drozdz D, et al. Assessment of long-term renal complications in extremely low birth weight children. Pediatr Nephrol. 2011;26:1095–103.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bacchetta J, Harambat J, Dubourg L, et al. Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int. 2009;76:445–52.

    Article  PubMed  Google Scholar 

  3. Starzec K, Klimek M, Grudzien A, et al. Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age. Pediatr Nephrol. 2016;31:2119–26.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rodriguez-Soriano J, Aguirre M, Oliveros R, et al. Long-term renal follow-up of extremely low birth weight infants. Pediatr Nephrol. 2005;20:579–84.

    Article  PubMed  Google Scholar 

  5. Clark PM, Bryant TN, Hall MA, et al. Neonatal renal function assessment. Arch Dis Child. 1989;64:1264–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Tsukahara H, Yoshimoto M, Saito M, et al. Assessment of tubular function in neonates using urinary beta 2-microglobulin. Pediatr Nephrol. 1990;4:512–4.

    Article  PubMed  CAS  Google Scholar 

  7. Tsukahara H, Hori C, Tsuchida S, et al. Urinary N-acetyl-β-d-glucosaminidase excretion in term and preterm neonates. J Paediatr Child Health. 1994;30:536–8.

    Article  PubMed  CAS  Google Scholar 

  8. Wilkins BH. Renal function in sick very low birthweight infants: 4. Glucose excretion. Arch Dis Child. 1992;67:1162–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Keijzer-Veen MG, Schrevel M, Finken MJ, et al. Microalbuminuria and lower glomerular filtration rate at young adult age in subjects born very premature and after intrauterine growth retardation. J Am Soc Nephrol. 2005;16:2762–8.

    Article  PubMed  CAS  Google Scholar 

  10. Russo LM, Sandoval RM, Campos SB, et al. Impaired tubular uptake explains albuminuria in early diabetic nephropathy. J Am Soc Nephrol. 2009;20:489–94.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Comper WD, Hilliard LM, Nikolic-Paterson DJ, et al. Disease-dependent mechanisms of albuminuria. Am J Physiol Renal Physiol. 2008;295:F1589-600.

    Article  PubMed  CAS  Google Scholar 

  12. Hoppe B, Leumann E, Milliner DSM. Urolithiasis and nephrocalcinosis in childhood. In: Geary DF, Schaefer F, editors. Comprehensive pediatric nephrology. Maryland Heights: Mosby Elsevier; 2008. pp. 499–525.

    Chapter  Google Scholar 

  13. Speeckaert M, SDelanghe J. Assessment of renal function. In: Turner N, Lamerie N, Goldsmith DJ, et al., editors. Oxford textbook of clinical nephrology. Oxford: Oxford University Press; 2016. pp. 61–66.

    Google Scholar 

  14. Ikeda A, Konta T, Takasaki S, et al. In a non-diabetic Japanese population, the combination of macroalbuminuria and increased urine β2-microglobulin predicts a decline of renal function: the Takahata study. Nephrol Dial Transpl. 2009;24:841–7.

    Article  CAS  Google Scholar 

  15. Hogg RJ, Portman RJ, Milliner D, et al. Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics. 2000;105:1242–9.

    Article  PubMed  CAS  Google Scholar 

  16. Poyrazoglu HM, Dusunsel R, Yazici C, et al. Urinary uric acid: creatinine ratios in healthy Turkish children. Pediatr Int. 2009;51:526–9.

    Article  PubMed  CAS  Google Scholar 

  17. Aoshima K. Epidemiology of renal tubular dysfunction in the inhabitants of a cadmium-polluted area in the Jinzu River basin in Toyama Prefecture. Tohoku J Exp Med. 1987;152:151–72.

    Article  PubMed  CAS  Google Scholar 

  18. Nakano M, Aoshima K, Katoh T, et al. Elevation of urinary trehalase activity in patients of itai–itai disease. Arch Toxicol. 1987;60:300–3.

