A2/A2B to B kidney transplantation outcomes: A single center 7-year experience.

INTRODUCTION: Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants. METHODS: This retrospective, single-center analysis included all adults who received A2/A2B to B deceased donor kidney transplants from December 2014 to June 2021 compared to B to B recipients. The effects of pre-transplant IgM/IgG titers, stratified as ≤1:8 and ≥1:16, on death-censored, rejection-free, and overall graft survival were tested. RESULTS: Fifty-three A2/A2B and 114 B to B adults were included with a median follow-up time of 32 months. Overall graft survival, patient survival, and rejection-free graft survival did not differ between the two groups. There were no differences between the groups' overall kidney function values (p > .80) or their temporal trajectories (time by group interaction p > .11). Unadjusted death-censored graft survival was lower in A2/A2B to B compared to B recipients (p = .03), but the effect was not significant (p = .195) after adjusting for any readmissions (p = .96), rejection episodes (p < .001) or BK infection (p = .76). We did not detect an effect of pre-transplant titer group on death-censored (p = .59), rejection-free (p = .61), or overall graft survival (p = .26) CONCLUSIONS: A2/A2B to B kidney transplants have comparable overall patient and graft survival, rejection-free graft survival, and longitudinal renal function compared to B to B transplants at our center. Allograft survival outcomes were not significantly different between patients with low and high pre-transplant anti-A1 IgM/IgG titers.

Twelve-month kidney and liver outcomes of kidney transplantation from Hepatitis C Viremic deceased donors to aviremic recipients.

INTRODUCTION: Utilization of hepatitis C viremic (HCV+) deceased donor kidneys (DDKT) for aviremic recipients increases opportunities for transplantation with excellent short-term outcomes. Our primary aim was to understand longer-term outcomes, specifically assessing kidney and liver function in the first year posttransplant. METHODS: This was a retrospective single-center study of adult DDKT recipients of HCV+ kidneys (cases) matched 1:1 to recipients of HCV- kidneys (comparators). Between-group outcomes were analyzed using comparisons of means and proportions, survival analysis methods, and multivariable mixed effects models. RESULTS: Sixty-five cases and 65 comparators had statistically comparable demographic and clinical characteristics. There were no between-group differences in serum creatinine or estimated glomerular filtration rate at month 12 (p = .662) or in their trajectories over months 1-12 (p > .292). Within the first 60 days, rates of liver function values >3 times upper limit of normal among cases were comparable to comparators for aspartate aminotransferase (AST) (14% vs. 6%, p = .242) and higher for alanine transaminase (ALT) (23% vs. 6%, p = .011). AST declined during the first 8 weeks (p = .005) and stabilized for both groups (p = .406) during the following 10 months. ALT declined during the first 8 weeks (p < .001), continued to decline over months 3-12 (p = .016), and the trajectory was unrelated to antiviral therapy initiation among cases. CONCLUSIONS: Aviremic recipients of HCV+ kidneys had comparable kidney outcomes to matched recipients of HCV- kidneys. Despite more HCV+ recipients having an elevation in ALT within the first 60 days, ALT values normalized with no identified liver complications attributed to HCV.

Predictors of renal recovery in recipients of liver transplant alone who met 2017 simultaneous liver-kidney transplant criteria.

BACKGROUND: Severe renal dysfunction is common among liver transplant (LT) candidates and often prompts simultaneous liver-kidney transplantation (SLKT) consideration. In view of 2017 United Network of Organ Sharing (UNOS) criteria for SLKT, we investigated the likelihood and predictors of renal recovery among patients who met the aforementioned criteria yet received liver transplant alone (LTA). METHODS: We retrospectively analyzed relative renal recovery (RRR; increase in eGFR to >30 ml/min) in adult LTA recipients between 1/2009 and 1/2019. RESULTS: Of 1165 LT recipients, 54 met 2017 UNOS criteria, with 37 receiving LTA. RRR occurred in 84% of LTA recipients, none of whom had pre-LT eGFR <20 ml/min. Sustained RRR (>180 days) occurred in 43% of patients. While prolonged pre-LT severe renal impairment (eGFR <30 ml/min) predicted failure to have sustained RRR (HR .19 per 90-day, CI .04-.87, p < .005), having an eGFR measurement of >30 ml/min within 90 days pre-LT (HR 5.52, CI 1.23-24.79, p .01) associated with achieving sustained RRR. Sustained RRR was protective against the composite outcome of renal replacement therapy, kidney transplant, and death (HR .21, p .01). CONCLUSION: LT candidates who meet 2017 UNOS criteria for SLKT yet undergo LTA can still have relative renal recovery post-LT, exceeding 80% on short-term follow-up and 40% on long-term follow-up. eGFR trends within 90 days pre-LT can predict sustained renal recovery, which appears protective of adverse outcomes. These recovery rates advocate for applying the more restrictive criteria for SLKT outlined in this article and increasing utilization of the safety net (SN) policy for those who do not meet the proposed criteria.

