DOI: 10.25259/ijn_42_2026 ISSN: 1998-3662

Compartment-Specific Distribution of CD68-Positive Macrophages and its Association with Chronic Kidney Injury Across Diverse Renal Disorders

Yashita Gupta, Swarnalata Gowrishankar, Neha Agrawal, Aishwarya John

Background

Macrophage infiltration is increasingly recognized as a contributor to chronic kidney injury. However, the clinicopathologic significance of compartment-specific localization of CD68-positive macrophages in native kidney biopsies remains incompletely defined. We evaluated the distribution of CD68-positive macrophages across renal compartments in diverse renal disorders and assess their association with chronic structural damage and renal function.

Materials and Methods

This cross-sectional study included 80 native kidney biopsies comprising minimal change disease (MCD, n = 10), chronic tubulointerstitial nephritis (CTIN, n = 10), IgA nephropathy (IgAN, n = 20), diabetic nephropathy (DN, n = 20), and lupus nephritis (LN, n = 20). CD68 immunohistochemistry was evaluated in the total tubulointerstitium, atrophic and inflamed tubulointerstitial areas, and glomeruli. Associations with interstitial fibrosis and tubular atrophy (IFTA) and serum creatinine were assessed using Spearman correlation. In LN, correlations with activity and chronicity indices were also evaluated.

Results

CD68-positive macrophage density in atrophic tubulointerstitial areas showed marked disease-wise variation, being highest in DN and lowest in MCD. Across the combined cohort, atrophic-area CD68 were correlated with IFTA (r = 0.74, p <0.001) and serum creatinine (r = 0.41, p <0.001). Inflamed area and total tubulointerstitial CD68 also correlated with IFTA and creatinine, whereas glomerular CD68 showed no significant association. In LN, inflamed-area CD68 correlated with activity index (r = 0.49, p = 0.03), while atrophic-area CD68 correlated strongly with chronicity index (r = 0.87, p <0.001).

Conclusion

Localization of CD68-positive macrophages within atrophic tubulointerstitial areas was associated with chronic kidney damage. These findings require validation in longitudinal studies.