BACKGROUND:The rice diet (RD), a low-sodium (<200 mg/d), low-protein (≈20 g/d), and low-fat (<5 g/d) diet was used to treat patients with malignant hypertension beginning in the 1940s, before any effective antihypertensive drugs were available. We retrospectively analyzed a curated cohort of RD patients with malignant hypertension to assess factors, including dietary adherence, associated with blood pressure (BP) reduction. METHODS:From 17 487 RD charts, we identified 544 malignant hypertension patients (baseline systolic BP ≥170 mm Hg and with concurrent retinal hemorrhage or papilledema), excluding those with diabetes, brain tumor, or prior sympathectomy. Outcome data were censored after any 30-day break in consecutive data. Baseline features, BP changes from baseline to week 4, and diet adherence (assessed by urinary chloride, UCl) were evaluated using summary statistics, univariate, and multivariable analyses. RESULTS:Most patients participated in the RD program before antihypertensive drugs were available; only 48 (8.8%) received any antihypertensive medications in the first month. The cohort (68.9% male) had a median baseline BP of 213/128 mm Hg and body mass index of 23.6 kg/m2. Median time in the program before censoring was 109 days; median total time in the RD program was 333 days. BP declined significantly within the first week, reaching 179/108 mm Hg at week 4. UCl dropped from 217 to 21 mg/dL by week 4. Lower UCl, higher baseline BP, and female sex, but not retinal hemorrhage or papilledema, were associated with greater systolic BP reduction. CONCLUSIONS:The low-sodium, low-fat, low-protein RD effectively lowered BP in malignant hypertension patients in 4 weeks, independent of antihypertensive medications.

Purpose Belatacept has been associated with less de novo specific antibody (dnDSA) development, but few publications have compared the incidence of dnDSA development between tacrolimus and belatacept-based immunosuppression regimens. The purpose of this study was to investigate the differences in dnDSA development and clinical outcomes between these two maintenance regimens in kidney transplant. Methods This was a retrospective, single center, cohort study of patients transplanted between 2013 and 2019 who received a de novo belatacept or tacrolimus-based immunosuppression regimen. The primary outcome was the incidence of dnDSA development (MFI ≥ 1000) at 36 months. Secondary outcomes included renal function, biopsy proven rejection (BPAR), and patient/graft survival. Results Ninety patients met inclusion criteria. The primary outcome occurred in 4 (8.9 %) belatacept patients and 6 (13.3 %) tacrolimus patients, with an overall median time to dnDSA of 300 days (p = 0.51). Class II dnDSA development occurred in 3 (6.7 %) belatacept patients and 6 (13.3 %) tacrolimus patients. Belatacept patients had a lower, but not significantly different, rate of developing BPAR (4.4 % vs 13.3 %, p = 0.13) and had superior renal function at 36 months (median 66 ml/min vs 53 ml/min, p < 0.01). Overall, there was excellent patient/graft survival at 36 months post-transplant. Conclusion De novo belatacept use did not result in a statistically significant difference in the development of dnDSAs but did show a numerically lower class II dnDSA and BPAR development. Overall, belatacept was associated with improved renal function as compared to tacrolimus-based regimens.

