Urinary Cystatin-C, a marker to assess and monitor neonatal kidney maturation and function: validation in twins.


Journal

Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714

Informations de publication

Date de publication:
03 2021
Historique:
received: 19 11 2019
accepted: 29 04 2020
revised: 14 04 2020
pubmed: 19 5 2020
medline: 15 1 2022
entrez: 19 5 2020
Statut: ppublish

Résumé

Nephrogenesis is a complex process of nephron formation and maturation that can be compromised by preterm delivery and intrauterine growth restriction. This study aimed to evaluate and compare urinary Cys-C levels with renal volume in a cohort of preterm and term twins, adequate for gestational age or intrauterine growth restricted, to investigate their values in different conditions of nephrogenesis. The study was performed on twins at 30-40 days of postnatal corrected age: renal volumes were measured by 3D ultrasound technology and urine samples were analyzed for Cystatin-C. A follow-up was performed by Cystatin-C. Renal volumes in preterm and intrauterine growth-restricted twins showed values significantly lower than those observed in term twins and were inversely correlated to urinary Cystatin-C levels. During the follow-up, intrauterine growth-restricted twins showed amplified levels of urinary Cystatin-C; in contrast, invariable or decreased levels were observed in adequate for gestational age twins. Urinary Cystatin-C, evaluated when intrauterine/extrauterine nephrogenesis could be considered completed, concurrently with renal volume assessment can improve the identification of neonates with initial kidney impairment. Its potential value as a useful marker in monitoring physiological/pathological renal conditions could be considered, mainly for neonates at elevated risk of developing long-term renal diseases. Urinary Cys-C levels are inversely correlated to renal volumes and reflect nephrogenesis conditions. No data in literature are reported regarding: (a) the concurrent assessment of renal volumes and urinary levels of Cystatin-C in preterm and term twins with different conditions of gestational life, i.e., AGA and IUGR and (b) the follow-up of IUGR and preterm neonates using the urinary Cys-C determination. The variations of urinary Cys-C levels, observed in the follow-up of preterm and/or IUGR neonates, support the usefulness of monitoring those neonates with altered nephrogenesis, who are later at risk for renal impairment and for long-term renal diseases.

Sections du résumé

BACKGROUND
Nephrogenesis is a complex process of nephron formation and maturation that can be compromised by preterm delivery and intrauterine growth restriction. This study aimed to evaluate and compare urinary Cys-C levels with renal volume in a cohort of preterm and term twins, adequate for gestational age or intrauterine growth restricted, to investigate their values in different conditions of nephrogenesis.
METHODS
The study was performed on twins at 30-40 days of postnatal corrected age: renal volumes were measured by 3D ultrasound technology and urine samples were analyzed for Cystatin-C. A follow-up was performed by Cystatin-C.
RESULTS
Renal volumes in preterm and intrauterine growth-restricted twins showed values significantly lower than those observed in term twins and were inversely correlated to urinary Cystatin-C levels. During the follow-up, intrauterine growth-restricted twins showed amplified levels of urinary Cystatin-C; in contrast, invariable or decreased levels were observed in adequate for gestational age twins.
CONCLUSIONS
Urinary Cystatin-C, evaluated when intrauterine/extrauterine nephrogenesis could be considered completed, concurrently with renal volume assessment can improve the identification of neonates with initial kidney impairment. Its potential value as a useful marker in monitoring physiological/pathological renal conditions could be considered, mainly for neonates at elevated risk of developing long-term renal diseases.
IMPACT
Urinary Cys-C levels are inversely correlated to renal volumes and reflect nephrogenesis conditions. No data in literature are reported regarding: (a) the concurrent assessment of renal volumes and urinary levels of Cystatin-C in preterm and term twins with different conditions of gestational life, i.e., AGA and IUGR and (b) the follow-up of IUGR and preterm neonates using the urinary Cys-C determination. The variations of urinary Cys-C levels, observed in the follow-up of preterm and/or IUGR neonates, support the usefulness of monitoring those neonates with altered nephrogenesis, who are later at risk for renal impairment and for long-term renal diseases.

