Novel indications for referral and care for simultaneous liver kidney transplant recipients.

PURPOSE OF REVIEW: Kidney dysfunction is challenging in liver transplant candidates to determine whether it is reversible or not. This review focuses on the pertinent data on how to best approach liver transplant candidates with kidney dysfunction in the current era after implementing the simultaneous liver kidney (SLK) allocation policy and safety net. RECENT FINDINGS: The implementation of the SLK policy inverted the steady rise in SLK transplants and improved the utilization of high-quality kidneys. Access to kidney transplantation following liver transplant alone (LTA) increased with favorable outcomes. Estimating GFR in liver transplant candidates remains challenging, and innovative methods are needed. SLK provided superior patient and graft survival compared to LTA only for patients with advanced CKD and dialysis at least 3 months. SLK can provide immunological protection against kidney rejection in highly sensitized candidates. Post-SLK transplant care is complex, with an increased risk of complications and hospitalization. SUMMARY: The SLK policy improved kidney access and utilization. Transplant centers are encouraged, under the safety net, to reserve SLK for liver transplant candidates with advanced CKD or dialysis at least 3 months while allowing lower thresholds for highly sensitized patients. Herein, we propose a practical approach to liver transplant candidates with kidney dysfunction.

Understanding Delayed Graft Function to Improve Organ Utilization and Patient Outcomes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Delayed graft function (DGF) is a common complication after kidney transplant. Despite extensive literature on the topic, the extant definition of DGF has not been conducive to advancing the scientific understanding of the influences and mechanisms contributing to its onset, duration, resolution, or long-term prognostic implications. In 2022, the National Kidney Foundation sponsored a multidisciplinary scientific workshop to comprehensively review the current state of knowledge about the diagnosis, therapy, and management of DGF and conducted a survey of relevant stakeholders on topics of clinical and regulatory interest. In this Special Report, we propose and defend a novel taxonomy for the clinical and research definitions of DGF, address key regulatory and clinical practice issues surrounding DGF, review the current state of therapies to reduce and/or attenuate DGF, offer considerations for clinical practice related to the outpatient management of DGF, and outline a prospective research and policy agenda.

A multicenter prospective study to define the natural history of BK viral infections in kidney transplantation.

BACKGROUND: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics. METHODS: We conducted a multicenter prospective observational study of incident kidney transplant recipients at six U.S. transplant centers. Participants were monitored every 4 weeks for BKV reactivation and followed for up to 24 months post-transplant. We used regression models (logistic, survival, mixed models) to study relationships between BK viremia/BKVN, clinical characteristics, and allograft function. RESULTS: We enrolled 335 participants. Fifty-eight (17%) developed BK viremia, 6 (2%) developed biopsy-proven BKVN, and 29 (9%) developed suspected/presumed BKVN (defined as BKV viral load > 10,000 copies/mL without biopsy). Male donor sex was associated with lower odds for BK viremia, whereas recipient Black race was associated with two-fold increased odds for BK viremia. Recipient female sex was associated with more rapid clearance of BK viremia. Persistent BK viremia/BKVN was associated with poorer allograft function by 24 months post-transplant. CONCLUSIONS: We identified multiple donor and recipient demographic factors associated with risk for BKV infection and poorer allograft function by 24 months post-transplant. This may help design future clinical trials of therapies to prevent or mitigate the deleterious impact of BKV reactivation on kidney transplant outcomes.

CKD in Recipients of Nonkidney Solid Organ Transplants: A Review.

Chronic kidney disease (CKD) after solid organ transplant is a common clinical presentation, affecting 10% to 20% of liver, heart, and lung transplant recipients and accounting for approximately 5% of the kidney transplant waiting list. The causes of CKD are different for different types of transplants and are not all, or even predominantly, due to calcineurin inhibitor toxicity, with significant heterogeneity particularly in liver transplant recipients. Many solid organ transplant recipients with advanced CKD benefit from kidney transplantation but have a higher rate of death while waitlisted and higher mortality after transplant than the general kidney failure population. Recent organ allocation policies and proposals have attempted to address the appropriate identification and prioritization of candidates in need of a kidney transplant, either simultaneous with or after nonkidney transplant. Future research should focus on predictive factors for individuals identified as being at high risk for progression to kidney failure and death and on strategies to preserve kidney function and minimize the CKD burden in this unique patient population.

