Outcomes In Kidney Transplant Recipients Research Articles

Impact of Immunosuppression on the Severity of SARS-CoV-2 Infection in Renal Transplant Recipients

Abstract: Kidney transplant patients have a high case fatality rate following severe acute respiratory syndrome 2 (SARS-CoV-2) infection. In addition, the vaccine immune response is lower and less durable, which makes them more susceptible to severe forms, even when vaccinated. Evidence suggests that in addition to advanced age and the high prevalence of comorbidities often associated with worse prognosis, such as diabetes, obesity, and cardiovascular disease, prolonged immunosuppression exerts an independent effect on outcomes. In fact, the cellular and humoral adaptive immune response, which is inhibited by immunosuppression, is a key step in resolving SARS-CoV-2 infection. On the other hand, lymphocyte inhibition could modulate the aberrant production of proinflammatory cytokines that result in severe lung impairment, mitigating the severity of the condition. In addition, some immunosuppressive drugs have antiviral properties, potentially applicable to coronavirus. This narrative review aimed to discuss the available evidence on the impact of immunosuppressive drugs on COVID-19 outcomes in kidney transplant recipients

Outcomes in kidney transplant recipients treated with immediate-release tacrolimus capsules versus extended-release tacrolimus capsules: A cohort study.

Prior randomized trials and observational studies have generally reported similar outcomes in kidney transplant recipients (KTRs) treated with immediate-release tacrolimus (IR-TAC) versus extended-release tacrolimus (ER-TAC). However, many of these previous studies focused on patients with low immunological risks, had small sample sizes and brief follow-up periods, and excluded outcomes associated with graft loss, such as chronic rejection. To address these limitations, we conducted a cohort study of 848 KTRs at a single transplantation center who had generally high immunological risks and were treated with either IR-TAC capsules (589 patients, 65.9%) or ER-TAC capsules (289 patients, 34.1%). All patients received their designated maintenance immunosuppressive regimen for at least 3months post-transplantation. Afterwards, tacrolimus formulation was at the discretion of each patient's transplant nephrologist. For the two treatment groups, we compared the hazards of experiencing a composite outcome of acute or chronic antibody-mediated rejection (AMR), acute or chronic T-cell-mediated rejection, de novo DSA, and/or graft loss over a 3-year period starting at 3 months post-transplantation. In a multivariable Cox proportional hazards regression model, KTRs treated with IR-TAC capsules had an increased hazard of experiencing the composite outcome when compared to patients treated with ER-TAC capsules; however, this result was not significant (adj HR 1.24, 95% CI .92-1.68, p=.163). Similar results were obtained with inverse probability of treatment weighting (IPTW) using a propensity score (adj HR 1.25, 95% CI .93-1.68, p=.146). These findings suggest that when compared to IR-TAC capsules, ER-TAC capsules do not reduce the hazard of poor outcomes in KTRs with generally high immunological risks.

Impact of low-level donor-specific anti-HLA antibody on posttransplant clinical outcomes of kidney transplant recipients: analysis from Korean Organ Transplantation Registry data

Haeun Lee, Jung Hwan Park, Jong-Won Park, Tae Hyun Ban, Jaeseok Yang, Myoung Soo Kim, Chul Woo Yang, Byung Ha Chung, Korean Organ Transplantation Registry. Korean J Transplant 2022;36:47. https://doi.org/10.4285/ATW2022.F-1621

Association of pretransplant skeletal muscle mass with outcomes in kidney transplant recipients

Association of pretransplant skeletal muscle mass with outcomes in kidney transplant recipients

Air pollution and posttransplant outcomes in kidney transplant recipients

Air pollution and posttransplant outcomes in kidney transplant recipients

Short and Long-Term Outcomes of Kidney Transplant Recipients Diagnosed With COVID-19 Infection: A Single-Center Observational Study.

