A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function

doi:10.5847/wjem.j.1920-8642.2020.01.003

Abstract

Abstract:

BACKGROUND: Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury (SA-AKI) than among patients with sepsis. However, the pathogenesis underlying SA-AKI remains unclear. We hypothesized that the source of infection affects development of SA-AKI. We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI.

METHODS: Between January 2013 and January 2018, 113 patients with SA-AKI admitted to our Emergency Center were identified and divided into two groups: those with pulmonary infections and those with other sources of infection. For each patient, we collected data from admission until either discharge or death. We also recorded the clinical outcome after 90 days for the discharged patients.

RESULTS: The most common source of infection was the lung (52/113 cases, 46%), followed by gastrointestinal (GI) (25/113 cases, 22.1%) and urinary (22/113, 19.5%) sources. Our analysis showed that patients with SA-AKI had a significantly worse outcome (30/52 cases, P<0.001) and poorer kidney recovery (P=0.015) with pulmonary sources of infection than those infected by another source. Data also showed that patients not infected by a pulmonary source more likely experienced shock (28/61 cases, P=0.037).

CONCLUSION: This study demonstrated that the source of infection influenced the outcome of SA-AKI patients in an independent manner. Lung injury may influence renal function in an as-yet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection.

Key words: Sepsis, Infection source, Acute kidney injury, Lung injury, Renal function

Yi-wen Fan, Shao-wei Jiang, Jia-meng Chen, Hui-qi Wang, Dan Liu, Shu-ming Pan, Cheng-jin Gao. A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function[J]. World Journal of Emergency Medicine, 2020, 11(1): 18-26.

Figures/Tables 9

Figure 1.

Table 1

Figure 2.

Figure 3.

Table 2

Figure 4.

Figure 5.

Figure 6.