The changing landscape of live kidney donation in the United States from 2005 to 2017.

The number of live kidney donors has declined since 2005. This decline parallels the evolving knowledge of risk for biologically related, black, and younger donors. To responsibly promote donation, we sought to identify declining low-risk donor subgroups that might serve as targets for future interventions. We analyzed a national registry of 77 427 donors and quantified the change in number of donors per 5-year increment from 2005 to 2017 using Poisson regression stratified by donor-recipient relationship and race/ethnicity. Among related donors aged <35, 35 to 49, and ≥50 years, white donors declined by 21%, 29%, and 3%; black donors declined by 30%, 31%, and 12%; Hispanic donors aged <35 and 35 to 49 years declined by 18% and 15%, and those aged ≥50 increased by 10%. Conversely, among unrelated donors aged <35, 35 to 49, and ≥50 years, white donors increased by 12%, 4%, and 24%; black donors aged <35 and 35 to 49 years did not change but those aged ≥50 years increased by 34%; Hispanic donors increased by 16%, 21%, and 46%. Unlike unrelated donors, related donors were less likely to donate in recent years across race/ethnicity. Although this decline might be understandable for related younger donors, it is less understandable for lower-risk related older donors (≥50 years). Biologically related older individuals are potential targets for interventions to promote donation.

Defining kidney allograft benefit from successful pancreas transplant: separating fact from fiction.

PURPOSE OF REVIEW: To define the natural history of kidney allograft loss related to recurrent diabetes following transplant, and to understand the potential benefit of pancreas transplantation upon kidney allograft survival. RECENT FINDINGS: A postulated benefit of simultaneous pancreas kidney transplant is that, unlike kidney transplant alone, euglycemia from the added pancreas allograft may confer a nephroprotective benefit and prevent recurrent diabetic nephropathy in the renal allograft. Recent large database analyses and long-term histological assessments have been published that assist in quantifying the problem of recurrent diabetic nephropathy and answering the question of the potential benefits of euglycemia. Further data may be extrapolated from larger single-center series that follow the prognosis of early posttransplant diabetes mellitus as another barometer of risk from diabetic nephropathy and graft loss. SUMMARY: Recurrent diabetic nephropathy following kidney transplant is a relatively rare, late occurrence and its clinical significance is significantly diminished by the competing risks of death and chronic alloimmune injury. Although there are hints of a protective effect upon kidney graft survival with pancreas transplant, these improvements are small and may take decades to appreciate. Clinical decision-making regarding pancreas transplant solely based upon nephroprotective effects of the kidney allograft should be avoided.

Live donor kidney - PAK versus SPK: how to decide?

PURPOSE OF REVIEW: Patients with type 1 diabetes and end stage renal disease face a complex choice when considering the relative risks and benefits of kidney transplant alone with or without subsequent pancreas after kidney transplant (PAK) or simultaneous kidney pancreas transplant (SPK). RECENT FINDINGS: SPK is considered the optimal treatment regarding long-term patient survival, but when also faced with the option of living donor kidney transplant with the potential for PAK later, the ideal option is less clear. SUMMARY: This review summarizes the current literature regarding SPK, living donor kidney transplant alone, and PAK transplant outcomes and examines the relative risks of pre- and posttransplant variables that impact patient and graft survival to help inform this complex treatment decision.

Current status of pancreas transplantation.