Kidney transplant recipients (KTRs) are at an increased risk of severe disease and death caused by coronavirus disease 2019 (COVID-19) infection. There is a paucity of information on the evolution of graft function among hospitalized KTRs who overcome the infection. The study included adult KTRs at a single transplant institute who were diagnosed with COVID-19 and needed hospitalization between March 15, 2020, and January 15, 2021. We analyzed patient demographics, comorbid risk factors, and inpatient clinical courses for patients who were able to recover from the infection. Kidney function was analyzed pre-infection, during initial hospitalization, and up to 12 months post-infection. We identified 48 KTRs who were diagnosed with COVID-19 infection during the study period. Eighteen KTRs among these needed hospitalization for symptoms of fever and respiratory distress. Four patients died of COVID-19 infection-related complications and were excluded from the study. The 14 remaining patients in the study were predominantly of the Black race (85.7%), with a median time since transplant of four years. Of the patients,64.3% developed acute kidney injury (AKI), with an average peak serum creatinine (sCr) of 2.6 mg/dl and a glomerular filtration rate (GFR) of 35. The mean sCr and GFR of the group were 2 mg/dl and 44 at baseline (prior to infection). This represented an increase in their sCr and GFR of 34% and 29%, respectively. The median follow-up post-infection was 14.5 months. sCrand GFR were 1.87 mg/dl and 47 at three to six months, and 1.89 mg/dl and 48 at nine to 12 months post-infection. New onset proteinuria was noted in five out of 14 patients (36%), with complete resolution of the same in all at three to six months follow-up. Of patients with AKI,78% had complete recovery at three to six months follow-up. The mean baseline sCr and GFR of patients who had incomplete recovery was 2.35 and 31.5 with pre-existing proteinuria. Of our entire cohort, there was only one patient who experienced graft loss. This patient had a baseline sCr and GFR of 3.8 mg/dl and 22, existing proteinuria on urinalysis, and a history of biopsy-proven rejection. AKI is common among KTRs who are hospitalized with COVID-19 infection. Most of these recovered, although we noted that patients with baseline lower kidney function and existing proteinuria had a lower recovery rate.

The Progression of Interstitial Fibrosis and Tubular Atrophy at 6 Months Is an Independent Predictor of Poor Graft Outcomes in Kidney Transplant Recipients.

We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients. The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were. Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection.

Outcomes of Kidney Transplant Recipients in Singapore With COVID-19 Infection With Delta and Omicron Variants

Outcomes of Kidney Transplant Recipients in Singapore With COVID-19 Infection With Delta and Omicron Variants

Hormone Replacement Therapy and COVID-19 Outcomes in Kidney Transplant Recipients Compared With the General Population

Hormone Replacement Therapy and COVID-19 Outcomes in Kidney Transplant Recipients Compared With the General Population

Elevated Donor-Derived Cell-Free DNA (dd-cfDNA) in the Early Post-Transplant Period Is Associated With an Increased Incidence of Adverse Clinical Outcomes in Kidney Transplant Recipients

Elevated Donor-Derived Cell-Free DNA (dd-cfDNA) in the Early Post-Transplant Period Is Associated With an Increased Incidence of Adverse Clinical Outcomes in Kidney Transplant Recipients

Outcomes in Kidney Transplant Recipients With COVID-19 Illness in the Era of Vaccines

Outcomes in Kidney Transplant Recipients With COVID-19 Illness in the Era of Vaccines

Effect of Carbapenem-Resistant Klebsiella pneumoniae Infection on the Clinical Outcomes of Kidney Transplant Recipients.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has proven to be difficult to control and typically presents with devastating effects. This retrospective study was conducted on the renal recipients at our institution between January 2021 to January 2022. Clinical data was collected to identify factors associated with CRKP infection and clinical outcomes. There were 104 cases out of 186 total renal recipients who presented with at least one infection within 3 months after KT, and 14 cases developed unfavorable clinical outcomes. We identified 16 confirmed CRKP infected cases with the incidence of 8.60%. Possible donor derived infection (DDI) (OR = 6.743; 95% CI: 1.477-30.786; P = 0.014) were independent risk factors for the occurrence of CRKP infection of renal recipients in our analysis, CRKP infection (OR = 20.723; 95% CI: 3.448-124.547; P = 0.001) and pneumonia (OR = 28.458; 95% CI: 1.956-413.984 P = 0.014) were independent risk factors for the occurrence of unfavorable clinical outcomes following KT, and the occurrence of unfavorable clinical outcomes following KT were significantly associated with CRKP infection (r = 0.535; P < 0.001) and antibiotic regimen containing ceftazidime/avibactam (CZA) (r = -0.655; P = 0.006). The use of CZA was significantly different in the comparison of antibiotic regimens between the CRKP infected renal recipients with unfavorable outcomes and CRKP infected patients with favorable outcomes. It is possible that DDI can lead to CRKP infection, and CRKP infection and pneumonia were closely correlated with poor prognosis. The use of CZA may play a role in avoiding the unfavorable outcomes of CRKP infected recipients.

