High Macrophage Densities in Native Kidney Biopsies Correlate With Renal Dysfunction and Promote ESRD
Maren Bettina Pfenning, Jessica Schmitz, Irina Scheffner, Kevin L. Schulte, Abedalrazag Khalifa, Hossein Tezval, Alexander Weidemann, Anke Kulschewski, Ulrich Kunzendorf, Sebastián Dietrich, Hermann Haller, Jan T. Kielstein, Wilfried Gwinner, Jan Hinrich Bräsen
Abstract
Introduction Macrophages and monocytes are main players in innate immunity. The relevance of mononuclear phagocyte infiltrates on clinical outcomes remains to be determined in native kidney diseases. Methods Our cross-sectional study included 324 patients with diagnostic renal biopsies comprising 17 disease entities and normal renal tissues for comparison. All samples were stained for CD68 + macrophages. Selected groups were further subtyped for CD14 + monocytes and CD163 + alternatively activated macrophages. Using precise pixel-based digital measurements, we quantified cell densities as positively stained areas in renal cortex and medulla as well as whole renal tissue. Laboratory and clinical data of all cases at the time of biopsy and additional follow-up data in 158 cases were accessible. Results Biopsies with renal disease consistently revealed higher CD68 + -macrophage densities and CD163 + -macrophage densities in cortex and medulla compared to controls. High macrophage densities correlated with impaired renal function at biopsy and at follow-up in all diseases and in diseases analyzed separately. High cortical CD68 + -macrophage densities preceded shorter renal survival, defined as requirement of permanent dialysis. CD14 + monocyte densities showed no difference compared to controls and did not correlate with renal function. Conclusion Precise quantification of macrophage densities in renal biopsies may contribute to risk stratification to identify patients with high risk for end-stage renal disease (ESRD) and might be a promising therapeutic target in renal disease.