Table 3

References 36

1	Siew ED, Deger SM. Recent advances in acute kidney injury epidemiology. Curr Opin Nephrol Hypertens. 2012; 21(3):309-17. doi: 10.1097/MNH.0b013e3283521d95 pmid: 22449946
2	Poukkanen M, Vaara ST, Pettila V, Kaukonen KM, Korhonen AM, Hovilehto S, et al. Acute kidney injury in patients with severe sepsis in Finnish Intensive Care Units. Acta Anaesthesiol Scand. 2013; 57(7):863-872. doi: 10.1111/aas.12133 pmid: 23713703
3	Koyner JL. Assessment and diagnosis of renal dysfunction in the ICU. Chest. 2012; 141(6):1584-94. doi: 10.1378/chest.11-1513
4	Fan PC, Chang CH, Tsai MH, Lin SM, Jenq CC, Hsu HH, et al. Predictive value of acute kidney injury in medical intensive care patients with sepsis originating from different infection sites. Am J Med Sci. 2012; 344(2):83-9. doi: 10.1097/MAJ.0b013e3182373d36
5	Sood M, Mandelzweig K, Rigatto C, Tangri N, Komenda P, Martinka G, et al. Non-pulmonary infections but not specific pathogens are associated with increased risk of AKI in septic shock. Intensive Care Med. 2014; 40(8):1080-8. doi: 10.1007/s00134-014-3361-1 pmid: 24981956
6	Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. doi: 10.1001/jama.2016.0287 pmid: 26903338
7	Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000; 342(18):1301-8. doi: 10.1056/NEJM200005043421801 pmid: 10793162
8	Zahar JR, Timsit JF, Garrouste-Orgeas M, Francais A, Vesin A, Descorps-Declere A, et al. Outcomes in severe sepsis and patients with septic shock: pathogen species and infection sites are not associated with mortality. Crit Care Med. 2011; 39(8):1886-95. doi: 10.1097/CCM.0b013e31821b827c pmid: 21516036
9	Chambers KA, Park AY, Banuelos RC, Darger BF, Akkanti BH, Macaluso A, et al. Outcomes of severe sepsis and septic shock patients after stratification by initial lactate value. World J Emerg Med. 2018; 9(2):113-7. pmid: 29576823
10	Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, et al. Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med. 2009; 180(9):861-6. doi: 10.1164/rccm.200812-1912OC pmid: 19696442
11	Yoshida J, Furugaki K, Oyama M. Perioperative antimicrobials in chest surgery patients positive for methicillin-resistant Staphylococcus aureus. Gen Thorac Cardiovasc Surg. 2010; 58(12):657-9. doi: 10.1007/s11748-009-0582-2 pmid: 21170640
12	Shorr AF, Bernard GR, Dhainaut JF, Russell JR, Macias WL, Nelson DR, et al. Protein C concentrations in severe sepsis: an early directional change in plasma levels predicts outcome. Crit Care. 2006; 10(3):R92. doi: 10.1186/cc4946 pmid: 16780598
13	Ahuja N, Andres-Hernando A, Altmann C, Bhargava R, Bacalja J, Webb RG, et al. Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice. Am J Physiol Renal Physiol. 2012; 303(6):F864-F872. doi: 10.1152/ajprenal.00025.2012
14	Bhargava R, Janssen W, Altmann C, Andres-Hernando A, Okamura K, Vandivier RW, et al. Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice. PLoS One. 2013; 8(5):e61405. doi: 10.1371/journal.pone.0061405 pmid: 23667439
15	Leligdowicz A, Dodek PM, Norena M, Wong H, Kumar A, Kumar A, et al. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med. 2014; 189(10):1204-13. doi: 10.1164/rccm.201310-1875OC pmid: 24635548
16	Volakli E, Spies C, Michalopoulos A, Groeneveld AB, Sakr Y, Vincent JL. Infections of respiratory or abdominal origin in ICU patients: what are the differences? Crit Care. 2010; 14(2):R32. doi: 10.1186/cc8909 pmid: 20230620
17	Nielsen SL, Roder B, Magnussen P, Engquist A, Frimodt-Moller N. Nosocomial pneumonia in an intensive care unit in a Danish university hospital: incidence, mortality and etiology. Scand J Infect Dis. 1992; 24(1):65-70. doi: 10.3109/00365549209048402 pmid: 1589727
18	Arumugam SK, Mudali I, Strandvik G, El-Menyar A, Al-Hassani A, Al-Thani H. Risk factors for ventilator-associated pneumonia in trauma patients: A descriptive analysis. World J Emerg Med. 2018; 9(3):203-10. pmid: 29796145
19	Rello J, Jubert P, Valles J, Artigas A, Rue M, Niederman MS. Evaluation of outcome for intubated patients with pneumonia due to Pseudomonas aeruginosa. Clin Infect Dis. 1996; 23(5):973-98. doi: 10.1093/clinids/23.5.973 pmid: 8922788
20	Stevens RM, Teres D, Skillman JJ, Feingold DS. Pneumonia in an intensive care unit. A 30-month experience. Arch Intern Med. 1974; 134(1):106-11. pmid: 4365670
21	Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013; 61(5):649-72. doi: 10.1053/j.ajkd.2013.02.349
22	Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM, et al. Acute kidney disease and renal recovery:consensus report of the Acute Disease Quality Initiative (ADQI) 16 workgroup. Nat Rev Nephrol, 2017; 13(4):241-57. doi: 10.1038/nrneph.2017.2 pmid: 28239173
23	Esper AM, Moss M, Lewis CA, Nisbet R, Mannino DM, Martin GS. The role of infection and comorbidity: Factors that influence disparities in sepsis. Crit Care Med. 2006; 34(10):2576-82. doi: 10.1097/01.CCM.0000239114.50519.0E pmid: 16915108
24	Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009; 302(21):2323-9. pmid: 19952319
25	Awad AS, Okusa MD. Distant organ injury following acute kidney injury. Am J Physiol Renal Physiol. 2007; 293(1):F28-F29. doi: 10.1152/ajprenal.00159.2007 pmid: 17429033
26	Darmon M, Clec'h C, Adrie C, Argaud L, Allaouchiche B, Azoulay E, et al. Acute respiratory distress syndrome and risk of AKI among critically ill patients. Clin J Am Soc Nephrol. 2014; 9(8):1347-53. doi: 10.2215/CJN.08300813 pmid: 24875195
27	Peng Q, Zhang L, Ai Y, Zhang L. Epidemiology of acute kidney injury in intensive care septic patients based on the KDIGO guidelines. Chin Med J (Engl). 2014; 127(10):1820-26.
28	Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. 2008; 34(1):17-60. doi: 10.1007/s00134-007-0934-2 pmid: 18058085
29	Carrigan SD, Scott G, Tabrizian M. Toward resolving the challenges of sepsis diagnosis. Clin Chem. 2004; 50(8):1301-14. doi: 10.1373/clinchem.2004.032144 pmid: 15166107
30	Van Amersfoort ES, Van Berkel TJ, Kuiper J. Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev. 2003; 16(3):379-414. doi: 10.1128/cmr.16.3.379-414.2003 pmid: 12857774
31	Barbar SD, Binquet C, Monchi M, Bruyere R, Quenot JP. Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial. Trials. 2014; 15:270. doi: 10.1186/1745-6215-15-270 pmid: 24998258
32	Kuiper JW, Groeneveld AB, Slutsky AS, Plotz FB. Mechanical ventilation and acute renal failure. Crit Care Med. 2005; 33(6):1408-15. doi: 10.1097/01.ccm.0000165808.30416.ef pmid: 15942363
33	Parra ER, Kairalla RA, Ribeiro de Carvalho CR, Eher E, Capelozzi VL. Inflammatory cell phenotyping of the pulmonary interstitium in idiopathic interstitial pneumonia. Respiration. 2007; 74(2):159-69. doi: 10.1159/000097133
34	Liu YC, Qi YM, Zhang H, Walline J, Zhu HD. A survey of ventilation strategies during cardiopulmonary resuscitation. World J Emerg Med. 2019; 10(4):222-7. doi: 10.5847/wjem.j.1920-8642.2019.04.005 pmid: 31534596
35	Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, et al. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1999; 282:54-61. doi: 10.1001/jama.282.1.54 pmid: 10404912
36	Liu KD, Glidden DV, Eisner MD, Parsons PE, Ware LB, Wheeler A, et al. Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury. Crit Care Med. 2007; 35(12):2755-61. pmid: 18074478

