Improving equity in kidney transplant allocation policies through a novel genetic metric: The Matched Donor Potential.

The demand for donors' kidneys continues to increase amid a shortage of available donors. Managing policies to thoughtfully allocate this scarce resource is a complex process. Although human leukocyte antigen (HLA) matching has been shown to prolong graft survival, its relative contribution to allocation schemes is empirically compromised owing to competing priorities. We explored using a new metric, Matched Donor Potential (MDP), to facilitate improved HLA matching while promoting equity. We interrogated all active kidney waitlist patients (N = 164 427), their corresponding unacceptable antigen files, and all effective donors in the Scientific Registry of Transplant Recipients (January 1, 2016-December 31, 2017). Cause-specific hazard functions were evaluated to assess the potential impact of the MDP metric on deceased donor transplant access rates for all candidates. Access was affected by ethnicity, blood group type, and calculated Panel Reactive Antibody (cPRA). Importantly, we show that access to transplantation is influenced by the patient's own HLA makeup regardless of their ethnicity and by the HLA makeup of effective donors. The MDP metric demonstrates a high association with access to transplantation. Adjusting Cox models to include this new metric resulted in improved access to kidney transplantation for waitlist candidates of minority heritage while significantly promoting HLA matching. Thus, the MDP metric accounts for balanced, equitable organ allocation algorithms.

Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes.

BACKGROUND: Many kidneys donated for transplant in the United States are discarded because of abnormal histology. Whether histology adds incremental value beyond usual donor attributes in assessing allograft quality is unknown. METHODS: This population-based study included patients who received a deceased donor kidney that had been biopsied before implantation according to a prespecified protocol in France and Belgium, where preimplantation biopsy findings are generally not used for decision making in the allocation process. We also studied kidneys that had been acquired from deceased United States donors for transplantation that were biopsied during allocation and discarded because of low organ quality. Using donor and recipient characteristics, we fit multivariable Cox models for death-censored graft failure and examined whether predictive accuracy (C index) improved after adding donor histology. We matched the discarded United States kidneys to similar kidneys transplanted in Europe and calculated predicted allograft survival. RESULTS: In the development cohort of 1629 kidney recipients at two French centers, adding donor histology to the model did not significantly improve prediction of long-term allograft failure. Analyses using an external validation cohort from two Belgian centers confirmed the lack of improved accuracy from adding histology. About 45% of 1103 United States kidneys discarded because of histologic findings could be accurately matched to very similar kidneys that had been transplanted in France; these discarded kidneys would be expected to have allograft survival of 93.1% at 1 year, 80.7% at 5 years, and 68.9% at 10 years. CONCLUSIONS: In this multicenter study, donor kidney histology assessment during allocation did not provide substantial incremental value in ascertaining organ quality. Many kidneys discarded on the basis of biopsy findings would likely benefit United States patients who are wait listed.

COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes.

BACKGROUND: COVID-19 has been associated with high morbidity and mortality in kidney transplant recipients. However, risk factors for COVID-19 disease in patients with kidney transplants remain poorly defined. METHODS: We enrolled patients who underwent kidney transplantation and were actively followed up in two hospitals in Paris on March 1st, 2020. Patients were screened for baseline and transplant characteristics, functional parameters, comorbidities, and immunosuppressive therapies. COVID-19 disease was assessed. Patients were followed up during the pandemic until April 30th, 2020 by the COVID-19 SLS KT survey program, including teleconsulting, at-home monitoring for patients with COVID-19, and a dedicated phone hotline platform. RESULTS: Among 1216 patients with kidney transplants enrolled, 66 (5%) patients were identified with COVID-19 disease, which is higher than the incidence observed in the general population in France (0.3%). Their mean age was 56.4±12.5 years, and 37 (56%) patients were men. The following factors were independently associated with COVID-19 disease: non-White ethnicity (adjusted odds ratio [OR], 2.17; 95% confidence interval [95% CI], 1.23 to 3.78; P=0.007), obesity (OR, 2.19; 95% CI, 1.19 to 4.05; P=0.01), asthma and chronic pulmonary disease (OR, 3.09; 95% CI, 1.49 to 6.41; P=0.002), and diabetes (OR, 3.33; 95% CI, 1.92 to 5.77; P<0.001). The mortality rate related to COVID-19 disease was 1% in the overall study population and 24% in COVID-19-positive patients. CONCLUSIONS: Patients with kidney transplants display a high risk of mortality. Non-White ethnicity and comorbidities such as obesity, diabetes, asthma, and chronic pulmonary disease were associated with higher risk of developing COVID-19 disease. It is imperative that policy makers urgently ensure the integration of such risk factors on response operations against COVID-19.

