A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients.

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

The Spanish Version of the Fear of Kidney Failure Questionnaire: Validity, Reliability, and Characterization of Living Donors With the Highest Fear of Kidney Failure.

BACKGROUND: Measures of fear of progression or recurrence of illnesses have been criticized for neglecting cross-cultural validity. Therefore, we assessed the psychometric properties of the Spanish version of the Fear of Kidney Failure Questionnaire (FKFQ), to determine whether postdonation fear of kidney failure (FKF) influenced the donors' psychosocial status, and define variables that characterized donors with high FKFQ scores. METHODS: We included 492 participants (211 donors) in a multicenter, 11-year, retrospective, cross-sectional study. Donors were classified with a Latent Class Analysis of the FKFQ-item scores and characterized with a multivariable logistic regression analysis. We calculated the risk ratio based on predicted marginal probabilities. RESULTS: The Spanish version of the FKFQ showed acceptable psychometric properties. FKF was uncommon among donors, but we detected a small subgroup (n = 21, 9.9%) with high FKF (mean FKFQ score = 14.5, 3.1 SD). Compared with other donors, these donors reported higher anxiety and depression (38% and 29% of potential anxiety and depressive disorders), worse quality of life, and less satisfaction with the donation. Donors with high FKFQ scores were characterized by higher neuroticism combined with postdonation physical symptoms that interfered with daily activities. CONCLUSIONS: The FKFQ was cross-culturally valid, and thus, it may be used to assess the FKF in Spanish-speaking donors. New interventions that promote positive affectivity and evidence-based treatments for worry could be adapted for treating FKF.

Psychosocial risk factors for impaired health-related quality of life in living kidney donors: results from the ELIPSY prospective study.

Living kidney donors' follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors' psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient's medical outcomes on their donor's psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors' 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering.

Use of De Novo mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Experience From Clinical Practice.

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.

Combination of calcineurin and mTOR inhibitors in kidney transplantation: a propensity score analysis based on current clinical practice.

INTRODUCTION: The TRANSFORM study demonstrated that an immunosuppression based on a combination of calcineurin inhibitors and de-novo mTOR inhibitors (mTORi) is safe and effective in kidney transplant recipients. However, data that validate this approach in clinical practice are currently missing. MATERIALS AND METHODS: Analysis of 401 kidney transplant recipients transplanted from June 2013 to December 2016. All patients received tacrolimus with prednisone in combination with either mycophenolate (n = 186) or mTORi (either everolimus or sirolimus, n = 215). A propensity score to receive mTORi was calculated based on the inverse probability of treatment weighting (IPTW) from the following parameters: age and sex of donor and recipient, BMI, previous transplants, diabetes, cPRA, dialysis before transplantation, dialysis vintage, type of donor, ABO-incompatibility, HLA-mismatches, induction and ischemia time. Median follow-up was 2.6 [1.9; 3.7] years. RESULTS: Cox-regression analysis suggests good results for mTORi versus MPA in terms of 1-year biopsy-proven acute rejection (BPAR, P = 0.063), 1-year graft loss (P = 0.025) and patient survival (P < 0.001). Results observed for BPAR and graft failure were largely attributed to those patients that would have been excluded by the TRANSFORM because of some exclusion criteria (52.9% of the population, P = 0.003 for 1-year BPAR and P = 0.040 for graft loss). In patients who met selection criteria for TRANSFORM, no effect of treatment for BPAR or graft failure was observed, while the beneficial effect on overall survival persisted. CONCLUSIONS: In a real-life setting, a protocol based on de-novo mTORi with tacrolimus and prednisone could be employed as a standard immunosuppressive regimen and was associated with good outcomes.

Impact of Discards for Living Donor Kidney Transplantation in a Transplant Program.