PURPOSE OF REVIEW: To review recent pancreas transplantation outcomes and indications and describe studies of the impact of pancreas transplant upon patient survival and secondary complications. RECENT FINDINGS: A number of surgical advances have occurred that have improved the early success rate of transplant, and modern immunosuppressive strategies have improved the rate of longer term allograft survival. Pancreas transplant is associated with a mortality benefit when performed in patients with end-stage renal disease in combination with kidney transplant, but questions regarding the impact upon secondary diabetic complications together with the risk assumed by the surgical procedure and the attendant immunosuppression in the nonuremic patient may have tempered enthusiasm for broader expansion of transplantation. Thus, despite these advances, the number of pancreas transplants performed annually is falling consistently. Efforts to define optimal donor and recipient characteristics and understand the pathophysiological impact of pancreas transplant are active areas of research that may lead to greater expansion of pancreas transplant in the future. SUMMARY: The review summarizes these advances, including the utilization patterns of pancreas transplant and current concepts of patient selection and graft monitoring, and places into perspective the current and future role of pancreas transplantation as a therapeutic option in diabetes.

The risk of acute rejection and the influence of induction agents in lower-risk African American kidney transplant recipients receiving modern immunosuppression.

BACKGROUND: While kidney transplant recipients of African American (AA) descent are frequently considered at increased risk of acute rejection, the value of induction therapy is not defined in settings of lower immunologic risk and modern immunosuppression. METHODS: Using the Scientific Registry of Transplant Recipients database, we identified 23,244 primary kidney transplant recipients with panel-reactive antibody (PRA) = 0% treated with TAC/MPA and prednisone from 2000 to 2008. We compared acute rejection, graft survival (GS), and patient survival rates among AA and non-AA and further stratified by induction therapy (none, IL2ra, or rATG). RESULTS: One-yr acute rejection was higher in AA than in non-AA overall (14.5% vs. 9.9%, hazard ratio [HR] for acute rejection [AR] 1.43, p < 0.0001) and was higher regardless of induction agent use. Induction therapy was associated with a reduction in AR, but no benefit in GS in AA or non-AA. In AA, rATG (adjusted relative risk [RR] 0.81, CI 0.70-0.94) and IL2ra (adjusted RR 0.80, CI 0.68-0.93) were similarly effective in reducing AR rates, but did not reach comparable outcomes as in non-AA. CONCLUSION: African Americans who are at otherwise lower immunologic risk have a higher risk of rejection despite modern immunosuppression. Depleting or non-depleting induction therapy similarly reduces but does not entirely mitigate this increased risk, with no impact on three-yr GS.

Acute kidney injury in kidney transplantation.

PURPOSE OF REVIEW: Acute kidney injury (AKI) in transplant recipients is a prevalent condition with a broad list of potential inciting causes. This review highlights recent data describing the epidemiology and long-term consequences of transplant AKI, novel interventions in the management of delayed graft function (DGF), and noninvasive diagnostic strategies. RECENT FINDINGS: The incidence and outcomes of nontransplant AKI are well documented, and similar data are emerging in the transplant setting with recent reports suggesting a high incidence rate and significant impact on long-term graft outcomes. DGF represents a 'pure' form of transplant AKI, and many interventional trials aiming to limit ischemia-reperfusion-induced injury have recently been reported or are currently ongoing. The search for accurate noninvasive predictors of DGF and acute rejection is ongoing and recent literature describes novel plasma and urine-based biomarkers as well as transcriptional profiling methods with high potential for clinical applicability. SUMMARY: AKI in transplant recipients is a frequent occurrence with significant potential for poor long-term graft outcomes. Recent efforts to limit ischemia-reperfusion injury and diagnose transplant AKI via noninvasive methods may help to minimize the impact of AKI on future graft function.

The impact of pre-transplant dialysis on simultaneous pancreas-kidney versus living donor kidney transplant outcomes.

