Elevated Tacrolimus Levels at Time of Diagnosis of COVID-19 Compared to Baseline Among Hospitalized Organ Transplant Recipients.

BACKGROUND: The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied. OBJECTIVE: To study the effect of COVID-19 on tacrolimus trough levels (primary outcome) in OTRs and the association of the later with acute kidney injury, bacterial infection, and oxygen requirements. METHODS: We studied adult (>18-year-old) hospitalized OTRs with COVID-19, who were receiving tacrolimus between 3/1 and 12/16/2020. RESULTS: Among 30 OTRs, 67% were men, 90% had a kidney transplant. Median age was 60.5 (interquartile range [IQR]: 45-68) years, median time from transplant 36 (IQR: 20-84) months. Tacrolimus troughs were higher on admission for COVID-19 than baseline (average over 6 months prior) (P = .001). Eighteen patients (60%) had admission tacrolimus trough >10, 5 (17%) >20 ng/mL. Patients with diarrhea had borderline higher tacrolimus troughs, compared to those without diarrhea (P = .09). Organ transplant recipients with a tacrolimus trough >10 ng/mL were more likely to have elevated aspartate aminotransferase on admission (P = .01) and require supplemental oxygen. (P = .026). CONCLUSION AND RELEVANCE: Tacrolimus trough levels were elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. Potential mechanisms are diarrhea and hepatic involvement in COVID-19. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed; management of immunosuppression should be individualized.

Successful recovery from COVID-19 in three kidney transplant recipients who received convalescent plasma therapy.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease that typically presents with greater severity in patients with underlying medical conditions or those who are immunosuppressed. We present a novel case series of three kidney transplant recipients with COVID-19 who recovered after receiving COVID-19 convalescent plasma (CCP) therapy. Physicians should be aware of this potentially useful treatment option. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical and allograft outcomes associated with CCP use in this population.

Patterns and predictors of fatigue following living donor nephrectomy: Findings from the KDOC Study.

This study sought to identify the prevalence, pattern, and predictors of clinical fatigue in 193 living kidney donors (LKDs) and 20 healthy controls (HCs) assessed at predonation and 1, 6, 12, and 24 months postdonation. Relative to HCs, LKDs had significantly higher fatigue severity (P = .01), interference (P = .03), frequency (P = .002), and intensity (P = .01), and lower vitality (P < .001), at 1-month postdonation. Using published criteria, significantly more LKDs experienced clinical fatigue at 1 month postdonation, compared to HCs, on both the Fatigue Symptom Inventory (60% vs. 37%, P < .001) and SF-36 Vitality scale (67% vs. 16%, P < .001). No differences in fatigue scores or clinical prevalence were observed at other time points. Nearly half (47%) reported persistent clinical fatigue from 1 to 6 months postdonation. Multivariable analyses demonstrated that LKDs presenting for evaluation with a history of affective disorder and low vitality, those with clinical mood disturbance and anxiety about future kidney failure after donation, and those with less physical activity engagement were at highest risk for persistent clinical fatigue 6 months postdonation. Findings confirm inclusion of fatigue risk in existing OPTN informed consent requirements, have important clinical implications in the care of LKDs, and underscore the need for further scientific examination in this population.

Pain expectancy, prevalence, severity, and patterns following donor nephrectomy: Findings from the KDOC Study.

Postoperative pain is an outcome of importance to potential living kidney donors (LKDs). We prospectively characterized the prevalence, severity, and patterns of acute or chronic postoperative pain in 193 LKDs at six transplant programs. Three pain measurements were obtained from donors on postoperative Day (POD) 1, 3, 7, 14, 21, 28, 35, 41, 49, and 56. The median pain rating total was highest on POD1 and declined from each assessment to the next until reaching a median pain-free score of 0 on POD49. In generalized linear mixed-model analysis, the mean pain score decreased at each pain assessment compared to the POD3 assessment. Pre-donation history of mood disorder (adjusted ratio of means [95% confidence interval (CI)]: 1.40 [0.99, 1.98]), reporting "severe" on any POD1 pain descriptors (adjusted ratio of means [95% CI]: 1.47 [1.12, 1.93]) and open nephrectomy (adjusted ratio of means [95% CI]: 2.61 [1.03, 6.62]) were associated with higher pain scores across time. Of the 179 LKDs who completed the final pain assessment, 74 (41%) met criteria for chronic postsurgical pain (CPSP), that is, any donation-related pain on POD56. Study findings have potential implications for LKD education, surgical consent, postdonation care, and outcome measurements.

