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Francesc Moreso,1 Irina B Torres,1 Gemma Costa-Requena,2 Daniel Serón1 1Nephrology Department, 2Psychiatry Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, Barcelona, Spain Abstract: Nonadherence to immunosuppressant treatment is common after renal transplantation involving >20% of patients. It is associated with cellular rejection, appearance of donor-specific antibodies, and chronic rejection. It has been estimated that nonadherence can be detected in approximately 50% of failing grafts. Since the evaluation of sociodemographic factors do not allow characterizing the target population, it is necessary to combine different measures of adherence (self-reporting and collateral reporting, pill counts, biological monitoring of blood samples, or others) to increase its diagnostic accuracy. During the last decade, it has been shown that the implementation of a multidimensional intervention including information, motivation, and behavioral interventions may lead to an improvement of adherence to treatment. On the other hand, it has been shown that one-off feedback from a nurse, simplification of treatment, or financial assistance programs offered little improvement. Thus, increasing the effectiveness of adherence interventions might have a far greater impact on the long-term outcome of renal transplants than any improvement in specific medical treatments. This will require coordinated action from health professionals, researchers, health planners, and policy makers. Keywords: renal transplantation, nonadherence, immunosuppressive treatment

In March 2017, a joint meeting between The Catalan Society of Transplantation and the Banff Foundation was held at the University of Barcelona. This was an opportunity for the Catalan Society of Transplantation to recognize the crucial contributions to transplant pathology made by Lorraine Racusen and Kim Solez, who created and actively contributed to the development of the International Banff Classification System. The ceremony of the Gold Medal took place on March 31 at the University of Barcelona; it consisted of a presentation of the contributions of Lorraine Racusen and Kim Solez to the development of transplant pathology. In this article, the presentation of these awardees with the Gold Medal of the Catalan Society of Transplantation is summarized. [ABSTRACT FROM AUTHOR]

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d‐negative antibody‐mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor‐specific antibody tests (anti‐HLA and non‐HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i‐IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell–mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus‐based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next‐generation clinical trials.

The natural history of renal allograft damage has been characterized in serial protocol biopsies. The prevalence of subclinical rejection (SCR) is maximal during the first months and it is associated with the progression of interstitial fibrosis/tubular atrophy (IF/TA) and a decreased graft survival. IF/TA rapidly progress during the first months and constitutes an independent predictor of graft survival. IF/TA associated with transplant vasculopathy, SCR, or transplant glomerulopathy implies a poorer prognosis than IF/TA without additional lesions. These observations suggest that protocol biopsies could be considered a surrogate of graft survival. Preliminary data suggest that the predictive value of protocol biopsies is not inferior to acute rejection or renal function. Additionally, protocol biopsies have been employed as a secondary efficacy variable in clinical trials. This strategy has been useful to demonstrate a decrease in the progression of IF/TA in some calcineurin-free regimens. Quantification of renal damage is associated with graft survival suggesting that quantitative parameters might improve the predictive value of protocol biopsies. Validation of protocol biopsies as a surrogate of graft survival is actively pursued, as the utility of classical surrogates of graft outcome such as acute rejection has become less useful because of its decreased prevalence with actual immunosuppression.Kidney International (2007) 72, 690–697; doi:10.1038/sj.ki.5002396; published online 27 June 2007 [ABSTRACT FROM AUTHOR]

Protocol renal allograft biopsies allow the early detection of histological damage in the renal allograft even before renal function deterioration or proteinuria appears. Two different lesions have attracted the main interest in protocol biopsy studies: subclinical rejection, namely, the presence of tubulo-interstitial inflammation and chronic allograft nephropathy, nowadays termed interstitial fibrosis/tubular atrophy (IF/TA), and the presence of tubulo-interstitial chronic lesions. The incidence of subclinical rejection is maximal after transplantation and decreases during the first few months despite the fact that this condition persists in a proportion of cases even in late protocol biopsies done after the first year. In studies of serial protocol biopsies, the presence of subclinical rejection is associated with a higher probability of the progression of chronic tubulo-interstitial lesions and, recently, it has been shown the subclinical rejection in early protocol biopsies is associated with poorer allograft survival. The incidence of IF/TA rapidly progresses after renal transplantation, following an exponential curve. Its presence is associated with a decreased graft survival and its predictive value on outcome is independent from other predictors of survival such as serum creatinine or acute rejection. The association of IF/TA with transplant vasculopathy, subclinical rejection or transplant glomerulopathy implies a poorer outcome than IF/TA without other histological lesions. Taken together, these data suggest that protocol biopsies allow the early detection of acute and chronic lesions and the recognition of different patterns of damage that are associated with allograft survival. [ABSTRACT FROM AUTHOR]

