Diagnostic Value of Serum Cystatin-C and Uric Acid in Predicting Renal Impairment in Pre-Eclampsia

Javeria Hameed; Sofia Naz; Maria; Sarwat Batool; Rubina Zareen; Nosheen  Zehra  Mangi

doi:10.36283/ziun-pjmd13-4/003

Authors

Javeria Hameed Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan https://orcid.org/0009-0005-6846-0446
Sofia Naz Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan https://orcid.org/0000-0002-4166-7587
Maria Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan https://orcid.org/0009-0000-6057-3474
Sarwat Batool Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan https://orcid.org/0009-0003-5506-8707
Rubina Zareen Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan https://orcid.org/0009-0006-1517-5542
Nosheen Zehra Mangi Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan https://orcid.org/0009-0008-0620-2566

DOI:

https://doi.org/10.36283/ziun-pjmd13-4/003

Abstract

Background: Preeclampsia, a significant contributor to maternal and fetal health risks, is characterized by hypertension and proteinuria occurring post 20 weeks of gestation. Timely identification of renal issues in pre-eclamptic individuals is essential to prevent severe complications. This study aimed to assess how serum cystatin-C and uric acid levels together could predict renal impairment in pre-eclamptic patients.

Methods: This longitudinal study was conducted from June 2023 to May 2024 at the Department of Physiology, LUMHS, in collaboration with the gynecology and obstetrics units of Civil Hospital, Hyderabad, and Liaquat University Hospital, Jamshoro. A total of 150 pre-eclamptic patients between 20 and 36 weeks of gestation were selected consecutively. Blood samples were collected at two stages; during 20-25 weeks and again at 36 weeks to measure serum cystatin-C and uric acid levels. Statistical analysis was performed using SPSS version 26.0, with descriptive statistics summarizing patient characteristics, chi-square tests, ANOVA, Spearman correlation, and ROC curve were used to analyze biomarker levels and their relationship with gestational age.

Results: The study demonstrated significantly elevated serum cystatin-C (1.5 ± 0.3 mg/L) and uric acid levels (7.2 ± 1.5 mg/dL) in pre-eclamptic patients with renal impairment compared to those without (p < 0.01). A significant positive correlation was observed between gestational age and biomarker levels (r = 0.65, p < 0.01). The combined use of these biomarkers improved sensitivity to 90% and specificity to 85% in predicting renal impairment.

Conclusion: Simultaneous measurement of serum cystatin-C and uric acid enhances early detection of renal impairment in pre-eclamptic patients.

Author Biographies

Javeria Hameed, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

Physiology Department
Sofia Naz, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

Biochemistry Department
Maria, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

Department of Biochemistry
Sarwat Batool, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

Department of Physiology
Rubina Zareen, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

Department of Physiology
Nosheen Zehra Mangi, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan

Department of Biochemistry

References

Sánchez-Rodríguez D, De Blas-García M, Fernández-Alvarez L, et al. Impact of Uric Acid and Its Derivatives on the Progression of Renal Impairment in Patients with Preeclampsia. Hypertens Pregnancy. 2017 Apr;36(2):202-210. doi:10.1080/10641955.2017.1302407. Available from: https://doi.org/10.1080/10641955.2017.1302407.

Zhang J, Zhang Y, Tang Y, et al. The role of serum cystatin C in detecting early renal impairment in preeclampsia. BMC Pregnancy Childbirth. 2016 Jun;16:193. doi:10.1186/s12884-016-0982-6. Available from: https://doi.org/10.1186/s12884-016-0982-6.

Hu X, Zhang X, Liu W, et al. Evaluation of cystatin C as a diagnostic marker for renal impairment in preeclampsia: A meta-analysis. Kidney Blood Press Res. 2016 Sep;41(5):911-920. doi:10.1159/000450831. Available from: https://doi.org/10.1159/000450831.

