Impact of Early Rejection Treatment on Infection Development in Kidney Transplant Recipients: A Propensity Analysis.

Introduction: The impact of renal allograft rejection treatment on infection development has not been formally defined in the literature. Methods: We conducted a retrospective cohort study of 185 rejection (case) and 185 nonrejection (control) kidney transplant patients treated at our institution from 2014 to 2020 to understand the impact of rejection on infection development. Propensity scoring was used to match cohorts. We collected data for infections within 6 months of rejection for the cases and 18 months posttransplant for controls. Results: In 370 patients, we identified 466 infections, 297 in the controls, and 169 in the cases. Urinary tract infections (38.9%) and cytomegalovirus viremia (13.7%) were most common. Cumulative incidence of infection between the case and controls was 2.17 (CI 1.54-3.05); p < 0.001. There was no difference in overall survival (HR 0.90, CI 0.49-1.66) or graft survival (HR 1.27, CI 0.74-2.20) between the groups. There was a significant difference in overall survival (HR 2.28, CI 1.14-4.55; p = 0.019) and graft survival (HR 1.98, CI 1.10-3.56; p = 0.023) when patients with infection were compared to those without. Conclusions: As previously understood, rejection treatment is a risk factor for subsequent infection development. Our data have defined this relationship more clearly. This study is unique, however, in that we found that infections, but not rejection, negatively impacted both overall patient survival and allograft survival, likely due to our institution's robust post-rejection protocols. Clinicians should monitor patients closely for infections in the post-rejection period and have a low threshold to treat these infections while also restarting appropriate prophylaxis.

Utilizing kidneys from a donor with bile-cast nephropathy.

Here we discuss the successful utilization of a pair of deceased donor kidneys with bile-cast nephropathy. The donor had a kidney donor profile index of 48% and an acute kidney injury requiring continuous renal replacement therapy. Peak donor bilirubin was 40.5 mg/dL, and renal wedge biopsies showed bile-cast nephropathy. Both recipients had delayed graft function lasting up to 4 weeks. The 4-month biopsies showed mild interstitial fibrosis, tubular atrophy, and a resolution of bile casts. These kidney allografts showed the reversible course of cholemic nephropathy and the potential for increasing the utilization of previously discarded kidneys.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

Current Therapies in Kidney Transplant Rejection.

Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is diagnosed through histological examination of kidney biopsy samples, which reveal the infiltration of mononuclear cells into the allograft tissue. Corticosteroids serve as the primary treatment for TCMR, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin. ABMR occurs due to the binding of antibodies to graft endothelial cells. The most common treatment for ABMR is plasmapheresis, although its efficacy is still a subject of debate. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also utilized to varying degrees, but their efficacy remains questionable. Management decisions for ABMR depend on the timing of the rejection episode and the presence of chronic changes. In managing both TCMR and ABMR, it is crucial to optimize immunosuppression and address adherence. However, further research is needed to explore newer therapeutics and evaluate their efficacy.

Post COVID-19 pulmonary complications in outpatient setting: Insights from a cross-sectional study in a rural academic hospital.

OBJECTIVE: Post COVID-19 disease pulmonary complications are generally expected among the hospitalized or elderly patients with multiple comorbidities given the gravity of the disease among such patients. However, non-hospitalized patients with less severe symptoms from COVID-19 disease have also been experiencing significant morbidity and difficulty functioning their activities of daily living. Therefore, we aim to characterize post COVID-19 pulmonary complications (symptomatology, clinical and radiological findings) in patients who did not require hospitalization but had significant outpatient visits secondary to COVID-19 sequelae. METHODS: This is a two part cross-sectional study based on a retrospective chart review. Patients with COVID-19 disease not requiring hospitalization but followed up at pulmonology clinic with respiratory symptoms were analyzed twice in an interval of 12 months. 23 patients in first cross-section group (followed up from December 2019 to June 2021) and 53 patients in second group (followed up from June 2021 to July 2022) were included in the analyses. Differences in mean and percentage of baseline characteristics and clinical outcomes between the two groups are analyzed using unpaired t-tests and Chi-squared tests respectively. Post COVID-19 disease symptoms are classified in to 3 different groups (mild, moderate and severe) based on duration of symptoms and presence or absence of hypoxia. RESULTS: Dyspnea on exertion (DOE) was the common compliant in majority of patients in both cross-section groups (43.5% vs 56.6%). Mean age in years were 33 and 50 in first and second cross-section groups respectively. Majority of the patients had mild and moderate symptoms in both groups (43.5% vs 9.4%, P = 0.0007; 43.5% vs 83%, P = 0.005). Mean duration of symptoms in first cross-section group was 3.8 whereas 10.5 months (P = 0.0001) in second cross-section group. CONCLUSION: Our study outlines the burden of post COVID-19 disease pulmonary complications in patient group where these complications are less expected. Strategies for the implementation of multidisciplinary post COVID-19 care clinic along with mass vaccination awareness campaigns in rural US should be prioritized to mitigate this existing burden.

COVID-19 in kidney transplantation-implications for immunosuppression and vaccination.

