Trends in the survival benefit of repeat kidney transplantation over the past 3 decades.

Repeat kidney transplantation (re-KT) is the preferred treatment for patients with graft failure. Changing allocation policies, widening the risk profile of recipients, and improving dialysis care may have altered the survival benefit of a re-KT. We characterized trends in re-KT survival benefit over 3 decades and tested whether it differed by age, race/ethnicity, sex, and panel reactive assay (PRA). By using the Scientific Registry of Transplant Recipient data, we identified 25 419 patients who underwent a re-KT from 1990 to 2019 and 25 419 waitlisted counterfactuals from the same year with the same waitlisted time following graft failure. In the adjusted analysis, a re-KT was associated with a lower risk of death (adjusted hazard ratio [aHR] = 0.63; 95% confidence interval [CI], 0.61-0.65). By using the 1990-1994 era as a reference (aHR = 0.77; 95% CI, 0.69-0.85), incremental improvements in the survival benefit were noted (1995-1999: aHR = 0.72; 95% CI, 0.67-0.78: 2000-2004: aHR = 0.59; 95% CI, 0.55-0.63: 2005-2009: aHR = 0.59; 95% CI, 0.56-0.63: 2010-2014: aHR = 0.57; 95% CI, 0.53-0.62: 2015-2019: aHR = 0.64; 95% CI, 0.57-0.73). The survival benefit of a re-KT was noted in both younger (age = 18-64 years: aHR = 0.63; 95% CI, 0.61-0.65) and older patients (age ≥65 years: aHR = 0.66; 95% CI, 0.58-0.74; Pinteraction = .45). Patients of all races/ethnicities demonstrated similar benefits with a re-KT. However, it varied by the sex of the recipient (female patients: aHR = 0.60; 95% CI, 0.56-0.63: male patients: aHR = 0.66; 95% CI, 0.63-0.68; Pinteraction = .004) and PRA (0-20: aHR = 0.69; 95% CI, 0.65-0.74: 21-80: aHR = 0.61; 95% CI, 0.57-0.66; Pinteraction = .02; >80: aHR = 0.57; 95% CI, 0.53-0.61; Pinteraction< .001). Our findings support the continued practice of a re-KT and efforts to overcome the medical, immunologic, and surgical challenges of a re-KT.

The role of renal resistive index as a prognostic tool in kidney transplantation: a systematic review.

BACKGROUND: In kidney transplant recipients (KTRs), observational data have reported conflicting findings about the utility of renal resistive index (RRI) in determining outcomes. This study aimed to synthesize the current literature and determine the prognostic role of RRI in KTRs. METHODS: The authors conducted a systematic review to assess the role of RRI in predicting death, graft failure, graft function and proteinuria. Of the 934 titles/abstracts reviewed, 26 studies were included. There was significant heterogeneity in RRI measurements and thresholds as well as in analytical methods, and a meta-analysis could not be performed. RESULTS: All included studies were observational and included 7049 KTRs. Eight studies analyzed death, of which five reported a significant association with higher RRI. In the remaining three, small sample sizes and lower/multiple RRI thresholds may have limited detection of a statistically significant difference. Three studies investigated all-cause graft failure, and an association with RRI was reported but varied by time of RRI measurement. Three out of five studies that analyzed a composite of patient and graft outcomes reported an association with RRI. Evidence analyzing death-censored graft failure, graft failure (unclear whether death-censored or all-cause), measures of graft function and proteinuria was conflicting. Most studies had a moderate to high risk of bias. CONCLUSIONS: RRI likely has a prognostic role in predicting patient outcomes, reflecting patient systemic vascular disease burden rather than graft hemodynamics. Since cardiovascular diseases are a major cause of death and graft loss, RRI may be explored as a noninvasive tool to risk-stratify KTRs.

Granulocyte colony-stimulating factor with or without immunosuppression reduction in neutropenic kidney transplant recipients.

