Management recommendations for kidney transplantation in patients with plasma cell dyscrasia.

Patients with plasma cell dyscrasia, including multiple myeloma, AL amyloidosis, and monoclonal gammopathy of renal significance, face a high burden of end-stage kidney disease, which limits survival and quality of life. Although kidney transplant offers potential benefits, it remains underused because of the high risk of recurrence and historically poor outcomes. A multidisciplinary panel of transplant nephrologists, hematologists/oncologists, and pathologists convened to evaluate contemporary evidence and evolving strategies in kidney transplant for plasma cell dyscrasias and end-stage kidney disease.

Transplant Onconephrology in Patients With Kidney Transplants.

Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after transplant than the general population, depending on the cancer type. Recent advances in cancer therapies have dramatically improved survival outcomes; however, patients with kidney transplants face unique challenges of immunosuppression management, cancer screening, and recurrence of cancer after transplant.

Outcomes of kidney transplant recipients with ESKD due to plasma cell dyscrasia: A case series.

Transplant centers have historically been reluctant to proceed with kidney transplantation in individuals with plasma cell dyscrasias (PCDs) due to concern for high rates of PCD recurrence and PCD-related mortality. As novel therapies for PCDs have improved hematologic outcomes, strategies to optimize kidney transplantation in individuals with PCD-mediated kidney disease are needed. In this single-center case series we discuss our protocol for the transplantation of individuals with ESKD attributed to PCD as well as the hematologic and allograft outcomes of 12 kidney transplant recipients with ESKD attributed to PCD.

The effect of kidney transplantation on left ventricular remodeling and global diastolic strain rate in end-stage renal disease.

Background: Diastolic dysfunction is an early marker of cardiac pathology in end-stage kidney disease (ESKD) patients. The ratio of transmitral filling velocity (E) to early diastolic strain rate (E/e'sr) is a novel non-invasive marker of early left ventricular (LV) filling pressure obtained using two-dimensional speckle tracking echocardiography (2DSTE).

Methods: In a prospective cohort of kidney transplant (KTX) recipients with echocardiograms performed pre-transplant we obtained repeat echocardiograms at 6 months following transplant.

Cohort and nested case-control study of cutaneous squamous cell carcinoma in solid organ transplant recipients, by medication.

Background: Knowledge is needed about the risk of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens.

Objective: Evaluate the risk of cSCC in relation to medications used by SOTRs.

Methods: The cohort and nest case-control study included 3308 SOTRs and 65,883 persons without transplantation during 2009-2019.

COVID-19 and Abdominal Transplant: A Stepwise Approach to Practice During Pandemic Conditions.

Background: The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease has transformed innumerable aspects of medical practice, particularly in the field of transplantation.

Main Body: Here we describe a single-center approach to creating a generalizable, comprehensive, and graduated set of recommendations to respond in stepwise fashion to the challenges posed by these conditions, and the underlying principles guiding such decisions.

Conclusions: Creation of a stepwise plan will allow transplant centers to respond in a dynamic fashion to the ongoing challenges posed by the COVID-19 pandemic.

A Virtual Crossmatch-based Strategy Facilitates Sharing of Deceased Donor Kidneys for Highly Sensitized Recipients.

Background: It is estimated that 19.2% of kidneys exported for candidates with >98% calculated panel reactive antibodies are transplanted into unintended recipients, most commonly due to positive physical crossmatch (PXM). We describe the application of a virtual crossmatch (VXM) that has resulted in a very low rate of transplantation into unintended recipients.

Nuclear Factor of Activated T Cell-regulated Cytokine Gene Expression for Adjustment of Tacrolimus in Kidney Transplant Recipients: A Randomized Controlled Pilot Trial.

Background: The aim of this pilot study was to assess the feasibility of a pharmacodynamics assay that measures Nuclear Factor of Activated T Cell-dependent cytokines expressed as % mean residual expression (MRE) to adjust tacrolimus (tac) dose (intervention [INT] arm) in comparison with the standard of care of tac trough levels (control [CTL] arm).

