High-sensitivity C-reactive protein as a predictive factor of acute kidney injury following aneurysmal subarachnoid hemorrhage: a prospective observational study

A Correction to this article is available

This article has been updated

Abstract

Background

High-sensitivity C-reactive protein (hs-CRP) is a well-recognized biomarker of neurologic complications and clinical outcome of stroke patients. However, whether hs-CRP can predict the occurrence of acute kidney injury (AKI) in aneurysmal subarachnoid hemorrhage (aSAH) patients is still unclear. The objective of this study was to assess the feasibility of using serum hs-CRP level to predict the occurrence of AKI in aSAH patients.

Methods

One hundred sixty-four aSAH patients were enrolled into a prospective observational study. AKI was diagnosed using the modified Kidney Disease Improving Global Outcomes (KDIGO) standard. The relationship between serum hs-CRP level at admission and occurrence of AKI was analyzed.

Results

AKI occurred in 17 patients (10.4%) in this cohort. Patients with AKI had significantly higher hs-CRP levels than those without. The mortality of the AKI group tends to be higher than that of the non-AKI group, but the difference was not statistically significant (4/17 (23.5%) vs. 13/147 (8.8%), P = 0.081). After adjusting for possible confounding factors including World Federation of Neurosurgical Societies grade, diabetes, and serum creatinine, multivariate analysis revealed that serum hs-CRP level and antibiotic therapy were both significant factors independently associated with AKI following aSAH (serum hs-CRP: OR = 1.2, 95% confidence interval (CI) = 1.1–1.3, P = 0.003; antibiotic therapy: OR = 5.8, 95%CI = 1.6–20.7, P = 0.007). Receiver operating characteristic curve analysis showed that hs-CRP had a sensitivity of 76.5% and a specificity of 64.6% for predicting the development of AKI on the basis of the best thresholds. The post hoc log-rank test revealed that patients having serum hs-CRP level > 6.6 mg/L had a significantly higher AKI rate than patients having serum hs-CRP level ≤ 6.6 mg/L (P = 0.001).

Conclusions

Serum hs-CRP level might be helpful as a predictor for the development of AKI in aSAH patients. Delayed cerebral ischemia occurrence rate and mortality of patients with AKI tend to be higher than those of patients without in this cohort; however, they were not significantly different.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

Change history

Abbreviations

hs-CRP:

High-sensitivity C-reactive protein

AKI:

Acute kidney injury

aSAH:

Aneurysmal subarachnoid hemorrhage

CTA:

Computed tomography angiography

DSA:

Digital subtraction angiography

WFNS:

World Federation of Neurosurgical Societies

MRA:

Magnetic resonance angiography

CSF:

Cerebrospinal fluid

KDIGO:

Kidney Disease Improving Global Outcomes

ROC:

Receiver operating characteristic

AUC:

Area under the curve

References

  1. 1.

    Ahmad A, Dempsey SK, Daneva Z, Azam M, Li N, Li P-L, Ritter JK et al (2018) Role of nitric oxide in the cardiovascular and renal systems. Int J Mol Sci 19:E2605

    PubMed  Google Scholar 

  2. 2.

    Al-Mufti F, Amuluru K, Damodara N, El-Ghanem M, Nuoman R et al (2018) Novel management strategies for medically-refractory vasospasm following aneurysmal subarachnoid hemorrhage. J Neurol Sci 390:44–51

    CAS  PubMed  Google Scholar 

  3. 3.

    Al-Mufti F, Misiolek KA, Roh D, Alawi A, Bauerschmidt A, Park S et al (2019) White blood cell count improves prediction of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. Neurosurgery 84:397–403

    PubMed  Google Scholar 

  4. 4.

    Badjatia N, Cremers S, Claassen J, Connolly ES, Mayer SA, Karmally W, Seres D (2018) Serum glutamine and hospital-acquired infections after aneurysmal subarachnoid hemorrhage. Neurology 91:e421–e426

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Bercker S, Winkelmann T, Busch T, Laudi S, Lindner D et al (2018) Hydroxyethyl starch for volume expansion after subarachnoid haemorrhage and renal function: results of a retrospective analysis. PLoS One 13:e0192832

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Chang CZ, Wu SC, Kwan AL, Hwang SL, Howng SL (2011) Magnesium lithospermate B alleviates the production of endothelin-1 through an NO-dependent mechanism and reduces experimental vasospasm in rats. Acta Neurochir 153:2211–2217

    PubMed  Google Scholar 

  7. 7.

    Chavakula V, Gross BA, Frerichs KU, Du R (2013) Contrast-induced nephropathy in patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care 19:157–160

    CAS  PubMed  Google Scholar 

  8. 8.

    Chen S, Li Q, Wu H, Krafft PR, Wang Z, Zhang JH (2014) The harmful effects of subarachnoid hemorrhage on extracerebral organs. Biomed Res Int 2014:858496

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Chen K, Wu Y, Wang Q, Wang J, Li X, Zhao Z, Zhou J (2015) The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy. J Crit Care 30(218):e211–e215

    Google Scholar 

  10. 10.

