Kidney transplantation is the optimal therapy for end‐stage renal disease, prolonging survival and reducing spending. Prior economic analyses of kidney transplantation, using Markov models, have ...generally assumed compatible, low‐risk donors. The economic implications of transplantation with high Kidney Donor Profile Index (KDPI) deceased donors, ABO incompatible living donors, and HLA incompatible living donors have not been assessed. The costs of transplantation and dialysis were compared with the use of discrete event simulation over a 10‐year period, with data from the United States Renal Data System, University HealthSystem Consortium, and literature review. Graft failure rates and expenditures were adjusted for donor characteristics. All transplantation options were associated with improved survival compared with dialysis (transplantation: 5.20‐6.34 quality‐adjusted life‐years QALYs vs dialysis: 4.03 QALYs). Living donor and low‐KDPI deceased donor transplantations were cost‐saving compared with dialysis, while transplantations using high‐KDPI deceased donor, ABO‐incompatible or HLA‐incompatible living donors were cost‐effective (<$100 000 per QALY). Predicted costs per QALY range from $39 939 for HLA‐compatible living donor transplantation to $80 486 for HLA‐incompatible donors compared with $72 476 for dialysis. In conclusion, kidney transplantation is cost‐effective across all donor types despite higher costs for marginal organs and innovative living donor practices.
Kidney transplant in contemporary practice remains cost‐effective despite a higher cost of transplant associated with donor quality and immunologic complexity. See Jay and Abecassis's editorial on page 1044.
Kidney graft survival has never been systematically compared between Europe and the United States.
Applying period analysis to first deceased-donor (DD) and living-donor kidney grafts from the United ...Network for Organ Sharing/Organ Procurement and Transplantation Network for the United States and the Collaborative Transplant Study for Europe, we compared overall and age-specific 1-, 5-, and 10-year graft survival for Europeans and white, African, and Hispanic Americans for the 2005 to 2008 period. A Cox regression model was used to adjust for differences in patient characteristics.
For the 2005 to 2008 period, 1-year survival for DD grafts was equal (91%) between Europeans and white and Hispanic Americans, whereas it was slightly lower for African Americans (89%). In contrast, overall 5- and 10-year graft survival rates were considerably higher for Europe (77 and 56%, respectively) than for any of the three U.S. populations (whites, 71 and 46%, Hispanic, 73 and 48%, and African American, 62 and 34%). Differences were largest for recipient ages 0 to 17 and 18 to 29 and generally increased beyond 3 to 4 years after transplantation. Survival patterns for living-donor grafts were similar as those seen for DD grafts. Adjusted hazard ratios for graft failure in United Network for Organ Sharing white Americans ranged between 1.5 and 2.3 (all P<0.001) for 2 to 5 years after transplantation, indicating that lower graft survival is not explained by differences in baseline patient characteristics.
Long-term kidney graft survival rates are markedly lower in the United States compared with Europe. Identifying actionable factors explaining long-term graft survival differences between Europe and the United States is a high priority for improving long-term graft survival.
From 5000 to 10 000 kidney patients die prematurely in the United States each year, and about 100 000 more suffer the debilitating effects of dialysis, because of a shortage of transplant kidneys. To ...reduce this shortage, many advocate having the government compensate kidney donors. This paper presents a comprehensive cost‐benefit analysis of such a change. It considers not only the substantial savings to society because kidney recipients would no longer need expensive dialysis treatments—$1.45 million per kidney recipient—but also estimates the monetary value of the longer and healthier lives that kidney recipients enjoy—about $1.3 million per recipient. These numbers dwarf the proposed $45 000‐per‐kidney compensation that might be needed to end the kidney shortage and eliminate the kidney transplant waiting list. From the viewpoint of society, the net benefit from saving thousands of lives each year and reducing the suffering of 100 000 more receiving dialysis would be about $46 billion per year, with the benefits exceeding the costs by a factor of 3. In addition, it would save taxpayers about $12 billion each year.
This analysis of a government program to compensate kidney donors indicates the monetary value of saving thousands of lives each year and reducing the suffering of a hundred thousand more on dialysis would be about $46 billion per year, and would save taxpayers about $12 billion a year.
The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused ...on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell–mediated rejection (TCMR), borderline, and antibody‐mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor‐specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.
This report focuses on the clarification of the criteria for chronic active T cell–mediated rejection and antibody‐mediated rejection and the optimization of the inflammation threshold for the diagnosis of borderline for acute T cell–mediated rejection, and discusses the potential to use machine learning in diagnostics and personalized therapeutics in solid organ transplantation.
COVID‐19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS‐CoV‐2 vaccines. We ...analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer‐BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS‐CoV‐2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti‐spike level was higher in the controls (31.05 41.8 vs. 200.5 65.1 AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 95% confidence interval 1.17–2.69), high‐dose corticosteroids in the last 12 months (1.3 1.09–1.86), maintenance with triple immunosuppression (1.43 1.06–2.15), and regimen that includes mycophenolate (1.47 1.26–2.27). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID‐19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.
Most kidney transplant recipients do not mount an appreciable anti‐spike antibody response to the BNT162b2 (Pfizer‐BioNTech) SARS‐CoV‐2 vaccine.
Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG‐degrading enzyme of Streptococcus pyogenes (IdeS imlifidase) were assessed in a single‐center, open‐label ascending‐dose study in ...highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 n = 3; 0.25 mg/kg ×1 n = 3, or 0.25 mg/kg ×2 n = 2). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti‐HLA was abolished. IdeS also cleaved the IgG‐type B cell receptor on CD19+ memory B cells. Anti‐IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA‐B7), detected by complement‐dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA‐incompatible donor (HLA‐B7+) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.
In highly sensitized patients with chronic kidney disease, the immunoglobulin G–degrading enzyme of Streptococcus pyogenes (imlifidase) degrades plasma IgG efficiently, reduces HLA antibodies substantially, and abolishes C1q binding to anti‐HLA, thus enabling HLA‐incompatible kidney transplantation.
According to preliminary data, seroconversion after mRNA SARS‐CoV‐2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop ...at least a cellular response that could offer a certain grade of protection against SARS‐CoV‐2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney‐pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA‐1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS‐CoV‐2‐pre‐immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS‐CoV‐2‐naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S‐ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA‐1273 SARS‐CoV‐2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.
Stable kidney or kidney‐pancreas transplant recipients exhibit lower than expected rates of cellular and humoral responses to the
Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this ...registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging.
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