Methods: We conducted a single-center randomized controlled trial involving 40 stable kidney transplant recipients over 1 year. In the INT arm, the dose of tac was reduced by 15% if the MRE was less than 20% and was increased by 15% if the MRE was greater than 60%.

Kidney Transplantation for Kidney Failure Due to Multiple Myeloma: Case Reports.

Transplantation centers have historically considered a history of multiple myeloma as a contraindication to kidney transplantation due to high recurrence rates and poor transplant survival. However, there have been significant advances in the treatment of multiple myeloma, with improved patient survival, which may allow for successful kidney transplantation in these patients. We report on 4 patients who underwent kidney transplantation at our institution between 2009 and 2015 after having achieved a very good partial response or better with chemotherapy and autologous stem cell transplantation.

An Update on Calcineurin Inhibitor-Free Regimens: The Need Persists, but the Landscape has Changed.

Calcineurin inhibitors (CNIs) have failed to improve long-term renal allograft survival. Their association with cardiovascular morbidity in addition to their suboptimal inhibition of a chronic alloimmune response has shifted investigative efforts toward CNI-free regimens. Sotrastaurin, a small molecule targeting protein kinase C isoforms, failed to provide adequate immunosuppression, whereas the Janus kinase 3 inhibitor tofacitinib's success in the treatment of rheumatoid arthritis led to biopharma's abandonment of it as a transplant agent.

Prediabetic living kidney donors have preserved kidney function at 10 years after donation.

Background: Potential living kidney donors with prediabetes are often excluded from donation because of concerns about the development of type 2 diabetes mellitus (DM) and progression to end-stage renal disease (ESRD). This strategy may be unnecessarily restrictive. Previous studies of living kidney donors have not specifically examined subsets with prediabetes.

Fatal transplant-associated west nile virus encephalitis and public health investigation-california, 2010.

Background: In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified.

Methods: A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology.

Ciprofloxacin prophylaxis in kidney transplant recipients reduces BK virus infection at 3 months but not at 1 year.

Background: BK polyomavirus (BKV) infection remains a significant cause of nephropathy and graft loss. Fluoroquinolones inhibit BKV replication in vitro, and small studies suggest in vivo benefit. A strategy of fluoroquinolone prophylaxis directed specifically against BKV has not been formally tested against a control group in kidney transplant recipients.

Mean arterial blood pressure while awaiting kidney transplantation is associated with the risk of primary nonfunction.

Background: Primary nonfunction (PNF) is a devastating outcome after kidney transplantation and is more common with kidneys from donors without a heartbeat or expanded criteria donors, or both. We investigated recipient-based risk factors for PNF independent of organ donor source.

Methods: We used a case-control study design and matched for the source of organ and year of transplantation; for each recipient with PNF, two recipients without PNF (controls) were randomly selected.

Novel strategies in immunosuppression: issues in perspective.

Recent findings suggest that a chronic alloimmune response is playing the dominant role in late allograft loss, challenging the notion that most grafts are lost due to the inexorable progression of calcineurin inhibitor (CNI) nephrotoxicity. CNIs have failed to improve long-term outcomes and are associated with multiple metabolic derangements. Thus, improvement in long-term allograft outcomes may depend on new agents with novel mechanisms of action, devoid of the toxicities associated with CNIs.

Managing the atazanavir-tacrolimus drug interaction in a renal transplant recipient.

Purpose: The management of the drug interaction between atazanavir and tacrolimus in a renal transplant recipient is described.

Summary: A 53-year-old African-American man with human immunodeficiency virus (HIV) received a renal transplant and was treated in accordance with a corticosteroid-sparing immunosuppressive protocol and maintenance immunosuppression with mycophenolate mofetil and tacrolimus. His highly active antiretroviral therapy included atazanavir 400 mg daily, abacavir 600 mg daily, and lamivudine 100 mg daily.