Cutaneous Microvascular Functional Reserve is Associated with Kidney Function and Histopathologic Injury in CKD: The...

Area of Science:

• Nephrology
• Cardiovascular Science
• Biomedical Engineering

Background:

• Microvascular dysfunction is a significant factor in chronic kidney disease (CKD) progression.
• Assessing microvascular function in CKD patients is challenging due to limited direct and reproducible methods.
• Laser Doppler flowmetry (LDF) offers a noninvasive approach to evaluate skin microvascular blood flow as a potential systemic health indicator.

Purpose of the Study:

• To investigate the relationship between LDF-derived microvascular function measures and kidney function (eGFR) in CKD patients.
• To explore the association of LDF measures with proteinuria (uPCR) and kidney histopathology (glomerulosclerosis, interstitial fibrosis, tubular atrophy).
• To identify distinct microvascular phenotypes in CKD using unsupervised clustering.

Main Methods:

• 150 CKD participants underwent a standardized forearm LDF protocol, measuring baseline perfusion and hyperemia response to local heating.
• Multivariable linear regression analyzed associations between LDF measures (resting perfusion, functional reserve) with eGFR and uPCR.
• Unsupervised k-means clustering identified microvascular phenotypes.
• LDF measures were correlated with kidney biopsy findings (glomerulosclerosis, interstitial fibrosis, tubular atrophy) in a subset of 20 participants.

Main Results:

• Higher resting perfusion and reduced microvascular functional reserve (assessed by LDF) were significantly associated with lower estimated glomerular filtration rate (eGFR) in CKD patients.
• No significant association was found between LDF measures and urine protein-to-creatinine ratio (uPCR).
• Four distinct microvascular phenotypes were identified.
• Increased resting perfusion and impaired functional reserve correlated with more severe glomerulosclerosis and interstitial fibrosis/tubular atrophy in kidney biopsies.

Conclusions:

• LDF-derived measures reflect clinically relevant systemic microvascular alterations in individuals with CKD.
• These findings suggest LDF can serve as a noninvasive biomarker for assessing kidney function and histopathologic injury in CKD.
• Cutaneous microvascular assessment using LDF may provide valuable insights into the systemic impact of CKD.