Cystatin C level and amikacin use in neonatal sepsis

  • Putu Diah Pratiwi Departement of Child Health, Medical School, Udayana University, Sanglah Hospital, Denpasar, Indonesia
  • I Wayan Dharma Artana Department of Child Health, Universitas Udayana Medical School/Sanglah Hospital, Denpasar, Bali
  • Ni Putu Veny Kartika Yantie Department of Child Health, Universitas Udayana Medical School/Sanglah Hospital, Denpasar, Bali
  • Hendra Santoso Department of Child Health, Universitas Udayana Medical School/Sanglah Hospital, Denpasar, Bali
  • I Gusti Ngurah Sanjaya Putra Department of Child Health, Universitas Udayana Medical School/Sanglah Hospital, Denpasar, Bali
  • Gusti Ayu Putu Nilawati Department of Child Health, Universitas Udayana Medical School/Sanglah Hospital, Denpasar, Bali
  • Ni Nyoman Metriani Nesa Department of Child Health, Universitas Udayana Medical School/Sanglah Hospital, Denpasar, Bali
Keywords: neonatal sepsis; cystatin C; renal function


Background Amikacin is the antibiotic of choice for eradicating bacteria in neonatal sepsis because of its effectiveness against Gram-negative bacteria. However, this drug has nephrotoxic effects. Monitoring kidney function in neonates is very important because amikacin can interfere with development of the kidney. Several studies have shown that serum cystatin C levels were closer to glomerular filtration rate (GFR) values ​​compared to serum creatinine levels.

Objective To evaluate cystatin C levels before and after administration of amikacin in neonates with sepsis.

Methods This prospective cohort study was conducted in one group with a pretest and posttest design. Thirty neonatal sepsis patients who received amikacin therapy at Sanglah General Hospital, Denpasar, Bali, were included by consecutive sampling. Their cystatin C levels were measured before and after receiving amikacin therapy. Data were normally distributed and analyzed by paired T-test, with a value of P<0.05 considered to be significant.

Results The mean difference was 0.23 [1.57 (SD 0.29) vs. 1.80 (SD 0.28)] mg/L with P value
< 0.001. There was different value of cystatin c level before and after amikacin therapy with deviation standard 0.25 with P<0.001 (alfa 5%).

Conclusion Cystatin C levels are significantly higher in neonates with sepsis after administration of amikacin.


Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: Evaluation of neonatal sepsis. Pediatr Clin North Am. 2013; 60: 367-89. doi : 10.1016/j.pcl.2012.12.003.

Lewis DB, Wilson CP. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In: Remington JS, Klein JO, Wilson CB, Baker CJ, eds. Infectious diseases of the fetus and newborn infant. 6th ed. Philadelphia: Saunders Elsevier; 2006. p. 87-210. doi : 10.1016/B0-72-160537-0/50006-2.

Darmstadt GL, Bhutta ZA, Cousens S, Adam T, Walker N, de Bernis L; Lancet Neonatal Survival Steering Team. Evidence-based, cost-effective interventions : How many newborn babies can we save? Lancet. 2005; 365: 977-88. doi : 10.1016/S0140-6736(05)71088-6.

Gomela TR, Cunningham MD, Eyal FG. Sepsis. In: Gomela TR, Cunningham MD, Eyal FG , eds. Neonatology: Management, procedures, on-call problems, diseases, and drug. 7th ed. New York: McGraw Hill; 2013. p. 865-73. ISBN: 978-0-07-177206-8.434-40.

Camacho-Gonzalez A, Gozales AC, Spearman PW, Stoll BJ. Neonatal infectious diseases: Evaluation of neonatal sepsis. Pediatr Clin N Am. 2013; 60:367-389. doi : 10.1016/j.pcl.2012.12.003.

Blackburn ST. Maternal, fetal, and neonatal physiology: A a clinical perspective. 3rd ed. Philadelphia: Saunders Elsevier; 2009. p. 953-64. ISBN: 978-1416029441.

Blackburn ST. Maternal, fetal and neonatal physiology. 2nd ed. Philadelphia: Elsevier; 2012. p. 1229-41. ISBN: 978-0721680125.

Alinejad S, Yousefichaijan P, Rezagholizamenjany M, Rafie Y, Kahbazi M, Arjmand A. Nephrotoxic effect of gentamicin and amikacin in neonates with infection. Nephro-Urol Mon. 2018 ; 10(2):e58580. doi : 10.5812/numonthly.58580.

Ahmed AM, Koura HM, Youssef H, Seoud I, Makar SH, Abdel-Razek AR, et al. Early detection of neonatal kidney disease in high risk neonates admitted to neonatal intensive care unit. WJMS. 2014; 11: 518-24. doi : 10.5829/idosi.wjms.2014.11.4.86239.

Alatas H, Ambarsari CG. Anatomi dan fisiologi ginjal. In: Rachmadi D, Sekarwana N, Hilmanto D, Garna H, eds. Buku Ajar Nefrologi Anak. Edisi Ketiga. Jakarta: BPIDAI; 2017. p. 1-28. ISBN: 978-602-0883-29-8.

Allegaert K, Mekahli D, van den Anker J. Cystatin C in newborns: A promising renal biomarker in search for standardization and validation. Journal Maternal Neonatal Medicine. 2015; 28: 1833-8. doi : 10.3109/14767058.2014.969236.

Novo ACACC, Sadeck LSR, Okay TS, Leone CR. Longitudinal study of cystatin c in healthy term newborns. Clinics. 2011; 66 : 217-20. doi : 10.1590/S1807-59322011000200006.

Cruzando LB, Gonzales EP, Martos ZM, Guitarte CB, Asencio MG, Lagares SL, et al. Serum cystatin c levels in preterm newborns in our setting : correlation with serum creatinine and preterm pathologies. Nefrologia. 2015; 35: 296-303. doi : 10.1016/j.nefro.2015.05.004.

