High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

Introduction: We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management. Methods: Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4). Results: Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring. Conclusions: One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

The use of lymphocyte-depleting antibodies in specific populations of kidney transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups. METHODS: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias. RESULTS: Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group. CONCLUSIONS: Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.

Experience with abatacept in refractory lupus nephritis.

Lupus nephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Responsiveness to treatment is crucial to avoid chronic kidney disease. New molecules have been developed in recent years to improve renal survival rates. Biological therapies as coadjutant to conventional induction treatment have been tested in randomized clinical trials with heterogeneous results. Like many others biologic therapies, Abatacept has not shown a clear benefit in the context of clinical trials. We present two cases of lupus nephritis patients in whom addition of abatacept resulted in complete remission of the renal disease. The first case described a 49-year-old male with class IV lupus nephritis with nephrotic range proteinuria and high immunological activity refractory to conventional treatment with cyclophosphamide and corticosteroids and multitarget therapy with tacrolimus, mycophenolate mofetil and prednisone. Several biological therapies (rituximab, belimumab and tocilizumab) were unsuccessfully tried, so that abatacept was added to his background multitarget therapy showing complete clinical response. The second case described a 52-year-old female with class IV lupus nephritis treated initially with conventional treatment with partial response. In successive renal flares with nephrotic proteinuria, she showed intolerance to rituximab and refractoriness to voclosporin. Finally, abatacept was added to her background therapy with MMF and PDN showing complete and maintained remission of the disease. In no case the use of abatacept was associated with serious adverse events. Based on our experience, abatacept should be considered as a safe rescue therapy in patients with refractory lupus nephritis and proteinuria with nephrotic range. In addition to this case, we reviewed the use of abatacept in lupus nephritis in the literature.

Evolution of kidney allograft loss causes over 40 years (1979-2019).

INTRODUCTION: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. METHODS AND PATIENTS: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). RESULTS: Between 1979 and 2019, 1522 transplants were performed. The median follow-up time was 56 (IQR 8-123) months. During follow-up, 722 (47.5%) grafts were lost: 483 (66.9%) due to graft failure and 239 (33.1%) due to death with functioning graft. The main causes of death were cardiovascular (25.1%), neoplasms (25.1%), and infectious diseases (21.8%). These causes were stable between the two periods of time. Only the unknown cause of death has decreased in the last period. The main cause of graft failure (loss of graft function) was the allograft chronic dysfunction (75%). When histologic information was available, antibody-mediated rejection (ABMR) and interstitial fibrosis/tubular atrophy (IF/TA) were the most frequent specific causes (15.9% and 12.6%). Of the graft failures, 213 (29.5%) were early (<1 year of transplantation). Vascular thrombosis was the main cause of early graft failure in the second period (2000-2019) (46.7%) and T-cell-mediated rejection (TCMR) was the main cause (31.3%) in the first period (1979-1999). The causes of late graft loss were similar between the two periods. CONCLUSIONS: The causes of kidney allograft recipient death are still due to cardiovascular and malignant diseases. Vascular thrombosis has emerged as a frequent cause of early graft loss in the most recent years. The evaluation of the causes of graft loss is necessary to improve kidney transplantation outcomes.

Evolución de las causas de pérdida del injerto en trasplante renal durante 40 años (1979-2019) / Evolution of kidney allograft loss causes over 40 years (1979-2019)

Introducción: La mejoría en la supervivencia del receptor y del injerto renal sufre un proceso de deceleración. La tasa de pérdida del injerto a medio y largo plazo permanece estable desde hace 25 años. Es fundamental conocer las causas de pérdida del injerto y los factores relacionados, así como identificar si se han producido cambios en las causas de pérdida del injerto en los últimos años. El objetivo del presente estudio fue evaluar las causas de pérdida del injerto según fallecimiento del receptor o pérdida del injerto con vuelta a diálisis/retrasplante, y analizar las causas específicas de pérdida del injerto en 2 épocas (1979-1999 y 2000-2019) para identificar cambios en el perfil de los injertos perdidos. Pacientes y métodos: Estudio retrospectivo de todos los trasplantes renales (TR) realizados en el Hospital del Mar (Barcelona) entre mayo-1979 y diciembre-2019. Consideramos pérdida del injerto el fallecimiento del paciente con injerto funcionante o el re-inicio de diálisis o retrasplante. Revisamos las causas de pérdida mediante información clínica e histológica, y analizamos los resultados en 2 periodos (1979-1999 y 2000-2019). (AU)

Introduction: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. Methods and patients: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). (AU)

Kidney Transplantation Outcomes From Donors After Controlled Circulatory Death: A Comparison With Expanded Criteria Brain Death Donors.