Identifiants

pubmed: 32422644
doi: 10.1038/s41390-020-0965-8
pii: 10.1038/s41390-020-0965-8
doi:

Substances chimiques

Biomarkers 0
Cystatin C 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Twin Study Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

932-939

Références

Charlton, J. R., Springsteen, C. H. & Carmody, J. B. Nephron number and its determinants in early life: a primer. Pediatr. Nephrol. 29, 2299–2308 (2014).
pubmed: 24488483
Merlet-Bénichou, C. et al. Nephron number: variability is the rule. Causes and consequences. Lab. Invest. 79, 515–527 (1999).
pubmed: 10334563
Black, M. J. et al. When birth comes early: effects on nephrogenesis. Nephrology 18, 180–182 (2013).
pubmed: 23279726
Saint-Faust, M., Boubred, F. & Simeoni, U. Renal development and neonatal adaptation. Am. J. Perinatol. 31, 773–780 (2014).
pubmed: 24623338
Sutherland, M. R. et al. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J. Am. Soc. Nephrol. 22, 1365–1374 (2011).
pubmed: 21636639 pmcid: 3137584
Bacchetta, J. et al. Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int. 76, 445–452 (2009).
pubmed: 19516242
Stritzke, A., Thomas, S., Amin, H., Fusch, C. & Lodha, A. Renal consequences of preterm birth. Mol. Cell. Pediatr. 4, 2 (2017).
pubmed: 28101838 pmcid: 5243236
Zaffanello, M. et al. Renal function and volume of infants born with a very low birth-weight: a preliminary cross-sectional study. Acta Paediatr. 99, 1192–1198 (2010).
pubmed: 20337778
Fox, N. S., Rebarber, A., Klauser, C. K., Roman, A. S. & Saltzman, D. H. Intrauterine growth restriction in twin pregnancies: incidence and associated risk factors. Am. J. Perinatol. 28, 267–272 (2011).
pubmed: 21128199
Townsend, R. & Khalil, A. Fetal growth restriction in twins. Best. Pract. Res. Clin. Obstet. Gynaecol. 49, 79–88 (2018).
pubmed: 29661565
Cleper, R. Mechanisms of compensatory renal growth. Pediatr. Endocrinol. Rev. 10, 152–163 (2012).
pubmed: 23469392
Rodríguez, M. M. et al. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr. Dev. Pathol. 7, 17–25 (2004).
pubmed: 15255031
Hughson, M., Farris, A. B., Douglas-Denton, R., Hoy, W. E. & Bertram, J. F. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int. 63, 2113–2122 (2003).
pubmed: 12753298
Mañalich, R., Reyes, L., Herrera, M., Melendi, C. & Fundora, I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 58, 770–773 (2000).
pubmed: 10916101
Gubhaju, L., Sutherland, M. R. & Black, M. J. Preterm birth and the kidney: implications for long-term renal health. Reprod. Sci. 18, 322–333 (2011).
pubmed: 21427457
Sutherland, M., Ryan, D., Black, M. J. & Kent, A. L. Long-term renal consequences of preterm birth. Clin. Perinatol. 41, 561–573 (2014).
pubmed: 25155727
Zohdi, V. et al. Low birth weight due to intrauterine growth restriction and/or preterm birth: effects on nephron number and long-term renal health. Int. J. Nephrol. 2012, 136942 (2012).
Starzec, K., Klimek, M., Grudzień, A., Jagła, M. & Kwinta, P. Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age. Pediatr. Nephrol. 3, 2119–2126 (2016).
van Vuuren, S. H. et al. Size and volume charts of fetal kidney, renal pelvis and adrenal gland. Ultrasound Obstet. Gynecol. 40, 659–664 (2012).
pubmed: 22581671
Vujic, A. et al. Sonographic assessment of normal kidney dimensions in the first year of life-a study of 992 healthy infants. Pediatr. Nephrol. 22, 1143–1150 (2007).
pubmed: 17401585
Erdemir, A. et al. Reference ranges for sonographic renal dimensions in preterm infants. Pediatr. Radiol. 43, 1475–1484 (2013).
pubmed: 23917587
Lim, Y.-J. et al. Ultrasonographic study of initial size and postnatal growth of kidneys in preterm infants. Neonatology 106, 107–113 (2014).
pubmed: 24852124
Gubhaju, L. et al. Assessment of renal functional maturation and injury in preterm neonates during the first month of life. Am. J. Physiol. Ren. Physiol. 307, 149–158 (2014).
Barbati, A. et al. Increased urinary cystatin-C levels correlate with reduced renal volumes in neonates with intrauterine growth restriction. Neonatology 109, 154–160 (2016).
pubmed: 26756983
Saeidi, B. et al. Impact of gestational age, sex, and postnatal age on urine biomarkers in premature neonates. Pediatr. Nephrol. 30, 2037–2044 (2015).