    Article  PubMed  CAS  Google Scholar 

  19. Uemura O, Nagai T, Ishikura K, et al. Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol. 2014;18:626–33.

    Article  PubMed  CAS  Google Scholar 

  20. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    Article  PubMed  CAS  Google Scholar 

  21. Hibi Y, Uemura O, Nagai T, et al. The ratios of urinary β2-microglobulin and NAG to creatinine vary with age in children. Pediatr Int. 2015;57:79–84.

    Article  PubMed  CAS  Google Scholar 

  22. Nishida M, Kawakatsu H, Komatsu H, et al. Values for urinary β2-microglobulin and N-acetyl-beta-d-glucosaminidase in normal healthy infants. Acta Paediatr Jpn. 1998;40:424–6.

    Article  PubMed  CAS  Google Scholar 

  23. Muzi-Filho H, Souza AM, Bezerra CG, et al. Rats undernourished in utero have altered Ca2+ signaling and reduced fertility in adulthood. Physiol Rep. 2015;3(10):3/10/e12587.

    Article  CAS  Google Scholar 

  24. Stiburkova B, Bleyer AJ. Changes in serum urate and urate excretion with age. Adv Chronic Kidney Dis. 2012;19:372–6.

    Article  PubMed  Google Scholar 

  25. Wilcox WD. Abnormal serum uric acid levels in children. J Pediatr. 1996;128:731–41.

    Article  PubMed  CAS  Google Scholar 

  26. Prieur B, Cordeau-Lossouarn L, Rotig A, et al. Perinatal maturation of rat kidney mitochondria. Biochem J. 1995;305:675–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Ashton N, Al-Wasil SH, Bond H, et al. The effect of a low-protein diet in pregnancy on offspring renal calcium handling. Am J Physiol Regul Integr Comp Physiol. 2007;293:R759–65.

    Article  PubMed  CAS  Google Scholar 

  28. Ribel-Madsen A, Ribel-Madsen R, Brons C, et al. Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men. Physiol Rep. 2016;4(19):4/19/e12977.

    Article  CAS  Google Scholar 

  29. Vasarhelyi B, Dobos M, Reusz GS, et al. Normal kidney function and elevated natriuresis in young men born with low birth weight. Pediatr Nephrol. 2000;15:96–100.

    Article  PubMed  CAS  Google Scholar 

  30. Awazu M, Arai M, Ohashi S, et al. Tubular dysfunction mimicking Dent’s disease in 2 infants born with extremely low birth weight. Case Rep Nephrol Dial. 2017;7:13–7.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pallet N, Chauvet S, Chasse JF, et al. Urinary retinol binding protein is a marker of the extent of interstitial kidney fibrosis. PLoS One. 2014;9:e84708.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Nauta FL, Scheven L, Meijer E, et al. Glomerular and tubular damage markers in individuals with progressive albuminuria. Clin J Am Soc Nephrol. 2013;8:1106–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Kazuya Matsumura, Yohei Matsuzaki, Mariko Hida, Kazushige Ikeda & Midori Awazu

  2. Department of Pediatrics, Hiratsuka City Hospital, Kanagawa, Japan

    Kazuya Matsumura

  3. Department of Neonatology, Yokohama Rosai Hospital, Kanagawa, Japan

    Mariko Hida

Authors
  1. Kazuya Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yohei Matsuzaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariko Hida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazushige Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Midori Awazu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Midori Awazu.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national ethical guidelines for medical and health research involving human subjects and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was not obtained but the option of opting out was provided as approved by the ethics committee at Keio University School of Medicine.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsumura, K., Matsuzaki, Y., Hida, M. et al. Tubular dysfunction in extremely low birth weight survivors. Clin Exp Nephrol 23, 395–401 (2019). https://doi.org/10.1007/s10157-018-1645-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-018-1645-4

Keywords

Search

Navigation