Refining Approaches to Fibrosis Control in Kidney Transplant Recipients

SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know?

Impact of Protease Inhibitor-Based Anti-Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients.

Advance Care Planning and Palliative Care Consultation in Kidney Transplantation

Progress in Dermatology: Cutaneous Oncology in Organ Transplant Recipients: Meeting the Challenge of Squamous Cell Carcinoma

Observations on improving COVID-19 vaccination responses in kidney transplant recipients: heterologous vaccination and immunosuppression modulation

Introduction Risk-to-benefit ratio of upper extremity allotransplantation (UEA), a non-vital transplantation procedure, remains to be clarified, as concerns have been raised regarding infectious, metabolic and malignant complications of lifelong immunosuppression. The aim of this study was to provide a relevant assessment of the infectious risk in UEA recipients. Infectious complications in UEA recipients were analyzed and compared to that of kidney transplant (KT) recipients who have the lowest rate of infections among the different populations of solid organ transplant recipients. Patients and Methods Matched cohort study among UEA and KT recipients from the prospectively maintained “International Registry on Hand and Composite Tissue Transplantation” (IRHCTT) and the French “Données Informatisées et VAlidées en Transplantation” (DIVAT) database. All UEA recipients reported to the IRHCTT between 1998 and 2016 were matched with KT recipients (1:5), according to age (±5 years), sex, CMV serostatus of donor and recipient and (depleting or not depleting) induction. Incidence and characteristics of all infectious events reported to the databases at three posttransplant periods (0-6 months, 7-12 months, >12 months) were analyzed. Results and Discussion Sixty-one UEA recipients were matched with 305 KT recipients. Mean (±SD) follow-up of UEA and KT recipients was 2583±1876 and 2230±1792 days, respectively (p=0.16). Immunosuppression regimen at 3 months posttransplant was similar. The number of acute rejection episodes during follow-up was higher in UEA recipients than in KT recipients (1.3±1.6 vs 0.4±0.7, p<0.01). During follow-up, 30 (50.8%) UEA recipients presented a total of 61 infectious events while 129 (42.3%) KT recipients presented 243 infectious events. Incidence rate of infectious events was higher in UEA recipients than in KT recipients during the first 6 months posttransplant (3.27 vs 1.95 events/1000 transplant-days, p=0.01). Thereafter, incidence rates of infections did not significantly differ between UEA and KT recipients: 0.61 vs 0.45 events/1000 transplant-days (7th-12th month posttransplant, p=0.5) and 0.15 vs 0.21 events/1000 transplant-days (>12th month posttransplant, p=0.11), respectively. Distribution of sites of infections was significantly different: while mucocutaneous infections predominated among UEA recipients at each of the three posttransplant periods (representing 28.6%, 50% and 30% of infectious events, respectively), urinary tract infections (28.6%, 23.8% and 33.9%) and pneumonia (17.3%, 42.9% and 28.2%) predominated among KT recipients. Conclusion Incidence rate of infectious events is higher in UEA recipients than in KT recipients during the first 6 months posttransplant. After the first 6 months posttransplant, incidence of infections is low, at worst equivalent to the incidence observed in young KT recipients. Distribution of infectious syndromes suggests less severe infections in UEA than in KT recipients.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

This study aims to evaluate allograft and patient outcomes among recipients of kidney transplants after non-renal solid organ transplants. We also aim to compare our findings with recipients of a repeat kidney transplant. We performed an analysis on kidney transplant recipients who underwent kidney transplantation after a non-renal solid organ transplant. Survival data were stratified into 2 groups: Group A (n=37) consisted of recipients of a kidney transplant after prior non-renal solid organ transplant, and Group B (n=330) consisted of recipients of a repeat kidney transplant. The 1-,5-, and 10-year graft survival (death-censored) for recipients of a kidney transplant post-non-renal solid organ transplant (Group A) were 97.3%, 91.5%, and 86.9%, compared with 97.9%, 90.2%, and 83.4% for recipients of a repeat kidney transplant (Group B) (p=.32). The 1-, 5-, and 10-year patient survival rates were 97.3%, 82.7%, and 79.1% in Group A compared to 97.9%, 90.2%, and 83.4% in Group B. Unadjusted overall patient survival was significantly lower for Group A (p=.017). Kidney transplant recipients who have undergone a previous non-renal solid organ transplant have similar allograft survival outcomes, but higher long-term mortality rates compared to repeat kidney transplant recipients.

Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine

Outcomes of Pediatric Kidney Transplantation in Recipients of a Previous Non-Renal Solid Organ Transplant.

