Advances in chronic kidney disease最新文献

Stark racial disparities in access to and receipt of kidney transplantation, especially living donor and pre-emptive transplantation, have persisted despite decades of investigation and intervention. The causes of these disparities are complex, are inter-related, and result from a cascade of structural barriers to transplantation which disproportionately impact minoritized individuals and communities. Structural barriers contributing to racial transplant inequities have been acknowledged but are often not fully explored with regard to transplant equity. We describe longstanding racial disparities in transplantation, and we discuss contributing structural barriers which occur along the transplant pathway including pretransplant health care, evaluation, referral processes, and the evaluation of transplant candidates. We also consider the role of multilevel socio-contextual influences on these processes. We believe focused efforts which apply an equity lens to key transplant processes and systems are required to achieve greater structural competency and, ultimately, racial transplant equity.

Despite an increase in the number of kidney transplants performed annually, there remain more than 90,000 individuals awaiting transplantation in the United States. As kidney transplantation has evolved, so has kidney allocation policies. The Kidney Allocation System, which was introduced in 2014, made significant strides to improve utility and equity, but regional and geographic disparities remain. Further modifications eliminating donor service areas have been introduced. Moving forward, systems involving continuous distribution and artificial intelligence may provide further advancement toward an ideal allocation system.

Access to transplant centers is a key barrier for kidney transplant evaluation and follow-up care for both the recipient and donor. Potential kidney transplant recipients and living kidney donors may face geographic, financial, and logistical challenges in engaging with a transplant center and maintaining post-transplant continuity of care. Telemedicine via synchronous video visits has the potential to overcome the access barrier to transplant centers. Transplant centers can start the evaluation process for potential recipients and donors via telemedicine, especially for those who have challenges to come for an in-person visit or when there are restrictions on clinic capacities, such as during a pandemic. Similarly, transplant centers can use telemedicine to sustain post-transplant follow-up care while avoiding the burden of travel and its associated costs. However, expansion to telemedicine-based kidney transplant services is substantially dependent on telemedicine infrastructure, insurer policy, and state regulations. In this review, we discuss the practice of telemedicine in kidney transplantation and its implications for expanding access to kidney transplant services and outreach from pretransplant evaluation to post-transplant follow-up care for the recipient and donor.

Young adult kidney transplant recipients experience poorer outcomes. Specifically worse allograft survival has been reported in the United States and worldwide. Pediatric to adult transition–related research has focused predominantly on medication nonadherence. However, the cause of worse graft outcomes in young adults is likely due to a multitude of complex factors. Consensus guidelines were issued to guide pediatric and adult transplant teams during the transition process. To what extent these transition guidelines are utilized and their impact on improving outcomes for young adult patients is unclear. The consensus guidelines serve as a useful resource, but investigation of the potential barriers to putting these transition guidelines into practice is lacking. One must consider the unique needs of medically complex patients, financial disincentives to transition programs, paucity of evidence-based data to support individual aspects of a transition program and their impact on transition success, and absence of strategies to address health care disparities, all of which can have a multiplicative risk for this population. Key transition research is needed to yield evidence-based data to support transition practices that are successful and truly improve outcomes in this high-risk transplant population. It will also allow better stewardship of transplant organs by optimizing outcomes and allograft longevity.

Diabetes mellitus (DM) is one of the most common complications after kidney transplantation and is associated with unfavorable outcomes including death. DM can be present before transplant but post-transplant DM (PTDM) refers to diabetes that is diagnosed after solid organ transplantation. Despite its high prevalence, optimal treatment to prevent complications of PTDM is unknown. Medical therapy of pre-existent DM or PTDM after transplant is challenging because of frequent interactions between antidiabetic and immunosuppressive agents. There is also frequent need for medication dose adjustments due to residual kidney disease and a higher risk of medication side effects in patients treated with immunosuppressive agents. Sodium-glucose cotransporter 2 inhibitors have demonstrated a favorable cardio-renal profile in patients with DM without a transplant and hence hold great promise in this patient population although there is concern about the higher risk of urinary tract infections. The significant gaps in our understanding of the pathophysiology, diagnosis, and management of DM after kidney transplantation need to be urgently addressed.