pubmed: 26001700 pmcid: 4581905
DeFreitas, M. J. et al. Longitudinal patterns of urine biomarkers in infants across gestational ages. Pediatr. Nephrol. 31, 1179–1188 (2016).
pubmed: 26862052
Hanna, M. et al. Early urinary biomarkers of acute kidney injury in preterm infants. Pediatr. Res. 80, 218–223 (2016).
pubmed: 27055185
Askenazi, D. J. et al. Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatr. Res. 70, 302–306 (2011).
pubmed: 21646940 pmcid: 3152663
Aisa, M. C. et al. Biochemical parameters of renal impairment/injury and surrogate markers of nephron number in intrauterine growth-restricted and preterm neonates at 30-40 days of postnatal corrected age. Pediatr. Nephrol. 31, 2277–2287 (2016).
pubmed: 27557556
Askenazi, D. J. et al. Urine biomarkers predict acute kidney injury in newborns. J. Pediatr. 161, 270–275 (2012).
pubmed: 22424940 pmcid: 3598122
Conti, M. et al. Urinary cystatin C as a specific marker of tubular dysfunction. Clin. Chem. Lab. Med. 44, 288–291 (2006).
pubmed: 16519600
Herget-Rosenthal, S., van Wijk, J. A. E., Bröcker-Preuss, M. & Bökenkamp, A. Increased urinary cystatin C reflects structural and functional renal tubular impairment independent of glomerular filtration rate. Clin. Biochem. 40, 946–951 (2007).
pubmed: 17537416
Koyner, J. L. et al. Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury. Clin. J. Am. Soc. Nephrol. 5, 2154–2165 (2010).
pubmed: 20798258 pmcid: 2994075
Shivkumar, S., Himes, K. P., Hutcheon, J. A. & Platt, R. W. An ultrasound-based fetal weight reference for twins. Am. J. Obstet. Gynecol. 213, 224.e1-9 (2015).
pubmed: 25899626
Abitbol, C. L. et al. Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate? J. Pediatr. 164, 1026.e2–1031.e2 (2014).
Tsuboi, N. et al. Clinicopathological assessment of the nephron number. Clin. Kidney 7, 107–114 (2014).
Stapleton, F. B., Jones, D. P. & Green, R. S. Acute renal failure in neonates: incidence, etiology and outcome. Pediatr. Nephrol. 1, 314–320 (1987).
pubmed: 3153295
Tsukahara, H. et al. Assessment of tubular function in neonates using urinary beta 2-microglobulin. Pediatr. Nephrol. 4, 512–514 (1990).
pubmed: 2242319
Awad, H., El-Safty, I., El-Barbary, M. & Imam, S. Evaluation of renal glomerular and tubular functional and structural integrity in neonates. Am. J. Med. Sci. 324, 261–266 (2002).
pubmed: 12449447
Fell, J. M., Thakkar, H., Newman, D. J. & Price, C. P. Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method. Acta Paediatr. 86, 518–522 (1997).
pubmed: 9183492
Galaske, R. G. Renal functional maturation: renal handling of proteins by mature and immature newborns. Eur. J. Pediatr. 145, 368–371 (1986).
pubmed: 3792381
Conti, M. et al. Should kidney tubular markers be adjusted for urine creatinine? The example of urinary cystatin C. Clin. Chem. Lab. Med. 47, 1553–1556 (2009).
pubmed: 19877765
Helmersson-Karlqvist, J., Ärnlöv, J., Carlsson, A. C., Lind, L. & Larsson, A. Urinary KIM-1, but not urinary cystatin C, should be corrected for urinary creatinine. Clin. Biochem. 49, 1164–1166 (2016).
pubmed: 27475248
Khosravi, N. et al. The value of urinary cystatin C level to predict neonatal kidney injury. Curr. Pharm. Des. 24, 3002–3004 (2018).
pubmed: 30227813

Auteurs

Antonella Barbati (A)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy. antonella.barbati@unipg.it.
Research Center of Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy. antonella.barbati@unipg.it.

Maria Cristina Aisa (MC)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.
GEBISA, Research Foundation, Perugia, Italy.

Benito Cappuccini (B)

GEBISA, Research Foundation, Perugia, Italy.
Department of Neonatology, Hospital S.M. della Misericordia, Perugia, Italy.

Mariarosalba Zamarra (M)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.

Sandro Gerli (S)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.
Research Center of Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy.
GEBISA, Research Foundation, Perugia, Italy.

Gian Carlo Di Renzo (GC)

Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy.
Research Center of Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy.
GEBISA, Research Foundation, Perugia, Italy.

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