Background: The Rice Diet (RD), a low-sodium (<150mg/day), low-protein (20g/day), low-fat (<5g/day), diet was used to treat patients with malignant hypertension (MH) beginning in the 1940's, before any effective anti-hypertensive drugs were available. We retrospectively analyzed a curated cohort of RD patients with MH to assess factors, including dietary adherence, associated with blood pressure (BP) reduction. Methods: From 17,487 RD charts, we identified 544 MH patients (baseline systolic BP (SBP)>=170 mmHg and with concurrent retinal hemorrhage and/or papilledema), excluding those with diabetes, brain tumor, or prior sympathectomy. Outcome data were censored after any 30-day break in consecutive data. Baseline features, BP changes from baseline to Week 4, and adherence (assessed by urinary chloride, UCl) were evaluated using summary statistics, univariate and multivariable analyses. Results: Most patients participated in the RD program before antihypertensive drugs were available; only 48 (4.2%) received any anti-hypertensive medications in the first month. The cohort (68.9% male) had a median baseline BP of 213/128 mmHg and BMI of 23.6 kg/m2. Median time in the program before censoring was 109 days; median total amount of time in the RD program was 333 days. BP declined significantly within the first week, reaching 179/108 mmHg at Week 4. UCl dropped from 217 to 21 mg/dL by Week 4. Lower UCl, higher baseline BP and female gender, but not retinal hemorrhage and/or papilledema, were associated with greater SBP reduction. Conclusion: The low-sodium, low-fat, low-protein RD effectively lowered BP in patients with MH in four weeks, independent of antihypertensive medications. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This is not a clinical trial. ### Funding Statement This project was made possible through the generous gifts of anonymous donors to Duke Nephrology. We are grateful for the support. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Execution of this study was approved by the Duke University Medical Center IRB (Pro00105257) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data can be made available upon written request.

Malignant hypertension (MH), severe arterial hypertension accompanied by retinal hemorrhage (Class III), papilledema (Class IV), or both was untreatable in 1942. Walter Kempner treated MH patients with a very low sodium (~200 mg/day), protein (~5% of calories), and fat (~5% of calories) diet with success in some patients. The scope and efficacy of this “Rice” Diet (RD) was not clear. We analyzed data from 563 non-diabetic MH patients treated from 1942-1988. The cohort, mostly male (69.4%) with a median age 51 years and median BMI 24.01 provided several interesting findings. First, the number of MH patients increased until the early 1950s, but then declined sharply by 1955, before effective pharmacotherapy was available. This sudden MH “disappearance” seems real, but is unexplained by therapy or other known events. Second, 341 MH patients showed that median survival more that doubled with RD treatment compared to untreated MH patients described by Keith-Wagner-Barker (KWB) in 1939. Third, the RD-diet survival benefit began after ~90-100 days into treatment. During the first ~90-100 RD days, survival closely tracks that of untreated MH patients described by KWB; thereafter, survival curves diverged substantially (e.g., calculated half-time survival for Class IV increased from 163.5 to 815.5 days, Figure ). Fourth, serial retinal photographs of 359 MH patients, showed that of 343 with initial hemorrhage, 36 of 177 patients surviving at 1 year (20%) still had hemorrhage; of 146 with initial papilledema, only 1 of 76 patients surviving at 1 year (1%) still had papilledema. Fifth, survival curves of MH patients with only hemorrhage or only papilledema were similar; however, survival was markedly shorter in those with both hemorrhage and papilledema, implying that the deleterious effects of vascular and neuropathic changes are independent of one another and additive. Remaining questions concern: why did MH “suddenly” disappear; how does RD impact vaculopathy; what factors impact survival trajectories.

Abstract Disclosure: F.A. Neelon: None. S. Sanoff: None. P. Lin: None. Hemoglobin and glucose react to form HbA1c, which persists until red blood cells (RBCs) are removed from circulation. Since RBCs survive approximately 122 days, HbA1c is usually measured at intervals of months to years, but more frequent measurement can illuminate changes in blood glucose (BG). We used Beach’s equation for the kinetics of HbA1c formation, to construct graphical depictions of how HbA1c should decline over the 122 days after a drop from constantly high to constantly normal BG levels. As part of routine patient care (not an experimental protocol), we measured HbA1c at 2-4-week intervals in a convenience sample of 10 patients (one of whom was evaluated on 2 occasions) with Type 2 diabetes, obesity, and elevated HbA1c who attended the now defunct Rice Diet Program (RDP) in Durham, NC. All were fed 3 meals/day, comprising 800-1000 kcal of rice, fruits, grains, and vegetables (70-90% carbohydrates) and 300 mg of sodium. Two patients were initially taking insulin; 1, glipizide; and 1, sitagliptin, exenatide, metformin; all hypoglycemic agents were eventually discontinued, and none added. Mean initial HbA1c of 9.7% (range, 8.3-11.7) fell to a mean of 6.2% (range 5.3-8.4) after a mean of 82 days (range, 41-139). Variability in final HbA1c values reflects, at least in part, variable duration of voluntary residence at the RDP. In 9 patients, HbA1c declined in close accordance with the course predicted for complete normalization of blood glucose from the very start of the diet; in 1 patient, HbA1c declined slowly for 25 days, after which the rate increased to near that for complete normalization of BG. Plots of Hb1c values extrapolate back through the point of origin, implying normalization of BG occurs within days of starting the RDP, and is maintained thereafter. Data from frequent measurement of HbA1c show: 1) Normalization of BG occurs almost immediately upon dietary restriction, implying that hyperglycemia in Type 2 diabetes is driven by daily calorie excess, not by accumulated calorie excess (ie, obesity). 2) Contrary to some misperceptions, a high-carbohydrate, sodium- and calorie-restricted diet is not deleterious to ― and may actually benefit ― glucose control in Type 2 diabetes. Presentation: 6/3/2024

