Renal transplantation remains the gold standard for treating end-stage renal disease, yet early identification of patients at risk for graft dysfunction is essential to improving outcomes. Lymphocytes play a key role in the immune response and transplant rejection. Fluctuations in postoperative lymphocyte counts may arise from surgical stress and immunosuppression. We conducted a retrospective study of prospectively collected data with 376 consecutive adult renal transplant recipients at a single center from 2015 to 2023. Lymphopenia was observed after kidney transplantation with nadir on post-operative day (POD) 3 and gradual recovery by POD5. Multivariable analysis revealed that POD5 lymphocyte count < 0.5x109 cells/L was associated with increased odds of acute rejection (OR = 2.97;p = 0.037). Rapid recovery from lymphopenia on POD3 to POD5 predicted lower odds of delayed graft function (OR = 0.38;p = 0.047), and delayed recovery from POD3 to POD4 predicted higher risk of 3-year graft failure (OR = 5.23; p = 0.025). These findings suggest that early lymphocyte trends may serve as accessible, clinically relevant biomarkers for graft prognosis following renal transplantation.
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.
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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.
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.
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.
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.
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.
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.
BACKGROUND: Online portals have been shown to be a valuable tool for patients to improve compliance with medical treatment in numerous studies across medical specialties. Our aim was to study the effects of the use of web-based applications that allow patients to track their appointments, labs, and provider visit notes on achievement of renal transplantation. STUDY DESIGN: This is a retrospective chart review of patients in 2 outpatient dialysis centers associated with a 719-bed tertiary care academic medical center. RESULTS: Nine percent of portal users at 3 years after initiation of hemodialysis were the recipients of kidney transplants vs 9% of nonusers. At 4 years, 23% of users were transplant recipients vs 13% of nonusers. At 5 years, 40% of users were transplant recipients vs 14% of nonusers. There was statistically significant divergence of the curves, with the greatest difference observed at 5 years (p = 0.047). In addition, increased number of logins per month was associated with shortened time to renal transplantation (p = 0.0067). CONCLUSIONS: Online portal use is associated with a higher likelihood of being approved as a transplantation candidate and increased number of logins is associated with shortened time to renal transplantation. (C) 2020 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.
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.
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.
Background: Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19 Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses To our knowledge, no case-control study of COVID-19 in OTR has been published to-date Methods: We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020 After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls) All patients were discharged from the hospital or died Results: 16 KTR had COVID-19 All 3 KTR off IS, who were excluded from further analyses, survived Median age was 54 (range: 34-65) years;5/13 KTR (38 4%) were men Median time from transplant was 41 (range: 1-203) months Two KTR, both transplanted >10 years ago, were managed as outpatients IS was reduced in 12/13 (92 3%), most often by discontinuation of the antimetabolite IL6 levels were >1,000 (normal: 10 ng/mL in 6/9 KTR (67%) (Table 1) Eleven KTR were hospitalized (84 6%) and matched with 44 controls One KTR, the only one treated with hydroxychloroquine, died (CFR 5 8%;7 6% in KTR on IS;9% in hospitalized KTR on IS) Four controls died (CFR: 9%;state CFR: 5 2%;inpatient CFR: 16 6%) There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls Four KTR (30 7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2) Conclusion: Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction Extremely high IL6 levels were common The role of IS and potential benefits from investigational treatments remain to be elucidated A larger multi-institutional study is underway (Table Presented)
Despite significant advances in transplantation of HIV-infected individuals, little is known about HIV coinfected patients with hepatitis C virus (HCV) genotypes other than genotype 1, especially when receiving HCV-infected organs with a different genotype. We describe the first case of kidney transplantation in a man coinfected with hepatitis C and HIV in our state. To our knowledge, this is also the first report of an HIV/HCV/HBV tri-infected patient with non-1 (2a) HCV genotype who received an HCV-infected kidney graft with the discordant genotype (1a), to which he converted after transplant. Our case study highlights the following: (1) transplant centers need to monitor wait times for an HCV-infected organ and regularly assess the risk of delaying HCV antiviral treatment for HCV-infected transplant candidates in anticipation of the transplant from an HCV-infected donor; (2) closer monitoring of tacrolimus levels during the early phases of anti-HCV protease inhibitor introduction and discontinuation may be indicated; (3) donor genotype transmission can occur; (4) HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation.
Abstract Background Observational studies suggest that half-dose valganciclovir (VGV) prophylaxis (450 mg daily for normal renal function) is as effective as full-dose (900 mg daily) in preventing CMV infection among kidney transplant recipients (KTR). However, this practice is not supported by current guidelines, for fear of selecting resistance, mainly in high-risk, i.e. donor CMV seropositive/recipient negative (D+/R-) KTR. Full-dose VGV is costly, and possibly associated with higher incidence of neutropenia and BK viremia. Our institution adopted half-dose VGV prophylaxis for R+ KTR in January 2018. Methods We included R+ KTR transplanted between 1/1/2014 and 12/31/2018 at our center. Data were censored at 1-year post-transplant, graft loss or death. Primary outcomes were early (< 6 months from transplant) and any CMV viremia. Secondary outcomes were neutropenia, BK viremia, graft loss and death. Categorical variables were compared with χ 2 or Fisher’s exact tests, continuous variables with the Mann-Whitney test. We used log-rank and Gray’s tests to compare cumulative incidence of outcomes, after adjustment by propensity score for differences in baseline characteristics. Results 106 R+ KTR received full-dose and 35 half-dose VGV. Antithymocyte globulin (ATG) induction was associated with significantly higher cumulative incidence of both early (P=0.017) and any (P=0.02) CMV viremia, compared to basiliximab induction (Fig. 1). After adjusting for gender and induction regimen, we noted a signal for higher cumulative incidence of any (P=0.044), but not early (P=0.598) CMV viremia in the full-dose VGV group (Fig. 2). There were no significant differences (P >0.1) in incidence of neutropenia, BK viremia, graft loss or death between the two groups. Cost savings were estimated at $2630 per CMV R+ KTR (Table 1). Table 1. Comparison of outcomes and cost between the two anti-CMV prophylaxis groups. Data are presented as n (%), unless otherwise indicated. Fig 1. Probability of CMV viremia in KTR who received ATG vs. basiliximab induction. Fig 2. Probability of CMV viremia in KTR who received full-dose vs. half-dose VGV prophylaxis. Conclusion In our pilot series, half-dose VGV was at least as effective as full-dose VGV in preventing CMV viremia in R+ RTR, and less costly. If larger scale studies verify generalizability of these results, half-dose VGV may be considered as standard of care for R+ KTR. In KTR, the antimetabolite probably contributes to neutropenia more than VGV prophylaxis. Disclosures All Authors: No reported disclosures
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.