High Macrophage Densities in Native Kidney Biopsies Correlate With Renal Dysfunction and Promote ESRD

Maren B Pfenning; Jessica Schmitz; Irina Scheffner; Kevin Schulte; Abedalrazag Khalifa; Hossein Tezval; Alexander Weidemann; Anke Kulschewski; Ulrich Kunzendorf; Sebastian Dietrich; Hermann Haller; Jan T Kielstein; Wilfried Gwinner; Jan H Bräsen

doi:10.1016/j.ekir.2022.11.015

High Macrophage Densities in Native Kidney Biopsies Correlate With Renal Dysfunction and Promote ESRD

Kidney Int Rep. 2022 Nov 29;8(2):341-356. doi: 10.1016/j.ekir.2022.11.015. eCollection 2023 Feb.

Authors

Affiliations

¹ Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Lower Saxony, Germany.
² Medical Department I, Gastroenterology, Hepatology and Nephrology, Clinics Passau, Passau, Bavaria, Germany.
³ Clinic for Kidney and Hypertension Diseases, Hannover Medical School, Hannover, Lower Saxony, Germany.
⁴ Clinic for Nephrology and Hypertension, Christian-Albrechts-University, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Schleswig-Holstein, Germany.
⁵ Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Lower Saxony, Germany.
⁶ Medical Clinic III - Nephrology and Dialysis, St. Vinzenz Hospital, Paderborn, North Rhine-Westphalia, Germany.
⁷ Clinic for Nephrology and Hypertension, University Hospital Oldenburg, Oldenburg, Lower Saxony, Germany.
⁸ Medical Clinic V, Nephrology, Rheumatology and Blood Purification, Academic Teaching Hospital Braunschweig, Braunschweig, Lower Saxony, Germany.

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.

Keywords: Dialysis risk; Digital pathology; Disease progression; Macrophage; Native kidney disease; Renal pathology.