The effect of pulsatile pump perfusion on hepatitis C transmission in kidney transplantation: A prospective pilot study.

With increasing utilization of hepatitis C (HCV) viremic donor organs, there may be a role for kidney pump perfusion to reduce viral load and prevent HCV transmission. We performed a prospective pilot study of HCV viremic donors; one kidney from each donor pair was pumped with perfusate exchanges and viral load testing at least every 4 hours. Donor, recipient, and transplant characteristics were obtained with clinical outcomes. Linear regression was performed to quantify the association between pump time and perfusate viral load. Six HCV viremic donors for six pairs of aviremic recipients were included. Perfusate of the pumped kidneys showed detectable virus throughout the pump cycles. Although perfusate viral levels decreased with increasing pump times, this was not statistically significant (ß = -.48, P = .36). All recipients had detectable HCV RNA postoperatively. The pumped cohort had an insignificantly reduced mean viral load compared to pumped recipients (1352 ± 2006 vs 26 170 ± 61 211, P = .09). Time to initiation of direct-acting antiviral was 32 ± 12 vs 26 ± 7 days (P = .17) and to undetectable levels was 66 ± 27 vs 55 ± 22 days (P = .82) for the pumped and unpumped cohorts, respectively. Pulsatile perfusion alone does not appear adequate to decrease HCV transmission. Future studies will need to explore additional ex vivo interventions to pumping.

Evaluation and care of international living kidney donor candidates: Strategies for addressing common considerations and challenges.

End-stage kidney disease patients in the United States may have family members or friends who are not US citizens or residents but are willing to serve as their living kidney donor in the United States ("international donors"). In July 2017, the American Society for Transplantation (AST) Live Donor Community of Practice (LDCOP) convened a multidisciplinary workgroup of experts in living donation care, including coordinators, social workers, donor advocates, administrators, and physicians, to evaluate educational gaps related to the evaluation and care of international donors. The evaluation of international living donor candidates is a resource-intensive process that raises key considerations for assessing risk of exploitation/inducement and addressing communication barriers, logistics barriers, and access to care in their home country. Through consensus-building discussions, we developed recommendations related to: (a) establishing program guidelines for international donor candidate evaluation and selection; (b) initial screening; (c) logistics planning; (d) comprehensive evaluation; and (e) postdonation care and follow-up. These recommendations are not intended to direct formal policy, but rather as guidance to help programs more efficiently and effectively structure and execute evaluations and care coordination. We also offer recommendations for research and advocacy to optimize the care of this unique group of living donors.

Care of international living kidney donor candidates in the United States: A survey of contemporary experience, practice, and challenges.

The evaluation and care of non-US citizen, non-US residents who wish to come to the United States to serve as international living kidney donors (ILKDs) can pose unique challenges. We surveyed US transplant programs to better understand practices related to ILKD care. We distributed the survey by email and professional society list-servs (Fall 2018, assessing 2017 experience). Eighty-five programs responded (36.8% program response rate), of which 80 considered ILKD candidates. Only 18 programs had written protocols for ILKD evaluation. Programs had a median of 3 (range: 0,75) ILKD candidates who initiated contact during the year, from origin countries spanning 6 continents. Fewer (median: 1, range: 0,25) were approved for donation. Program-reported reasons for not completing ILKD evaluations included visa barriers (58.6%), inability to complete evaluation (34.3%), concerns regarding follow-up (31.4%) or other healthcare access (28.6%), and financial impacts (21.4%). Programs that did not evaluate ILKDs reported similar concerns. Staff time required to evaluate ILKDs was estimated as 1.5-to-3-times (47.9%) or >3-times (32.9%) that needed for domestic candidates. Among programs accepting ILKDs, on average 55% reported successful completion of 1-year follow-up. ILKD evaluation is a resource-intensive process with variable outcomes. Planning and commitment are necessary to care for this unique candidate group.

A randomized, placebo-controlled phase I trial of live, attenuated herpes zoster vaccine in subjects with end-stage renal disease immunized prior to renal transplantation.

