Clinical management strategies for recipients with renal graft loss / 器官移植

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.

Identification of M1 macrophage-related genes in rejection after kidney transplantation based on weighted gene co-expression network analysis / 器官移植

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4+ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

Progress in self-expanding metallic ureteral stent in the treatment of ureteral stricture in renal allografts / 器官移植

Ureteral stricture in renal allografts is one of the common postoperative complications in kidney transplant recipients. Due to short ureter in renal allografts, endovascular treatment should be adopted before reconstruction surgery to avoid irreversible injury. Alleviating renal allograft injury, easing obstruction or establishing drainage channel are the key measures to treat ureteral stricture. In endovascular treatment, balloon dilatation and internal incision yield high recurrence rate, and long-term indwelling of self-expanding metallic ureteral stents may be a better option. Compared with traditional stents, metallic stents may maintain urinary tract patency for a long time and mitigate the irritation of lower urinary tract symptoms,with different indications and efficacy. Although all metallic stents may be displaced and occluded, it still plays a positive role in the treatment of ureteral stricture in renal allografts. In this article, the application of self-expanding metallic ureteral stent in ureteral stricture of renal allografts was mainly illustrated, aiming to provide reference for optimizing the treatment of ureteral stricture in renal allografts.

Embolización transcatéter del injerto renal en pacientes con síndrome de intolerancia: reporte de tres casos en un grupo de trasplantes

Introducción el síndrome de intolerancia es un proceso inflamatorio que ocurre hasta en un tercio de los pacientes con pérdida del injerto. Cuando no se obtiene una mejoría de los síntomas con el manejo médico, se indica la realización de nefrectomía del riñón trasplantado, sin embargo, este es un procedimiento invasivo que puede estar asociado a mayor morbilidad y mortalidad. Dada la fragilidad de estos pacientes, se plantea la embolización transcatéter del injerto como una alternativa válida y menos invasiva para el tratamiento de este síndrome. Objetivo describir el uso de la embolización transcatéter como tratamiento al síndrome de intolerancia del injerto. Presentación del caso se reportan tres casos clínicos de pacientes con sintomatología de entre 15 y 20 días de evolución, consistentes en dolor y tumefacción sobre riñón trasplantado y otros signos y síntomas reportados fueron fiebre, hiporexia, pérdida de peso y hematuria macroscópica. Se describe la evolución de los síntomas que en ninguno de los casos expuestos tuvieron mejoría con el ajuste inmunosupresor, descartando en todos los casos etiología infecciosa y estableciéndose así la sospecha síndrome de intolerancia del injerto. Los pacientes fueron manejados con embolización transcatéter de la arteria del riñón trasplantado y el éxito del tratamiento se definió por la resolución de los síntomas. Discusión y conclusión entre las primeras 24-48 horas posprocedimiento, los pacientes presentaron una evolución satisfactoria y, finalmente, egreso. La embolización transcatéter del injerto es una alternativa segura a la nefrectomía del trasplante y que es menos invasiva para el tratamiento del síndrome de intolerancia del injerto.

Background The renal graft intolerance syndrome is an inflammatory process that occurs in one third of the kidney transplant patients with graft loss. If medical treatment for intolerance graft syndrome is not effective, there is an indication of graft nephrectomy. However, graft nephrectomy has higher morbidity and mortality compared to non-invasive techniques. Due to a high fragility in kidney transplant patients, the renal arterial embolization has become a useful minimally invasive therapeutic option for intolerance graft syndrome. Objective We aim to describe the use of renal arterial embolization for renal graft intolerance syndrome. Case presentation We report three clinical cases who were admitted to the emergency department for a history of twenty days of graft pain and swelling. These patients had fever, hyporexia, weight loss and macroscopic hematuria. None of the cases had clinical improvement with immunosuppression adjustment and a diagnosis of renal graft intolerance syndrome was made dismissing infection. Patients were treated with renal arterial embolization and its procedure success were determined as the symptom's resolution. Discussion and conclusion After 24- and 48-hours post-embolization, patients were successfully recovered and discharged in the hospital. Renal graft arterial embolization is a safe and non-invasive alternative to graft nephrectomy to treat renal intolerance syndrome.