Variables	Counts	Mean±SD	Median	Percentage in total patients (n=113)
Age(year)		72.49±12.25	74.00
Age group (n)
≤60	15			13.3
>60, <80	60			53.1
≥80	38			33.6
Gender (n)
Male	63			55.8
Female	50			44.2
Blood routine tests
WBC (×10⁹)		15.49±7.91	15.30
Percent of the lymphocytes (%)		6.46±5.09	5.10
Percent of the neutrophil (%)		87.60±8.22	89.80
NLR		24.07±20.57	18.00
PLT (×10⁹)		128.11±75.49	123.5
APACHE II on admission		19.96±7.10	20
SOFA on admission		7.14±3.75	6
KDIGO (n)
KDIGO 2	50			44.2
KDIGO 3	63			55.8
RRT	38			33.6
Death (n)	44			38.9
Death time (n=44)		15.11±18.03	9.5
Renal recovery at 90 days from ICU admission (n)
Full recovery	52			46
Partial recovery	35			31
Non-recovery	26			23

Variables	OG (n=61)	PG (n=52)	P
90 days death (n)	14	30	<0.001
Death time (days)	12.50±15.98 (n=14)	16.33±19.04 (n=30)	0.518
Renal recovery (n)			0.015
Full recovery	34	18
Partial recovery	19	16
Non-recovery	8	18

Variables	OG (n=61)	PG (n=52)	P
Sex (n)			0.057
Male	29	34
Female	32	18
Age(±SD)	70.75±12.85	74.52±11.28	0.104
Urea on admission (mmol/L)	22.48±13.65	20.39±10.23	0.365
Creatinine on admission (μmol/L)	341.53±227.83	271.07±155.08	0.062
APACHE II on admission	19.10±6.85	20.96±7.32	0.166
SOFA on admission	7.16±3.49	7.12±4.06	0.946
Blood routine tests
WBC (×10⁹)	16.85±8.18	13.88±7.32	0.046
Percent of the lymphocytes (%)	6.36±5.84	6.59±4.10	0.806
Percent of the neutrophil (%)	87.94±8.71	87.20±7.66	0.637
NLR	28.50±24.7	18.85±12	0.01
PLT (×10⁹)	116.72±72.73	141.25±77.16	0.086
Shock (n)			0.037
No	33	38
Yes	28	14

