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.

Should Transplant Nephrology Pursue Recognition from the Accreditation Council for Graduate Medical Education (ACGME)?

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.

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.

Prospective observational study to validate a next-generation sequencing blood RNA signature to predict early kidney transplant rejection.

The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.

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.

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.

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.

Impact of Social Media on Self-Referral Patterns for Living Kidney Donation.

Background: As the organ-shortage crisis continues to worsen, many patients in need of a kidney transplant have turned to social media to find a living donor. The effect of social media on living kidney donation is not known. The goal of this study is to investigate the influence of social media on those interested in donating a kidney. Methods: Self-referrals for living kidney donation from December 2016 to March 2019 were retrospectively reviewed. Age, sex, race, and relationship of individuals petitioned through social media (SM) were compared with those petitioned through verbal communication (VC). Data were analyzed using chi-squared tests, with z tests of column proportions, and multivariable logistic regression. Results: A total of 7817 individuals (53% SM, 36% VC, and 10% other) were self-referred for living kidney donation. The analysis sample included 6737 adults petitioned through SM (n=3999) or VC (n=2738). Half (n=3933) of the individuals reported an altruistic relationship, and 94% of these respondents were petitioned through SM. Although univariate analyses indicated that SM respondents were younger, more likely female, more likely White, and more likely to have directed altruistic intent than those petitioned through VC (all P<0.05), multivariable logistic regression demonstrated that only decreased age, female sex, and relationship were significantly related to likelihood of SM use (all P<0.001). Conclusions: The use of SM to petition living kidney donors is prevalent and accounts for a greater proportion of respondents compared with VC. SM respondents tend to be younger, female, and altruistic compared with VC. Directed altruistic interest in kidney donation is almost exclusively generated through SM.

Mechanisms of Drug-Induced Interstitial Nephritis.

Drug-induced acute interstitial nephritis (DI-AIN) is a drug hypersensitivity reaction (DHR) that manifests 7 to 10 days after exposure to the culprit drug. DHRs account for fewer than 15% of reported adverse drug reactions. The kidneys are susceptible to DHR because: (1) the high renal blood flow whereby antigens are filtered, secreted, or concentrated, and (2) it is a major site of excretion for drugs and drug metabolites. More than 250 different drugs from various classes have been incriminated as causative agents of DI-AIN, the third most common cause of acute kidney injury in the hospital. DI-AIN must be differentiated from drug-induced nephrotoxic acute tubular necrosis because of their differing pathophysiology and treatment. DI-AIN begins with antigen processing and presentation to local dendritic cells. The dendritic cells activate T cells, and the subsequent effector phase of the immune response is mediated by various cytokines. Incriminated antigenic mechanisms include response to a conjugation product of the drug or its metabolite with a host protein (eg, beta-lactam or sulfonamide antibiotic) or the direct binding of the drug to a particular host allele to elicit a hypersensitivity response (eg, certain anti-epileptic drugs). If the offending drug is not identified and discontinued in a timely manner, irreversible fibrosis and chronic kidney disease will occur. The core structure of each drug or its metabolite is an antigenic determinant, and the host interaction is termed the structure-activity relationship. Differing structure-activity relationships accounts for effect, hypersensitivity, and cross-reactivity among and between classes. The essence of management of DI-AIN lies with the four sequential steps: anticipation, diagnosis, treatment, and prevention. Corticosteroids are used in the treatment of DI-AIN because of their potent anti-inflammatory effects on T cells and eosinophils. Anticipation and prevention require notifying the patient that DI-AIN is an idiosyncratic, hypersensitivity reaction that recurs on re-exposure, and the drug should be avoided.