INTRODUCTION: Neutropenia post-kidney transplantation is associated with adverse graft and patient outcomes. We aimed to analyze the effect of granulocyte colony-stimulating factor (G-CSF) use with and without immunosuppression reduction on graft outcomes in neutropenic recipients. METHODS: In this retrospective cohort study, we identified 120 recipients with neutropenia, within the first-year post-transplant. RESULTS: Of these, 45.0% underwent no intervention, 17.5% had immunosuppression reduced, 18.3% were only given G-CSF, and 19.2% had both interventions. Overall, 61 patients experienced the composite outcome of de-novo DSA, biopsy-proven acute rejection, and all-cause graft failure and the cumulative incidence of this outcome did not vary by any of the four interventions (p = .93). When stratifying the cohort by G-CSF use alone, those who received G-CSF were more likely to have had severe neutropenia (<500/mm3 : 51.1% vs. 12.0%, p < .001), and immunosuppression reduction (51.1% vs. 28.0%, p = .003). However, the composite outcome was not different in the G-CSF and no G-CSF cohort (53.3% vs. 49.3%, p = .67), and in a multivariate model, G-CSF use was not associated with this outcome (aHR = 1.18, 95% CI: .61-2.30). However, a trend towards higher DSA production was noted in the G-CSF cohort (87.5% vs. 62.2%) and this observation warrants prospective evaluation. CONCLUSION: Overall, we conclude that G-CSF use with or without immunosuppression reduction was not associated with graft outcomes.

Comparing outcomes of third and fourth kidney transplantation in older and younger patients.

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18-64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59-3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33-0.41 and aHR = 0.31, 95% CI: 0.24-0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.

Immunosuppression practices during the COVID-19 pandemic: A multinational survey study of transplant programs.

During the COVID-19 pandemic, there has been wide heterogeneity in the medical management of transplant recipients. We aimed to pragmatically capture immunosuppression practices globally following the early months of the pandemic. From June to September 2020, we surveyed 1267 physicians; 40.5% from 71 countries participated. Management decisions were made on a case-by-case basis by the majority (69.6%) of the programs. Overall, 76.8% performed ≥1 transplantation and many commented on avoiding high-risk transplantations. For induction, 26.5% were less likely to give T-cell depletion and 14.8% were more likely to give non-depleting agents. These practices varied by program-level factors more so than the COVID-19 burden. In patients with mild, moderate and severe COVID-19 symptoms 59.7%, 76.0%, and 79.5% decreased/stopped anti-metabolites, 23.2%, 45.4%, and 68.2% decreased/stopped calcineurin inhibitors, and 25.7%, 43.9%, and 57.7% decreased/stopped mTOR inhibitors, respectively. Also, 2.1%, 30.6%, and 46.0% increased steroids in patients with mild, moderate, and severe COVID-19 symptoms. For prevalent transplant recipients, some programs also reported decreasing/stopping steroids (1.8%), anti-metabolites (10.3%), calcineurin inhibitors (4.1%), and mTOR inhibitors (5.5%). Transplant programs changed immunosuppression practices but also avoided high-risk transplants and increased maintenance steroids. The long-term ramifications of these practices remain to be seen as programs face the aftermath of the pandemic.

Thrombotic Microangiopathy in a Pregnant Woman With Kidney Transplantation: A Case Report.

BACKGROUND: The differential diagnosis of thrombotic microangiopathy (TMA) in pregnancy includes common conditions, such as preeclampsia. In women with kidney transplantation, additional causes of TMA must be considered. CASE: A 22-year-old primigravid woman with a transplanted kidney presented with fetal growth restriction, hypertension, acute kidney injury, and hemolysis at 28 weeks gestation. While her clinical presentation was initially consistent with preeclampsia, hemolysis persisted beyond 1 week postpartum. Diagnoses of TMA associated with tacrolimus and antibody-mediated rejection were considered. An elevated tacrolimus level likely contributed to her TMA and a decrease in dosage improved her clinical picture and laboratory markers. CONCLUSION: We report the case of a pregnant kidney transplant recipient with TMA. A multidisciplinary approach is required to optimize the maternal health outcomes in this complex population.

Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation.

Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell-depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all-cause mortality, CVE-related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL-2 receptor antagonist (IL-2RA), 33.3% received anti-thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL-2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92-1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89-1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00-1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all-cause or CVE-related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.

A case report on lipofuscin deposition in a graft biopsy two years after kidney transplantation: an insignificant bystander or a pathogenic benefactor?

BACKGROUND: Lipofuscin deposition is a characteristic manifestation of aging. There is very limited literature in humans and in animals describing these deposits in native kidneys. Overall, it is thought to be non-pathogenic and successful transplants from a donor with lipofuscin deposits have been reported. We present the case of a patient who underwent a kidney transplant and a for-cause biopsy post-transplantation incidentally revealed lipofuscin deposition. CASE PRESENTATION: A 48-year old gentleman with a past medical history of diabetes, hypertension, coronary artery disease, and ischemic and then hemorrhagic cardiovascular accident underwent a successful kidney transplant. His donor was an expanded criteria donor with no major past medical history. Post-transplant course was complicated by delayed graft function requiring one dialysis treatment for hyperkalemia. After that he had an uneventful course and achieved a baseline creatinine of 1.2 mg/dL, with no proteinuria. On a routine 19-month follow-up he was noted to have proteinuria and an antibody against the major-histocompatibility-complex class I-related chain A. A graft biopsy revealed acute antibody-mediated rejection and impressive lipofuscin deposition. He was subsequently treated with an antibody-mediated rejection protocol that included high dose steroids, Rituximab, plasmapheresis, and intravenous immunoglobulin, but responded poorly to this regimen. A 6-month follow up biopsy continued to show lipofuscin deposition, with similar microvascular injury scores and 12-months later his creatinine remained stable but his proteinuria worsened. Patient was struggling with recurrent infectious episodes requiring hospitalizations and thus no further diagnostic or therapeutic treatments were pursued. CONCLUSIONS: Lipofuscin deposition has been reported in solid organ transplants but the significance and cause are not well understood. Several physiologic and some pathologic causes to these deposits have been reported including age, diabetes, medications and a genetic syndrome. We propose that immunologic causes such as rejection in the presence of other risk factors could potentiate the oxidative stress leading to excessive lipofuscin deposition in kidney transplants. In the case of our patient, we conclude that these deposits were likely recipient-derived, and postulate that the cumulative burden of inflammation from rejection, and underlying medical conditions led to increased lipofuscin deposition. We speculate them to be an innocent bystander.

Machine perfusion and long-term kidney transplant recipient outcomes across allograft risk strata.

Background: The use of machine perfusion (MP) in kidney transplantation lowers delayed graft function (DGF) and improves 1-year graft survival in some, but not all, grafts. These associations have not been explored in grafts stratified by the Kidney Donor Profile index (KDPI). Methods: We analyzed 78 207 deceased-donor recipients using the Scientific Registry of Transplant Recipients data from 2006 to 2013. The cohort was stratified using the standard criteria donor/expanded criteria donor (ECD)/donation after cardiac death (DCD)/donation after brain death (DBD) classification and the KDPI scores. In each subgroup, MP use was compared with cold storage. Results: The overall DGF rate was 25.4% and MP use was associated with significantly lower DGF in all but the ECD-DCD donor subgroup. Using the donor source classification, the use of MP did not decrease death-censored graft failure (DCGF), except in the ECD-DCD subgroup from 0 to 1 year {adjusted hazard ratio [aHR] 0.56 [95% confidence interval (CI) 0.32-0.98]}. In the ECD-DBD subgroup, higher DCGF from 1 to 5 years was noted [aHR 1.15 (95% CI 1.01-1.31)]. Also, MP did not lower all-cause graft failure except in the ECD-DCD subgroup from 0 to 1 year [aHR = 0.59 (95% CI 0.38-0.91)]. Using the KDPI classification, MP did not lower DCGF or all-cause graft failure, but in the ≤70 subgroup, higher DCGF [aHR 1.16 (95% CI 1.05-1.27)] and higher all-cause graft failure [aHR 1.10 (95% CI 1.02-1.18)] was noted. Lastly, MP was not associated with mortality in any subgroup. Conclusions: Overall, MP did not lower DCGF. Neither classification better risk-stratified kidneys that have superior graft survival with MP. We question their widespread use in all allografts as an ideal approach to organ preservation.