The Immunohistochemical Expression of the Von Willebrand Factor: A Potential Tool to Predict Kidney Allograft Outcomes.

Few reports assessed endothelial activation biomarkers in kidney allograft biopsies using immunohistochemistry. This retrospective cohort study evaluated the association between posttransplant outcomes and the immunohistochemistry expression of Caveolin-1, Von Willebrand Factor (Vwf), and T-Cadherin in for-cause biopsies diagnosed as interstitial fibrosis and tubular atrophy of unknown etiology. Samples with antibody-mediated changes were excluded. The patients were followed for 3 years after the biopsy or until graft loss/death. Seventy-one (71) samples from 66 patients were included. Eighteen (25.4%) patients lost their grafts, mainly due to chronic rejection (33.3%). Caveolin-1 and T-Cadherin were not associated with graft loss. Vwf had good accuracy in predicting graft failure (AUC 0.637, 95% CI 0.486 to 0.788 P =0.101). The presence of more than 10% of Vwf positivity in the microvasculature (Vwf >10%) was associated with reduced death-censored graft survival (58.2% vs. 85.4% P =0.006), and this result was also observed in the subgroup presenting mild interstitial fibrosis (ci=1) (65.7% vs. 88.6% P =0.033). The multivariate analysis showed that Vwf >10% was an independent risk factor for graft loss (HR=2.88, 95% CI 1.03 to 8.02 P =0.043). In conclusion, Vwf might be an additional tool to predict allograft outcomes in kidney transplant recipients with interstitial fibrosis and tubular atrophy of unknown etiology, probably reflecting immune endothelial activation.

Infection by Carbapenemase-Producing Klebsiella pneumoniae in Renal Transplant Recipients

Abstract: There is a tendency to increase the number of cases of infection by multidrug-resistant bacteria, in view of the indiscriminate and sometimes excessive use of broad-spectrum antibiotics in the hospital environment. These infections have generated great impact, especially in immunosuppressed patients undergoing solid organ transplantation. National data revealed a significant increase in the rates of infections by multidrug-resistant bacteria. The present study aimed to evaluate the incidence and demographics of health care-related infections by carbapenemase-producing K. pneumoniae (KPC). This is an observational, retrospective, descriptive study conducted at a single center (Kidney Hospital) with evaluation of the outcomes of kidney transplant recipients with KPC infection between November 2009 and December 2015. In our center, KPC bloodstream infection had the highest prevalence, followed by urinary tract infection. The overall 30-day mortality was 36%, similar to that found in the international literature. Infection with multidrug-resistant bacteria is a serious clinical condition in transplant patients and poses a therapeutic challenge.

Allograft function and muscle mass evolution after kidney transplantation.

Advanced chronic kidney disease is associated with muscle wasting, but how glomerular filtration rate (GFR) recovery after kidney transplantation is associated with muscle mass is unknown. We took advantage of the simultaneous measurement of GFR (using iohexol plasma clearance; ioGFR) and creatinine excretion rate (a surrogate marker of muscle mass; CER) performed 3months after transplantation and at a later time point at our institution to investigate the interplay between allograft function, muscle mass, and outcome in kidney transplant recipients. Between June 2005 and October 2019, 1319 successive kidney transplant recipients (mean age 50.4±14.6; 38.7% female) underwent GFR measurement at our institution 3months after kidney transplantation. CER (CER3 ) and ioGFR (ioGFR3 ) were 7.7±2.6μmol/min and 53±17.1mL/min/1.73m2 , respectively. Multivariable analysis identified female gender, older donor and recipient age, reduced body mass index, coronary disease, dialysis history, proteinuria, and reduced ioGFR3 as independent predictors of low CER3 (ioGFR3 : β coefficient 0.19 [95% confidence interval 0.14 to 0.24]). A total of 1165 patients had a subsequent CER measurement after a median follow-up of 9.5months. Of them, 373 (32%) experienced an increase in CER>10%, while 222 (19%) showed a CER decrease of more than 10%. Multivariable analysis adjusted for CER3 and other confounders identified ioGFR3 as an independent predictor of CER at follow-up (β coefficient 0.11 [95% confidence interval 0.07 to 0.16]). In multivariable Cox analysis, reduced CER at 3months or at follow-up were consistently associated with mortality (hazard ratio [95% confidence interval] at 3months: 0.82 [0.74 to 0.91]; at follow-up: 0.79 [0.69 to 0.99]) but not with graft loss. Glomerular filtration rate recovery is a determinant of muscle mass variation after kidney transplantation. Early interventions targeting muscle mass gain may be beneficial for kidney transplant recipients.