Background.Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplant with or without acute rejection. [ABSTRACT FROM PUBLISHER]

Renal transplant recipients have a high incidence of cutaneous complications such as neoplasia and viral or fungal infections. Morphologic alterations of epidermal Langerhans cells (LC) have furthermore been described in these patients. Since these changes have been mainly found in sun-exposed skin, a direct effect of immunosuppressive therapy remains a matter of discussion. A quantitative and morphometric study of epidermal LC in non-exposed skin was performed in 28 renal transplant patients (RTP). RTP were divided in two groups according to immunosuppressive treatment: group A; azathioprine + prednisone (14 cases) and group B; cyclosporine + prednisone (14 cases). Twenty sex-age matched non-immunosuppressed patients acted as controls (group C). Epidermal sheets were obtained by incubation in EDTA and stained for ATPase activity and with the monoclonal antibody T6 (CD1) using the avidin-biotin peroxidase method. Langerhans cells were counted using a calibrated graticule (400X) and expressed as the mean number of LC/mm2. The mean area of the LC and the number of primary dendrites (pd) and secondary dendrites (sd) were determined with a morphometer adapted to an Apple II computer. The mean number of positive cells in controls was: ATPase, 677±157; T6, 695±164. Patients in group A had the maximum reduction in both ATPase and T6 LC density (ATPase, 339±142; T6, 402±194). Patients in group B had an intermediate reduction in the number of LC (ATPase, 494±121; T6, 529±112). [ABSTRACT FROM AUTHOR]

Forty-three biopsies were performed between 30 and 60 min after reperfusion. Patients (22 males/21 females, mean age 41 ±12 years, mean donor age 32 ±14 years) were treated either with antilymphocytic globulin, cyclosporin, and prednisolone (24 cases), or OKT3, cyclosporin, and prednisolone (19 cases). Ten patients had delayed post-transplant renal function (DPRF), defined as haemodialysis requirements after surgery, and seven patients had acute rejection 11 ±16 days post-transplant. Kidneys were perfused with a hypertonic solution containing mannitol. All patients were followed up for at least 30 months. During follow-up, five patients lost their grafts due chronic rejection, two patients due to non-compliance and one due to recurrence of focal seg-mental glomerulosclerosis. One patient died from heart infarction. Biopsies were stained with H&E, Masson's trichrome, periodic acid-Schiff (PAS) and silver methenamine. Interstitial fibrosis, interstitial oedema, tubular vacuolization, and peritubular capillary oedema were measured using a semiquantitative scale. Five 400 × magnification micrographs of cortical inter-stitium from silver-methenamine-stained sections were used to measure percentage of interstitial surface with a morphometer. Interstitial surface was 18.7 ±6.2% (range 3.2–35.3%). A positive correlation was found between interstitial surface and donor age (= 0.469, =0.0015). No relationship was found between warm and cold ischaemia times and tubular vacuolization or peritubular capillary oedema. Patients with DPRF had a significantly increased interstitial surface (23 ±8%) when compared with patients without DPRF (17 ±5%), (=0.014). There was a positive relationship between interstitial surface and number of days required to achieve a plasma creatinine of 300 μmol/1 after surgery, this fitted an exponential curve (=0.578, =0.0012). Patients who had an episode of acute rejection were not included in this calculation. A positive correlation was also found between interstitial surface and plasma creatinine at 12 months (=0.692, =0.0001), 18 months (=0.713, =0.0001), and 24 months (=0.586, =0.0023) after surgery. Patients who lost their grafts during follow-up were not included in this calculation. The relationship between interstitial surface and plasma creatinine 30 months after transplantation was not significant. There was no relation between tubular vacuolization or peritubular capillary oedema and number of days required to achieve a plasma creatinine of 300 μmol/1 or plasma creatinine 12, 18, 24, and 30 months after transplantation. We conclude that assessment of donor renal biopsies may help to predict post-transplant renal function. The increase of interstitial surface due to pre-existing fibrosis is associated with poor post-transplant graft performance. [ABSTRACT FROM PUBLISHER]