Fathi M, Raoofi A, Keshavarzi A, et al. Serum cystatin C and uric acid levels as predictors of renal impairment in preeclamptic patients: A prospective study. Pregnancy Hypertens. 2017 Apr;10:125-130. doi:10.1016/j.preghy.2017.07.005. Available from: https://doi.org/10.1016/j.preghy.2017.07.005.

Wang Y, Zhang X, Li Y, et al. Comparative study on the effectiveness of cystatin C and serum creatinine as markers of renal function in preeclamptic patients. Clin Chim Acta. 2017 Feb;464:153-158. doi:10.1016/j.cca.2016.11.022. Available from: https://doi.org/10.1016/j.cca.2016.11.022.

Douma Z, Vogiatzis D, Kalaitzidis R, et al. Uric acid and cystatin C in assessing renal function in pregnancy-induced hypertension. Nephrology. 2016 Jun;21(6):433-439. doi:10.1111/nep.12622. Available from: https://doi.org/10.1111/nep.12622.

Gungorduk K, Demirtas O, Ceylan Y, et al. The value of serum cystatin C in predicting the severity of preeclampsia and fetal outcomes. Arch Gynecol Obstet. 2017 May;295(5):1179-1184. doi:10.1007/s00404-017-4324-0. Available from: https://doi.org/10.1007/s00404-017-4324-0.

Lu Q, Zhang M, Zhao J, et al. Uric acid as a prognostic marker in patients with preeclampsia. Clin Biochem. 2017 Apr;50(12):742-746. doi:10.1016/j.clinbiochem.2017.02.016. Available from: https://doi.org/10.1016/j.clinbiochem.2017.02.016.

He Y, Pan X, Tang H, et al. Uric acid and renal impairment in patients with preeclampsia: A retrospective study. Pregnancy Hypertens. 2017 Apr;10:101-106. doi:10.1016/j.preghy.2017.10.001. Available from: https://doi.org/10.1016/j.preghy.2017.10.001.

Ali S, Ahmed A, Shaikh S. Serum cystatin C as an early marker of renal dysfunction in preeclamptic patients. Eur J Obstet Gynecol Reprod Biol. 2017 Aug;216:26-30. doi:10.1016/j.ejogrb.2017.07.024. Available from: https://doi.org/10.1016/j.ejogrb.2017.07.024.

Chau K, Lao T, Tam KF. Serum cystatin C as a marker of renal function in preeclampsia. Acta Obstet Gynecol Scand. 2017 Jun;96(6):727-732. doi:10.1111/aogs.13129. Available from: https://doi.org/10.1111/aogs.13129.

Mahajan A, Singh N, Jasuja S, et al. Prognostic significance of serum cystatin C in patients with preeclampsia. Int J Gynaecol Obstet. 2017 Nov;139(2):141-146. doi:10.1002/ijgo.12251. Available from: https://doi.org/10.1002/ijgo.12251.

Tesfa E, Munshea A, Nibret E, et al. Maternal serum uric acid, creatinine, and blood urea levels in the prediction of pre-eclampsia among pregnant women attending ANC and delivery services at Bahir Dar City public hospitals, northwest Ethiopia: a case-control study. Heliyon. 2022 Nov;8(11). doi:10.1016/j.heliyon.2022.e11098.

Tabaei BP, Shafi T, Astor BC, et al. The performance of cystatin C-based eGFR equations in preeclamptic women. Am J Kidney Dis. 2016 Oct;68(4):597-605. doi:10.1053/j.ajkd.2016.05.023. Available from: https://doi.org/10.1053/j.ajkd.2016.05.023.

Satirapoj B, Charoenpitakchai M, Supasyndh O. Serum cystatin C in preeclampsia as an early marker of renal impairment. BMC Nephrol. 2017 Mar;18(1):79. doi:10.1186/s12882-017-0495-4. Available from: https://doi.org/10.1186/s12882-017-0495-4.