Hyperammonemia syndrome due to Ureaplasma urealyticum in a kidney transplant recipient: A case of disseminated disease from a fluoroquinolone-resistant isolate.

Ureaplasma species (spp.) are common colonizers of the urogenital tract but may cause systemic infection in immunocompromised patients. They release significant amounts of ammonia via urea hydrolysis and have been recently implicated in the pathogenesis of hyperammonemia syndrome after organ transplantation. We describe a unique case of hyperammonemia syndrome after kidney transplant caused by U urealyticum infection, and the first, to our knowledge, case of a fluoroquinolone-resistant Ureaplasma strain causing hyperammonemia syndrome. A 17-year-old female developed intermittent fevers, rising creatinine, sterile pyuria and debilitating polyarthritis approximately 1 year after kidney transplant. Serum ammonia level was elevated, and urine PCR was positive for U urealyticum. Near the end of treatment with levofloxacin, she had rebound hyperammonemia, which preceded clinical relapse of polyarthritis and encephalopathy. Blood and urine PCR and synovial fluid culture were positive for U urealyticum. Susceptibility testing showed fluoroquinolone resistance, but she responded well to azithromycin and doxycycline. The frequency of Ureaplasma spp. infection in immunocompromised patients is probably underestimated due to diagnostic challenges. Ammonia levels were helpful biomarkers of response to antimicrobial therapy in our case. Susceptibility testing of clinical isolates should be pursued. In serious Ureaplasma spp. infections, particularly in immunocompromised patients, two empiric antibiotics may be indicated given the potential for antimicrobial resistance.

Beyond stigma: Understanding the "inclined abstainers" in military behavioral health-care utilization.

Low treatment utilization in Soldiers with combat-related Posttraumatic Stress Disorder (PTSD) is an ongoing issue. The critical concern is to better understand factors which prohibit a Soldier with PTSD who wants help from seeking treatment (an "inclined abstainer"). A total of 537 Active Duty Soldiers on a US Army post completed a brief survey comprising psychometrically validated measures of stigma, behavioral health treatment beliefs, resilience, PTSD symptoms, and treatment intentions. Health-care records were prospectively tracked for 12 months to determine the relation between survey answers and treatment utilization. Sixty-three percent of those who acknowledged having a mental health-related problem did not seek help within a one-year period. Greater severity of PTSD symptoms was associated with an increased likelihood of behavioral health engagement. Soldiers that were classified as "inclined abstainers" were also more likely to endorse negative beliefs about psychotherapy and report higher levels of resilience as compared to "inclined actors." These results suggest that a treatment model of PTSD emphasizing self-efficacy and self-reliance, while addressing negative beliefs about psychotherapy, may help promote engagement of behavioral health services among Active Duty Soldiers.

A single-center analysis of early readmission after renal transplantation.

BACKGROUND: Thirty-day readmission rates (early hospital readmission, EHR) are an important benchmark for quality improvement. Nationally, patients undergoing renal transplantation incur a 31% EHR rate. While national databases provide useful data, the impact of EHR on individual centers has received little attention. We proposed that an institutional review of EHR after renal transplantation may provide a benchmark for individual transplant programs and identify modifiable program-specific issues to reduce EHR. METHODS: We reviewed 269 consecutive kidney transplant recipients over a five-year period (2012-2016). Early hospital readmission was modeled using generalized linear modeling assuming a binary distribution. RESULTS: About 21% of patients were readmitted within 30 days. Deceased kidney donation (DD), delayed graft functioning (DGF), anti-thymocyte globulin (ATG) induction, diabetes, public insurance, weekend discharge, and low glomerular filtration rate (eGFR) at discharge were all identified as risk factors for readmission. Early hospital readmission was not correlated with risk of death (5.4% at 44 months: HR 2.2 (95% CI [0.7, 6.6]; P = 0.1473) or graft loss. CONCLUSIONS: EHR after renal transplantation is common. Certain factors may predict an increased risk for EHR. A multi-disciplinary approach to discharge planning may limit some EHR, but most complications and adverse events are unpredictable and require hospital-level of care.

Organ donation and imminent death: pro position.