Human leukocyte antigen (HLA)–incompatible kidney transplantation offers survival benefit compared with ongoing dialysis. There have been considerable advances in the last decade to allow for increased access to transplant for the HLA-sensitized kidney transplant candidates. These include increased priority in the kidney allocation system, kidney paired donation, and novel desensitization strategies. A better understanding of the role of B cells, plasma cells, and complement and inflammatory cytokines in the pathophysiology of HLA antibody–mediated allograft injury has led to the use of novel therapeutics for desensitization and treatment of antibody-mediated rejection. Here we discuss current approaches to kidney transplantation in HLA-sensitized kidney transplant candidates.

In this review, we discuss the increasing prevalence of obesity among people with chronic and end-stage kidney disease (ESKD) and implications for kidney transplant (KT) candidate selection and management. Although people with obesity and ESKD receive survival and quality-of-life benefits from KT, most KT programs maintain strict body mass index (BMI) cutoffs to determine transplant eligibility. However, BMI does not distinguish between visceral adiposity, which confers higher cardiovascular risks and risks of perioperative and adverse posttransplant outcomes, and muscle mass, which is protective in ESKD. Furthermore, requirements for patients with obesity to lose weight before KT should be balanced with the findings of numerous studies that show weight loss is a risk factor for death among patients with ESKD, independent of starting BMI. Data suggest that KT is associated with survival benefits relative to remaining on dialysis for candidates with obesity although recipients without obesity have higher delayed graft function rates and longer transplant hospitalization durations. Research is needed to determine the optimal body composition metrics for KT candidacy assessments and risk stratification. In addition, ESKD-specific obesity management guidelines are needed that will address the neurologic, behavioral, socioeconomic, and physical underpinnings of this increasingly common disease.

Nonkidney solid organ transplants (NKSOTs) are increasing in the United States with improving long-term allograft and patient survival. CKD is prevalent in patients with NKSOT and is associated with increased morbidity and mortality especially in those who progress to end-stage kidney disease. Calcineurin inhibitor nephrotoxicity is a main contributor to CKD after NKSOT, but other factors in the pretransplant, peritransplant, and post-transplant period can predispose to progressive kidney dysfunction. The management of CKD after NKSOT generally follows society guidelines for native kidney disease. Kidney-protective and calcineurin inhibitor–sparing immunosuppression has been explored in this population and warrants a discussion with transplant teams. Kidney transplantation in NKSOT recipients remains the kidney replacement therapy of choice for suitable candidates, as it provides a survival benefit over remaining on dialysis.

Transplantation remains the optimal mode of kidney replacement therapy, but unfortunately long-term graft survival after 1 year remains suboptimal. The main mechanism of chronic allograft injury is alloimmune, and current clinical monitoring of kidney transplants includes measuring serum creatinine, proteinuria, and immunosuppressive drug levels. The most important biomarker routinely monitored is human leukocyte antigen (HLA) donor-specific antibodies (DSAs) with the frequency based on underlying immunologic risk. HLA-DSA should be measured if there is graft dysfunction, immunosuppression minimization, or nonadherence. Antibody strength is semiquantitatively estimated as mean fluorescence intensity, with titration studies for equivocal cases and for following response to treatment. Determination of in vitro C1q or C3d positivity or HLA-DSA IgG subclass analysis remains of uncertain significance, but we do not recommend these for routine use. Current evidence does not support routine monitoring of non-HLA antibodies except anti-angiotensin II type 1 receptor antibodies when the phenotype is appropriate. The monitoring of both donor-derived cell-free DNA in blood or gene expression profiling of serum and/or urine may detect subclinical rejection, although mainly as a supplement and not as a replacement for biopsy. The optimal frequency and cost-effectiveness of using these noninvasive assays remain to be determined. We review the available literature and make recommendations.