One size does not fit all: Differential benefits of simultaneous liver-kidney transplantation by eligibility criteria.

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.

Daratumumab Use Prior to Kidney Transplant and T Cell-Mediated Rejection: A Case Report.

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.

BK virus nephropathy in non-renal solid organ transplant recipients: Are we looking hard enough?

We retrospectively examined the clinical characteristics, pathological features, and outcomes of BK viremia and nephropathy in a population of non-renal solid organ transplant patients (NRSOT) referred for outpatient nephrology consultation over a period of 5 years. In the entire cohort of liver, heart, and lung transplant recipients referred to this clinic, 14% percent were found to have BK viremia with a median peak serum BK viral load of 35 500 copies/ml (range 250 to 21 100 000 copies/ml). BK viremia resolved in six of the seventeen patients (35%). Four out of five patients biopsied showed BK virus (BKV) nephropathy. Eleven out of seventeen patients with BK viremia developed advanced (stage 4 or 5) chronic kidney disease. Four patients developed rejection of their solid organ transplant within the first year post detection of BK viremia after immunosuppression reduction. We conclude that a multi-center study is required to evaluate whether implementation of a systematic BK screening program would be effective in early detection and management of this problem in the NRSOT population.

Definition and Analysis of Textbook Outcome: A Novel Quality Measure in Kidney Transplantation.

BACKGROUND: "Textbook outcome" (TO) is a novel composite quality measure that encompasses multiple postoperative endpoints, representing the ideal "textbook" hospitalization for complex surgical procedures. We defined TO for kidney transplantation using a cohort from a high-volume institution. METHODS: Adult patients who underwent isolated kidney transplantation at our institution between 2016 and 2019 were included. TO was defined by clinician consensus at our institution to include freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay > 75th percentile of kidney transplant patients, 90-day mortality, 30-day acute rejection, delayed graft function, and discharge with a Foley catheter. Recipient, operative, financial characteristics, and post-transplant patient, graft, and rejection-free survival were compared between patients who achieved and failed to achieve TO. RESULTS: A total of 557 kidney transplant patients were included. Of those, 245 (44%) achieved TO. The most common reasons for TO failure were delayed graft function (N = 157, 50%) and hospital readmission within 30 days (N = 155, 50%); the least common was mortality within 90 days (N = 6, 2%). Patient, graft, and rejection-free survival were significantly improved among patients who achieved TO. On average, patients who achieved TO incurred approximately $50,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in kidney transplantation was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer transplant centers a detailed performance breakdown to identify aspects of perioperative care in need of process improvement.

A population-based study of prevalence and risk factors of chronic kidney disease in León, Nicaragua.

BACKGROUND: Recent studies have shown an excess of chronic kidney disease (CKD) among younger adult males in the Pacific coastal region of Nicaragua and suggest a non-conventional CKD etiology in this region. These studies have been conducted in small, non-representative populations. OBJECTIVES: We conducted a large population-based cross-sectional study to estimate CKD prevalence in León, Nicaragua, and to evaluate the association between previously investigated risk factors and CKD. METHODS: Estimated glomerular filtration rate, derived using the MDRD equation, was assessed to determine CKD status of 2275 León residents. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios. León CKD prevalence was also standardized to the demographic distributions of the León Health and Demographic Surveillance System and the León 2005 Census. RESULTS: CKD prevalence was 9.1%; twice as high for males (13.8%) than females (5.8%). In addition to gender, older age, rural zone, lower education level, and self-reported high blood pressure, more years of agricultural work, lija (unregulated alcohol) consumption, and higher levels of daily water consumption were significantly associated with CKD. Notably, self-reported diabetes was associated with CKD in adjusted models for females but not males. CONCLUSIONS: Our findings are comparable to those found in regional studies and further support the hypothesis of a Mesoamerican Nephropathy.

CONTEXTE: Selon de récentes études, il existerait une prévalence d'insuffisance rénale chronique (IRC) excessive chez les jeunes adultes de sexe masculin de la côte du Pacifique du Nicaragua. Ces études, qui ont été conduites sur des échantillons non représentatifs de la population, suggèrent une étiologie non classique de l'IRC dans cette région. OBJECTIFS DE L'ÉTUDE: Nous avons effectué une étude transversale portant sur un vaste échantillon de population, afin de pouvoir estimer la prévalence d'IRC dans la ville nicaraguéenne de León, d'une part, et évaluer la présence de liens entre l'IRC et certains facteurs de risque ayant été étudiés, d'autre part. MÉTHODE: Pour déterminer le statut d'IRC de 2275 résidents de la ville de León, nous avons utilisé le débit de filtration glomérulaire estimé, selon l'équation du MDRD. Une régression logistique multivariée a été utilisée pour estimer les ratios de probabilité corrigés de prévalence. La prévalence d'IRC de León a également été normalisée sur la base de la distribution démographique du Health and Demographic Surveillance System de León et avec son recensement de 2005. RÉSULTATS: La prévalence d'IRC était de 9,1%; elle était deux fois plus élevée chez les hommes (13,8%) que chez les femmes (5,8%). D'autres facteurs ont été liés de façon significative à l'IRC: la vieillesse, la vie rurale, un niveau d'éducation faible, une hypertension autodéclarée, plusieurs années de travail en agriculture, et la consommation de lija (alcool non contrôlé) et de grandes quantités d'eau. Le diabète autodéclaré était également lié à l'IRC dans les modèles ajustés chez les femmes, mais non chez les homm es. CONCLUSIONS: Nos résultats sont comparables à ceux des études locales et supportent l'hypothèse de l'existence d'une néphropathie méso-américaine.

