MO494: The Prospective Roles of Urinary Dickkopf-3 for Detecting Renal Function Deterioration and Monitoring Chronic Kidney Disease Progression: Systematic Review of Cohort Studies

Abstract

BACKGROUND AND AIMS Chronic kidney disease (CKD) is a worldwide health problem whose incremental prevalence. Early detection and proper monitoring of renal dysfunction can decrease morbidity and mortality among CKD patients. Estimated glomerular filtration rate (eGFR) and albuminuria have been used for monitoring CKD progression. Unfortunately, substantial CKD patients’ proportion might undergo CKD progression through non-proteinuric pathways. Dickkopf-3 (DKK3), stress-induced renal tubular epithelial-derived glycoprotein, is a key driver of tubulointerstitial fibrosis through the canonical Wnt/β-catenin signaling pathway. This study aims to evaluate the role of DKK3 in detecting and monitoring renal dysfunction and CKD progression. METHOD Comprehensive literature searching was performed through the online databases of PubMed, EMBASE, ScienceDirect and The Cochrane Library. This study followed the PRISMA guidelines. The inclusion criteria are all cohort studies that assess the correlation and clinical implications of increased urinary DKK3 with CKD progression. The quality of included studies was accessed by using the Newcastle–Ottawa Scale. RESULTS Six cohort studies matched the inclusion criteria. Urinary DKK3-to-creatinine >4000 pg/mg was independently associated with annual eGFR decline among early CKD stages. A multivariate analysis study suggested that 24-h urinary DKK3 was independently associated with the annual Kt/V decline among peritoneal dialysis patients. Increased urinary DKK3 was associated with a significant eGFR decline in 6 months among IgA nephropathy patients. A cohort study suggested that populations with microalbuminuria were significantly susceptible to prevalent cardiovascular diseases, prevalent CKD, and new-onset CKD risks. Urinary DKK3 was associated with significant incremental risks for declining eGFR and proteinuria as well as CKD progression risks in chronic obstructive pulmonary disease (COPD) patients. In a study, involving CKD patients who underwent coronary angiography, the baseline urinary DKK3-to-creatinine ratio was superior to serum cystatin-C and serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), predicting both acute kidney injury (AKI) and persistent renal dysfunction. A cardiac surgery study showed that high urinary DKK3-to-creatinine ratio >471 pg/mg was significantly associated with AKI, persistent renal dysfunction and dialysis dependency. CONCLUSION Dickkopf-3 shows promising prospective roles for detecting early renal dysfunction and monitoring CKD progression. Nevertheless, further studies are warranted to confirm its promising prospective role.

Plasma Biomarker Dickkopf-3 and its Association with Chronic Kidney Disease:Review Article

“…They generate a variety of bioactive chemicals that keep the harm going and ultimately result in the epithelial-mesenchymal transition and irreversible scarring of the kidneys. The latter is referred to as tubulointerstitial fibrosis, and it is the pathological hallmark of numerous CKD entities with various underlying causes that eventually result in organ failure (4) . However, there are currently no biomarkers for this particular renal pathologic course.…”

“…Numerous factors can either activate or inhibit Wnt signaling. In addition to the activity and/or concentration of the ligands and co-activators/co-inhibitors, important parameters in influencing the Wnt signaling include the time and duration of activity, as well as the interaction with other cytokine-triggered pathways (4) .…”

“…DKK3 appears to be a part of evolutionary conserved gene clusters that are expressed during disease (or "stress") states and re-expressed during developmental processes. Because of this, it is intriguing since prior in vitro studies showed that DKK3 can, depending on the tissue examined, either activate or repress canonical Wnt/b-catenin signaling (4) .…”

“…Currently, the glomerular filtration rate (GFR) and albuminuria are acknowledged indicators of the long-term progression of CKD. Patients with CKD of diverse etiologies are categorised in the kidney disease based on their estimated GFR (e-GFR) and albuminuria: kidney disease progression is classified according to Improving Global Outcomes (KDIGO) standards as low, moderate, high, or extremely high (4) .…”

“…These are heavily dependent on albuminuria and e-GFR, but they also take other clinical and biochemical factors into account. (4) .…”