    Connolly ES, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J et al (2012) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:1711–1737

    Google Scholar 

  11. 11.

    Csajbok LZ, Nylen K, Ost M, Sonander H, Nellgard B (2015) In-hospital C-reactive protein predicts outcome after aneurysmal subarachnoid haemorrhage treated by endovascular coiling. Acta Anaesthesiol Scand 59:255–264

    CAS  PubMed  Google Scholar 

  12. 12.

    Dhar R, Diringer MN (2008) The burden of the systemic inflammatory response predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care 8:404–412

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Diringer MN, Bleck TP, Claude Hemphill J, Menon D, Shutter L et al (2011) Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. J Neurocrit Care 15:211–240

    Google Scholar 

  14. 14.

    Drenckhahn C, Brabetz C, Major S, Wiesenthal D, Woitzik J, Dreier JP et al (2013) Criteria for the diagnosis of noninfectious and infectious complications after aneurysmal subarachnoid hemorrhage in DISCHARGE-1. Acta Neurochir Suppl 115:153–159

    PubMed  Google Scholar 

  15. 15.

    Flechet M, Guiza F, Schetz M, Wouters P, Vanhorebeek I et al (2017) AKIpredictor, an online prognostic calculator for acute kidney injury in adult critically ill patients: development, validation and comparison to serum neutrophil gelatinase-associated lipocalin. Intensive Care Med 43:764–773

    CAS  PubMed  Google Scholar 

  16. 16.

    Frijns CJ, Fijnheer R, Algra A, van Mourik JA, van Gijn J, Rinkel GJ (2006) Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome. J Neurol Neurosurg Psychiatry 77:77–83

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE et al (2009) Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke 40:1963–1968

    PubMed  Google Scholar 

  18. 18.

    Hall A, O'Kane R (2018) The extracranial consequences of subarachnoid hemorrhage. World Neurosurg 109:381–392

    PubMed  Google Scholar 

  19. 19.

    Hauer EM, Stark D, Staykov D, Steigleder T, Schwab S, Bardutzky J (2011) Early continuous hypertonic saline infusion in patients with severe cerebrovascular disease. Crit Care Med 39:1766–1772

    CAS  PubMed  Google Scholar 

  20. 20.

    Jeon YT, Lee JH, Lee H, Lee HK, Hwang JW, Lim YJ, Park HP et al (2012) The postoperative C-reactive protein level can be a useful prognostic factor for poor outcome and symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 24:317–324

    PubMed  Google Scholar 

  21. 21.

    Kumar AB, Shi Y, Shotwell MS, Richards J, Ehrenfeld JM (2015) Hypernatremia is a significant risk factor for acute kidney injury after subarachnoid hemorrhage: a retrospective analysis. Neurocrit Care 22:184–191

    PubMed  Google Scholar 

  22. 22.

    Lazaridis C, Naval N (2010) Risk factors and medical management of vasospasm after subarachnoid hemorrhage. Neurosurg Clin N Am 21:353–364

    PubMed  Google Scholar 

  23. 23.

    Lee HG, Kim WK, Yeon JY, Kim JS, Kim KH, Jeon P, Hong SC (2018) Contrast-induced acute kidney injury after coil embolization for aneurysmal subarachnoid hemorrhage. Yonsei Med J 59:107–112

    PubMed  Google Scholar 

  24. 24.

    Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL (2018) Vancomycin plus piperacillin-tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med 46:12–20

    CAS  PubMed  Google Scholar 

  25. 25.

    Mackey J, Khoury JC, Alwell K, Moomaw CJ, Kissela BM, Flaherty ML et al (2016) Stable incidence but declining case-fatality rates of subarachnoid hemorrhage in a population. Neurology 87:2192–2197

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    McWilliam SJ, Antoine DJ, Jorgensen AL, Smyth RL, Pirmohamed M (2018) Urinary biomarkers of aminoglycoside-induced nephrotoxicity in cystic fibrosis: kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Sci Rep 8:5094

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Mizuno T, Sato W, Ishikawa K, Shinjo H, Miyagawa Y, Noda Y et al (2012) KDIGO (Kidney Disease: Improving Global Outcomes) criteria could be a useful outcome predictor of cisplatin-induced acute kidney injury. Oncology 82:354–359

    CAS  PubMed  Google Scholar 

  28. 28.

    Mukerji SS, Buchbinder BR, Singhal AB (2015) Reversible cerebral vasoconstriction syndrome with reversible renal artery stenosis. Neurology 85:201–202

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Prowle JR (2015) Measurement of AKI biomarkers in the ICU: still striving for appropriate clinical indications. Intensive Care Med 41:541–543

    PubMed  Google Scholar 

  30. 30.

    Rampoldi B, Tessarolo S, Giubbilini P, Gaia P, Corino SD et al (2018) Neutrophil gelatinase-associated lipocalin and acute kidney injury in endovascular aneurysm repair or open aortic repair: a pilot study. Biochem Med (Zagreb) 28:010904

    Google Scholar 

  31. 31.