BACKGROUND: Solid organ transplant recipients are at increased risk for reactivation of herpes zoster, or shingles, and have a higher frequency of serious complications including post-herpetic neuralgia. A live, attenuated shingles vaccine is effective and approved for individuals 50 years and older. The vaccine is contraindicated following transplantation, but may be used in patients with renal failure. Utilization of the vaccine has been poor in patients with end-stage renal disease, including those awaiting transplant, owing to concerns for safety, efficacy, and potential sensitization prior to transplant. METHODS: We conducted a phase I, randomized, placebo-controlled study of the safety and immunogenicity of live, attenuated Oka strain shingles vaccine in subjects prior to or awaiting renal transplant at 3 US centers. Subjects received vaccine a minimum of 4 weeks prior to transplant. RESULTS: The vaccine was safe and well-tolerated. There were no cases of herpes zoster or rash illness. There was no change in donor-specific antibody or calculated panel reactive antibody after vaccination during the follow-up period. There were no rejection episodes. There was a significant 2.1-fold rise in geometric mean titer of anti-VZV antibody at 5 weeks post-vaccine. CONCLUSIONS: The data suggest that the shingles vaccine is safe in subjects with ESRD awaiting transplant. Antibody responses were similar to those seen previously in adults >50 years of age and are consistent with a protective response.

Pathologic femur fracture due to a brown tumor in a patient with secondary hyperparathyroidism and vitamin D-resistant rickets.

Vitamin D-resistant rickets is the common clinical outcome of multiple genetic mutations that alter the regulation of phosphorus and vitamin D metabolism, mainly through their effects on fibroblast growth factor 23 (FGF-23). These diseases typically present in childhood with the classic physical examination finding of nutritional rickets, such as genu varum/valgum and rachitic rosary. Treatment, which is aimed at improving severe bone disease with vitamin D and phosphorus supplementation, can cause secondary hyperparathyroidism and/or kidney failure from nephrocalcinosis over the life of the patient. Although FGF-23 has been shown to downregulate parathyroid hormone in vitro, its effect on parathyroid secretion in disease states such as chronic kidney disease and X-linked hypophosphatemic rickets is unclear because elevations in FGF-23 and parathyroid hormone levels characterize both of these disease states. We describe a case of vitamin D-resistant rickets that presented with a femur fracture through a brown tumor. Radiographs show the combination of severe bony abnormalities associated with both long-standing hyperparathyroidism and vitamin D-resistant rickets.

Multidimensional approach to invasive species prevention.

Nonindigenous species (NIS) cause global biotic homogenization and extinctions, with commercial shipping being a leading vector for spread of aquatic NIS. To reduce transport of NIS by ships, regulations requiring ballast water exchange (BWE) have been implemented by numerous countries. BWE appears to effectively reduce risk for freshwater ports, but provides only moderate protection of marine ports. In the near future, ships may be required to undertake ballast water treatment (BWT) to meet numeric performance standards, and BWE may be phased out of use. However, there are concerns that BWT systems may not operate reliably in fresh or turbid water, or both. Consequently, it has been proposed that BWE could be used in combination with BWT to maximize the positive benefits of both management strategies for protection of freshwater ports. We compared the biological efficacy of "BWE plus BWT" against "BWT alone" at a ballast water treatment experimental test facility. Our comparative evaluation showed that even though BWT alone significantly reduced abundances of all tested organism groups except total heterotrophic bacteria, the BWE plus BWT strategy significantly reduced abundances for all groups and furthermore resulted in significantly lower abundances of most groups when compared to BWT alone. Our study clearly demonstrates potential benefits of combining BWE with BWT to reduce invasion risk of freshwater organisms transported in ships' ballast water, and it should be of interest to policy makers and environmental managers.

Effects of Voice and Biographic Data on Face Encoding.

There are various perceptual and informational cues for recognizing people. How these interact in the recognition process is of interest. Our goal was to determine if the encoding of faces was enhanced by the concurrent presence of a voice, biographic data, or both. Using a between-subject design, four groups of 10 subjects learned the identities of 24 faces seen in video-clips. Half of the faces were seen only with their names, while the other half had additional information. For the first group this was the person's voice, for the second, it was biographic data, and for the third, both voice and biographic data. In a fourth control group, the additional information was the voice of a generic narrator relating non-biographic information. In the retrieval phase, subjects performed a familiarity task and then a face-to-name identification task with dynamic faces alone. Our results consistently showed no benefit to face encoding with additional information, for either the familiarity or identification task. Tests for equivalency indicated that facilitative effects of a voice or biographic data on face encoding were not likely to exceed 3% in accuracy. We conclude that face encoding is minimally influenced by cross-modal information from voices or biographic data.

