Assessing the role of Chemokine (C–C motif) ligand 14 in AKI: a European consensus meeting

Figures & data

Figure 1. Overview of the four-step Delphi method used in the Roundtable Meeting. Each step was a distinct process that was completed before the following step was initiated. Results and discussions from each step were independently analysed and used to inform the direction and content of the following steps, e.g. if the group were split on a topic, then clarifying questions were crafted to guide the discussions in the following step(s) to identify and explore points of consensus or difference. GPP3, Good Publication Practice 3.

Table 1. Ranking of the challenges for adopting the chemokine (C-C motif) ligand 14 biomarker.

Challenges for adopting the CCL14 biomarker	Points (Max 64)
Lack of guidelines and recommendations for patient management based on CCL14 biomarker results	49
Insufficient evidence for specific clinical actions based on biomarker results	47
Lack of awareness of the role of the CCL14 biomarker	42
Internal cost containment policies	40
Lack of staffing resources	33
Lack of dedicated hospital educational resources	32
Laboratory department considerations	32
Administrative barriers	31
Other factors influencing clinicians’ decision-making	30
Lack of awareness of increased costs/economic burden associated with PS-AKI	29
Lack of awareness of persistent severe AKI (PS-AKI) and its impact on outcomes	27
Lack of routine AKI staging	26
Lack of specific local AKI management protocols	24
Low incidence of AKI Stage 2–3	12

The points assigned per challenge were: Not challenging = 0 points, Slightly Challenging = 1 point, Moderately challenging = 2 points, Very Challenging = 3 points, Extremely Challenging = 4 points.

Table 2. Ranking of populations likely to gain clinical benefit from chemokine (C-C motif) ligand 14 implementation.

Population	Points (Max 64)
AKI Stage 2 or 3 patients with cardiac surgery-associated AKI (CSA-AKI)	53
AKI Stage 2 or 3 patients with heart failure	53
AKI Stage 2 or 3 patients with sepsis	52
AKI Stage 2 or 3 surgery-associated AKI (other than cardiac) patients	50
All AKI Stage 3 patients	50
AKI Stage 2 or 3 patients with trauma	49
AKI Stage 2 or 3 in patients with risk factors for CKD (proteinuria, diabetes, etc.)	49
All AKI Stage 2 patients	47
AKI Stage 2 or 3 in patients with CKD	45

The points assigned per population were: Very Unlikely = 0 points, Somewhat Unlikely = 1 point, Equally Likely/Unlikely = 2 points, Somewhat Likely = 3 points, Very Likely = 4 points.

Table 3. Ranking of the level of concern about modifying several areas of the treatment plan.

	Points (Max 64)
Treatment Plan Area	CCL14 ≤ 1.30 ng/mL	CCL14 > 1.30 ng/mL and ≤ 13 ng/mL	CCL14 > 13 ng/mL
Discussions on renal replacement therapy initiation	16	44	48
Discussions with family on patient prognosis	23	37	42
Diuretic management	21	39	44
Drug dosing	23	35	41
Enhance diagnostic work-up (e.g. labs, images)	18	39	44
Exposure to nephrotoxins	23	39	44
Fluid management (type of solution)	17	28	36
Fluid management (volume)	19	37	46
Follow-up medical planning after discharge (outpatient care)	18	36	40
Hemodynamic management/monitoring	18	40	46
Nephrology consultation	14	31	35
Nutritional management	17	30	31
Strict urine output monitoring (e.g. foley catheter, continuous urinary output monitoring)	17	38	45

The points assigned per treatment area were: Not At All Concerned = 0 points, Slightly Concerned = 1 point, Moderately Concerned = 2 points, Very Concerned = 3 points, Extremely Concerned = 4 points.

Table 4. Consensus voting: Actions based on chemokine (C-C motif) ligand 14 biomarker results.