COVID-19 pandemic continues to challenge the transplant community, given increased morbidity and mortality associated with the disease and poor response to prevention measures such as vaccination. Transplant recipients have a diminished response to both mRNA and vector-based vaccines compared to dialysis and the general population. The currently available assays to measure response to vaccination includes commercially available antibody assays for anti-Spike Ab, or anti- Receptor Binding Domain Ab. Positive antibody testing on the assays does not always correlate with neutralizing antibodies unless the antibody levels are high. Vaccinations help with boosting polyfunctional CD4+ T cell response, which continues to improve with subsequent booster doses. Ongoing efforts to improve vaccine response by using additional booster doses and heterologous vaccine combinations are underway. There is improved antibody response in moderate responders; however, the ones with poor response to initial vaccination doses, continue to have a poor response to sequential boosters. Factors associated with poor vaccine response include diabetes, older age, specific immunosuppressants such as belatacept, and high dose mycophenolate. In poor responders, a decrease in immunosuppression can increase response to vaccination. COVID infection or vaccination has not been associated with an increased risk of rejection. Pre- and Post-exposure monoclonal antibodies are available to provide further protection against COVID infection, especially in poor vaccine responders. However, the efficacy is challenged by the emergence of new viral strains. A recently approved bivalent vaccine offers better protection against the Omicron variant.

Infections following rejection therapies in kidney and liver transplant recipients.

INTRODUCTION: Infections are known complications of solid-organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection. METHODS: This is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment. RESULTS: We identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver-kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients. CONCLUSIONS: Infections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver-kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow-up in kidney transplant patients.

Duration of delayed graft function and its impact on graft outcomes in deceased donor kidney transplantation.

BACKGROUND: There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function. METHODS: We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14-27 DGF days, > 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions. RESULTS: 1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. CONCLUSIONS: Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting < 28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival. TRIAL REGISTRATION: Retrospective study approved by Mayo Clinic IRB number ID: 20-011561.

The impact of COVID-19 on kidney transplant care.

The SARS-CoV-2 virus precipitated the coronavirus 2019 (COVID-19) pandemic, which placed considerable strain on healthcare systems and necessitated immediate and rapid alterations in the delivery of healthcare. In the transplant population, COVID-19 directly impacts an inherently vulnerable population in the setting of immunosuppression and co-morbidities, but also further complicates the clinical evaluation and management of kidney transplant candidates and recipients in a strained healthcare environment being challenged by the pandemic. Many transplant centers around the world saw mortality rate spikes in organ recipients related to COVID-19, and changes in care delivery abound. This review evaluates the care of the kidney transplant patient through all phases of the process including pre-operative evaluations, perioperative care, post-transplantation considerations, and how the global pandemic has changed the way we care for our patients.

Successful outcomes with transplanting kidneys from deceased donors with acute kidney injuryon temporary renal replacement therapy.

BACKGROUND AND OBJECTIVES: We aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT). MATERIALS AND METHODS: A total of 172 recipients received a kidney from donors with acute kidney injury stage 3 (AKIN3) requiring RRT. We compared the study group to 528 recipients who received a kidney from donors with AKIN stage 3 not on RRT and 463 recipients who received < 85% Kidney Donor Profile Index (KDPI) AKIN stage 0 kidney. RESULTS: The study group donors were younger compared to the 2 control groups. Despite higher DGF in the study group, the length of hospital stay and acute rejection were similar. Death censored graft survival (96% AKIN3-RRT vs. 97%AKIN3 no RRT vs. 96% KDPI < 85% AKIN0, P = 0.26) and patient survival with functioning graft at 1 year (95% across all groups, P = 0.402) were similar. The estimated glomerular filtration rate were similar across the 3 groups after first month. Interstitial fibrosis and tubular atrophy score ≥ 2 on protocol biopsy at time 0, 4 and 12 months were similar. Primary nonfunction was rare and associated with high KDPI. CONCLUSIONS: Transplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes.

When are you too old to get a kidney transplants?

PURPOSE OF REVIEW: With the increasing incidence and prevalence of ESRD in the elderly, we are now transplanting more elderly patients. Although we know from previous reports that transplantation provides increased survival advantage and/or quality of life when compared to being on dialysis, we also know that transplantation is not the best option for all patients. In this review, we try to identify the upper age limit (if any) for deceased donor renal transplantation, predictive factors that can identify the risks for transplant outcomes, frailty, and immunosenescence. RECENT FINDINGS: Review of data over the last 5 years have identified certain risk predictors and outcomes that might be helpful in evaluation of the elderly transplant recipient, which we aim to summarize in this review. SUMMARY: Identifying predictors to risk stratify elderly patients and promote transplantation is much needed. Modifiable risks should be addressed to ensure more candidates become transplantable. A combination of physical, medical, and immunological markers to better identify recipients is imperative for future research gearing towards precision medicine.

Sleep-disordered breathing as a delayed complication of iatrogenic vocal cord trauma.

A case of a 55-year-old woman with iatrogenic vocal cord trauma and sleep-related symptoms is reported. In particular, this case highlights sleep-disordered breathing as a delayed complication after iatrogenic vocal cord trauma. The patient developed acute stridor from a contralateral vocal cord hematoma following vocal fold injection for right vocal cord paralysis. Acute respiratory symptoms resolved with oxygen, steroids, and nebulized therapy, but nocturnal symptoms persisted and polysomnography revealed sleep-related hypoventilation and mild obstructive sleep apnea. Positive pressure therapy was successfully used to ameliorate her symptoms and treat sleep-disordered breathing until her hematoma resolved. In addition to the typically acute respiratory symptoms that may result from vocal cord dysfunction, sleep-disordered breathing may also present as a significant subacute or chronic problem. Management of the acute respiratory symptoms is relatively well established, but clinicians should be alert for more subtle nocturnal symptoms that may require further study with polysomnography.