BackgroundIn the early 1940s, before antihypertensive drugs were available, the Rice Diet Programme (RDP) was developed to treat severe hypertension and, later, diabetes and obesity. Despite significant advancements in dietary management for these conditions since then, debates remain regarding the proper guidelines for sodium and macronutrients intakes. The patient care records of RDP offer a unique source of longitudinal examination of a very low sodium (<10 mmol/day), fat, cholesterol and protein diet on blood pressure (BP), other health markers and survival.MethodsIn 2019, the Rice Diet Database Project (RDDP) digitised handwritten patient care records and retinal photographs of 17 487 RDP participants, establishing a digital database for analyses. Manual transcription accuracy exceeded 97%. We used regression models to investigate the impact of dietary adherence on systolic BP (SBP) and body weight. Further, we performed Kaplan-Meier survival analysis to compare 5-year survival probability of participants defined by baseline level of SBP.ResultsThe database encompasses a wide array of health markers, including BP, weight, urine chloride (UCl) concentration and retinal features that offer a unique resource for studying the impact of the RDP on hypertension, diabetes and obesity. Initial analysis shows reductions in BP and weight as well as improved survival in participants with severe hypertension, underscoring the effectiveness of the diet. The data also permit examining the safety of extreme dietary sodium reduction.The database has numerous strengths (large patient population; extensive, long-term measurements and the use of UCl excretion to document dietary adherence) and limitations (missing data; temporal changes in methodologies over 50 years and lack of control subjects).ConclusionThe RDDP database allows exploration of the effects of a diet extremely low in sodium, protein, fat and cholesterol on health indicators and patient survival. This report highlights the database’s potential for detailed and intricate future analyses.

Key Points Incidence of ESKD in the first year after primary organ transplant ranges from 2.4% to 3.6% and from 1.4% to 1.8% in the second year post-transplant. National data sources do not currently collect sufficiently reliable follow-up data to identify pretransplant predictors of ESKD. Background Careful selection of multiorgan transplant candidates is required to avoid unintended consequences to patients waiting for kidney transplant alone. The need for a safety net among heart and lung transplant recipients is unknown. The objective of this study was to quantify the incidence of kidney failure after liver, heart, or lung transplantation and identify pretransplant predictors of post-transplant kidney failure. Methods A retrospective cross-sectional study of adults who received liver, heart, or lung transplant between January 1, 2008, and December 31, 2018, was conducted using data from the Scientific Registry of Transplant Recipient and the United States Renal Data System. Post-transplant renal failure was defined as ( 1 ) new start of dialysis, ( 2 ) eGFR of <25 ml/min, ( 3 ) a new waitlisting for a kidney transplant, or ( 4 ) receipt of a kidney transplant. Results The final descriptive cohort included 53,620 liver transplant recipients, 22,042 heart transplant recipients, and 10,688 lung transplant recipients. In the first year post-transplant, the probability of ESKD was comparable among heart transplant recipients (0.036; 95% confidence interval [CI], 0.033 to 0.038) and liver transplant recipients (0.033; 95% CI, 0.031 to 0.035) but was markedly lower in lung transplant recipients (0.024; 95% CI, 0.021 to 0.027). In the second year post-transplant, the probability of ESKD was comparable among liver (0.016; 95% CI, 0.015 to 0.017), lung (0.018; 95% CI, 0.015 to 0.021), and heart transplant recipients (0.014; 95% CI, 0.013 to 0.016). Conclusions Candidates for thoracic transplant would likely benefit from a safety net policy similar to the one enacted in 2017 for liver transplant so as to maintain judicious patient selection for simultaneous multiorgan transplant. National data sources do not currently collect sufficiently reliable follow-up data to identify pretransplant predictors of ESKD, pointing to a need for transplant centers to consistently report kidney impairment data to national databases.