PURPOSE OF REVIEW: Donation after cardiac death is associated with many problems including ischemic injury, high rates of delayed allograft function, prolonged time to asystole, and frequent organ discard. Imminent death donation (IDD) has been proposed as a separate category of organ donation: distinct from living donation and donation after cardiac death. RECENT FINDINGS: A protocol for IDD was developed at Rhode Island Hospital and published in the ethics literature. The United Network for Organ Sharing (UNOS) Ethics Committee reviewed the protocol and stated that IDD was ethically appropriate in some cases. A wider review by a working group within UNOS concluded similarly, but felt that a myriad of policy revisions would be required and were concerned about a possible negative impact on public trust in organ donation. Nonetheless, IDD and other nontraditional strategies continue to be proposed, implemented in other countries and discussed by patients and donor families. SUMMARY: This review, on the 'Pro' side of IDD, proposes that the medical community continue to work toward implementing IDD. Donor family's wishes are best met by organ donation, successful outcomes for the recipients, and a dignified death for their loved one. In some cases, IDD is the best strategy to meet these goals.

Immunosuppression in the failing and failed transplant kidney: optimizing outcomes.

There is little data to guide clinicians on the optimal management of immunosuppression in patients whose kidney transplant has failed and who have returned to dialysis. Nor is there robust data on whether to perform a transplant nephrectomy. Finally, management of late stage chronic kidney disease, including deciding on dialysis initiation, modality and access planning, must occur simultaneously with efforts aimed at preserving the failing kidney and residual renal function for as long as possible. In this article, we will review the evidence on these topics and suggest areas for improvement.

Unexpected Medical Conditions Discovered During Live Donor Kidney Evaluation: Single Center Study.

OBJECTIVES: Living donor kidney transplantation (LDKT) is the preferred method of treatment for patients with end-stage kidney disease. Potential living kidney donors (PLKD) are evaluated through a thorough medical, psychological and surgical work-up to ensure successful transplantation with minimal risks to all parties involved. The transplant center at Rhode Island Hospital has noticed an increasing number of PLKDs excluded from donation due to conditions newly diagnosed during the screening process. Our objective is to understand the local trends underlying the high PLKD exclusion rates in the context of newly diagnosed conditions, age, race, and sex of the excluded donors. STUDY DESIGN AND METHODS: Our study is a retrospective electronic medical record review of the 429 PLKDs screened at Rhode Island Hospital Kidney Transplant Center between December 2012 and April 2023. Age, race, gender, relationship to recipient, and reasons for exclusion were collected from the medical record for each PLKD. CONCLUSION: 115 of the 429 total PLKDs screened were excluded for newly diagnosed conditions, the most common of which were renal issues (49%), diabetes mellitus (33%), and hypertension (13%), with many comorbid diagnoses. While these donors were able to receive proper treatment after their diagnosis, the earliest intervention possible yields the best prognosis. The high prevalence of treatable yet undiagnosed conditions raise many public health concerns, such as primary care gaps or discontinuous healthcare, and increases awareness about the importance of follow-up care for the excluded PLKDs.

Assessment of surgical residents in a vascular anastomosis laboratory.

BACKGROUND: We designed a simple, low-cost workshop to teach surgical residents the basic skills of vascular anastomosis. We studied our ability to identify objective procedural and end-product metrics that could be used to measure improvement in vascular anastomotic skill before and after training. MATERIALS AND METHODS: Ten postgraduate year 2 residents without previous vascular surgery experience and four attending surgeons (expert) performed end-to-side anastomosis using a synthetic graft. The residents were taught the basic skills of vascular anastomosis during three didactic workshops. The objective metrics included volume leakage after saline perfusion (leak) and the time needed to complete the anastomosis. Penalty points were assigned for broken sutures, air knots, locking sutures, and failure to maintain an outside-in to inside-out technique. The leak, time, and penalties before and after training were compared. RESULTS: The mean leak was 70.4 ± 13.7 mL and the mean completion time was 18.7 ± 3 min for the pretraining group versus 45.3 ± 10.6 mL (P < 0.01) and 8.5 ± 1 min (P < 0.001), respectively, for the attending group. After training, significant improvement was seen in resident leak (46.7 ± 6.8 mL; P < 0.001) and completion time (14.4 ± 3 min; P < 0.01). Leak was similar between the post-training and expert groups (46.7 ± 6.8 mL and 45.3 ± 10.6 mL, respectively; P = 0.77); however, a significant difference for the completion time remained (14.4 ± 3.0 min and 8.5 ± 1 min, respectively; P < 0.01). The mean number of technical errors improved from 2.7 in the pretraining group to zero for the post-training group after completing the workshop. CONCLUSIONS: We have reported an easy to implement workshop for teaching surgical residents the basic skills of performing vascular anastomosis.