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes - a retrospective cohort study.

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death-censored graft failure (DCGF). Of 274 KT eligible for analysis, 59% were from expanded criteria donor. RR was modeled as a categorical variable, using a previously identified terminal threshold of 0.4, and 0.2 mmHg/ml/min (median in our cohort). Hazard ratios (HR) of DCGF were 3.23 [95% confidence interval (CI): 1.12-9.34, P = 0.03] and 2.67 [95% CI: 1.14-6.31, P = 0.02] in univariable models, and 2.67 [95% CI: 0.91-7.86, P = 0.07] and 2.42 [95% CI: 1.02-5.72, P = 0.04] in multivariable models, when RR threshold was 0.4 and 0.2, respectively. Increasing risk of DCGF was observed when RR over the course of HMP was modeled using mixed linear regression models: HR of 1.31 [95% CI: 1.07-1.59, P < 0.01] and 1.25 [95% CI: 1.00-1.55, P = 0.05], in univariable and multivariable models, respectively. This suggests that RR during HMP is a predictor of long-term KT outcomes. Prospective studies are needed to assess the survival benefit of patients receiving KT with higher RR in comparison with staying wait-listed.

Self-Reported Employment Status and Social Participation After Successful Kidney Transplantation.

INTRODUCTION: Kidney transplantation (KTX) is considered the treatment of choice for most individuals with end-stage kidney disease. The purpose of this study was to assess the employment status and social participation after successful KTX. METHODS: This was a retrospective cross-sectional study. Eligible participants were patients who received a transplant ≥1 year ago and who were previously on hemodialysis (HD) for ≥1 year. Two hundred individuals participated in this study. RESULTS: A significant number (93.5%) of patients reported they were working prior to HD versus 35% while on HD. Only 14% reported receiving disability benefits prior to HD versus 75% receiving disability while on HD. Comparing transplant recipients with pre-HD patients, 35.5% versus 93.5% reported working, and 74.5% versus 14% reported receiving disability benefits, respectively. After transplant, patients were more likely to join recreational clubs, travel frequently, and participate in recreational/religious activities and social events than when they were on HD. CONCLUSION: Posttransplant, these individuals are more likely to participate in social and leisure activities, but the majority did not resume employment and continued to receive disability payments. Future studies could explore barriers to employment in patients who underwent successful transplantation and the causes and factors as to why these individuals continue to receive disability benefits.

Comparing 10-yr renal outcomes in deceased donor and living donor liver transplants.

Few studies have explored whether the type of LT, deceased donor LT (DDLT) or living donor LT (LDLT), impacts long-term renal outcomes. We performed a retrospective analysis of 220 LT recipients at our institution to study their renal outcomes at 10 yr. Exclusion criteria were age ≤ 18 yr, graft survival ≤ 6 months, and multiorgan transplants; 108 DDLTs and 62 LDLTs were eligible. At baseline, DDLTs had a lower eGFR than LDLTs and 10.2% of DDLTs were on dialysis as compared to 0% of LDLTs. At 10 yr, seven DDLT and three LDLT recipients required dialysis or renal transplant (p = 0.75). In recipients with graft survival >6 months, DDLTs had a slower decline in eGFR as compared to LDLTs (p < 0.01). Among LDLTs, the decline in eGFR continued over the entire 10-yr period, whereas among DDLTs, the decline in eGFR slowed significantly after six months (p = 0.01). This difference between the two groups was not seen among patients in the highest quartile of baseline eGFR. Patient survival and graft survival were similar. In conclusion, the incidence of end-stage renal disease was similar in both DDLT and LDLT patients, but LDLT recipients seem to have a more sustained decline in eGFR when compared with DDLT recipients.

Are Differences in Living Kidney Donation Rates a Sex or a Gender Disparity?