BACKGROUND:Interventions to improve racial equity in access to living donor kidney transplants (LDKT) have focused primarily on patients, ignoring the contributions of clinicians, transplant centers, and health system factors. Obtaining access to LDKT is a complex, multi-step process involving patients, their families, clinicians, and health system functions. An implementation science framework can help elucidate multi-level barriers to achieving racial equity in LDKT and guide the implementation of interventions targeted at all levels.METHODS:We adopted the Pragmatic Robust Implementation and Sustainability Model (PRISM), an implementation science framework for racial equity in LDKT. The purpose was to provide a guide for assessment, inform intervention design, and support planning for the implementation of interventions.RESULTS:We applied 4 main PRISM domains to racial equity in LDKT: Organizational Characteristics, Program Components, External Environment, and Patient Characteristics. We specified elements within each domain that consider perspectives of the health system, transplant center, clinical staff, and patients.CONCLUSION:The applied PRISM framework provides a foundation for the examination of multi-level influences across the entirety of LDKT care. Researchers, quality improvement staff, and clinicians can use the applied PRISM framework to guide the assessment of inequities, support collaborative intervention development, monitor intervention implementation, and inform resource allocation to improve equity in access to LDKT.

Introduction: The residential Rice Diet Program at Duke (RDP) has been shown to be effective in treating patients with malignant hypertension (MH) using a low salt (5 meq/d), low protein (5% kcal), and low fat (5% kcal) diet with no anti-hypertensive medications. Our team examined the RDP medical records and further clarified the identification of 710 MH patients by limiting the criteria of an averaged systolic blood pressure (SBP)>170 mmHg to be met ±7 and a documented non-diabetic hemorrhrage and/or papilledema to be met ± 30 days of starting RDP, respectively. Methods: Wilcoxon ranked-sum was used to compare baseline and week-4 blood pressures (BPs), weight, and urine chloride (uCl, a measure of low-salt diet adherence). Linear regression was used to examine the association between baseline age, gender, SBP, last weight measure and uCl change with SBP change at week-4. Retina evaluation were compared between baseline and last measure using Chi-Square and Fisher’s Exact tests. Results: Male patients (p=.048) and those with a greater change in uCl (p=.001) had a greater reduction in SBP at week-4 ( Table ). Those with a higher baseline SBP had a lower reduction in SBP (p<.001), while baseline age and last weight measure had no effect. The proportion of MH patients with either hemorrhage alone, papilledema alone or both, reduced during RDP participation (p<.001). Conclusion: The RDP significantly lowered BPs, weight and uCl in MH patients within 4-week of starting RDP. The proportion of patients with documented retinal hemorrhage and/or papilledema also reduced significantly during participation in RDP. The mechanisms of the diet’s impact merit further investigation.