BACKGROUND: Pre-transplant dialysis is known to affect kidney graft survival. Here, we report the impact of pre-transplant dialysis on patient and graft survival of type 1 diabetic recipients of either a simultaneous pancreas-kidney (SPK) or living donor kidney (LDK) transplant. METHODS: Using the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database, 6822 adult type 1 diabetic recipients transplanted through 2000-2011 were identified. Patients were categorized based on pre-transplant dialysis time (DT): preemptive recipients (P-LDK, n = 498; P-SPK, n = 1529), recipients with <1 year of DT (0-1 year DT; LDK n = 582, SPK n = 1700), and those with 1-2 years DT (1-2 year DT; LDK n = 301, SPK n = 2212). Seven-year patient and kidney survival were examined. RESULTS: Compared with the P-SPK group, both 0-1 year DT and 1-2 year DT SPK recipients had lower 7-year patient survival (89, 84 & 84% respectively; log-rank P-value versus P-SPK = 0.01 & <0.001). For LDK groups, DT > 1 year was associated with inferior patient survival (7-year survival 76% versus 87% for P-LDK, P-value versus P-LDK = 0.009). Comparing P-LDK to all other SPK groups, there was no significant difference in 7-year patient or kidney survival. CONCLUSIONS: Preemptive transplantation is associated with the highest patient survival in both LDK and SPK. Compared with the P-LDK group, DT > 1 year is associated with lower patient survival among LDK recipients, but there is no difference in survival with dialysis up to 2 years with SPK. These results highlight the differential impact of DT on LDK and SPK transplantation.

Trends in immune function assay (ImmuKnow; Cylex™) results in the first year post-transplant and relationship to BK virus infection.

BACKGROUND: The ImmuKnow assay is a functional T-cell assay (TCA) that may quantify cellular immune responsiveness following renal transplantation. Using a standard protocol of TCA sampling in the first year post-transplant, we examined changes in TCA values over time and tested for an association between TCA and BK virus (BKV) infection as a marker of over-immunosuppression. METHODS: We performed a single-center retrospective analysis of 897 TCA results in 414 renal transplant recipients obtained at 0 (N = 122), 1 (N = 316), 6 (N = 258) and 12 (N = 201) months post-transplant from May 2005 to July 2009 with concurrent urine and blood BKV polymerase chain reaction measurements. RESULTS: Nearly 40% of patients experienced a decrease in TCA of >150 ng/mL from 1 to 6 months (mean 466-356 ng/mL, P < 0.0001) and remained stable from 6 to 12 months (mean 357 versus 370 ng/mL, P = 0.33). Neither a change in TCA of >150 ng/mL nor a TCA value of ≤ 225 ng/mL were associated with a diagnosis of BKV infection at 1 or 6 months, while TCA ≤ 225 ng/mL was associated with BKV infection at 12 months (P = 0.005). CONCLUSIONS: A reduction in TCA from 1 to 6 months post-transplant is common and is not associated with conditions of over-immunosuppression, rendering the interpretation of changes in TCA during this time period difficult. BKV infection is associated with low TCA values at 12 months, suggesting that patients with low TCA values after 6 months may benefit from potential tailoring of immunosuppression or more aggressive monitoring to prevent subsequent BKV infection.

Pancreas transplant options for patients with type 1 diabetes mellitus and chronic kidney disease: simultaneous pancreas kidney or pancreas after kidney?

PURPOSE OF REVIEW: For patients with type 1 diabetes and chronic kidney disease, the benefits of kidney transplantation vs. dialysis have long been appreciated. However, until recently, the added benefit of pancreas transplantation has been less well defined. RECENT FINDINGS: A number of articles now suggest a long-term survival advantage with simultaneous pancreas kidney (SPK) transplantation, with concurrent improvements in pancreas after kidney transplantation. Although supportive of pancreas transplantation as the preferred therapy for this population, this creates a difficult decision-making process for the patient with type 1 diabetes mellitus and a living donor: should one proceed with living donor transplant and consider pancreas transplantation subsequently, or should one wait for an SPK transplant? SUMMARY: The purpose of this review is to synthesize current data regarding pancreas treatment options and couple this with a discussion of current organ utilization to better understand the advantages and disadvantages of each of these strategies. This in turn may inform clinicians and aid in counseling for the individual patient.