[1]	Li-wei Duan, Jin-long Qu, Jian Wan, Yong-hua Xu, Yi Shan, Li-xue Wu, Jin-hao Zheng, Wei-wei Jiang, Qi-tong Chen, Yan Zhu, Jian Zhou, Wen-bo Yu, Lei Pei, Xi Song, Wen-fang Li, Zhao-fen Lin. Effects of viral infection and microbial diversity on patients with sepsis: A retrospective study based on metagenomic next-generation sequencing [J]. World Journal of Emergency Medicine, 2021, 12(1): 29-35.
[2]	Hai-jiang Zhou, Tian-fei Lan, Shu-bin Guo. Outcome prediction value of National Early Warning Score in septic patients with community-acquired pneumonia in emergency department: A single-center retrospective cohort study [J]. World Journal of Emergency Medicine, 2020, 11(4): 206-215.
[3]	Yu-ming Wang, Yan-jun Zheng, Ying Chen, Yun-chuan Huang, Wei-wei Chen, Ran Ji, Li-li Xu, Zhi-tao Yang, Hui-qiu Sheng, Hong-ping Qu, En-qiang Mao, Er-zhen Chen. Effects of fluid balance on prognosis of acute respiratory distress syndrome patients secondary to sepsis [J]. World Journal of Emergency Medicine, 2020, 11(4): 216-222.
[4]	Miao Yuan, Ding-yi Yan, Fang-shi Xu, Yi-di Zhao, Yang Zhou, Long-fei Pan. Effects of sepsis on hippocampal volume and memory function [J]. World Journal of Emergency Medicine, 2020, 11(4): 223-230.
[5]	Wen-peng Yin, Jia-bao Li, Xiao-fang Zheng, Le An, Huan Shao, Chun-sheng Li. Effect of neutrophil CD64 for diagnosing sepsis in emergency department [J]. World Journal of Emergency Medicine, 2020, 11(2): 79-86.
[6]	Shao-hua Liu, Huo-yan Liang, Hong-yi Li, Xian-fei Ding, Tong-wen Sun, Jing Wang. Effect of low high-density lipoprotein levels on mortality of septic patients: A systematic review and meta-analysis of cohort studies [J]. World Journal of Emergency Medicine, 2020, 11(2): 109-116.
[7]	Kimberly A. Chambers, Adam Y. Park, Rosa C. Banuelos, Bryan F. Darger, Bindu H. Akkanti, Annamaria Macaluso, Manoj Thangam, Pratik B. Doshi. Outcomes of severe sepsis and septic shock patients after stratification by initial lactate value [J]. World Journal of Emergency Medicine, 2018, 9(2): 113-117.
[8]	Muhammad Akbar Baig, Hira Shahzad, Erfan Hussain, Asad Mian. Validating a point of care lactate meter in adult patients with sepsis presenting to the emergency department of a tertiary care hospital of a low- to middle-income country [J]. World Journal of Emergency Medicine, 2017, 8(3): 184-189.
[9]	Ming Wei, Yan-jie Gong, Ling Tu, Jia Li, Ying-hong Liang, Yi-hua Zhang. Expression of phosphatidylinositol-3 kinase and effects of inhibitor Wortmannin on expression of tumor necrosis factor-α in severe acute pancreatitis associated with acute lung injury [J]. World Journal of Emergency Medicine, 2015, 6(4): 299-304.
[10]	Chao Cao, Tao Ma, Yan-fen Chai, Song-tao Shou. The role of regulatory T cells in immune dysfunction during sepsis [J]. World Journal of Emergency Medicine, 2015, 6(1): 5-9.
[11]	Zhi-wei Liu, Hai-ying Wang, Lan Guan, Bin Zhao. Regulatory effects of hydrogen sulfide on alveolar epithelial cell endoplasmic reticulum stress in rats with acute lung injury [J]. World Journal of Emergency Medicine, 2015, 6(1): 67-73.
[12]	Kun Chen, Qiu-xiang Zhou, Hong-wei Shan, Wen-fang Li, Zhao-fen Lin. Prognostic value of CD4⁺CD25⁺ Tregs as a valuable biomarker for patients with sepsis in ICU [J]. World Journal of Emergency Medicine, 2015, 6(1): 40-43.
[13]	Hui Fu, Qiao-sheng Wang, Qiong Luo, Si Tan, Hua Su, Shi-lin Tang, Zheng-liang Zhao, Li-ping Huang. Simvastatin inhibits apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax [J]. World Journal of Emergency Medicine, 2014, 5(4): 291-297.
[14]	Qi Zou, Wei Wen, Xin-chao Zhang. Presepsin as a novel sepsis biomarker [J]. World Journal of Emergency Medicine, 2014, 5(1): 16-19.
[15]	Nishant Raj Pandey, Yu-yao Bian, Song-tao Shou. Significance of blood pressure variability in patients with sepsis [J]. World Journal of Emergency Medicine, 2014, 5(1): 42-47.