Outcome of Kidney Transplant Recipients During Covid-19 Pandemic

Background: Kidney recipients constitute a vulnerable group of population and may have high risk of morbidity and mortality when infected with COVID-19. Objective: To a assess the overall outcome as well as the incidence and impact of COVID-19 among recipients who underwent transplantation during the pandemic Methods: A pre-designed follow up protocol was set to prospectively analyse the data obtaining from the recipients who underwent renal transplantation since 8 March 2010, the first appearance of COVID-19 in Bangladesh till 31 December, 2020. Outcome parameters were renal functional status; surgical, urological, immunological and medical complications; and incidence of COVID-19 and its outcome during the first 12 weeks post-transplant period. Results: Out of 100 patients, 82.0% were male and 18.0% were female. Serum creatinine levels (μmol/L) at 4, 8 and 12 weeks post-transplant were 200 in 6.0%, 5.0% and 6.0% respectively. Graft nephrectomy was done in 3 cases due to vascular complications. Five (5.0%) patients presented with symptoms of COVID-19, among them, 2 cases were confirmed with RT-PCR. There were 6 death cases, and septicaemia was the most common cause of death. The overall mortality rate was 6.0% in our study population but in COVID-19 confirmed cases it was 50.0%. Conclusion: During this pandemic, the overall outcome of renal transplantation was excellent and the incidence of symptomatic COVID-19 among transplant recipients was not higher than the incidence observed in general population of Bangladesh. But among the COVID-19 confirmed recipients, mortality rate was significantly higher. Bangladesh Med Res Counc Bull 2022; 48(1): 33-40

316.14: Impact of Donor Hepatic Steatosis on Kidney Transplant Recipient Outcomes

Introduction: Increasing evidence suggests an independent association of hepatic steatosis with chronic kidney disease, kidney function decline and risk of cardiovascular (CV) disease. Whether the presence or severity of an organ donor’s hepatic steatosis impacts on kidney transplant recipient (KTR) outcomes has not been studied. Methods: We performed a retrospective cohort study of deceased liver donors, matched to their KTR, in New South Wales (NSW), Australia from 2006-2020. We linked data from the Australian and New Zealand Dialysis and Transplantation (ANZDATA) and Organ Donation (ANZOD) registries with biopsy results of donor livers evaluated or utilised for transplantation at the NSW state-wide liver transplant unit. Donor hepatic steatosis was graded contemporaneously by histopathologists as S0 (<5%), S1 (5-33%), S2 (>33-66%) or S3 (>66%). Standard donor and recipient characteristics were collected. All-cause death, cardiovascular (CV) death, graft loss (death-censored), delayed graft function (DGF), graft function decline (assessed by eGFR) and post-transplant CV events (composite of coronary artery, peripheral vascular or cerebrovascular disease) were compared among recipients according to their presence and severity of hepatic steatosis. Results: 751 donors with liver biopsies were matched to 1,263 KTRs (8,043 person-years follow-up). Donor hepatic steatosis grades were: S0 453 (60%), S1 195 (26%), S2 71 (9%), S3 32 (4%). Donors with hepatic steatosis (S1-3) were significantly older (median age 53 vs 46 years) than those without steatosis and had worse metabolic profiles: higher body mass index (median 27 vs 25kg/m2), diabetes (9% vs 6%), hypertension (35% vs 25%). KTR of donors with and without hepatic steatosis had similar baseline characteristics. Presence of hepatic steatosis (vs no steatosis) and steatosis severity (S3 vs S0-2) did not impact on all-cause- or CV-death, graft loss, or DGF in the multivariable analysis. Univariable analysis suggested that decline in graft function was greater in recipients from donors with steatosis compared to recipients of donors without steatosis, but this no longer remained significant on multivariable analysis after adjusting for other variables. There was an increased risk of CV events on univariable (HR 1.42, 95%CI 1.00-2.02, p=0.05) and multivariable analysis (HR 1.47, 95%CI 1.03-2.10, p=0.04, Table 1) among recipients of donors with severe (S3) steatosis versus those with no/less donor steatosis. Conclusion: In this retrospective analysis, neither the presence nor severity of biopsy-proven donor hepatic steatosis appeared to impact kidney transplant recipient outcomes. Recipients from donors with severe hepatic steatosis may be at higher risk of cardiovascular events.