The role of the upper and lower face in the recognition of facial identity in dynamic stimuli.

Studies with static faces find that upper face halves are more easily recognized than lower face halves-an upper-face advantage. However, faces are usually encountered as dynamic stimuli, and there is evidence that dynamic information influences face identity recognition. This raises the question of whether dynamic faces also show an upper-face advantage. The objective of this study was to examine whether familiarity for recently learned faces was more accurate for upper or lower face halves, and whether this depended upon whether the face was presented as static or dynamic. In Experiment 1, subjects learned a total of 12 faces--6 static images and 6 dynamic video-clips of actors in silent conversation. In experiment 2, subjects learned 12 faces, all dynamic video-clips. During the testing phase of Experiments 1 (between subjects) and 2 (within subjects), subjects were asked to recognize upper and lower face halves from either static images and/or dynamic clips. The data did not provide evidence for a difference in the upper-face advantage between static and dynamic faces. However, in both experiments, we found an upper-face advantage, consistent with prior literature, for female faces, but not for male faces. In conclusion, the use of dynamic stimuli may have little effect on the presence of an upper-face advantage, especially when the static comparison contains a series of static images, rather than a single static image, and is of sufficient image quality. Future studies could investigate the influence of face gender on the presence of an upper-face advantage.

Long-term management of the kidney transplant recipient.

Due to the successes of kidney transplantation, patients with allografts are enjoying long-term survival. In addition to care of the allograft with lifelong administration of immunosuppressive medications, common medical conditions must be recognized and managed appropriately. With constraints on the transplant centers and patient considerations of finance and geography, it is recognized that community providers will play an ever increasing role in the care of the kidney transplant recipient. Guidelines for understanding and managing some of the more important common general medical problems, including care as it relates to cardiovascular disease, chronic kidney disease, transplant-related issues, and general health maintenance, are reviewed in this article.

Evaluation of living kidney donors: variables that affect donation.

Approximately 10000 deceased donor organs are available yearly for 85 000 US patients awaiting kidney transplant. Living kidney donation is essential to close this gap and offers better survival rates. However, nationally, 80% of potential donors evaluated fail to donate. Nurse coordinators who perform predonation screening and education need additional insight into the large number of potential donors who fail to complete the donation process. Reasons for nondonation in donor candidates undergoing medical evaluation, and variables affecting nondonation at Vanderbilt University Medical Center between 2004 and 2009 are examined. Multivariable logistic regression models are used to test the effects of age and race on donation status and reasons for nondonation. Summary data are frequencies, percentages, and means (SD). The sample included 706 candidates (63% female, 80% white; mean age, 40 [SD, 12] years). Almost half (46%) received clearance to donate. Undiagnosed hypertension (14%), abnormal glucose tolerance (10%), and protein-urea (9%) were the most prevalent medical reasons for nondonation. About 13% of candidates changed their minds during evaluation. Analyses demonstrated an increased likelihood of older candidates (P < .001) and a decreased likelihood of white candidates (P = .007) being excluded from donation. Within the nondonation group, increased age was associated with undiagnosed hypertension and abnormal glucose tolerance (both race-adjusted, P = .01). Younger candidates (race-adjusted, P = .003) and African Americans (age-adjusted, P = .04) were more likely to decide against donation. The most prevalent medical reasons for nondonation could be identified through enhanced prescreening, and improved preevaluation education could decrease nondonation rates.

Disseminated Nocardiosis in Kidney Transplant Recipients: A Report of 2 Cases.

Nocardiosis is a rare, life-threatening opportunistic infection caused by bacteria in the environment that predominantly affects immunocompromised patients. Nocardiosis most commonly involves the lungs but can disseminate to other organs. Disseminated nocardiosis, defined as Nocardia infection involving 2 or more organ systems, requires early detection and treatment because of high morbidity and mortality. We report 2 cases of disseminated nocardiosis with pulmonary and central nervous system involvement in kidney transplant recipients. Nocardiosis should be suspected in immunocompromised patients with fever and lung mass, although atypical presentations involving almost any organ can be seen. Solid organ transplant recipients are at greatest risk for Nocardia infection within the first 1 to 2 years after transplantation. However, the patients presented here developed disseminated nocardiosis several years after transplantation, which has important implications. Nocardiosis is treated with 2 to 6 weeks of empiric induction antibiotics, followed by 6 to 12 months of maintenance antibiotics based on antimicrobial susceptibility testing.

Effects of Faces and Voices on the Encoding of Biographic Information.