OBJECTIVE: Living donor kidney transplantation (LDKT) is the best treatment for end-stage renal disease. In this setting, a significant percentage of transplants are not undertaken because of medical and nonmedical reasons of both donors and recipients. However, the impact of these discards in a transplant program has not been identified thoroughly so far. Our objective was to clarify key reasons for exclusion of LDKTs and the consequences for the discarded transplant candidates in the following 5 years. METHODS: Analysis of donors' and recipients' characteristics of 781 couples evaluated in our hospital from January 2005 to December 2013. The consequences of discards in transplant candidates were analyzed in the cohort 2012 to 2013 (n = 106) and followed up until October 2018. RESULTS: In our study group, 402 (51.5%) LDKT couples were successfully donated, and 379 (48.5%) were excluded. Donor and transplant recipient candidates discarded were older at the evaluation (55.07 ± 12.14 years vs 51.73 ± 10.93 years, P < .001; 48.81 ± 14.05 years vs 44.62 ± 13.91 years, P < .001, respectively). The most frequent reason for kidney discard was medical contraindication found in the potential donor (47.5%; low eGFR, diabetes mellitus, impaired glucose tolerance, high blood pressure, cardiovascular pathology casually found during evaluation, and proteinuria). Of the discarded candidates from 2012 to 2013, 36.8% received a deceased donor kidney transplant, 17% a LDKT with another donor, 7.5% stayed on the waiting list, 18.9% died, 3.8% were excluded from the waiting list, and 14.2% were lost to follow-up. CONCLUSIONS: In most cases, transplantation was not undertaken because of donor pathology. Fifty-three percent of the discarded patients were eventually transplanted, with a 31.4% probability to receive an organ from another living donor.

Postinfectious Acute Glomerulonephritis in Renal Transplantation: An Emergent Aetiology of Renal Allograft Loss.

Despite the high incidence of posttransplant infections, postinfectious acute glomerulonephritis (PIAGN) in renal allograft is a rare entity, without effective treatment and a bad prognosis. We describe two cases of PIAGN: the first one was developed 2 years after kidney transplantation, secondary to Staphylococcus aureus bacteremia with presence of extracapillary proliferation in biopsy. The patient was treated with methylprednisolone and plasma exchanges without response, remaining dialysis dependent. The second case was reported 5 years after kidney transplantation, secondary to influenza A infection. Kidney biopsy showed an IgA-dominant PIAGN and methylprednisolone boluses were initiated without clinical response, suffering a progressive worsening and loss of kidney graft. Due to the aggressive clinical course of this entity, PIAGN should be considered in the differential diagnosis of acute kidney graft failure in the context of an infection. Elderly patients have a higher risk of more severe acute renal dysfunction, requiring dialysis in a great proportion of cases.

Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection.

BACKGROUND: Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. METHODS: To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. RESULTS: We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. CONCLUSIONS: Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications. TRIAL REGISTRATION: Agencia Española de Medicametos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTR-INM-2017-01.

Assessment of donor satisfaction as an essential part of living donor kidney transplantation: an eleven-year retrospective study.

Living kidney donors seem highly satisfied with donation. However, previous studies measure satisfaction by a single-item or by simply questioning donors' willingness to donate again or to recommend living donation. With the aim of analyzing whether satisfaction with donation is a multidimensional construct, thus allowing a more specific characterization of dissatisfied donors, 332 living kidney donors (2005-2015) answered a renewed version of the European Living Donation and Public Health Project satisfaction survey. Exploratory factor-analyses suggested that satisfaction was composed of three-factors: violation of donors' expectancies about donation; interference of donation on daily activities, and pain and discomfort. Donors reported high levels of satisfaction. However, cluster-analysis identified a subgroup characterized by a higher discrepancy between the expected and the actually experienced during donation, higher interference on daily activities, and higher pain and discomfort. Most of them considered that hospital discharge was premature, suffered economic losses and perceived worse health outcomes of their recipients. Single questions assessing donors' willingness to donate again or to recommend living donation were unable to differentiate between clusters. In summary, donor's satisfaction seems better characterized by three dimensions than by single questions.

Pancreas outcomes between living and deceased kidney donor in pancreas after kidney transplantation patients.

Background: Pancreas outcomes in pancreas after kidney transplantation (PAK) patients have been reported as being inferior to those of patients who receive simultaneous pancreas and kidney transplantation (SPK). The influence of the kidney donor (i.e. living versus deceased) has never been previously addressed. Methods: We retrospectively analysed all pancreas transplants performed in a single centre since 2007 and compared the outcomes between those patients who had previously received a living-donor kidney transplant (pancreas transplantation after living-donor kidney transplantation, PAldK; n = 18) or a deceased-donor kidney transplant (pancreas transplantation after deceased-donor kidney transplantation, PAddK; n = 28), using SPK (n = 139) recipients as a reference. Results: Pancreas survival was similar between all groups, but inferior for PAldK when including only those with a functioning graft at day 90 post-transplantation (P = 0.004). Pancreas acute rejection was significantly increased in PAldK (67%; 1.8 ± 1.4 episodes/graft) when compared with PAddK (25%) and SPK (32%) (P < 0.05) patients. In a multivariate Cox regression model including known risk factors for pancreas rejection, PAldK was the only predictor of acute rejection (hazard ratio 6.82, 95% confidence interval 1.51-30.70, P < 0.05). No association was found between donor-recipient HLA mismatches and graft rejection. Repeated HLA mismatches between kidney and pancreas donors (0 versus 1-6) did not correlate with pancreas graft rejection or survival in either PAK transplantation group (P > 0.05). Conclusion: Pancreas graft outcomes are worse for PAldK when compared with PAddK and SPK patients.