    Rennie TJW, De Souza N, Donnan PT et al (2018) Risk of acute kidney injury following community prescription of antibiotics: self-controlled case series. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfy187

  32. 32.

    Romero FR, Cataneo DC, Cataneo AJ (2014) C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage. Acta Cir Bras 29:340–345

    PubMed  Google Scholar 

  33. 33.

    Rumalla K, Mittal MK (2016) Acute renal failure in aneurysmal subarachnoid hemorrhage: nationwide analysis of hospitalizations in the United States. World Neurosurg 91:542–547

    PubMed  Google Scholar 

  34. 34.

    Salem S, Jankowski V, Asare Y, Liehn E, Welker P, Raya-Bermudez A et al (2015) Identification of the vasoconstriction-inhibiting factor (VIF), a potent endogenous cofactor of angiotensin II acting on the angiotensin II type 2 receptor. Circulation 131:1426–1434

    CAS  PubMed  Google Scholar 

  35. 35.

    Sam R, Hart P, Haghighat R, Ing TS (2012) Hypervolemic hypernatremia in patients recovering from acute kidney injury in the intensive care unit. Clin Exp Nephrol 16:136–146

    PubMed  Google Scholar 

  36. 36.

    Sawada A, Kawanishi K, Morikawa SA, Davey P, Dreischulte T, Bell S (2018) Biopsy-proven vancomycin-induced acute kidney injury: a case report and literature review. BMC Nephrol 19:72

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Schuiling WJ, Dennesen PJ, Rinkel GJ (2005) Extracerebral organ dysfunction in the acute stage after aneurysmal subarachnoid hemorrhage. Neurocrit Care 3:1–10

    PubMed  Google Scholar 

  38. 38.

    Shah SR, Tunio SA, Arshad MH, Moazzam Z, Noorani K, Feroze AM et al (2015) Acute kidney injury recognition and management: a review of the literature and current evidence. Glob J Health Sci 8:120–124

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Shen J, Karki M, Jiang T, Zhao B (2018) Complications associated with diagnostic cerebral angiography: a retrospective analysis of 644 consecutive cerebral angiographic cases. Neurol India 66:1154–1158

    PubMed  Google Scholar 

  40. 40.

    Srinivasan A, Aggarwal A, Gaudihalli S, Mohanty M, Dhandapani M, Singh H et al (2016) Impact of early leukocytosis and elevated high-sensitivity C-reactive protein on delayed cerebral ischemia and neurologic outcome after subarachnoid hemorrhage. World Neurosurg 90:91–95

    PubMed  Google Scholar 

  41. 41.

    Tam AK, Ilodigwe D, Mocco J, Mayer S, Kassell N, Ruefenacht D, Schmiedek P et al (2010) Impact of systemic inflammatory response syndrome on vasospasm, cerebral infarction, and outcome after subarachnoid hemorrhage: exploratory analysis of CONSCIOUS-1 database. Neurocrit Care 13:182–189

    PubMed  Google Scholar 

  42. 42.

    Tujjar O, Belloni I, Hougardy JM, Scolletta S, Vincent JL, Creteur J et al (2017) Acute kidney injury after subarachnoid hemorrhage. J Neurosurg Anesthesiol 29:140–149

    PubMed  Google Scholar 

  43. 43.

    Zacharia BE, Ducruet AF, Hickman ZL, Grobelny B, Fernandez L et al (2009) Renal dysfunction as an independent predictor of outcome after aneurysmal subarachnoid hemorrhage: a single-center cohort study. Stroke 40:2375–2381

    PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to all colleagues who participated in providing cases (Dr. Jiawei Cai and Dr. Fuxin Lin).

Funding

This study was supported by grants from the Key Clinical Specialty Discipline Construction Program of Fujian, P.R.C., and the major project of Fujian Provincial Department of Science and Technology (No. 2014YZ0003).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Qing-Xi Tang.

Ethics declarations

Conflict of interest

De-Zhi Kang received grants from the Key Clinical Specialty Discipline Construction Program of Fujian, P.R.C., and the major project of Fujian Provincial Department of Science and Technology (No. 2014YZ0003). All other 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/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures in the study were approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (Fujian, China).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Comments

This paper reports an association between admission plasma levels of high-sensitivity C-reactive protein and development within 14 days of acute kidney injury in patients with aneurysmal subarachnoid haemorrhage. This is an interesting observation, which warrants consideration regarding the mechanism of association. However, as a clinician I probably would not add this relatively expensive test to my prognostic toolbox at this time.

Kirsten Moeller

Copenhagen, Denmark

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Vascular Neurosurgery - Aneurysm

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, BH., He, Q., Ding, CY. et al. High-sensitivity C-reactive protein as a predictive factor of acute kidney injury following aneurysmal subarachnoid hemorrhage: a prospective observational study. Acta Neurochir 161, 1783–1791 (2019). https://doi.org/10.1007/s00701-019-04006-z

Download citation

Keywords

  • Acute kidney injury
  • Aneurysmal subarachnoid hemorrhage
  • High-sensitivity C-reactive protein