Novel Biomarkers in CKD

Summary

This script delves into novel biomarkers for early diagnosis and management of Chronic Kidney Disease (CKD). It highlights the limitations of traditional markers like creatinine and cystatin C, and emphasizes the need for new indicators that can detect renal dysfunction and specific types of injury earlier. The presentation reviews various emerging biomarkers, including beta trace protein, NGAL, and others, which reflect renal function changes, tubular damage, endothelial dysfunction, inflammation, and metabolism. The goal is to improve diagnostic accuracy, guide treatment, and predict disease progression, with a call for further validation through larger studies.

Takeaways

• 📈 Chronic Kidney Disease (CKD) is a significant health issue, becoming the fourth most common cause of death in the Philippines, surpassing tuberculosis, and affecting an estimated 843.6 million individuals worldwide in 2017.
• 🔍 Ideal CKD biomarkers should be able to screen, confirm, and stage CKD, as well as stratify risks and guide treatments.
• 📊 Traditional biomarkers like creatinine, cystatin C, and urine albumin are used for CKD diagnosis, but they often rise late in the disease progression, indicating significant kidney function reduction.
• 🆕 New biomarkers for CKD are sought to provide better indicators of renal dysfunction than GFR and to reflect specific types of injury and associated cardiovascular risks.
• 🧬 Beta trace protein and beta-2 microglobulin are low molecular weight proteins that, when found in urine, suggest proximal tubular damage and could serve as early indicators of reduced GFR.
• 🚑 NGAL (Neutrophil Gelatinase-Associated Lipocalin) and KIM-1 (Kidney Injury Molecule-1) are emerging as early biomarkers of CKD, indicating tubular epithelial cell injury.
• 🧪 NAG (N-acetyl-β-D-glucosaminidase), an enzyme mainly found in lysosomes of proximal tubular cells, is another promising biomarker for proximal tubular damage in CKD.
• 🩸 Liver-type fatty acid-binding protein (LFABP) is expressed in response to injury to proximal tubular cells and could be a biomarker for CKD, reflecting endothelial damage.
• 🔄 Endothelial dysfunction in CKD is characterized by a reduction in nitric oxide and increased levels of asymmetric dimethylarginine (ADMA), which is an independent risk marker for cardiovascular disease.
• 💊 Inflammation is a key aspect of CKD, with inflammatory markers such as interleukins and tumor necrosis factor receptors showing increased levels in CKD patients, potentially serving as prognostic indicators.
• 🧬 Metabolic profiling, including the analysis of urinary lysine and histidine, may offer insights into CKD and could be developed into future biomarkers for the disease.

Q & A

What is the significance of discussing novel biomarkers in chronic kidney disease (CKD)?

Novel biomarkers in CKD are significant for early diagnosis, formulating diagnostic plans, and recommending their use as adjuncts to current tools. They can help identify the disease before significant kidney function reduction occurs, leading to better treatment outcomes.

How does the prevalence of CKD compare to other health conditions globally and in the Philippines?

CKD is a prominent cause of death and suffering, affecting an estimated 843.6 million individuals worldwide in 2017. In the Philippines, at least 7 million Filipinos have CKD, with one developing it every hour, and it became the fourth most common cause of death in 2019, overtaking tuberculosis.

What are the ideal measurements for CKD and what are the limitations of traditional biomarkers?

Ideal measurements for CKD should screen, confirm, and stage the disease, stratify risks for outcomes, and guide treatments. Traditional biomarkers like creatinine, cystatin C, and albuminuria have limitations as they often rise only after significant kidney function has been lost, making them late indicators.

What is the KDIGO heatmap and how is it used in CKD diagnosis?

The KDIGO heatmap is a tool used to grade or stage CKD patients based on estimated Glomerular Filtration Rate (eGFR) and urine albumin levels. It helps in assessing the degree of kidney dysfunction and the presence of damage.

Why is there a need for new biomarkers for CKD diagnosis?

New biomarkers are needed because they can serve as better indicators of renal dysfunction than GFR, mark specific types of injury, reflect changes in renal function, and indicate damage before it becomes irreversible, thus allowing for earlier intervention.

What are some examples of novel biomarkers discussed in the script for early detection of CKD?

Examples include beta trace protein, beta-2 microglobulin, NGAL (Neutrophil Gelatinase-Associated Lipocalin), KIM-1 (Kidney Injury Molecule-1), NAG (N-acetyl-β-D-glucosaminidase), and L-FABP (Liver-Type Fatty Acid Binding Protein).

How do beta trace protein and beta-2 microglobulin function as potential CKD biomarkers?

Beta trace protein and beta-2 microglobulin are low molecular weight proteins filtered by the glomeruli and almost completely reabsorbed by the proximal tubules. An increase in these proteins in the final urine suggests tubular damage and can serve as early indicators of decreased GFR.

What role do NGAL and KIM-1 play in the early detection of CKD?

NGAL and KIM-1 are expressed by tubular epithelial cells in response to injury and can be found increased in the urine before the development of irreversible tubular atrophy and fibrosis, making them potential early biomarkers of CKD.

How do markers of endothelial dysfunction, such as ADMA and fetuin-A, relate to CKD?

ADMA (Asymmetric Dimethylarginine) and fetuin-A are markers that reflect pathological alterations in endothelial integrity. They are associated with reduced nitric oxide levels, contributing to endothelial dysfunction, which is an early event in CKD progression.

What is the potential of inflammatory markers in CKD diagnosis and management?

Inflammatory markers like interleukins and tumor necrosis factor receptors have been shown to increase in CKD and are associated with disease morbidity and cardiovascular mortality. They may be used as diagnostic markers and targets for anti-inflammatory therapies to slow CKD progression.

What are the future directions for the use of novel biomarkers in CKD management?

The future directions include the identification of reliable early biomarkers of CKD that can improve the accuracy of current diagnostic methods. The additional use of these biomarkers may enhance the estimation of GFR and provide insights into the pathophysiological mechanisms underlying the disease, potentially leading to more targeted therapies.