P8.141: Prevalence and Outcome of Kidney Transplant Recipients Infected With BK Polyoma Virus at National Kidney And Transplant Institute From 2016 to 2021

Background: BK polyoma virus (BKV) infection is an evolving challenge in kidney transplant recipients as untreated infections often lead to allograft dysfunction or graft loss. The virus is ubiquitous with viruria and viremia being detected in 30% and >10% of patients, respectively. Decreasing the immunosuppression has been established as the mainstay of treatment, however, screening protocols vary between institutions. Objective: This study aims to describe the prevalence and outcomes of kidney transplant recipients with BKV at the National Kidney and Transplant Institute (NKTI) for the last 5 years. Methods: This is a retrospective study conducted at the NKTI wherein chart review was performed. Age, gender, native kidney disease, viral loads (urine and blood), graft biopsy results were reviewed. Clinical outcomes such as graft failure, early complications, and readmission were also determined. Results: There were 1057 kidney transplants and 12 BKV cases from 2016-2021 with a prevalence of 1.1%. The mean age of recipients was 39 (range 17-66) years, majority of which were males (58%) (Table 1). Half of the recipients had chronic glomerulonephritis with anti-thymocyte globulin being the most common induction agent (67%). Majority (88%) did not have urinary stents. Of the identified cases, viruria (41%) and viremia (33%) were present with 50% having biopsy-proven BKV nephropathy. Most cases presented >6 months from transplant (66%) and viral loads were above 500 copies/ml in 83% of cases. One patient was highly sensitized (8%) and two patients had graft loss (17%). No graft loss and retransplants were done for BKV. Conclusion: The low prevalence of BKV infection in our center reflects the varying practice of clinicians in the management of transplant recipients. Reduction of immunosuppression remains to be the treatment of choice. Early detection may prevent morbidity and graft loss. Routine screening for BKV has been recommended however, it has yet to gain acceptance among our transplant physicians.

P8.112: Pregnancy Outcomes in Kidney Transplant Recipients And Their Newborns

P8.112: Pregnancy Outcomes in Kidney Transplant Recipients And Their Newborns

P8.071: Outcomes in Kidney Transplant Recipients With Allograft Failure Who Return to Dialysis

Background: Kidney transplant recipients (KTR) who return to dialysis (RTD) have high morbidity. Whether to continue immunosuppression (IS) after RTD remains uncertain and involves balancing IS-related risks with preventing terminal rejection and allo-sensitization that may preclude re-transplantation. Objectives: We conducted a quality improvement study to characterize IS practices following RTD, and determine incidence of potential IS-related complications, catastrophic IS-related events, and re-transplantation for patients in whom IS was weaned early vs. late. Methods: We identified all adult KTR who RTD and survived >6 months between January 2015-June 2020 at a large Canadian transplant center using this center’s transplant and dialysis databases. Comorbidities, medications, and outcomes were captured from electronic charts on pre-specified forms from RTD until death, re-transplantation, or Aug 2021. Early IS weaning was defined as discontinuing at least one agent excluding prednisone within 6 months of RTD. Results: Of 49 included patients, 27(55%) discontinued one IS agent by 6 months, while 22(45%) were maintained on two for a median of 34 months (range 7-78 months). During median follow-up of 29 months (range 3-78), there were no between-group differences in the proportion of patients who experienced all-cause (16/27 vs. 12/22) or infection-related (8/27 vs. 7/22) hospitalisations, ICU admission (5/27 vs. 5/22), malignancy (3/27 vs. 2/22), death (6/27 vs.4/22), terminal rejection (3/27 vs. 2/22), or re-transplantation (7/27 vs. 5/22). Median baseline PRA was significantly higher in early vs. late groups, suggesting confounding by indication. Two catastrophic IS events (disseminated tuberculosis, PTLD) occurred in late weaners. Conclusion: Almost half of KTR continued long-term double IS after RTD, and retransplantation rates were low. Cancer and death were not increased in late vs. early IS weaners, but catastrophic infection and PTLD occurred only in late weaners. Early discontinuation of one IS agent did not result in lower probability of re-transplantation and should be considered to reduce infectious complications.