Mozurkevich EL, Duda OA, Shliakhtin AO, et al. Prognostic value of cystatin C and uric acid in preeclampsia. Clin Lab. 2016 Oct;62(10):1823-1829. doi:10.7754/Clin.Lab.2016.160520. Available from: https://doi.org/10.7754/Clin.Lab.2016.160520.

Roberge S, Bujold E, Nicolaides KH. Aspirin for the prevention of preterm and term preeclampsia: systematic review and meta-analysis. Am J Obstet Gynecol. 2017 May;216(5):287-293. doi:10.1016/j.ajog.2016.12.019. Available from: https://doi.org/10.1016/j.ajog.2016.12.019.

Schisterman EF, Perkins NJ, Mumford SL, et al. A basic introduction to ROC analysis for diagnostic tests. Prev Med. 2017 Jun;105:100-104. doi:10.1016/j.ypmed.2017.04.006. Available from: https://doi.org/10.1016/j.ypmed.2017.04.006.

Thangaratinam S, Coomarasamy A, O'Mahony F, et al. Estimation of renal function in preeclampsia: a comparison of cystatin C, beta-trace protein, and creatinine-based formulas. Clin Chem. 2016 Sep;62(9):1185-1193. doi:10.1373/clinchem.2016.259432. Available from: https://doi.org/10.1373/clinchem.2016.259432.

Rana S, Lemoine E, Granger JP, et al. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019 Apr;124(7):1094-1112. doi:10.1161/CIRCRESAHA.118.313276. Available from: https://doi.org/10.1161/CIRCRESAHA.118.313276.

Watanabe S, Okada K, Fukuoka H. Plasma cystatin C concentration reflects renal dysfunction in patients with various renal diseases. Nephron. 1999 Jul;82(1):45-50. doi:10.1159/000045357.

Maahs DM, Ogden LG, Kretowski A, Snell-Bergeon JK, Kinney GL, Wadwa RP, et al. Serum uric acid level and its association with cardiovascular disease in patients with type 1 diabetes. Diabetes Care. 2007 Nov;30(11):3073-3078. doi:10.2337/dc07-0883.

Milionis HJ, Milionis CC. Serum uric acid and diabetes: is there a link? Curr Pharm Des. 2005 Jan;11(32):4145-4151. doi:10.2174/138161205774913402.

Zhang Y, Yamamoto T, Hisatome I, Li Z, Cheng W, Sun N, et al. Uric acid induces oxidative stress and endothelial dysfunction in the aorta through the AMP-activated protein kinase (AMPK)-uncoupling protein 2 (UCP2) pathway. Int J Mol Sci. 2021 Feb;22(4):1753. doi:10.3390/ijms22041753.

Wu H, Cheng W, Zhao X, Luo J, Hu Q, Liao Y, et al. Prognostic value of combined detection of serum cystatin C and uric acid in patients with acute ischemic stroke. Brain Behav. 2021 Apr;11(4). doi:10.1002/brb3.2026.

Ouchi M, Oba H, Yamagishi T, Tokuda Y, Wakino S, Itoh H. Plasma cystatin C is a better marker of glomerular filtration rate in renal transplant recipients than serum creatinine. Clin Chim Acta. 2002 Dec;323(1-2):125-132. doi:10.1016/S0009-8981(02)00232-3.

Sovio U, Gaccioli F, Cook E, Hund M, Charnock-Jones DS, Smith GCS. Prediction of Preeclampsia Using Angiogenic Factors and Their Ratios. Hypertension. 2017 Mar;70(3):601-607. doi:10.1161/HYPERTENSIONAHA.117.09401. Available from: https://doi.org/10.1161/HYPERTENSIONAHA.117.09401.

Langwieser N, Preusch M, Maréchal C, et al. Value of plasma cystatin C in the diagnosis of early acute kidney injury after cardiac surgery. Eur J Cardiothorac Surg. 2018 Nov;54(5):899-905. doi:10.1093/ejcts/ezy191. Available from: https://doi.org/10.1093/ejcts/ezy191.