The sum of kidney donor profile index and estimated post-transplant survival scale and their correlation with egfr decline in deceased donor kidney recipients

Background: The impact of donor quality on post-kidney transplant survival may vary by candidate condition. Objective: Analyzing the combined use of the Kidney Donor Profile Index (KDPI) and the estimated post-transplant survival (EPTS) scale and their correlation with the estimated glomerular filtration rate (eGFR) decline in deceased-donor kidney recipients (DDKR). Methods: This was a retrospective, observational cohort study. We included DDKRs between 2015 and 2017 at a national third-level hospital. Results: We analyzed 68 DDKR. The mean age at transplant was 41 ± 14 years, 47 (69%) had sensitization events, 18 (26%) had delayed graft function, and 16 (23%) acute rejection. The graft survival at 12 and 36 months was 98.1% (95% CI 94-100) and 83.7% (95% CI 65-100), respectively. The Pearson correlation coefficient between the percentage reduction in the annual eGFR and the sum of EPTS and KDPI scales was r = 0.61, p < 0.001. The correlation coefficient between the percentage reduction in the annual eGFR and the EPTS and KDPI scales separately was r = 0.55, p < 0.001, and r = 0.53, p < 0.001, respectively. Conclusions: The sum of EPTS and KDPI scales can provide a better donor-recipient relationship and has a moderately positive correlation with the decrease in eGFR in DDKR.

A retrospective study ofsimultaneous pancreas-kidney transplantation from a single-center experience / 中华器官移植杂志

Objective To explore the surgical indications for pancreas-kidney surgery and summarize the experiences of ,selecting surgical approaches ,formulating immunosuppressive regimens and preventing complications .Methods A total of 145 donor simultaneous pancreas-kidney transplants in uremic patients with T1DM/T2DM between 2002 and 2018 were retrospectively analyzed .Based upon surgical approaches and immunosuppressive agents ,they were divided into three eras of 2002-2010 ,2011-2014 and 2015-2018 respectively .Patient profiles ,survival outcomes of patient and graft , surgical techniques ,immunosuppressive agents and incidence of common complications were compared among different groups .Results The overall 1/3/5-year patient and graft survival rates of three groups were above 75％ and the survival rates of group Ⅰ were inferior to those of groups Ⅱ and Ⅲ(P<0 .001) .The overall 1/3/5-year pancreas graft survival rates were the highest in group Ⅲ and the lowest in group Ⅱ (P=0 .004) .In the 2015-2018 group ,ipsilateral pancreas-kidney transplantation and SE-ED surgery were more preferred .Regarding the incidence of complications ,graft thrombosis frequently occurred from 2011 to 2014 and intestinal obstruction was more common from 2002 to 2010 .For univariable analysis of graft loss ,anticoagulation programme with argatroban monohydrate were 0 .28 times likely to lose pancreas graft (OR= 0 .28 ,95％ CI:0 .09-0 .86) and T1DM patients were 4 times likely to have kidney graft loss (OR=4 .08 ,95％ CI:1 .37-12 .15) .Conclusions SPK is an effective treatment for uremic diabetics . Effective perioperative management and preventing complications are crucial for prolonging patient and graft survivals .