Outcomes in kidney transplant recipients from older living donors.

BACKGROUND: Previous studies demonstrate that graft survival from older living kidney donors (LD; age>60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD. METHODS: Using the United Network for Organ Sharing database from 1994 to 2012, recipients were categorized by donor status: SCD, expanded criteria donor (ECD), or LD (by donor age: <60, 60-64, 65-69, ≥70 years). Adjusted models, controlling for donor and recipient risk factors, evaluated graft and recipient survivals. RESULTS: Of 250,827 kidney transplants during the study period, 92,646 were LD kidneys, with 4.5% of these recipients (n=4,186) transplanted with older LD kidneys. The use of LD donors 60 years or older increased significantly from 3.6% in 1994 to 7.4% in 2011. Transplant recipients with older LD kidneys had significantly lower graft and overall survival compared to younger LD recipients. Compared to SCD recipients, graft survival was decreased in recipients with LD 70 years or older, but overall survival was similar. Older LD kidney recipients had better graft and overall survival than ECD recipients. CONCLUSIONS: As use of older kidney donors increases, overall survival among kidney transplant recipients from older living donors was similar to or better than SCD recipients, better than ECD recipients, but worse than younger LD recipients. With increasing kidney donation from older adults to alleviate profound organ shortages, the use of older kidney donors appears to be an equivalent or beneficial alternative to awaiting deceased donor kidneys.

The role of therapeutic apheresis in high immunologic risk renal transplantation: a review of current trends.

Immunologic sensitization, defined by the presence of antibodies directed against donor human leukocyte antigen (or so called donor-specific antibodies [DSA]), is common among those awaiting kidney transplantation, and is associated with worse outcomes following transplant. Existing DSA have historically been screened for pretransplant using complement-dependent cytotoxic crossmatching and their risk circumnavigated through policies that prohibit transplants between incompatible donor-recipient pairs. This risk avoidance strategy maximizes outcomes following transplant, but at the expense of limiting access to transplant for sensitized individuals. Over the last decade, the field of kidney transplantation has moved to actively modify the risks posed by DSA, rather than to simply avoid them. More sensitive detection methods have provided detailed immunologic risk stratification of potential donor-recipient pairs. Desensitization protocols, in which therapeutic aphaeresis plays a central role, have been used to reduce the potential harms posed by DSA. More recently, desensitization and paired donor exchange programs have been used in combination to expand transplantation to highly sensitized patients with incompatible living donors. It is likely that this combination of risk mitigation and avoidance strategies will be used together more often to both maximize individuals' access to transplant, and optimize patient and graft outcomes.

Therapeutic apheresis before and after kidney transplantation.

Kidney transplantation is considered the treatment of choice for most individuals with end-stage kidney disease, as well as the most cost-effective renal replacement therapy for the health care system that serves them. Immunologic sensitization, defined by the presence of antibodies directed against foreign HLA (or so called, donor specific antibodies, or DSA), is a significant barrier to kidney transplantation. Further, the presence of DSA is associated with an increase in the incidence of antibody-mediated rejection and decreased graft survival following transplantation. Therapeutic plasma exchange, an extracorporeal therapy directed at removing plasma proteins, including DSA, has proven to be an important part of a comprehensive strategy to minimize the effect of sensitization before, and following kidney transplantation. As such, it offers the promise of increasing access to transplantation, as well as improving outcomes following transplantation. In this concise narrative review, we describe more specifically the benefits of kidney transplantation, the epidemiology of kidney transplantation in the United States, the clinical significance of anti-HLA antibodies, and the evidence supporting a role for therapeutic plasma exchange before and after kidney transplantation.

Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua.

BACKGROUND AND OBJECTIVES: Endemic renal insufficiency (RI) of unknown etiology is a major public health issue with high mortality in the Pacific coastal regions of Central America. We studied RI in León and Chinandega, Nicaragua, evaluating associations with known risk factors and hypothesized exposures. METHODS: A cross-sectional survey was conducted with assessment of medical, social, and occupational history and exposures in conjunction with measurement of serum creatinine. Cases were defined by an estimated glomerular filtration rate (eGFR) 140 or diastolic blood pressure (DBP) > 90 mmHg, or in reporting diabetes. Agricultural labor was associated with RI (OR = 2.48, 95%CI: 1.59, 3.89, p < 0.0001). There was no association with agricultural non-field work (OR = 0.91, 95%CI: 0.60, 1.38, p = 0.65). Consumption of unregulated alcohol ("lija") was associated with RI (OR = 2.10, 95%CI: 1.31, 3.39, p = 0.0023), as was drinking 5 L or more of water per day (OR = 3.59 vs. 1 L 95%CI: 1.52, 4.46, p = 0.0035). CONCLUSIONS: Agricultural field labor and lija consumption were associated with RI in this region. Water intake may also be important. Identifying specific risk factors for RI within these exposures, such as individual pesticides or lija ingredients, may facilitate prevention in a setting where dialysis and transplantation are limited.