Survey of Salary and Job Satisfaction of Transplant Nephrologists in the United States.

BACKGROUND AND OBJECTIVES: There are no standardized benchmarks to measure productivity and compensation of transplant nephrologists in the United States, and consequently, criteria set for general nephrologists are often used. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A web-based survey was sent to 809 nephrologists who were members of the American Society of Transplantation to gather data on measures of productivity, compensation, and job satisfaction. Factors associated with higher total compensation and job satisfaction were examined. RESULTS: Of 365 respondents, 260 were actively practicing in the United States and provided data on compensation. Clinical productivity was assessed variably, and although 194 (76%) had their work relative value units (wRVUs) reported to them, only 107 (44%) had an established RVU target. Two hundred thirty-four respondents (90%) had fixed base compensation, and 172 (66%) received a bonus on the basis of clinical workload (68%), academic productivity (31%), service (32%), and/or teaching responsibility (31%). Only 127 respondents (49%) filled out time studies, and 92 (35%) received some compensation for nonbillable transplant activity. Mean total compensation (base salary and bonus) was $274,460±$91,509. The unadjusted mean total compensation was higher with older age and was higher for men; Hispanic and White respondents; adult care transplant nephrologists; residents of the western United States; US medical school graduates; nonuniversity hospital employees; and those with an administrative title, higher academic rank, and a higher number of years in practice. Two hundred and nine respondents (80%) thought their compensation was unfair, and 180 (70%) lacked a clear understanding of how they were compensated. One hundred forty-five respondents (55%) reported being satisfied or highly satisfied with their job. Job satisfaction was greater among those with higher amounts of compensation and US medical school graduates. CONCLUSIONS: We report significant heterogeneity in the assessment of productivity and compensation for transplant nephrologists and the association of compensation with job satisfaction.

The role of kidney-pancreas transplantation in diabetic kidney disease.

For patients with type 1 diabetes, innovations in insulin formulations and delivery have improved the ability to achieve excellent blood glucose control. However, it is uncommon to achieve euglycemia, particularly while avoiding complications arising from hypoglycemia. Pancreas transplantation remains the only broadly applied treatment strategy that can result in normalization of blood glucose, but this must be weighed against the risks of a surgical procedure and subsequent immunosuppression. To improve this risk/benefit ratio, pancreas transplantation is typically performed in patients with kidney failure who are to undergo kidney transplantation and immunosuppression (simultaneous pancreas-kidney transplant) or who have undergone kidney transplant and are obligated to the use of immunosuppressive medications (pancreas after kidney transplant). The purpose of this review is to clarify the benefit of an added pancreas transplant in these clinical settings and formulate an approach to the patient with type 1 diabetes as they approach kidney failure.

Polyomavirus nephropathy: a current perspective and clinical considerations.

During the last decade, the human polyomaviruses (BK virus and, much less commonly, JC virus) have entered the realm of routine clinical decision making for providers caring for kidney transplant recipients. The emergence of polyomavirus-associated nephropathy (PVAN) as an important clinical entity coincided with the development and use of more potent immunosuppression agents, currently the only clear risk factor for reactivation of the virus. Ongoing efforts to define the pathogenesis, clinical presentation, and appropriate management of PVAN have led to a greater ability to prevent and control viral-induced interstitial nephritis despite continued deficiencies in our understanding of risk factors for disease and lack of published prospective polyomavirus-specific antiviral trials. The purpose of this review is to summarize advances made during the last decade and highlight emerging data that address common clinical considerations the clinician currently faces in the understanding and management of PVAN.

Standard criteria donor pancreas donation status is associated with improved kidney transplant outcomes.