Bortezomib for refractory acute antibody-mediated rejection in kidney transplant recipients: A single-centre case series.

AIM: Acute antibody-mediated rejection (ABMR) after kidney transplantation (KT) is associated with poor allograft survival. Current therapies for ABMR are able to deplete B-lymphocytes but do not target plasma cells. Bortezomib is a proteasome inhibitor that can eliminate plasma cells and has demonstrated utility in the treatment of ABMR. METHODS: A retrospective study was carried out from 2010 to 2014, including all patients with ABMR refractory to conventional treatment who received bortezomib. Bortezomib (1.3 mg/m(2) ) was administered intravenously on days 1, 4, 8, and 11. Renal function, graft survival, follow-up biopsies, and donor-specific antibodies (DSA) were recorded. RESULTS: We identified seven patients. Of these, high immunological risk was found in 6 of 7, preformed DSA were found in 5 of 7, flow cytometry crossmatch was positive in 4 of 7, and desensitization before KTx was provided in 6 of 7 patients. ABMR was diagnosed at a median of 90 days (8-167) post-KT. After bortezomib therapy, renal function improved or stabilized in 5 of 7 patients and progressively deteriorated in 2 of 7, leading to haemodialysis after 7 and 11 months, respectively. Follow-up kidney biopsies showed persistence of ABMR in 2 of 7, chronic active ABMR 3 of 7 and inactive chronic lesions in 2 of 7. DSA titres significantly decreased after treatment (P = 0.028). All patients experienced mild adverse events. After a follow-up of 22 ± 18 months, three grafts were lost (42%) and four remained functioning. CONCLUSION: Bortezomib could be useful as an adjuvant therapy for ABMR refractory to conventional treatment with acceptable mid-term outcomes in these severe cases. More research is needed to develop strategies to better preserve graft function after refractory ABMR.

Eculizumab in pregnancy-associated atypical hemolytic uremic syndrome: insights for optimizing management.

Pregnancy-associated atypical hemolytic uremic syndrome is a systemic disease associated with high morbidity and mortality rates, caused by dysregulation of the alternative complement pathway, leading to uncontrolled complement activation resulting in thrombotic microangiopathy. This condition can be effectively treated by anti-C5 therapy, which controls complement activation. Treatment can be safely discontinued after complete remission and resolution of the precipitating cause, especially in patients with a low-risk genetic profile.

Can EPS development be avoided with early interventions? The potential role of tamoxifen--a single-center study.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Identification of patients at high risk for EPS ("EPS-prone") and delivery of appropriate interventions might prevent its development. Our aim was to evaluate the clinical characteristics and outcomes of all EPS and EPS-prone patients diagnosed at our PD unit. METHODS: For a 30-year period representing our entire PD experience, we retrospectively identified all patients with EPS (diagnosed according to International Society for Peritoneal Dialysis criteria) and all patients defined as EPS-prone because they met at least 2 established criteria (severe peritonitis, PD vintage greater than 3 years, severe hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure). RESULTS: Of 679 PD patients, we identified 20 with EPS, for an overall prevalence of 2.9%. Mean age at diagnosis was 50.2 ± 16.4 years, with a median PD time of 77.96 months (range: 44.36 - 102.7 months) and a median follow-up of 30.91 months (range: 4.6 - 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen, 10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with 25% mortality related to EPS. Another 14 patients were identified as EPS-prone. Median follow-up was 54.05 months (range: 11.9 - 87.04 months). All received tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We observed no differences in baseline data between the groups, but the group with EPS had been on PD longer (84 ± 53 months vs 39 ± 20 months, p = 0.002) and had a higher cumulative number of days of peritoneal inflammation from peritonitis (17.2 ± 11.1 days vs 9.8 ± 7.9 days, p = 0.015). Overall mortality was similar in the groups. The incidence of EPS declined during our three decades of experience (5.6%, 3.9%, and 0.3%). CONCLUSIONS: Being a serious, life-threatening complication of PD, EPS requires high suspicion to allow for prompt diagnosis and treatment. Early detection of EPS-prone states and delivery of appropriate intervention might prevent EPS development. Tamoxifen seems to be a key strategy in prevention, but caution should be used in interpreting our results. Additional randomized controlled studies are needed.