BACKGROUND: The persistent shortage of optimal kidney donors and the progressive increase in patients on the waiting list have led to an expansion of the acceptance criteria, such as donors after controlled cardiac death (cDCD) and donors after brain death with expanded criteria (DBD-EC). Some concerns and doubts about survival outcomes achieved with these allografts are still present. Our aim was to compare transplant outcomes from cDCD vs DBD-EC. METHODS: A retrospective single-center observational study including all kidney transplant (KT) donors from all cDCD and DBD-EC (>60 years) from January 2015 to January 2022 was performed. We analyzed clinical characteristics, early clinical outcomes, and patient and graft survival rates. RESULTS: 129 cDCD and 166 DBD-EC KT recipients were included. The median follow-up was 30,2 months. DBD-EC were older and had more comorbidities than cDCD. KTs from cDCD and DBD-EC showed similar rates of delayed graft function and primary nonfunction. Patient survival at 1 year was similar (85% DBD-EC vs 90% cDCD, P = .32). Death-censored graft survival at 1 year was similar among young cDCD (18-59 years) and elderly DBD (60-69 years; 97% vs 92.3%, P = .2). Recipient age and expanded criteria in KT from cDCD were related to worse early graft outcomes. The outcomes achieved with KT from cDCD were similar to those observed in older and more comorbid DBD donors. This assumption is worth consideration when choosing the most suitable donor for each recipient.

Expanding Criteria in Controlled Cardiac Death Donors: Now With 70-Year-Old Donors.

BACKGROUND: Outcomes of kidney transplant (KT) after controlled cardiac death with older donors are under review. We aimed to analyze early and midterm clinical outcomes using older (≥70 years) controlled cardiac death donors (cDCD). METHODS: Retrospective observational single-center study including all KTs from donors ≥70 years from cDCD and donors after brain death (DBD) performed from January 2017 to January 2022. We performed a comparative study between the 2 groups (cDCD and DBD). An analysis of clinical characteristics, early clinical outcomes, and patient and graft survival rates was made. RESULTS: We included 25 cDCD KTs and 63 DBD KTs ≥70 years. The median follow-up was 18.7 months. Recipients from cDCD were more comorbid. Donors from DBD showed higher hypertension and stroke rate. The KTs from older cDCD showed similar delayed graft function rate (cDCD: 34.6% vs DBD extended criteria donor: 35.3%, P = .59) and primary nonfunction (cDCD 16% vs DBD 17.4%, P = .85) compared with older DBD. Medium (3 years) graft death-censored survival was satisfying (cDCD 73% vs DBD 72%) despite a relevant early graft failure rate in both groups (cDCD 16% vs DBD 23%, P = .26). No differences were observed in patient survival at year 1 (cDCD 94% vs DBD 93%, P = .62). CONCLUSIONS: In our series, the outcomes with older cDCD are similar compared with older DBD. Although older donors showed an increase of early graft failure, these kidneys allowed us to maximize the opportunities for candidates that otherwise should remain on dialysis.

Graft survival differences in kidney transplants related to recipient sex and age.

Background: In recent years, there has been increasing interest in studying differences in recipient sex in renal disease treatment, access to renal replacement therapy, and subsequent outcomes. Our aim was to find out whether there are differences in outcomes after renal transplantation between female and male kidney transplant recipients in our series, particularly in adults under 60 years of age during long-term follow-up. Methods: This was a retrospective study of our kidney transplant series (n = 1,101) to compare graft survival depending on the sex of the recipient in the entire series and patients < 60 years of age (n = 687) during long-term follow-up. Results: We observed no association between recipient sex and graft survival throughout the series, regardless of recipient sex. However, adult female recipients under 60 years of age had lower graft survival than male recipients (p = 0.040). Pre-transplant sensitization (HR 2.438, p = 0.002) and donor age (HR: 1.021, p = 0.017) were the independent variables associated with graft failure. Conclusion: Female recipients younger than 60 years of age had lower graft survival than male recipients, although there were no gender differences in graft or patient survival in the overall study population. Recipient sex per se was not related to graft failure, but the greater immunological risk in women and more frequent use of expanded criteria donors in female recipients under 60 years of age were the main factors related to their poorer graft survival. Further studies and new strategies are needed to identify these differences and develop the best approach to address them.