Nailfold Capillary Density and Kidney Injury in CKD

Microvascular dysfunction plays a key role in the development and progression of chronic kidney disease (CKD). Evaluation of capillaries by microscopy of the nailfolds may provide noninvasive insight into systemic microvascular health, but its relationship with kidney function, proteinuria, and kidney histopathology in patients with CKD remains unknown.

We conducted a cross-sectional analysis of adults with CKD stages 2-5 (estimated glomerular filtration rate [eGFR] < 90 ml/min per 1.73 m²) recruited from nephrology outpatient clinics at a single academic medical center between January 2023 and December 2025. Participants underwent assessment of third and fourth finger nailfold microvascular structure and function using high-resolution video capillaroscopy at 100× magnification. The density of erythrocyte-perfused capillaries (capillaries/mm²) was quantified at baseline, after the release of arterial occlusion (HA) (hyperemic response), and during venous congestion (OA) using a deep learning-based image analysis pipeline. Associations between capillary density measures and kidney function (eGFR) and urine protein-to-creatinine ratio (uPCR) were evaluated using multivariable regression models. In a subset of participants who underwent clinically indicated kidney biopsy, capillary density measures were examined for associations with histopathologic findings, including glomerulosclerosis (GS) and interstitial fibrosis and tubular atrophy (IFTA), using similar multivariable models.

Among 189 participants with CKD, mean (standard deviation [SD]) age was 63 (16) years; 49% were female, 42% had diabetes, and 87% had hypertension. Mean (SD) baseline capillary density was 54 (15) capillaries/mm². The mean eGFR was 41 (22) ml/min per 1.73 m² and median (interquartile range [IQR]) uPCR was 0.31 [IQR: 0.11-1.8] mg/mg. In adjusted models, higher capillary density was associated with higher eGFR (β, 0.33; 95% confidence interval [CI], 0.25-0.41) and lower uPCR (β -1.1; 95% CI -1.7 to -0.5) independent of CKD risk factors. Results were similar evaluating capillary count at HA and OA. Among the subset of 36 participants with kidney biopsy data, lower capillary density was associated with greater GS and IFTA severity, which remained significant after adjustment for demographic factors, eGFR, and proteinuria.

Finger nailfold capillary density is associated with kidney function, proteinuria, and biopsy markers of chronic kidney injury among adults with CKD. Capillaroscopy may provide a noninvasive tool to identify vascular and interstitial damage above and beyond eGFR and proteinuria in patients with CKD.