Experiencia de 30 años en una unidad de diálisis peritoneal: supervivencia a largo plazo / Thirty years in a peritoneal dialysis unit: long-term survival

INTRODUCCIÓN: La diálisis peritoneal (DP) es una técnica establecida de tratamiento renal sustitutivo que gracias a los avances tecnológicos y clínicos ha mejorado sus tasas de supervivencia en los últimos años. OBJETIVOS: Evaluar la supervivencia del paciente y la técnica en DP a lo largo de 30 años y según las décadas para consolidar su utilidad sanitaria. MÉTODOS: Estudio retrospectivo de cohorte de todos los pacientes del programa de DP del Hospital Universitario La Paz (Madrid) desde 1980 a 2010. Variables demográficas y clínicas fueron recolectadas de los registros clínicos. RESULTADOS: Se incluyeron 667 pacientes, 54,4 % varones, con edad media de 51,47 años y una mediana de seguimiento de 23,1 meses. Se observó un aumento progresivo de pacientes incidentes, especialmente en DP automatizada (DPA). La supervivencia del paciente a 5 años fue de 54 %, con una mediana de 64,66 meses, con un aumento significativo en la última década (p = 0,000). La edad, la comorbilidad, el sexo masculino, la DP crónica ambulatoria (DPCA) y la diabetes fueron predictores de la supervivencia del paciente. La supervivencia de la técnica a los 5 años fue del 64,2 % y la mediana de 82 meses. El éxito de la técnica fue mayor en jóvenes, en DPA y con menor comorbilidad

BACKGROUND AND OBJECTIVE: Peritoneal dialysis (PD) is an establish renal replacement therapy that has evolved in the last decades thanks to technological and clinical advances showing improving survival rates. The aim of this study was to evaluate the patient and technique survival in PD over 30 years of experience and in the different decades. PATIENTS AND METHOD: Retrospective cohort study including all patients in the PD unit of the Hospital Universitario La Paz (Madrid), from 1980 to 2010. Demographics and clinical variables were collected from medical records. RESULTS: A total of 667 patients were included, 54.4% males, with a mean age of 51.47 years and a median follow-up of 23.1 months. There was an increased in PD incident patients, especially in automatic PD (APD). Patient survival at 5 years was 54%, with a median of 64.66 months, increasing significantly in the last decade (p = 0.000). Age, comorbidity, male sex, chronic ambulatory PD and diabetes were independently predictor of patient survival. Technique survival at 5 years was 64.2% and median 82 months. Younger patients, in APD and with less comorbity showed better technique survival. CONCLUSIONS: Over 30 years of experience we found an increased in incident patients. Age, comorbidity and diabetes were still the main predictors of survival

Thirty years in a peritoneal dialysis unit: long-term survival.

INTRODUCTION: Peritoneal dialysis (PD) is an established renal replacement therapy technique which thanks to the technological and clinical advances has improved its survival rates in recent years. OBJECTIVES: The aim of this study was to evaluate patient and technique survival in PD over 30 years, according to the different decades in order to consolidate its usefulness in healthcare. METHOD: Retrospective cohort study including all patients in the PD programme of the Hospital Universitario La Paz (Madrid), from 1980 to 2010. Demographic and clinical variables were collected from medical records. RESULTS: A total of 667 patients were included, 54.4% male, with a mean age of 51.47 years and a median follow-up period of 23.1 months. There was a progressive increase in PD incident patients, especially in automated PD (APD). Patient survival at 5 years was 54%, with a median of 64.66 months, increasing significantly in the last decade (P=.000). Age, comorbidity, male sex, chronic ambulatory PD (CAPD) and diabetes were predictors of patient survival. Technique survival at 5 years was 64.2% with a median of 82 months. The success of the technique was greater in younger patients on APD and with lower comorbidity. CONCLUSIONS: Over 30 years, we found an increase in incident patients. Age, comorbidity and diabetes still continue to be the main determining factors for survival.