Immunosuppression after renal allograft failure: a survey of US practices.

BACKGROUND: Little data exist to guide the management of immunosuppression after renal graft failure. More aggressive tapering of immunosuppressive medications may reduce the risk of infection, but may increase the risk of rejection and sensitization. METHODS: To document current practices in the US, we emailed a questionnaire to medical and surgical transplant directors as identified by the United Network for Organ Sharing (UNOS). RESULTS: Emails were sent to 221 programs, of which 93 (42.1%) responded. About 24.7% of respondents reported adjusting immunosuppression according to a standard protocol; 75.3% said practices are physician dependent. The majority said that 80 or 100% of patients are off all immunosuppression one yr after returning to dialysis. The most important factors cited in deciding whether to stop immunosuppression were plans to retransplant (40.2%) and signs and symptoms of rejection (37.0%). When asked which immunosuppressive medications are continued indefinitely, 21.5% responded prednisone and 71.0% said none. Respondents most commonly said they performed graft nephrectomy only if there are signs and symptoms of rejection (47.3%) or if signs and symptoms of rejection fail to respond to steroids (34.4%). CONCLUSIONS: In the absence of good data to guide decisions on immunosuppression in patients with failed allografts, practices in the US vary greatly. More data are needed to determine which policies lead to the best outcomes.

Obstructive Uropathy due to Bilateral Sliding Hernia in a Renal Transplant Patient with Incidental RCC in Native Kidney.

BACKGROUND: Ureteral obstruction is a common complication after kidney transplantation. Ureteral obstruction caused by inguinal hernia, however, is a rare complication of transplantation and requires urgent surgical repair to prevent allograft loss.  Case presentation: A 58-year-old man presented with allograft dysfunction 18-years after renal transplant. He was compliant with medications and given the long duration of allograft survival, a primary renal etiology was suspected. Thus, the initial work-up included allograft biopsy that was unremarkable. Three months later, worsening allograft function prompted further evaluation. At this time, allograft ultrasound and computed tomography led to the diagnosis of ureteral obstruction due to uretero-inguinal herniation of left kidney transplant secondary to bilateral sliding inguinal hernias. The patient was also found to have incidental renal cell carcinoma of the left native kidney. A percutaneous nephrostomy tube was placed and then followed by surgical repair with ureteral reimplantation, herniorrhaphy with mesh, and left native nephrectomy. CONCLUSIONS: Mechanical obstruction can occur years after kidney transplantation. Even though it is uncommon, ureteral obstruction due to inguinal herniation is critical. Early detection of this complication and surgery can salvage the allograft and prolong function. ABBREVIATIONS: RCC: renal cell carcinoma; PCN: Percutaneous Nephrostomy; ACKD: Acquired Cystic Kidney Disease.

Appendicocecal Loop Urinary Diversion in a Transplant Kidney: Case Report, Literature Review.

Urinary diversion in renal transplant patients can take a variety of forms - bladder augmentation, continent cutaneous pouch, or intestinal conduits, to name a few. Herein, we present a unique case of an appendicocecal urinary diversion in a patient with history of end stage renal disease, pelvic radiation, and complex surgical history who underwent deceased-donor renal transplantation. During the renal transplant, the transplant ureterovesical anastomosis could not be performed due to inherent anatomical hindrances. A temporary modified cutaneous ureterostomy using a single-J stent was therefore used for drainage of the transplant kidney. Given that the cutaneous ureterostomy was not a durable, long-term option, we sought to develop a creative surgical solution. This report presents a unique case of urinary diversion post renal transplant and reviews the literature of renal transplantation in patients with anatomical abnormalities.

Emotion-related regulatory difficulties contribute to negative psychological outcomes in active-duty Iraq war soldiers with and without posttraumatic stress disorder.

Data suggest military personnel involved in U.S. military initiatives in Iraq and Afghanistan are returning from deployment with elevated rates of mental health diagnoses, including posttraumatic stress disorder (PTSD). The aim of this study was to examine difficulties with emotion regulation as a potential contributory mechanism by which soldiers have poorer psychological outcomes, such as depression, dissociation, alcohol abuse, and interpersonal difficulties. Participants were 44 active-duty male service members who comprised three groups, including those deployed with and without diagnosed PTSD and those prior to deployment. Participants in the PTSD group scored significantly higher on measures of self-reported depression, trauma-related dissociation, alcohol misuse, and social adjustment difficulties than did comparison groups. Importantly, difficulties with emotion regulation were found to partially mediate the relationship between PTSD and depression, poor social adjustment, and trauma-related depersonalization but not alcohol misuse. Emotion-regulation difficulties are important to consider in the relationship between PTSD and additional psychological outcomes in recently deployed personnel. Implications for treatment are briefly discussed.