Study of systemic fungal infections in renal transplant recipients

Background: Despite technical, immunological, and therapeutic advances in the field of renal transplantation, infections remain a major barrier to successful outcome. Fungal infections (14%) after renal transplantation, despite a lower incidence than bacterial and viral infections, remain a major cause of morbidity and mortality. This study was conducted to assess the impact of invasive fungal infections in our renal transplant recipients. Aim: To study the clinical profile, risk factors for acquiring fungal infections, its outcome and the factors influencing outcome in living and deceased donor renal transplant recipients. Materials and methods: Renal transplant recipients both cadaveric and living-related during the time period between August 2008 and May 2011 admitted with systemic fungal infections in nephrology ward were included in the study. Data gathered included age, sex, date of transplantation, date of diagnosis, fungal pathogen, organs affected by infection, treatment and patient outcome. Microsoft excel 2007, Binomial and Student t tests were used for statistical analysis. Observation: Twenty two patients were diagnosed with systemic fungal infections during this period. The mean age of the study patients was 35.55 years. The male to female ratio was 1.75:1.Candida species (62%) are the commonest organisms causing fungal infection. Fungal infections commonly occurred in gastrointestinal tract (GIT), lung and urinary tract, each 22%. Fifty percent of patients with fungal infections expired. Graft loss occurred in 41% of patients. Conclusion: The mortality rate was 50%. Bone marrow suppression {Leukopenia (50%)} and hypoalbuminemia (59%) contributed to high mortality. Overall immunosuppression should be monitored periodically and kept at optimal level just enough to avoid rejection, thereby avoiding opportunistic infections.

Injertos cutáneos, hábito de fumar y diabetes mellitus tipo 2 / Skin graft, smoking and diabetes mellitus type 2

El tabaco y la hiperglucemia reducen significativamente el éxito de los injertos cutáneos. El estrés oxidativo y la disfunción endotelial son factores que se asocian tanto al tabaquismo como a la diabetes mellitus (DM) tipo 2. El objetivo de este estudio fue constatar si existe una asociación entre estos factores de riesgo y el descenso en el porcentaje de éxito de los injertos en pérdidas cutáneas de diversa etiología. Estudio bicéntrico, retrospectivo, de casos y controles, llevado a cabo de enero 2000 a diciembre 2009, en los centros hospitalarios de Reina Sofía (Córdoba, España) y Birmingham (Alabama, EE.UU.), con 2457 pacientes que cumplían los criterios de inclusión. El éxito del injerto p ara cada grupo fue analizado mediante chi-cuadrado. El intervalo de confianza fue del 95%. El hábito de fumar y la DM tipo 2 disminuyeron el porcentaje de éxito de los injertos comparados con sus grupos controles, siendo el efecto de la DM tipo 2 mayor que el del tabaco. Se observó un descenso altamente significativo del porcentaje de injertos prendidos, del 18% en el grupo de fumadores (de 86% a 68%), y del 25% en el grupo de los diabéticos (de 78% a 53%). El cálculo de OR demostró asociación entre los factores de riesgo estudiados y el menor éxito de los injertos cutáneos, siendo mayor para la DM tipo 2. En conclusión: la DM tipo 2 y el hábito de fumar son factores que influyen negativamente en el éxito de los injertos cutáneos.

Smoking and hyperglycemia decrease the success of skin graft survival in specific circumstances. It is well known that smoking and diabetes mellitus (DM) type 2 increase the oxidative and impair the endothelial function. The objective of this retrospective study was to determine if smoking and DM type 2 are factors associated with lower skin graft survival, in different etiologies of the injury associated to the skin loss. It was a bicentric, retrospective, cross sectional case control study, carried out on 2457 medical patients who met the inclusion criteria. It was carried out over a 10 years period between January 2000-December 2009, at Reina Sofía University Hospital (Córdoba, Spain) and UAB Hospital at Birmingham (Alabama, USA). The percentage of successful graft for each group and its control were analyzed by Chi-square test. The confidence interval chosen for statistical differences was 95%. Smoking and DM type 2 decreased the percentage of skin graft survival when compared with their control groups. DM type 2 was associated with greater negative success on skin graft survival than smoking when compared with their control groups.. There was a statistically significant drop in skin graft of 18% in smoking group (range: 68-86%) and 25% in DM type 2 group (53-78%). The OR showed a clear association between the risk factors studied and the lower skin graft success, being stronger for DM type 2. In conclusion, DM type 2 and smoking are factors associated to lower skin graft take.

