Correlation between urinary albumin to creatinine ratio and systemic glycocalyx degradation in pediatric sepsis
AbstractBackground: Increased capillary permeability in sepsis is associated with several complications and worse outcomes. Glycocalyx degradation, marked by increased serum syndecan-1 levels, alters vascular permeability, which can manifest as albuminuria in the glomerulus. Therefore, elevated urinary albumin to creatinine ratio (ACR) potentially provides an index of systemic glycocalyx degradation. The aim of this study was to analyze the correlation between urinary ACR and serum syndecan-1 levels.
Methods: A longitudinal prospective study with repeated cross-sectional design was conducted on children with sepsis in pediatric intensive care unit, we evaluated serum syndecan-1 levels and urinary ACR on days 1, 2, 3, and 7. A descriptive study on healthy children was also conducted to determine the reference value of syndecan-1 in children.
Results: 49 subjects with sepsis were recruited. Based on the data of the healthy children group (n=30), syndecan-1 level of >90th percentile (41.42 ng/mL) was defined as systemic glycocalyx degradation. The correlation coefficients (r) between urinary ACR and syndecan-1 levels were 0.32 (p<0.001) from all examination days (162 specimens), 0.298 (p=0.038) on day 1, and 0.469 (p=0.002) on day 3. The area under the curve of urinary ACR and systemic glycocalyx degradation was 65.7% (95% CI 54.5%–77%; p=0.012). Urinary ACR ≥157.5 mg/g was determined as the cut-off point for glycocalyx degradation, with a sensitivity of 77.4% and a specificity of 48%.
Conclusion: Urinary ACR showed a weak correlation with systemic glycocalyx degradation, indicating that the pathophysiology of elevated urinary ACR in sepsis is not merely related to glycocalyx degradation.
Watson RS, Carcillo JA, Linde-Zwirble WT, Clemont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003;167(5):695–701. https://doi.org/10.1164/rccm.200207-682OC
Pawitan JA. Potential agents against plasma leakage. ISRN Pharmacol. 2011;2011:975048. https://doi.org/10.5402/2011/975048
Chappell D, Westphal M, Jacob M. The impact of the glycocalyx on microcirculatory oxygen distribution in critical illness. Curr Opin Anaesthesiol. 2009;22(2):155–62. https://doi.org/10.1097/ACO.0b013e328328d1b6
Ochonidky P, Henning RH, van Dokkum RP, de Zeeuw D. Microalbuminuria and endothelial dysfunction: emerging targets for primary prevention of end-organ damage. J Cardiovasc Pharmacol. 2006;47:S151–62. https://doi.org/10.1097/00005344-200606001-00009
Bendjelid K, Giraud R, Siegenthaler N, Michard F. Validation of a new transpulmonary thermodilution system to assess global end-diastolic volume and extravascular lung water. Crit Care. 2010;14(6):R209. https://doi.org/10.1186/cc9332
Chelazzi C, Villa G, Mancinelli P, De Gaudio AR, Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care. 2015;19(1):26. https://doi.org/10.1186/s13054-015-0741-z
Donati A, Tibboel D, Ince C. Towards integrative physiological monitoring of the critically ill: from cardiovascular to microcirculatory and cellular function monitoring at the bedside. Crit Care. 2013;17(Suppl1):S5. https://doi.org/10.1186/cc11503
Johansen ME. Hemostasis and endothelial damage during sepsis. Dan Med J. 2015;62(8):B5135.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney inter., Suppl. 2013;3:1–150.
Singh A, Satchell SC. Microalbuminuria: causes and implications. Pediatr Nephrol. 2011;26(11):1957–65. https://doi.org/10.1007/s00467-011-1777-1
Bhadade RR, de Souza R, Harde MJ, Sridhar B. Microalbuminuria: a biomarker of sepsis and efficacy of treatment in patients admitted to a medical intensive care unit of a tertiary referral center. J Postgrad Med. 2014;60(2):145–50. https://doi.org/10.4103/0022-3859.132320
Anil AB, Anil M, Yildiz M, Kamit Can F, Bal A, Gokalp G, et al. The importance of microalbuminuria in predicting patient outcome in a PICU. Pediatr Crit Care Med. 2014;15(5):e220–5. https://doi.org/10.1097/PCC.0000000000000113
Salmon AH, Satchell SC. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J Pathol. 2012;226(4):562–74. https://doi.org/10.1002/path.3964
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005;6(1):2–8. https://doi.org/10.1097/01.PCC.0000149131.72248.E6
Kwak BO, Lee ST, Chung S, Kim KS. Microalbuminuria in normal Korean children. Yonsei Med J. 2011;52(3):476–81. https://doi.org/10.3349/ymj.2011.52.3.476
Varda NM. Microalbuminuria in pediatric patients with hypertension. Health. 2013;5(4A):40–6. https://doi.org/10.4236/health.2013.54A006
Hurtado A, Cancino R, Figueroa J, Padilla E, Morales C, Ortiz I, et al. Microalbuminuria in healthy adolescents: a comparative study at high altitude and at sea level. Open Urol Nephrol J. 2014;7:82–5. https://doi.org/10.2174/1874303X01407010082
Çekiç C, Kırcı A, Vatansever S, Aslan F, Yilmaz HE, Alper E, et al. Serum syndecan-1 levels and its relationship to disease activity in patients with Crohn's disease. Gastroenterol Res Pract. 2015;2015:850351. https://doi.org/10.1155/2015/850351
Thorburn K, Baines PB. Broken barriers, biomarkers, and blocking antibodies—endothelial activation in sepsis*: no snowflake in an avalanche ever feels responsible. –Voltaire/François-Marie Arouet (1694–1778). Pediatr Crit Care Med. 2013;14(7): 720–1. https://doi.org/10.1097/PCC.0b013e31829b1ea8
Teng YH, Aquino RS, Park PW. Molecular functions of syndecan-1 in disease. Matrix Biol. 2011;31(1):3–16. https://doi.org/10.1016/j.matbio.2011.10.001
Ostrowski SR, Haase N, Müller RB, Møller MH, Pott FC, Perner A, et al. Association between biomarkers of endothelial injury and hypocoagulability in patients with severe sepsis: a prospective study. Crit Care. 2015;19(1):191. https://doi.org/10.1186/s13054-015-0918-5
Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, et al. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007;116(17):1896–906. https://doi.org/10.1161/CIRCULATIONAHA.106.684852
D'Amico G, Bazzi C. Pathophysiology of proteinuria. Kidney Int. 2003;63(3):809–25. https://doi.org/10.1046/j.1523-1755.2003.00840.x
Saragih RA, Mandei JM, Yuniar I, Dewi R, Pardede SO, Pudjiadi A, et al. Using pRIFLE criteria for acute kidney injury in critically ill children. Paeditr Indones. 2013;53(1):32–6. https://doi.org/10.14238/pi53.1.2013.32-6
Ackan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007; 71(10):1028–35. https://doi.org/10.1038/sj.ki.5002231
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