Disparities in Acceptance of Deceased Donor Kidneys Between the United States and France and Estimated Effects of Increased US Acceptance.

IMPORTANCE: Approximately 3500 donated kidneys are discarded in the United States each year, drawing concern from Medicare and advocacy groups. OBJECTIVE: To estimate the effects of more aggressive allograft acceptance practices on the donor pool and allograft survival for the population of US wait-listed kidney transplant candidates. DESIGN, SETTING, AND PARTICIPANTS: A nationwide study using validated registries from the United States and France comprising comprehensive cohorts of deceased donors with organs offered to kidney transplant centers between January 1, 2004, and December 31, 2014. Data were analyzed between September 1, 2018, and April 5, 2019. MAIN OUTCOMES AND MEASURES: The primary outcome was kidney allograft discard. The secondary outcome was allograft failure after transplantation. We used logistic regression to model organ acceptance and discard practices in both countries. We then quantified using computer simulation models the number of kidneys discarded in the United States that a more aggressive system would have instead used for transplantation. Finally, based on actual survival data, we quantified the additional years of allograft life that a redesigned US system would have saved. FINDINGS: In the United States, 156 089 kidneys were recovered from deceased donors between 2004 and 2014, of which 128 102 were transplanted, and 27 987 (17.9%) were discarded. In France, among the 29 984 kidneys recovered between 2004 and 2014, 27 252 were transplanted, and 2732 (9.1%, P < .001 vs United States) were discarded. The mean (SD) age of kidneys transplanted in the United States was 36.51 (17.02) years vs 50.91 (17.34) years in France (P < .001). Kidney quality showed little change in the United States over time (mean [SD] kidney donor risk index [KDRI], 1.30 [0.48] in 2004 vs 1.32 [0.46] in 2014), whereas a steadily rising KDRI in France reflected a temporal trend of more aggressive organ use (mean [SD] KDRI, 1.37 [0.47] in 2004 vs 1.74 [0.72] in 2014; P < .001). We applied the French-based allocation model to the population of US deceased donor kidneys and found that 17 435 (62%) of kidneys discarded in the United States would have instead been transplanted under the French system. We further determined that a redesigned system with more aggressive organ acceptance practices would generate an additional 132 445 allograft life-years in the United States over the 10-year observation period. CONCLUSIONS AND RELEVANCE: Greater acceptance of kidneys from deceased donors who are older and have more comorbidities could provide major survival benefits to the population of US wait-listed patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03723668.

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: effects on long-term renal function after liver transplantation.

BACKGROUND & AIMS: The incidence of organic renal lesions in patients with end-stage liver disease is unknown. The goal of this study was to make a prospective evaluation of renal histological lesions in a group of unselected patients awaiting liver transplantation. METHODS: Sixty cirrhotic patients underwent a renal biopsy via the transjugular route. The potential effect of renal lesions on renal function was evaluated five years after transplantation. RESULTS: The yield of biopsies enabling satisfactory analysis was 77%, and no major complications occurred. Proteinuria>0.5 g/day was observed in only 8.7% of these patients, microscopic haematuria in 4.3%, creatinine levels>133 mmol/L (1.5mg/dl) in 10.9%, and Modification of the Diet in Renal Disease (MDRD) clearance<60 ml/min in 13.0%. Twenty-five patients (55.3%) had a morphological diagnosis of renal disease, 15 displayed IgA nephropathy and immunofluorescence testing showed that 12 had specific diabetic linear staining for IgG and albumin, of whom seven had associated histological lesions of diabetic nephropathy. Five years after liver transplantation, renal function had significantly deteriorated more in patients with initial diabetic lesions than in those with normal histology or IgA nephropathy alone. CONCLUSIONS: In patients with end-stage liver disease, IgA nephropathy and diabetic lesions were frequently found despite the absence of renal impairment and/or urinalysis anomalies. Our results strongly suggest that severe renal failure develops preferentially in liver transplant recipients with diabetes or carbohydrate intolerance, and that pre-existing arterial lesions may favour the nephrotoxicity of calcineurin inhibitors. Diabetes prior to transplantation needs to be strictly managed and requires a renal sparing immunosuppressive regimen after transplantation.

