Life on the list: an exploratory study of the life world of individuals waiting for a kidney transplant

Kidney transplantation is the treatment of choice for many individuals with end stage renal disease (ESRD), as transplantation is reported to offer a greater quality of life than renal dialysis. At the end of March 2008 there were 6980 people on the active transplant list for kidney or kidney and pancreas transplants. However, during the previous year a total of 1453 deceased donor kidney transplants were carried out1, illustrating the mismatch between demand for and availability of kidneys for transplant. Whilst the Government has pledged to improve transplant services and to address the organ shortage, individuals on the kidney transplant list are currently facing an average wait of more than two years. Individuals waiting for a kidney transplant face complex challenges, which are currently poorly researched. An insight into the experience of waiting for a kidney transplant and how individuals interpret that wait could contribute to clinical knowledge and lead to improved support for these individuals. It could also raise public awareness about the issues involved in waiting for a kidney transplant, potentially encouraging donatio

Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

Background:The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes. Methods:Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression. Results:Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16-) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients. Conclusions:In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation

A Pre-transplant Blood-based Lipid Signature for Prediction of Antibody-mediated Rejection in Kidney Transplant Patients

Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients. Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to create Linear Discrimination Analysis with regularized correction (RLDA). Changes over time were estimated using sparse partial least square method which is validated by permutation testing. T-test was performed to compare two time points for the same group and groups at matched time points. JMP Pro 13 and MetaboAnalyst were used in the analysis of the Data. Results. A comparison of lipids classes on the day of transplant revealed PLs relative concentration differences between SC and AMR. Concentration of phosphatidylcholine (PC) was significantly diminished in AMR, while there was a trend for increased concentration of lysophosphatidylcholine (LPC). AMR group also showed significantly lower concentration of phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), plasmanylethanolamine (PE-O), and plasmenylethanolamine (PE-P). Our data demonstrated that there are significant differences in the lipidome between SC and AMR on the day of transplant. The analysis identified 7 distinct lipids that discriminated between AMR and SC (AUC) =0.95 (95%CI=0.84- 0.98), R2=0.63 (95%CI=0.4-0.8). A sPLSDA analysis of the data revealed a statistically significant alteration in the lipid profile at 6 months post-transplant compared to the day of transplant. The analysis revealed a panel of 13 lipids that were found to differentiate the two groups at 6 month post-transplant . Further data analysis confirms the presence of a sustained lipid metabolic difference between SC and AMR over time that distinguish between the patients with favorable and non-favorable transplant outcomes. Conclusion. This study demonstrates the potential of the pre-transplant lipidome towards determining AMR in kidney transplant patients, raising the possibility of using this information in risk stratification of patients about to undergo transplant.https://scholarscompass.vcu.edu/gradposters/1086/thumbnail.jp

Cost of lifetime immunosuppression coverage for kidney transplant recipients.

On January 1, 2000, Medicare extended the coverage of immunosuppression medications from 3 years to life for elderly and disabled kidney transplant recipients. This research estimates the impact of extending this lifetime coverage to all kidney transplant recipients on Medicare\u27s cash flows. The study finds that extending coverage to all kidney transplant recipients would have increased Medicare\u27s net cash outflows if the coverage were extended for patients of all income levels. There is evidence that extending coverage to only patients in the lowest income quartile could have resulted in a net cost savings to Medicare

Patient-Benefactors Support New Kidney Transplant Center

December 14, 2017 was a landmark day at Jefferson: the ribbon cutting ceremony of the Nicoletti Kidney Transplant Center at Jefferson. This milestone venture – bringing together research, education and clinical care in one space – came to fruition thanks to a $2.5 million lead gift from the Robert V. Nicoletti Family Trust. The Center emphasizes living donor transplantation, something that is very personal to the Nicoletti family. In early 2006, Jefferson doctors determined that the patriarch of the family, businessman and philanthropist Robert (Bob) V. Nicoletti, needed a kidney transplant. Seven members of his family immediately volunteered to donate a kidney. Ultimately, only one was deemed compatible: Bob’s youngest daughter, Lori Nicoletti Peruto, Esq. This life-saving kidney gave Bob – who passed away in February 2016 at 85 years-old – another 10 loving years with his children and grandchildren. Inspired by the care they received at Jefferson, the Nicolettis became steadfast and generous supporters of the Jefferson Transplant Institute. In late 2015, Bob and his three children, Mark R. Nicoletti, Sr., Lori Nicoletti Peruto, Esq., and Donna Nicoletti Ferrier, along with their spouses, provided the leadership gift to name the new Center. This kicked off a campaign supported by other grateful patients, Jefferson leadership and community partners to build a more robust living donor kidney transplant program. Pennye Goodman was also inspired to give back after receiving a life-saving kidney in 2004 from her brother, Gregory Tettemer. “Through the generosity of my brother, the skills of the Jefferson team and the grace of God, I have been blessed with many years of excellent health. We are proud to support this new Center that will ease the burden of the transplant journey for patients and their families.” Living donor transplants generally work better and last almost twice as long as deceased donor transplants. With more than 600 patients on Jefferson’s organ transplant wait list, this campaign and the resources provided to patients and families in the Nicoletti Kidney Transplant Center come at a critical time. The Center not only simplifies the patient journey, but it also expands our dedicated multidisciplinary team and supports clinical research. To learn about supporting the Nicoletti Kidney Transplant Center at Jefferson, visit Jefferson.edu/GiveJTI or contact Kelly Austin in the Office of Institutional Advancement at 215-955-6383