David S, Whooley MA,, Joachim H, Ali S, Shlipak MG. Association of cystatin c and estimated gfr with inflammatory biomarkers: The Heart and Soul Study. Nephrol Dial Transplant. 2007; 22: 1087-1092. doi : 10.1093/ndt/gfl744.

Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis. American Journal of Kidney Diseas. 2002; 40: 221-6. doi : 10.1053/ajkd.2002.34487

Hoek FJ, Kemperman FA, Krediet RT. A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant. 2003; 18:2024-31. doi : 10.1093/ndt/gfg349.

Onopiuk A, Tokarzewicz A, Gorodkiewicz E. Cystatin C: A kidney function biomarker: Advances in clinical chemistry. 2nd ed. Inc. Poland: Elsevier. 2014; 68:57-69. doi : 10.1016/bs.acc.2014.11.007.

Mukesh PK, Bakul J. Assesment of renal functions in neonate of perinatal asphyxia. Int J of Res in Med. 2016. p. 105-8.

Devarajan P. Biomarker for the early detection of acute kidney injury. Curr Opin Pediartr. 2011; 23: 194-200. doi : 10.1097/MOP.0b013e328343f4dd.

Sarkar PD, Rajeshwari G, Shivaprakash TM. Cystatin C-A novel marker of glomerular filtration rate: A review. Indian Journal of Clinical Biochemistry. 2005; 20:139-44. doi : 10.1007/BF02893060.

El-Salam MA, Zaher MM, Abd R, Mohamed ES, Yossef L, Shall A, et al. Comparison of some urinary biomarker of acute kidney injury in term new born with and without asphyxia. Jcmd 2014; 4:23-8. doi : 10.5923/j.cmd.20140402.02.

Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AA, Vernekar SN. Marker of renal function tests. N Am J Med Sci. 2010; 2: 170-3. PMC3354405.

Brunton LL, Chabner BA, Knollmann BC. The pharmacological basis of therapeutics. 12th edition. New York: McGraw-Hill; 2011. p. 124- 78.

Cotten CM. Antibiotic stewardship: Reassessment of guidline for management of neonatal sepsis. Clin Perinatol. 2015; 42: 195-x. doi : 10.1016/j.clp.2014.10.007.

Davis PG, Jacobs S. Neonatal pharmacopoeia. 2nd ed. Australia: Pharmacy Dept. 2005. p. 24-6.

Fatmawati D. Pola bakteri dan kepekaan bakteri terhadap antibiotika di RSUP Sanglah. Denpasar: Departemen Mikrobiologi RSUP Sanglah; 2017. p. 25-64.

Pacifi GM. Clinical pharmacokinetics of aminoglycosides in the neonate: A review. Eur J Clin Phamacol. 2009; 65:419-427. doi : 10.1007/s00228-008-0599-y.

Samiee-Zafarghandy S, van den Anker JN. Nephotoxic effects of aminoglycosides on the developing kidney. Journal of Pediatric and Neonatal Individualized Medicine. 2013; 2: 1-7. doi : 10.7363/020227.

Satroasmoro S, Ismael S. Dasar-dasar metodelogi penelitian klinis. Jakarta: Sagung Seto. 2014. p. 348-83.

Mortazavi F, Hosseinpour SS, Nejati N. Acute kidney failure in neonatal period. Iranian Journal of Kidney Disease. 2009; 3:136-40.

Mathur NB, Agarwal HS, Maria A. Acute renal failure in neonatal sepsis. Indian Journal of Pediatrics. 2006; 73: 499-502. doi : 10.1007/BF02759894.

Price CP, Finney H. Developments in the assessment of glomerular filtration rate. Clinica Chimica Acta. 2000; 297:55-66. doi : 10.1016/s0009-8981(00)00233-3.

Guignard JP, Gouyon JB. Glomerular filtration rate in neonates. In: Oh W, Guignard JP, Baumgart S, eds. Nephrology and fluid/electrolyte physiology. Neonatology Questions and Controversies. 1st ed. Philadelphia: Elsevier; 2008. p. 79-96. doi : 10.1016/B978-1-4160-3163-5.50011-7.

Finney H, Newman DJ, Thakkar H, Fell JME, Price CP. Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child. 2000; 82:71-5. doi : 10.1136/adc.82.1.71.

Kandasamy Y, Smith R, Wright I. Measuring cystatin c to determine renal function in neonates. Pcccmjournal. 2013; 14: 318-22. doi : 10.1097/PCC.0b013e318271f4a5.

Menardaniawati D, Effendi SH, Rahayuningsih SE. Kadar cystatin C serum penanda fungsi ginjal bayi prematur. Sari Pediatri. 2013; 15: 17-22. doi : 10.14238/sp15.1.2013.17-22.

Mussap M, Plebani M. Biochemistry and clinical role of human cystatin C. Critical Reviewsin Clinical Laboratory Sciences. 2004; 41: 467-550. doi : 10.1080/10408360490504934.

Maruniak-Chudek I, Owsianka-Podlesny T, Wróblewska J, Jadamus-Niebrój D. Is serum cystatin C a better marker of kidney function than serum creatinine in septic newborns? Postepy Hig Med Dosw. 2012; 66:175-180. doi : 10.5604/17322693.988679.

How to Cite
Pratiwi P, Artana IW, Yantie NP, Santoso H, Putra IG, Nilawati GA, Nesa NN. Cystatin C level and amikacin use in neonatal sepsis. PI [Internet]. 27Nov.2019 [cited 31Mar.2023];60(1):1-. Available from:
Received 2019-05-29
Accepted 2019-11-27
Published 2019-11-27