Association of Histological Features of Cortical and Medullary Peritubular Capillaries With Progressive CKD.

RATIONALE & OBJECTIVE: Peritubular capillary (PTC) rarefaction occurs in chronic kidney disease (CKD), but the independent association of PTC histological features with CKD progression is uncertain. Assessment of this relationship was the principal aim of this study. STUDY DESIGN: Historical cohort study. SETTING & POPULATION: Patients who underwent radical nephrectomy for a kidney tumor. EXPOSURE: PTC histological features including density, mean area, major axis length, and circularity, were defined in the cortex (excluding regions of interstitial fibrosis and tubular atrophy [IFTA]) and medulla using previously developed deep learning models. OUTCOMES: Progressive CKD was defined as the composite of dialysis, kidney transplantation, a sustained decline in estimated glomerular filtration rate (eGFR) of ≥30%, or a sustained eGFR <10 mL/min/1.73 m2 that was ≥5 mL/min/1.73 m2 lower that the post-nephrectomy value. ANALYTICAL APPROACH: Cox proportional hazards analysis where follow-up was censored at death, cancer recurrence, or the last serum creatinine value adjusted for chronic histological changes (IFTA, glomerulosclerosis, arteriosclerosis, and arteriolar hyalinosis), and the CKD risk factors of age, sex, body mass index, hypertension, diabetes, eGFR, and proteinuria. RESULTS: 94 (6.1%) of 1553 patients, followed for a mean of 4.3 years, experienced progressive CKD. A mean of 28,055 PTCs and 332 glomeruli were detected in each wedge section. In cortical and medullary tissue, a lower density of PTCs and PTCs that were more circular and less elongated were associated with progressive CKD in analyses adjusted for kidney function and CKD risk factors. After additional adjustment for chronic histological changes, only cortical PTCs that were more circular and less elongated were associated with progressive CKD. LIMITATIONS: Study limited to patients who underwent a radical nephrectomy for a tumor. CONCLUSIONS: Reduction and simplification of the microvasculature in non-scarred regions of cortex and medulla are associated with progressive CKD.