What is the relevance of systematic aorto-femoral Doppler ultrasound in the preoperative assessment of patients awaiting first kidney transplantation: a monocentric prospective study.

BACKGROUND: The purpose of our study was to study the relevance of a systematic aorto-femoral colour Doppler ultrasound (DUS) in the evaluation of first renal transplant receivers. METHODS: We prospectively studied 100 consecutive first renal transplant (RT) receivers. All patients had a preoperative physical examination with a careful vascular system evaluation including assessment of risk factors and colour DUS of aortic, iliac and femoral arteries. Renal transplantation was planned in the right iliac fossa with end-to-lateral vascular anastomoses. Clinical parameters, DUS results, operative and post-operative parameters at 3 months were compared according to the vascular assessment. RESULTS: Among the 84 patients presenting with a normal preoperative physical arterial examination, 12 patients (14.3%) had an abnormal DUS, revealing atherosclerotic arteries, but no case of arterial stenosis. Among the 16 patients with abnormal physical arterial examination, 10 patients (62.5%) had abnormal DUS, including 4 cases of iliac stenosis. In 3 of the 16 patients (18.8%), DUS revealed right iliac artery stenosis requiring a modification in the surgical procedure. No additional vascular procedure was reported in the case of normal preoperative vascular examination. No technical problems during arterial anastomosis and no post-transplantation arterial complications were reported. In multivariate analysis, abnormal physical examination was the most significant risk factor of atherosclerotic infiltration in DUS. CONCLUSION: The abnormality of arterial physical examination is the best clinical predictor of abnormal DUS in preoperative assessment of renal transplant receivers. However, the low sensitivity and positive predictive value of the physical examination do not support the conclusion that DUS can be avoided in patients with normal arterial physical examination. Nevertheless, in the case of arterial physical abnormality, 'for case' DUS is critical and helps in the surgical strategy in approximately 20% of cases.

[Incidence and management of anemia in renal transplantation: an observational-French study]. / Incidence et prise en charge de l'anémie en transplantation rénale: une étude observationnelle française.

The management of anemia after kidney transplantation remains poorly explored. The Management of Anemia in French Kidney Transplant Patients (MATRIX) study is an observational study conducted in 10 academic hospitals among kidney-transplant patients designed to evaluate the prevalence, associated factors and management of post-transplant anemia. Over two consecutive weeks, 418 recipients (males: 248; age: 50.8+/-12.7 years) were included, all were transplanted for more than six months. Mean serum creatinine (Scr) was 152+/-67 micromol/l and mean hemoglobin (Hb) was 12.4+/-1.8 g/dl (males: 12.8+/-1.9 g/dl; females 11.9+/-1.6 g/dl). Irrespective of the delay following transplantation, 23% of patients (n=95) were severely anemic (Hb < or = 11 g/dl). Eighteen percent of the patients received an antianemic treatment (10% oral iron, 7% erythropoiesis stimulating agents (ESA), 4% folic acid) and only 35% of the severely anemic patients were actually treated (n=33). A significantly-negative correlation was observed between eGFR and Hb levels (R= -0.347, p<0.02). Ninety-six percent of the 193 patients transplanted for more than six months and a Scr greater than 150 micromol/l (n=185) suffered at least one comorbidity (89% hypertension, 32% hypercholesterolemia, 13% diabetes); this group represent the second cohort. Seventy-four percent of them were treated with mycophenolate mofetil, 16% with azathioprine, and 62% with an ACEI or angiotensin II receptor antagonists. Since the transplantation, 127 patients (66%) have been anemic (Hb < or = 11 g/dl) and 58% (n=112) were treated (iron and/or ESA, respectively 81 and 55%). Among the patients not treated for anemia, 74% had an Hb level below 12g/dl. ESA-treated patients received a mean dose of 8500 UI+/-2800 per week. Anemia is under-diagnosed and under-treated in renal-transplant recipients, despite its high prevalence. As expected, a correlation between renal function and Hb levels was observed, as in CKD patients. Prospective studies are underway to assess the consequences of postkidney transplant anemia on quality of life, cardiovascular morbidity and chronic allograft nephropathy and to define the benefit of the treatment.