There is growing interest in daratumumab in the solid organ transplant realm owing to the potential immunomodulatory effects on CD38-expressing cells, primarily plasma cells, as they have a key role in antibody production. In particular there is interest in use of daratumumab for desensitization and potential treatment for antibody-mediated rejection. However, ongoing investigation with daratumumab has shown potential immunologic concerns in vitro, with a significant increase in populations of CD4-positive cytotoxic T cells and CD8-positive helper T cells in both peripheral blood and bone marrow that could lead to acute T cell-mediated rejection in the solid organ transplant patient. To date, there are no published reports of an association with daratumumab use and T cell-mediated rejection in vivo. In this case report we present what is to our knowledge the first documented case of an early severe T cell-mediated rejection in a low-immunologic-risk living-donor kidney transplant recipient who received daratumumab for multiple myeloma maintenance prior to transplant.

Standard eligibility criteria for simultaneous liver-kidney transplantation (SLK) are in place in the United States. We hypothesize that the benefit associated with SLK over liver transplant alone differs by patient, depending on the specific SLK criteria met. We analyzed a retrospective US cohort of 5446 adult liver transplant or SLK recipients between January 1, 2015, and December 31, 2018, who are potentially qualified for SLK. Exposure was a receipt of SLK. We tested effect modification by the specific SLK eligibility criteria met (end-stage kidney disease, acute kidney injury, chronic kidney disease, or unknown). The primary outcome was death within 1 year of a liver transplant. We used a modified Cox regression analysis containing an interaction term of SLK * time from transplant. Two hundred ten (9%) SLK recipients and 351 (11%) liver-alone recipients died in 1 year. In the overall population, SLK was associated with a mortality benefit over liver transplant on the day of the transplant, without adjustment [HR: 0.59 (95% CI, 0.46-0.76)] and with adjustment [aHR: 0.50 (95% CI, 0.35-0.71)]. However, when SLK eligibility criteria were included, only in patients with end-stage kidney disease was SLK associated with a sustained survival benefit at day 0 [HR: 0.17 (0.08-0.35)] up to 288 (95% CI, 120-649) days post-transplant. Benefit within the first year post-transplant associated with SLK over liver-alone transplantation was only pronounced in patients with end-stage kidney disease but not present in patients meeting other criteria for SLK. A "strict SLK liberal Safety Net" strategy may warrant consideration at the national policy level.

BACKGROUND:Manufacturer recommendations for conversion from immediate-release to extended-release tacrolimus, Envarsus XR®, suggests 80% of the total daily dose of the immediate-release formulation. This conversion has not consistently achieved therapeutic levels in the kidney transplant population.OBJECTIVES:To determine if a reliable weight-based dosing strategy could be utilized to transition kidney transplant patients from immediate-release to extended-release tacrolimus. This may help establish a safe protocol to guide transition between formulations.METHODS:Retrospective, single-center study of adult kidney transplant recipients between July 2015 and December 2018. Excluded patients received dual organs, lacked appropriately drawn tacrolimus levels, or were prescribed interacting medications. Patients were identified by querying prescriptions for extended-release tacrolimus and chart review was performed to exclude any patients without sufficient follow-up after transition.RESULTS:30 patients who transitioned from immediate-release tacrolimus to tacrolimus XR were included in the final analysis. The median weight-based dose of tacrolimus XR that achieved a therapeutic level among the cohort was 0.158 mg/kg/day (Q1-Q3: 0.0587-0.221), which was about 80% of the original median weight-based immediate-release tacrolimus dose. Therapeutic dosing strategies were widely variable, represented by an R2 of 0.33 on linear regression. There was a statistically significant difference in median weight-based dosing strategies among patients of various racial backgrounds (p = 0.0148).CONCLUSIONS:A weight-based dose of tacrolimus XR could not reliably predict a therapeutic level among the total cohort due to the wide inter-patient variability. The median weight-based rate of conversion from immediate-release to extended-release tacrolimus was 80%.

Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene expression patterns in circulating leukocytes are associated with some clinical outcomes, although larger studies are needed to develop accurate predictive classifiers of these events.