ABO-incompatible renal transplantation: From saline flushes to antigen-specific immunoadsorption-Tools to overcome the barrier / 대한혈액학회지

On April 23, 1951, a 30-year-old woman received the first intentional ABOi (ABO incompatible) renal transplantation in Boston. At that time, it was commonly believed that intensely rinsing the graft to remove blood would be sufficient to overcome any immunological problems associated with blood type incompatibility. However, when the abovementioned patient and another ABOi transplant recipient died within a month, Humes and colleagues arrived at the same conclusion: "We do not feel that renal transplantation in the presence of blood incompatibility is wise." In the decades that followed, we learned that the oligosaccharide surface antigens representing the ABO-blood group antigens are expressed not only on erythrocytes but also on cells from various tissues, including the vascular endothelium. The growing gap between organ demand and availability has sparked efforts to overcome the ABO barrier. After its disappointing results in the early 1970s, Japan became the leader of this endeavor in the 1980s. All protocols are based on 2 strategies: removal of preformed antibodies with extracorporeal techniques and inhibition of ongoing antibody production. Successful ABOi renal transplantation became possible with the advent of splenectomy, new immunosuppressive drugs (e.g., rituximab, a monoclonal antibody against CD20), and extracorporeal methods such as antigen-specific immunoadsorption. This review summarizes the underlying pathophysiology of ABOi transplantation and the different protocols available. Further, we briefly touch potential short- and long-term problems, particularly the incidence of infectious complications and malignancies, that can arise with high-intensity immunosuppressive therapy.

The early loss of intraportally transplanted islets / 国际外科学杂志

The intraportal islet transplantation is the most hopeful method for the treatment of type 1 dia-betes mellitus. However about 70% of transplanted islets would be destroyed in the early two weeks after transplantation, only a few parts of them could engraft in liver and become functional. This results in the lower efficiency of islet transplantation. Here we review the reasons of this early islet loss and its preventive strategies.

Association of posttransplantation proteinuria with allograft loss in transplant kidney biopsy-proven recipients / 대한내과학회지

BACKGROUND: Previous studies reported a poor prognosis in patients with persistent proteinuria later in the posttransplantation course, suggesting that posttransplantation proteinuria is a marker for graft failure. This study was undertaken to elucidate the role of proteinuria after renal transplantation in the pathogenesis and outcome of allograft dysfunction in transplant biopsy-proven recipients. METHODS: We retrospectively analyzed the data from 55 patients who underwent transplant renal biopsy for proteinuria and/or azotemia occurring beyond 1 year after transplantation. Proteinuria was considered as significant when >or=30 mg/dL, and the results of transplant biopsy were categorized according to the Banff 97 classification. Logistic regression was used to estimate odds ratios (OR) for graft loss associated with proteinuria and transplant pathology. RESULTS: The patients were followed for 86.0 +/- 32.8 (mean +/- SD) months after transplantation, and transplant biopsy was performed at 54.1 +/- 31.0 months. Proteinuria at 1 year after transplantation was noted in 29.1% of the patients, and it was not significantly associated with graft loss (OR=1.94, 95% CI 0.59-6.41). In addition, proteinuria at the time of transplant biopsy was not significantly associated with graft loss, and none of each category of transplant pathology was significantly associated with graft loss. Chronic allograft nephropathy was the most frequent transplant pathology, and only glomerulonephritis was significantly associated with proteinuria at the time of transplant biopsy. On the other hand, graft loss was significantly associated with the presence of proteinuria both at 1 year after transplant biopsy and at the final follow-up. CONCLUSION: These results suggest that posttransplantation proteinuria is an important marker of graft dysfunction but may not be predictive of graft loss in biopsy-proven cases. Appropriate management guided by the results of transplant biopsy may improve the outcome.