Reverse Transplant Tourism

In this article, we propose a novel form of kidney swap, which we label “Reverse Transplant Tourism.” This proposal has the potential to increase the number of successful transplants in the US at a time of great need, while reducing costs. It also will provide benefits to impoverished international patients with willing, compatible donors who otherwise would have no access to transplantation. Instead of non-US kidney donors being offered money through a black market middleman in exchange for one of their kidneys, Reverse Transplant Tourism would provide a legal and ethical exchange of living donor kidneys through kidney-paired donation. In this way, the donors will not receive money for their kidneys, but rather will receive a transplant for someone they love, while also helping a US pair who would otherwise be unable to transplant due to biological incompatibility

Characterizing pre-transplant and post-transplant kidney rejection risk by B cell immune repertoire sequencing.

Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection. Here we characterize the peripheral blood immune repertoire of individuals before and after kidney transplant using B cell receptor sequencing in a longitudinal clinical study. Individuals who develop rejection after transplantation have a more diverse immune repertoire before transplant, suggesting a predisposition for post-transplant rejection risk. Additionally, over 2 years of follow-up, patients who develop rejection demonstrate a specific set of expanded clones that persist after the rejection. While there is an overall reduction of peripheral B cell diversity, likely due to increased general immunosuppression exposure in this cohort, the detection of specific IGHV gene usage across all rejecting patients supports that a common pool of immunogenic antigens may drive post-transplant rejection. Our findings may have clinical implications for the prediction and clinical management of kidney transplant rejection

The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome

Donor-reactive immunity plays a major role in rejection after kidney transplantation, but analysis of donor-reactive T-cells is not applied routinely. However, it has been shown that this could help to identify patients at risk of acute rejection. A major obstacle is the limited quantity or quality of the required allogenic stimulator cells, including a limited availability of donor-splenocytes or an insufficient HLA-matching with HLA-bank cells. To overcome these limitations, we developed a novel assay, termed the TreaT (Transplant reactive T-cells)-assay. We cultivated renal tubular epithelial cells from the urine of kidney transplant patients and used them as stimulators for donor-reactive T-cells, which we analyzed by flow cytometry. We could demonstrate that using the TreaT-assay the quantification and characterization of alloreactive T-cells is superior to other stimulators. In a pilot study, the number of pre-transplant alloreactive T-cells negatively correlated with the post-transplant eGFR. Frequencies of pre-transplant CD161+ alloreactive CD4+ T-cells and granzyme B producing alloreactive CD8+ T-cells were substantially higher in patients with early acute rejection compared to patients without complications. In conclusion, we established a novel assay for the assessment of donor-reactive memory T-cells based on kidney cells with the potential to predict early acute rejection and post-transplant eGFR

Progression of endothelial dysfunction, atherosclerosis, and arterial stiffness in stable kidney transplant patients: a pilot study.

BACKGROUND: Kidney transplant patients suffer from vascular abnormalities and high cardiovascular event rates, despite initial improvements post-transplantation. The nature of the progression of vascular abnormalities in the longer term is unknown. This pilot study investigated changes in vascular abnormalities over time in stable kidney transplant patients long after transplantation. METHODS: Brachial artery flow-mediated dilation (FMD), nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial pressure index, and common carotid artery intima-media thickness (CCA-IMT) were assessed in 18 kidney transplant patients and 17 controls at baseline and 3-6 months after. RESULTS: There was no difference in age (51 ± 13 vs. 46 ± 11; P = 0.19), body mass index (26 ± 5 vs. 25 ± 3; P = 0.49), serum cholesterol (4.54 ± 0.96 vs. 5.14 ± 1.13; P = 0.10), systolic blood pressure (BP) (132 ± 12 vs. 126 ± 12; P = 0.13), diastolic BP (82 ± 9 vs. 77 ± 8; P = 0.10), or diabetes status (3 vs. 0; P = 0.08) between transplant patients and controls. No difference existed in vascular markers between patients and controls at baseline. In transplant patients, FMD decreased (- 1.52 ± 2.74; P = 0.03), cf-PWV increased (0.62 ± 1.06; P = 0.03), and CCA-IMT increased (0.35 ± 0.53; P = 0.02). No changes were observed in controls. CONCLUSION: Markers of vascular structure and function worsen in the post-transplant period on long-term follow-up, which may explain the continued high cardiovascular event rates in this population

NEPHROTOXICITY OF CYCLOSPORIN A IN LIVER AND KIDNEY TRANSPLANT PATIENTS

In six of twelve orthotopic liver recipients nephrotoxicity was noted after 13-22 days of treatment with 16·3±2·9 (SEM) mg/kg per day of cyclosporin A (CyA). With a decrease in the daily CyA dose to 9·2±2·3 (SEM) mg/kg kidney function returned to normal. No hepatic rejections occurred on this lowered CyA dose. In 4 out of 66 kidney recipients a switch from a CyA dose of 5·2-10·7 mg/kg daily to azathioprine was done 4-8 months after transplant because of unsatisfactory kidney function, suspected to be due to nephrotoxicity. In three patients, this resulted in an improved graft function. A fourth transplant was lost to an irreversible rejection 13 days later. Thus CyA is nephrotoxic but this toxicity is easily reversed, even after many months of treatment, and the ease with which this complication can be managed suggests that nephrotoxicity should not diminish the high expectations that transplant surgeons have for CyA. © 1981