Consensus Statement	Response (N = 16)
	Disagree n (%)	Somewhat disagree n (%)	Neither agree nor disagree n (%)	Somewhat agree n (%)	Agree n (%)
CCL14 biomarker results can help support a patient-centred approach for timely and targeted clinical decisions in patients with moderate or severe AKI when AKI management is the primary concern.	0 (0)	0 (0)	2 (12.5)	9 (56.3)	5 (31.3)
CCL14 biomarker results can help prioritize AKI resources, care processes, and workflows, including diagnostic work-up, monitoring, discussions with family on patient prognosis and follow-up planning.	0 (0)	1 (6.3)	2 (12.5)	5 (31.3)	8 (50.0)
CCL14 biomarker results can help prioritize AKI management decisions including fluid management (volume), diuretic use, strict urine output monitoring, and nephrotoxic exposure.	0 (0)	2 (12.5)	3 (18.8)	8 (50)	3 (18.8)
CCL14 biomarker results can help prioritize AKI management decisions, including hemodynamic management and monitoring.	0 (0)	3 (18.8)	4 (25)	7 (43.8)	2 (12.5)
CCL14 biomarker results can help prioritize discussions on RRT initiation in highest risk PS-AKI patients, and RRT avoidance in patients likely to recover renal function.	0 (0)	0 (0)	1 (6.3)	5 (31.3)	10 (62.3)
CCL14 biomarker results ≤ 1.30 ng/mL can be informative for certain aspects of AKI management and care processes of care, including drug dosing, exposure to nephrotoxins and family discussions on patient prognosis.	0 (0)	2 (12.5)	5 (31.3)	2 (12.5)	7 (43.8)
CCL14 biomarker results > 1.30 ng/mL and ≤ 13 ng/mL increase the level of concern to modify the AKI treatment plan, specific adjustment needs to be contextualized to the different clinical scenarios.	0 (0)	0 (0)	2 (12.5)	7 (43.8)	7 (43.8)
CCL14 biomarker results > 13 ng/mL increase the level of concern to modify the AKI treatment plan and are informative for certain aspects of AKI management and care processes, including fluid/hemodynamic management and monitoring.	0 (0)	1 (6.3)	3 (18.8)	5 (31.3)	7 (43.8)
CCL14 biomarker results > 13 ng/mL increase the level of concern to modify the AKI treatment plan and are informative for certain aspects of AKI management and care processes, including discussion on RRT initiation, strict urine output monitoring and diuretic management.	0 (0)	0 (0)	1 (6.3)	7 (43.8)	8 (50.0)

Table 5. Post-hoc analyses between chemokine (C-C motif) ligand 14cutoff levels.

	CCL14 Medium – Low		CCL14 High – Medium		CCL14 High – Low
Points (max 64)
	Mean difference (95% CI)	p-Value	Mean Difference (95% CI)	p-Value	Mean Difference (95% CI)	p-Value
Overall	17.6 (14.6, 20.7)	<0.001	5.3 (1.5, 9.1)	0.004	22.9 (19.6, 26.2)	<0.001
On Likert scale (0–4)
Overall	1.1 (0.88, 1.32)	0.183	0.3 (0.11, 0.56)	>0.999	1.4 (1.19, 1.68)	<0.001

Table 6. Post-hoc analyses between chemokine (C-C motif) ligand 14cutoff values per treatment plan on likert scale.

	CCL14 Medium – Low		CCL14 High – Medium		CCL14 High – Low
Treatment Plan Area	Mean Difference (95% CI)	p-Value	Mean Difference (95% CI)	p-Value	Mean Difference (95% CI)	p-Value
Discussions on renal replacement therapy (RRT) initiation	1.8 (1.02, 2.48)	0.023	0.3 (−0.46, 0.96)	0.980	2.0 (1.19, 2.81)	0.009
Discussions with family on patient prognosis	0.9 (0.07, 1.68)	0.623	0.3 (−0.47, 1.09)	0.959	1.2 (0.30, 2.08)	0.335
Diuretic management	1.1 (0.36, 1.89)	0.370	0.3 (−0.42, 1.05)	0.967	1.4 (0.60, 2.28)	0.147
Drug dosing	0.8 (−0.11, 1.61)	0.722	0.4 (−0.48, 1.23)	0.926	1.1 (0.21, 2.04)	0.391
Enhance diagnostic work-up (e.g. labs, images)	1.3 (0.62, 2.01)	0.182	0.3 (−0.42, 1.05)	0.967	1.6 (0.80, 2.45)	0.065
Exposure to nephrotoxins	1.0 (0.11, 1.89)	0.500	0.3 (−0.63, 1.25)	0.927	1.3 (0.28, 2.34)	0.270
Fluid management (type of solution)	0.7 (−0.23, 1.60)	0.755	0.5 (−0.50, 1.50)	0.841	1.2 (0.17, 2.21)	0.355
Fluid management (volume)	1.1 (0.27, 1.98)	0.383	0.6 (−0.32, 1.45)	0.839	1.7 (0.74, 2.64)	0.075
Follow-up medical planning after discharge (outpatient care)	1.1 (0.35, 1.90)	0.372	0.3 (−0.57, 1.07)	0.964	1.4 (0.50, 2.25)	0.193
Hemodynamic management/monitoring	1.4 (0.59, 2.16)	0.170	0.4 (−0.37, 1.12)	0.952	1.8 (0.88, 2.62)	0.044
Nephrology consultation	1.1 (0.18, 1.94)	0.443	0.3 (−0.66, 1.16)	0.949	1.3 (0.34, 2.28)	0.258
Nutritional management	0.8 (−0.07, 1.69)	0.666	0.1 (−0.84, 0.96)	0.979	0.9 (−0.11, 1.86)	0.601
Strict urine output monitoring (e.g. foley catheter, continuous urinary output monitoring)	1.3 (0.41, 2.21)	0.242	0.4 (−0.46, 1.33)	0.895	1.8 (0.82, 2.68)	0.054

Data availability statement

The data underlying this article are available in the article and in its online supplementary material.