Sex-disaggregated data reveal significant disparities in living kidney donation, with more female than male living kidney donors in most countries and proportions over 60% in some countries. We summarize the present state of knowledge with respect to the potential drivers of this disparity and argue that it is primarily driven by gender-related factors. First, we present the differences between sex and gender and then proceed to summarize the potential medical reasons that have been proposed to explain why males are less likely to be living kidney donors than females, such as the higher prevalence of kidney failure in males. We then present counterarguments as to why biological sex differences are not enough to explain lower living kidney donation among males, such as a higher prevalence of chronic kidney disease among females, which could affect donation rates. We argue that gender differences likely provide a better explanation as to why there are more women than men living kidney donors and explore the role of economic and social factors, as well as gender roles and expectations, in affecting living kidney donation among both men and women. We conclude with the need for a gender analysis to explain this complex psychosocial phenomenon in living kidney donation.

Experiences of living kidney donors: A synthesis of unsolicited patient narratives.

INTRODUCTION: Despite the lauded benefits of living kidney donation, there is growing evidence of the challenges that living kidney donors (LKD) encounter in their donation trajectory and gaps in healthcare service provision. However, most of the evidence is derived from research conducted by clinicians or academic investigators. Significantly less attention has been devoted to analyzing unsolicited accounts of LKDs' experiences. METHODS: We conducted a review and synthesis of published unsolicited first-person narratives of LKDs and aimed to synthesize their experiences and identify care needs. Four electronic databases were searched and 27 LKD narratives were included in our final analysis. Thematic synthesis was used to generate themes inductively. RESULTS: Although the majority of LKDs reported the act of donation to be a fulfilling experience, almost 48% reported encountering challenges in the care that they received. Also, 29% of LKDs reported experiencing an adverse clinical event. Five distinct themes emerged surrounding the donation experience and healthcare needs: 1) Educational needs due to perceived lack of transparency and compensating for knowledge gaps; 2) Respect for donor autonomy due to coercive influences from family or healthcare providers, lack of respect for donor preferences and loopholes in the consent process; 3) Unmet care needs related to poor communication with healthcare providers, coordination issues and inconsistent and inadequate long-term care; 4) Unanticipated outcomes due to economic costs and the emotional burden of donation; and 5) Contributing beyond the donation event by advocating for a balanced view of donation and generating support mechanisms. CONCLUSION: In this synthesis of LKDs narratives, important care gaps and the need to advocate for a balanced perspective on living kidney donation were highlighted. Our review underscores the value of patients' own stories as critical evidence that can inform improvement in healthcare service delivery.

Understanding the Healthcare Needs of Living Kidney Donors Using the Picker Principles of Patient-centered Care: A Scoping Review.

Living kidney donors (LKDs) undertake a complex and multifaceted journey when pursuing donation and have several unmet healthcare needs. A comprehensive understanding of these needs across their entire donation trajectory can help develop a patient-centered care model. We conducted a scoping review to synthesize empirical evidence, published since 2000, on LKDs' experiences with healthcare from when they decided to pursue donation to postdonation care, and what they reported as their care needs. We categorized them according to the 8 Picker principles of patient-centered care. Of the 4514 articles screened, 47 were included. Ample literature highlighted the need for (1) holistic, adaptable, and linguistically appropriate approaches to education and information; (2) systematic, consistent, and proactive coordination and integration of care; and (3) self-management and preparation to optimize perioperative physical comfort. Some literature highlighted the need for (4) better continuity and transition of care postdonation. Two key unmet needs were the lack of (5) a holistic psychosocial evaluation predonation and predischarge to provide emotional support and alleviation of fear and anxiety; and (6) access to specialty and psychosocial services postdonation especially when adverse events occurred. Limited literature explored the principles of (7) respect for patients' values, preferences, and expressed needs; and (8) involvement of family and friends as caregivers. We summarize several unmet healthcare needs of LKDs throughout their donation journey and highlight knowledge gaps. Addressing them can improve their well-being and experiences, and potentially address inequities in living kidney donation and increase living donor kidney transplantation.