Ester Gallo

Loss of nephrin expression in glomeruli of kidney-transplanted patients under m-TOR inhibitor therapy.

The development of proteinuria has been observed in kidney‐transplanted patients on m‐TOR inhibitor (m‐TORi) treatment. Recent studies suggest that m‐TORi(s) may alter the behavior and integrity of glomerular podocytes. We analyzed renal biopsies from kidney‐transplanted patients and evaluated the expression of nephrin, a critical component of the glomerular slit‐diaphragm. In a group of patients on ‘de novo’ m‐TORi‐treatment, the expression of nephrin within glomeruli was significantly reduced in all cases compared to pretransplant donor biopsies. Biopsies from control transplant patients not treated with m‐TORi(s) failed to present a loss of nephrin. In a group of patients subsequently converted to m‐TORi‐treatment, a protocol biopsy performed before introduction of m‐TORi was also available. The expression of nephrin in the pre‐m‐TORi biopsies was similar to that observed in the pretransplant donor biopsies but was significantly reduced after introduction of m‐TORi(s). Proteinuria increased after the m‐TORi inititiation in this group. However, in some cases proteinuria remained normal despite reduction of nephrin. In vitro, sirolimus downregulated nephrin expression by human podocytes. Our results suggest that m‐TORi(s) may affect nephrin expression in kidney‐transplanted patients, consistently with the observation in vitro on cultured podocytes.

Analysis of Four Scoring Systems and Monocentric Experience to Optimize Criteria for Marginal Kidney Transplantation

There is a strong need among the transplantation community to identify common criteria to utilize the pool of expanded criteria donors (ECD), considering the disparity between organ demand and supply as well as the benefits of transplantation on long-term mortality compared with survival on dialysis, also in patients transplanted with these organs. The purpose of this article was to analyze scoring systems proposed in literature by Nyberg, Anglicheau, Rao (Kidney Donor Risk Index), and Schold, seeking to verify whether our clinical and histological allocation strategy matched the Nyberg score. Herein we have reported the results of a preliminary retrospective study on the 5-year outcomes of organs from 60 marginal donors, who were older than 50 years and histologically evaluated before implantation. The donors matched Nyberg class C and D, that is, marginal donors. We noted a tendency toward an association between global and vascular scores with class D (odds ratio 2.2 and 4.3, respectively). Kaplan-Meier graft survival curves were similar to Nyberg data: 83% for class C versus 73% for class D at 5 years. Without any comparison to the Nyberg score, the only feature that was predictive of renal function at 5 years in our population was hypertension in the donor. Further studies are required to identify which of the scoring systems--clinical and/or histological--is more suitable to allocate ECD kidneys and to predict recipient outcomes.

Treatment with plasmapheresis, immunoglobulins and rituximab for chronic-active antibody-mediated rejection in kidney transplantation: Clinical, immunological and pathological results

AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection (cAMR) settings. METHODS We compared 21 kidney transplant recipients (KTRs) with a diagnosis of cAMR in a retrospective case-control analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab (PE-IVIG-RTX group) vs 12 patients (control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody (DSA) characteristics (MFI and C1q-fixing ability) were also investigated. RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group (33.3%) and 4/12 in the control group (33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo (min 12-max 18) and 15 mo (min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cAMR diagnosis were also similar in both groups. Only microvascular inflammation (glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients (87.5%) in the PE-IVIG-RTX group (median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome. CONCLUSION Our data showed no difference in the two year post-treatment outcome of kidney grafts treated with PE-IVIG-RTX for cAMR diagnosis, however there were notable improvements in microvascular inflammation in post-therapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.