Early interstitial macrophage infiltration with mild dysfunction is associated with subsequent kidney graft loss

Abstract

Macrophage infiltration is associated with unfavorable kidney graft outcome in protocol biopsies, but few studies have evaluated its impact on clinical practice. We therefore prospectively evaluated 37 kidney transplant recipients (KTRs) who underwent kidney biopsy due to slight increases in serum creatinine, or mild proteinuria (>0.3 g/24 hr), in the first post‐transplant year. Banff score, CD68+ count (score 0‐3) by immunohistochemistry, and 1‐year DSA were assessed. DGF was reported in 10 (27%) patients, 6 (16%) had normal biopsy, 7 (19%) borderline lesions, 13 (35%) IFTA, and 11 (30%) other lesions. Fifteen KTRs had grade 3 CD68+ infiltration, and 47% developed de novo DSA. During a 6.2 ± 2.7 year follow‐up, four patients (11%) suffered from biopsy‐proven T‐cell rejection, 17 KTRs (46%) lost their graft (12 in the grade 3 CD68+ group). Graft survival was lower in KTRs with grade 3 CD68+ infiltration (P = 0.0074; log‐rank test). Grade 3 CD68+ infiltrate was an independent predictor of graft loss (HR 5.41, 95% CI 1.74‐16.8; P = 0.003), together with more severe graft dysfunction at biopsy (HR 6.41, 95% CI 2.57‐16; P < 0.001). We conclude that grade 3 CD68+ interstitial infiltration is associated with increased risk of subsequent graft loss independent of other factors.

Allorecognition and the spectrum of kidney transplant rejection

“…146 Allograft infiltration and accumulation of monocytes/macrophages have been described as a potential diagnostic marker of transplant rejection, 147 as CD68 þ macrophage infiltration was significantly elevated in ABMR and associated with graft failure. [148][149][150][151] In preclinical models, monocyte and macrophage depletion prevented or reduced microvasculature damage in murine kidney and cardiac transplantation, indicating a causal role of monocytes and macrophages. 152,153 Infiltration of monocytes and macrophages in rejection was historically considered as secondary to T-cell activation, resulting in a delayed-type hypersensitivity response, or secondary to "danger" signals following graft injury.…”

Seeking Standardized Definitions for HLA-incompatible Kidney Transplants: A Systematic Review

“…A total of 6656 records underwent title and abstract screening. The full-text review was undertaken for 886 eligible articles; of these 78 articles discussed HLA incompatibility at the level of the antigen mismatch only, 64-141 whereas 163 articles assessed incompatibility by molecular genotyping, molecular mismatch analysis, and/or pretransplant DSA verification by solid-phase and/or by cell-based assays. 3,142-303 The Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram outlining the article selection process is provided in Figure 1.…”