BACKGROUND: Organ donor characteristics can be used to predict outcomes in kidney transplantation. We hypothesized that pancreas donation status could reflect organ quality and be predictive of kidney graft outcomes following Standard Criteria Donor (SCD) kidney transplantation. METHODS: We performed a retrospective analysis of deceased donor kidney alone (DD KA) transplants reported to SRTR from 1992 to 2005. Group 1 = kidney alone recipients from pancreas donors (KA, P+) and Group 2 = kidney alone recipients from non-pancreas donors (KA, P-). We compared patient and graft survival between groups at 10-yr post-transplant. RESULTS: Group 1 (KA, P+) comprised 19 633 (20%) recipients and Group 2 (KA, P-) comprised 78 737 (80%) recipients. Ten-yr graft survival for Group 1 vs. Group 2 was 42.6% and 36.9% (p < 0.0001), respectively. Pancreas donation status (non-pancreas donor) was associated with a hazard ratio for graft loss of 1.23 on univariate analysis (p < 0.0001), and KA, P-remained an independent risk factor for graft failure at 10 yr, HR 1.09 (p < 0.0001). CONCLUSION: Donor pancreas donation status is an independent predictor of improved outcomes of SCD kidney recipients. Further study of the pancreas organ donor pre-procurement is warranted to optimize not only pancreas utilization but also kidney graft outcomes.

Corticosteroid elimination in simultaneous liver-kidney transplantation recipients.

BACKGROUND: Simultaneous liver-kidney transplantation (SLK) has more than doubled since 2002. While less common in kidney transplant alone recipients (KTA), corticosteroid discontinuation is performed routinely in liver transplantation, raising the question of optimal immunosuppression for SLK recipients. METHODS: A retrospective case series of 16 SLK recipients under a steroid withdrawal protocol was performed to compare short-term outcomes to a contemporaneous cohort of 32 KTA recipients. RESULTS: In 69% of SLK recipients, corticosteroids were eliminated compared to 3% of KTA recipients, p < 0.0001. When comparing SLK and KTA recipients one yr post-transplant, there were no significant differences in renal graft rejection (23.1% vs. 6.3%), death-censored renal graft survival (100% vs. 97%), estimated glomerular filtration rate (74.4 vs. 62.6 mL/min), serum creatinine (1.10 vs. 1.39 mg/dL), or maintenance immunosuppression, respectively. CONCLUSIONS: Corticosteroids may be withdrawn safely in SLK recipients with one-yr renal outcomes comparable to a KTA cohort.

Academic achievement and employment in young adults with end-stage kidney disease.

BACKGROUND: Young adults with end-stage kidney disease (ESKD) are at a pivotal stage of life: progressing through education, seeking employment and developing relationships. We set out to explore how ESKD impacts education and employment attainment in a matched UK and USA patient cohort. Moreover, we aimed to determine if there were significant differences in reported perceptions of impact. DESIGN: A mixed methods design combining previously validated quantitative questionnaire surveys and qualitative semi-structured interviews. PARTICIPANTS: Young people with ESKD aged 18-30 years (N = 27), attending single-centre follow-up in Oxford, UK were matched with 27 comparable young people aged 19-30 years, under follow-up in Denver, USA. Twelve of these patients from Denver were selected for interview. MEASUREMENTS: Self-report questionnaires surveyed patient demographics, educational and employment achievement and experiences. Questionnaire categorical data for matched pairs were analysed using Bowker's test of symmetry. Sequential flow analyses of interview content delineated perception patterns through thematic coding. RESULTS: Sixty percent of non-student Oxford participants were employed compared with 41% in Denver (p = 0.023). Forty-four percent of Oxford patients compared with 52% in Denver, reported illness had made it difficult to gain employment (p = 0.88). In Oxford, 32% completed high school as their highest educational achievement, versus 68% in Denver (p = 0.22). Qualitative themes included fatigue, self-esteem loss, social isolation and low mood. The impact of dialysis and poor understanding from educators/employers resulted in lost work time, and/or limited educational attainment. CONCLUSION: ESKD profoundly impacts on education and employment of young adults in the United States and United Kingdom, generating substantial barriers. Poor understanding appears prevalent amongst educators and employers. Healthcare providers must recognise these problems and invest resources towards tailored support in order to improve associated psychosocial and clinical outcomes.