There are multiple forms of knowledge about people. Whether diverse person-related data interact is of interest regarding the more general issue of integration of multi-source information about the world. Our goal was to examine whether perception of a person's face or voice enhanced the encoding of their biographic data. We performed three experiments. In the first experiment, subjects learned the biographic data of a character with or without a video clip of their face. In the second experiment, they learned the character's data with an audio clip of either a generic narrator's voice or the character's voice relating the same biographic information. In the third experiment, an audiovisual clip of both the face and voice of either a generic narrator or the character accompanied the learning of biographic data. After learning, a test phase presented biographic data alone, and subjects were tested first for familiarity and second for matching of biographic data to the name. The results showed equivalent learning of biographic data across all three experiments, and none showed evidence that a character's face or voice enhanced the learning of biographic information. We conclude that the simultaneous processing of perceptual representations of people may not modulate the encoding of biographic data.

Caring for the pregnant kidney transplant recipient.

As fertility can be restored to normal soon after a kidney transplant, it is important for physicians caring for recipients to be able to inform the patient about the potential risks of pregnancy. Current opinion is that pregnancy can be successful if carried out under optimal circumstances, including stable allograft function for at least one yr post-transplant without rejection, good control of blood pressure, and appropriate adjustment of immunosuppression and other known teratogenic medications prior to conception. In planning for pregnancy, one should discuss pregnancy outcomes and risks to both the mother and fetus. During pregnancy, it is important to pay close attention to medical complications such as worsening of hypertension and development of preeclampsia; risk of infection, in particular of the urinary tract; and worsening anemia. Pregnant recipients should be managed in close conjunction with a high-risk obstetrician.

Kidney Transplantation From Hepatitis C Viremic Deceased Donors to Aviremic Recipients in a Real-world Setting.

Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV-) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting. METHODS: This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV- donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody. Data were analyzed using summary statistics, t-tests, and chi-square tests for between-group comparisons, and linear mixed-effects models for longitudinal data. RESULTS: Each group consisted of 50 recipients with no significant differences in baseline characteristics. The 6-mo longitudinal trajectory of serum creatinine and estimated glomerular filtration rate did not differ between groups. All recipients had similar rates of acute rejection and readmissions (all P > 0.05). One case lost the allograft 151 d posttransplant because of acute rejection, and 1 comparator died on postoperative day 7 from cardiac arrest. HCV+ recipients initiated DAA on average 29 ± 11 d posttransplant. Ninety-eight percent achieved sustained virologic response at 4 and 12 wks with the first course of therapy; 1 patient had persistent HCV infection and was cured with a second course of DAA. CONCLUSIONS: Aviremic recipients of HCV+ DDKT with delayed DAA initiation posttransplant had similar short-term outcomes compared with matched recipient comparators of HCV- donors.

Lower risk of urinary tract infection with low-dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid-withdrawal immunosuppression regimen.

BACKGROUND: Urinary tract infections (UTI) are common in renal transplant recipients. Trimethoprim/sulfamethoxazole (TMP/SMZ) in moderate to high daily doses prevents Pneumocystis jiroveci (PCP) and reduces the risk of UTI in renal transplant patients. Low-dose TMP/SMZ also reduces the risk of PCP, although its ability to reduce the risk of UTI is uncertain. DESIGN: Retrospective review of 158 patients who received a renal transplant without corticosteroids for maintenance immunosuppression. RESULTS: Forty percent of patients initially prescribed TMP/SMZ ultimately stopped this medication early because of an adverse reaction. Urinary infection occurred in 16% without a significant difference in the risk of UTI between those treated with dapsone vs. those treated with TMP/SMZ (HR [95%CI]: 1.7 [0.75, 3.9], p = 0.2). In the subset of patients who were older than age 47 yr (mean age for this cohort, SD ± 6.2 yr), those treated with dapsone originally or who switched from TMP/SMZ to dapsone had a greater risk of UTI compared to patients who remained on TMP/SMZ (HR [95%CI]: 4.3 [1.2, 15.5], p = 0.024). CONCLUSIONS: For renal transplant recipients over the age of 47 yr, treated without long-term glucocorticoids, our retrospective data suggest that low-dose TMP/SMZ is associated with a lower risk of UTI compared to dapsone prophylaxis.

HMG-CoA reductase inhibitors in kidney transplant recipients receiving tacrolimus: statins not associated with improved patient or graft survival.

BACKGROUND: The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival. METHODS: We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival. RESULTS: 36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models. CONCLUSIONS: In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.