BACKGROUND:Recent years have seen major advancements in xenotransplantation: the first pig-to-human heart transplant, the development of a brain-dead recipient model for kidney xenotransplantation, and the registration of the first xenokidney clinical trial. The attitudes of patients with kidney disease or transplants on xenotransplantation and an assessment of their reservations and considerations regarding the technology are crucial to successful clinical translation and eventual widespread implementation. METHODS:This systematic review was registered through PROSPERO (CRD42022344581) prior to initiation of the study and reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. We included studies that evaluated attitudes towards and willingness to undergo xenotransplantation in patients with end-stage renal disease (ESRD), including those who had already undergone transplantation. MEDLINE (via Ovid), Embase (via Elsevier), and Web of Science (via Clarivate) were searched from database inception to July 15, 2022 by an experienced medical librarian for studies on xenotransplantation and attitudes. Abstracts and full text were screened using Covidence software and data items regarding study methodology, patient demographics, and attitudes regarding xenotransplantation were extracted using Microsoft Excel. Risk of bias assessments were performed using the Critical Appraisal Skills Programmed and National Institute of Health study quality assessment tools. RESULTS:Of 1992 studies identified, 14 studies met the inclusion criteria. These studies were conducted across eight countries, four in the United States, for a total of 3114 patients on the kidney waitlist or with a kidney transplant. All patients were over 17 years old and 58% were male. Acceptance of a xenotransplant was assessed using surveys in 12 studies. Sixty-three percent (n = 1354) of kidney patients reported that they would accept a xenotransplant with function comparable to that of an allotransplant. Acceptance of xenografts with inferior function to allografts (15%) or as bridge organs (35%) to allotransplantation was lower. Specific concerns expressed by patients included graft function, infection, social stigma, and animal rights. Subgroup analyses showed higher acceptance in already transplanted compared to waitlist patients and white compared to Black Americans. CONCLUSION:An understanding of patient attitudes and reservations is key to the successful execution of the first xenotransplantation clinical trials. This study compiles important factors to consider, such as patient concerns, attitudes regarding practical clinical scenarios for the use of xenotransplantation, and the impact of demographic factors on acceptance of this emerging technology.

Background. Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)–positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients with donor-derived HCV infection without significant adverse effects, although variability remains in the timing and duration of antivirals. Methods. This retrospective study analyzed all adult HCV-NAAT–negative transplant recipients who received an organ from HCV-NAAT–positive donors from November 24, 2018, to March 31, 2022, at Duke University Medical Center with protocolized delay of DAA initiation until after hospital discharge, with at least 180-d follow-up on all patients. Transplant and HCV-related outcomes were analyzed. Results. Two hundred eleven transplants (111 kidneys, 41 livers, 34 hearts, and 25 lungs) were performed from HCV-NAAT–positive donors to HCV-NAAT–negative recipients. Ninety percent of recipients became viremic within 7 d posttransplant. Ninety-nine percent of recipients were initiated on pangenotypic DAAs in the outpatient setting a median of 52 d posttransplant, most commonly with 12-wk courses of sofosbuvir–velpatasvir (lungs) and glecaprevir–pibrentasvir (heart, kidney, and liver). Ninety-seven percent of recipients had SVR after a first-line DAA; all ultimately achieved SVR at 12 wk after subsequent treatment courses. The median peak HCV RNA for all organ systems was 2 436 512 IU/mL; the median time from antiviral to undetectable RNA was 48 d, although differences were noted between organ groups. No patient deaths or graft losses were directly attributable to HCV infection. Conclusions. One hundred percent of transplant recipients of HCV-NAAT–positive organs ultimately developed SVR without significant adverse effects when HCV antivirals were initiated in the outpatient setting after transplant hospitalization, suggesting that this real-world treatment pathway is a viable option.

Using novel drugs targeting lymphocyte costimulation, cytokines, antibody, complement, and plasma cells, we have developed strategies in a non-human primate model to modulate the B cell response to incompatible kidney transplants. After more than two decades of research supported by mechanistic studies, this has resulted in clinically relevant approaches that are currently enrolling in clinical trials or preparing for such. In this manner, we aim to address the problems of HLA sensitization for very highly sensitized patients awaiting transplantation and the unmet need of effective treatment for antibody-mediated rejection.