Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study

Schunk, Stefan; Zarbock, Alexander; Meersch, Melanie; Küllmar, Mira; Kellum, John A.; Schmit, David; Wagner, Michaela; Triem, Sarah; Wagenpfeil, Stefan; Gröne, Hermann–Josef; Schäfers, Hans‐Joachim; Fliser, Danilo; Speer, Thimoteus; Zewinger, Stephen

doi:10.1016/s0140-6736(19)30769-x

Cited by 118 publications

(89 citation statements)

References 30 publications

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“…Several novel biomarkers have been shown to detect AKI earlier and are more sensitive than sCr (Table). [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] For any prevention strategies to be effective, patients with high risk need to be identified before kidney insults result in kidney damage, and AKI needs to be diagnosed as early as possible. Downloaded From: https://jamanetwork.com/ on 10/31/2020 Damage markers indicate structural damage that may or may not be associated with reduced kidney function.…”

Section: Introductionmentioning

confidence: 99%

Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference

et al. 2020

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IMPORTANCE In the last decade, new biomarkers for acute kidney injury (AKI) have been identified and studied in clinical trials. Guidance is needed regarding how best to incorporate them into clinical practice. OBJECTIVE To develop recommendations on AKI biomarkers based on existing data and expert consensus for practicing clinicians and researchers. EVIDENCE REVIEW At the 23rd Acute Disease Quality Initiative meeting, a meeting of 23 international experts in critical care, nephrology, and related specialties, the panel focused on 4 broad areas, as follows: (1) AKI risk assessment; (2) AKI prediction and prevention; (3) AKI diagnosis, etiology, and management; and (4) AKI progression and kidney recovery. A literature search revealed more than 65 000 articles published between 1965 and May 2019. In a modified Delphi process, recommendations and consensus statements were developed based on existing data, with 90% agreement among panel members required for final adoption. Recommendations were graded using the Grading of Recommendations, Assessment, Development and Evaluations system. FINDINGS The panel developed 11 consensus statements for biomarker use and 14 research recommendations. The key suggestions were that a combination of damage and functional biomarkers, along with clinical information, be used to identify high-risk patient groups, improve the diagnostic accuracy of AKI, improve processes of care, and assist the management of AKI. CONCLUSIONS AND RELEVANCE Current evidence from clinical studies supports the use of new biomarkers in prevention and management of AKI. Substantial gaps in knowledge remain, and more research is necessary.

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Section: Introductionmentioning

confidence: 99%

Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference

et al. 2020

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“…24 Further, in patients about to undergo major cardiac surgery, preoperative urinary DKK3 levels are associated with postoperative acute kidney injury and future loss of renal function. 25 Animal experiments showed that renal tubular epithelial cells appear to be the main source of urinary DKK3 and DKK3 in urine has been proposed as a marker for renal tubular damage and renal tubules at risk. [24][25][26][27] In this study, which investigated DKK3 levels in plasma rather than in urine, a relationship was identified between kidney function and DKK3 plasma levels.…”

Section: Discussionmentioning

confidence: 99%

A combined bioinformatics, experimental and clinical approach to identify novel cardiac‐specific heart failure biomarkers: is Dickkopf‐3 (DKK3) a possible candidate?

Piek

Suthahar

Voors

et al. 2020

European J of Heart Fail

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Aims Cardiac specificity provides an advantage in correlating heart failure (HF) biomarker plasma levels with indices of cardiac function and remodelling, as shown for natriuretic peptides. Using bioinformatics, we explored the cardiac specificity of secreted proteins and investigated in more detail the relationship of Dickkopf‐3 (DKK3) gene expression and DKK3 plasma concentrations with cardiac function and remodelling in (pre)clinical studies. Methods and results The cardiac specificity of secreted proteins was determined using RNAseq data for a large panel of organs and tissues. This showed that natriuretic peptides (NPPA and NPPB) are highly cardiac‐specific (>99%), whereas other HF biomarkers, including galectin‐3 (Gal‐3, LGALS3) and growth differentiation factor‐15 (GDF‐15), lack cardiac specificity (<4%). DKK3 was cardiac‐enriched (44%), warranting further investigation. In three different HF mouse models, cardiac Dkk3 expression was altered, but DKK3 plasma concentrations were not. In humans, DKK3 plasma concentrations were higher in HF patients (n = 2090) in comparison with age‐ and sex‐matched controls without HF (n = 240) (46.4 ng/mL vs. 36.3 ng/mL; P < 0.001). Multivariate regression analysis revealed that DKK3 was strongly associated with HF risk factors and comorbidities, including age, kidney function and atrial fibrillation. After correction for existing prediction models, DKK3 did not independently predict HF outcome [all‐cause mortality/HF hospitalization, hazard ratio 1.13 (0.79–1.61) per DKK3 doubling; P = 0.503]. Conclusions Of actively secreted HF biomarkers, only natriuretic peptides showed high cardiac specificity. Despite a cardiac specificity of 44%, secreted DKK3 had limited additional diagnostic and prognostic value.

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“…AKI is condition currently associated with increased short-term morbidity and mortality [6]. Its incidence has increased exponentially in recent years, given factors such as aging and multiple comorbidities [7].…”

Section: Biomarkers In Akimentioning

confidence: 99%

Biomarkers in acute kidney injury

Pájaro-Galvis¹

2020

J Clini Nephrol

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Acute kidney injury is a common condition associated with high morbidity and short-term mortality. Its pathophysiology varies according to the numerous conditions associated with its genesis. Biomarkers allow detecting changes at the level of kidney function; therefore, they play an important role in the prevention, early diagnosis, therapeutic response and prognosis of acute kidney injury. The search for biomarkers for acute kidney injury began over 15 years ago; initially, only serum creatinine was available for diagnosis. However, throughout history, great advances have been made in research, which have allowed the fi nding of new biomarkers in order to improve the health and quality of life of patients. A narrative review of the literature is carried out on the basis of available scientifi c evidence to clarify the role and importance of biomarkers in the context of acute renal injury. serum creatinine (sCr), knowing that a signi icant reduction in the glomerular iltration rate will increase the sCr [1]. Until the year 2002, there was no standardized de inition More Information

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Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study

Cited by 118 publications

References 30 publications

Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference

Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference

A combined bioinformatics, experimental and clinical approach to identify novel cardiac‐specific heart failure biomarkers: is Dickkopf‐3 (DKK3) a possible candidate?

Biomarkers in acute kidney injury

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