The case for kidney donation before end-of-life care.

Donation after cardiac death (DCD) is associated with many problems, including ischemic injury, high rates of delayed allograft function, and frequent organ discard. Furthermore, many potential DCD donors fail to progress to asystole in a manner that would enable safe organ transplantation and no organs are recovered. DCD protocols are based upon the principle that the donor must be declared dead prior to organ recovery. A new protocol is proposed whereby after a donor family agrees to withdrawal of life-sustaining treatments, premortem nephrectomy is performed in advance of end-of-life management. Since nephrectomy should not cause the donor's death, this approach satisfies the dead donor rule. The donor family's wishes are best met by organ donation, successful outcomes for the recipients, and a dignified death for the deceased. This proposal improves the likelihood of achieving these objectives.

Coronavirus Disease 2019 in Kidney Transplant Recipients: Single-Center Experience and Case-Control Study.

BACKGROUND: Kidney transplant recipients (KTR) are considered high-risk for morbidity and mortality from coronavirus disease 2019 (COVID-19). However, some studies did not show worse outcomes compared to non-transplant patients and there is little data about immunosuppressant drug levels and secondary infections in KTR with COVID-19. Herein, we describe our single-center experience with COVID-19 in KTR. METHODS: We captured KTR diagnosed with COVID-19 between March 1, 2020 and May 18, 2020. After exclusion of KTR on hemodialysis and off immunosuppression, we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by age and sex (controls). RESULTS: Eleven KTR were hospitalized and matched with 44 controls. One KTR and 4 controls died (case fatality rate: 9.1%). There were no significant differences in length of stay or clinical outcomes between KTR and controls. Tacrolimus or sirolimus levels were >10 ng/mL in 6 out of 9 KTR (67%). Bacterial infections were more frequent in KTR (36.3%), compared with controls (6.8%, P = .02). CONCLUSIONS: In our small case series, unlike earlier reports from the pandemic epicenters, the clinical outcomes of KTR with COVID-19 were comparable to those of non-transplant patients. Calcineurin or mammalian target of rapamycin inhibitor (mTOR) levels were high. Bacterial infections were more common in KTR, compared with controls.

Low-Dose Valganciclovir Prophylaxis Is Safe and Cost-Saving in CMV-Seropositive Kidney Transplant Recipients.

Introduction: Observational studies suggest that low-dose valganciclovir prophylaxis (450 mg daily for normal renal function) is as effective as and perhaps safer than standard-dose valganciclovir (900 mg daily) in preventing CMV infection among kidney transplant recipients. However, this practice is not supported by current guidelines due to concerns for breakthrough infection from resistant CMV, mainly in high-risk CMV donor-seropositive/recipient-seronegative kidney transplant recipients. Standard-dose valganciclovir is costly and possibly associated with higher incidence of neutropenia and BKV DNAemia. Our institution adopted low-dose valganciclovir prophylaxis for intermediate-risk (seropositive) kidney transplant recipients in January 2018. Research Question: To analyze the efficacy (CMV DNAemia), safety (BK virus DNAemia, neutropenia, graft loss, and death), and cost savings associated with this change. Design: We retrospectively compared the above outcomes between CMV-seropositive kidney transplant recipients who received low-dose and standard-dose valganciclovir, transplanted within our institution, between 1/19/2014 and 7/15/2019, using propensity score-adjusted competing risk analyses. We also compared cost estimates between the two dosing regimens, for 3 months of prophylaxis, and for different percentage of patient-weeks with normal renal function, using the current average wholesale price of valganciclovir. Results: We studied 179 CMV-seropositive kidney transplant recipients, of whom 55 received low-dose and 124 standard-dose valganciclovir. The majority received nonlymphocyte depleting induction (basiliximab). Low-dose valganciclovir was at least as effective and safe as, and more cost-saving than standard-dose valganciclovir. Conclusion: This single-center study contributes to mounting evidence for future guidelines to be adjusted in favor of low-dose valganciclovir prophylaxis in CMV-seropositive kidney transplant recipients.