Morphologic patterns and treatment of transplant glomerulopathy: A retrospective analysis

Abstract

Transplant glomerulopathy is mainly due to chronic antibody-mediated rejection and actually represents a major cause of long-term allograft failure. The lack of effective treatment remains a serious problem in transplantation. A retrospective and uni-center study was performed in 48 kidney allograft recipients with transplant glomerulopathy between January 2010 and December 2015. Median time for diagnosis was 7.1 (3.6-11.8) years post-transplant. Light microscopy showed severity of transplant glomerulopathy in the majority of patients (cg1=10.4%; cg2=20.8%; cg3=68.8%). Moderate microvascular inflammation was present in 56.3% (g+ptc≥2), and almost half of recipients (51.1%) were C4d positive in immunofluorescence. Female gender (P=.001), age (P=.043), renal dysfunction (P=.002), acute rejection episodes (P=.026), and anti-HLA class II antibodies (P=.004) were associated with kidney allograft failure. Treatment of transplant glomerulopathy was performed in 67.6% of patients. The histologic and laboratory features that led to a therapeutic intervention were score ptc (P=.021), C4d (P=.03), and the presence of anti-HLA antibodies (P=.029), whereas score ah (P=.005) was associated with conservative measure. The overall cumulative kidney allograft survival at 10 years was 75%. Treatment of transplant glomerulopathy was ineffective to improve long-term kidney allograft survival.

The time dependency of renal allograft histology

“…Very few studies take the percentage glomerulosclerosis into account in outcome prediction, likely because glomerulosclerosis is not included in the Banff classification and therefore remains under reported. We recently demonstrated a highly significant association between glomerulosclerosis, proteinuria, and graft outcome in univariate analysis, but glomerulosclerosis was not retained in multivariate models [43,47,65], which supports the concept that glomerulosclerosis is a secondary phenomenon and not an independent factor in graft outcome. More systematic inclusion of glomerulosclerosis in studies reporting on renal allograft histology, and in predictive models, seems necessary to elucidate the relevance of this lesion for prognostication (see below).…”

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

“…C4d+ in this study was found to be associated with inferior allograft survival only in univariate analysis. Abreu et al [26] demonstrated in a retrospective study that C4d+ TG cases were more likely to be treated with intravenous Ig and/or rituximab. Nevertheless, in this study, we observed that these treating modalities did not improve TG prognosis, which is compatible with a recently published study [27].…”

Proteinuria, Estimated Glomerular Filtration Rate and Urinary Retinol-Binding Protein as Clinical Predictors of Long-Term Allograft Outcomes in Transplant Glomerulopathy

“…Abreau et al [5] demonstrated that PRA class II was associated with graft failure while Julie et al [25] and Layla et al [6] consistently showed that allograft survival/failure was independent of PRA levels. We failed to find PRA predictive of allograft survival in both univariate and multivariate analysis, which did not necessarily negate previous findings.…”

“…Although we have analyzed the associations of variables at the time of biopsy with long-tern allograft outcome, therapeutic influences and pathologic factors that may also influence allograft survival were not accounted for in this study. However, recent studies have indicated that currently available treatment modalities for TG is ineffective to improve kidney allograft survival [5,30,31]. Additionally, patients included in this study are predominantly composed of forcause biopsy.…”

“…The identification of clinical characteristics at the time of TG diagnosis that are predictable of future renal allograft dysfunction would greatly facilitate clinical prognostication for individual TG patient, which would ideally be explored in a large representative cohort. However, a few studies available were limited by their small sample size, short follow-up time and discordant conclusions [5,6].…”