Prospective randomized study of individual and group psychotherapy versus controls in recipients of renal transplants

The pharmacokinetics of mycophenolic acid (MPA) and its glucuronide (mycophenolic acid phenolic glucuronide, MPAG) in lupus nephritis (LN) have not been fully characterized. The aim of this study was to evaluate the pharmacokinetics of MPA and MPAG in LN patients by comparing the pharmacokinetics with those of kidney transplant (KT) recipients. Six LN patients (World Health Organization class IV and V) and 24 KT recipients [8 recipients treated with tacrolimus (Tac) and 16 with cyclosporine (CyA)] during the early posttransplantation period were enrolled. Pharmacokinetic parameters of MPA and MPAG were compared between LN patients and Tac-treated or CyA-treated KT recipients. The area under the concentration-time curve (AUC0-12) of MPA normalized to mycophenolate mofetil (MMF) dose (mg/kg) was significantly lower in LN patients and CyA-treated KT recipients than in Tac-treated KT recipients [median (range), 2.19 (0.87-4.23), 2.36 (1.13-5.74), and 4.86 (3.25-6.75) microg x h/mL per mg/kg, P < 0.05 and P < 0.01, respectively]. Dose-normalized MPAG AUC0-12 was significantly lower in LN patients and slightly lower in Tac-treated KT recipients than in CyA-treated KT recipients [median (range), 35.0 (8.34-69.8), 51.6 (34.4-94.8), and 84.1 (34.7-152) microg x h/mL per mg/kg, P < 0.05 and P = 0.13, respectively]. The ratio of MPA AUC5-12 to AUC0-12, an estimate of MPA enterohepatic recirculation, was slightly higher in LN patients and Tac-treated KT recipients than in CyA-treated KT recipients [median (range), 0.44 (0.35-0.56), 0.45 (0.42-0.61), and 0.34 (0.22-0.55), P = 0.29 and P = 0.10, respectively]. Serum creatinine was significantly lower in LN patients than in Tac-treated and CyA-treated KT recipients. In conclusion, the pharmacokinetics of MPA in LN patients is characterized by high MPA clearance and in CyA-treated KT recipients. Despite this higher clearance of MPA, MPAG AUC0-12 was lower in LN patients most likely due to better renal function in LN patients.

BackgroundCMV infection is common post-kidney transplant (KT). Valganciclovir (VGC) prophylaxis (Px) has lessened CMV infection among high-risk (CMV D+/R-) KT recipients (KTRs), but VGC can induce neutropenia. We quantified the burden of CMV infection among CMV D+/R- KTRs and healthcare resources required to manage these patients (pts).MethodsRetrospective study of pts undergoing KT between Jan 2014-Dec 2018. Study and control groups (gps) were CMV D+/R- and R+ KTRs, respectively. Standard post-KT immunosuppression was tacrolimus and mycophenolate mofetil (MMF). D+/R- and R+ KTRs received VGC Px (900 mg/day) for 6 and 3 months (mos), respectively.ResultsClinical characteristics did not differ between D+/R- (n=131) and R+ (n=140) pts. Median VGC Px duration was longer for D+/R- (183 vs 104 days, p< .01). Within the first 6 mos post KT, a higher proportion of D+/R- KTRs received ≥1-course of granulocyte-stimulating factor (G-CSF) (15% vs 6%, p=.02). VGC Px was stopped prematurely/intermittently in 20% and 10% of D+/R- and R+, respectively, due to neutropenia (p=0.02); corresponding data for stopping MMF for ≥1 mos were 32% and 21% (p=.05). 50% of D+/R- pts received < 3 mos Px. Leukopenia prompted hospitalization in 3% of D+/R- vs 0% of R+ pts (p=.05). CMV infections did not differ between gps (7% vs 6%, p=.80); however, VGC-resistant CMV was higher in D+/R- gp (3% vs 0%, p=.05). Between 6-12 mos post-KT, D+/R- KTRs had higher rates of CMV infection (24% vs 4%,p< .01), VGC resistance (5% vs 0%, p=.01), hospitalization due to CMV (11% vs 2%, p=.01), MD intervention (22% vs 2%,p< .01), and infectious disease (ID) referral (8% vs 2%,p= .04). 57% of CMV resistance was observed in pts who prematurely stopped VGC. Hospitalizations were longer for CMV infections in D+/R- KTRs (8 vs 1 d, p< .01). There was a trend toward higher rejection for D+/R- KTRs (13% vs 6%, p=.09).ConclusionUniversal VGC Px in D+/R- KTR remains challenging and requires significant resources for monitoring and intervention for neutropenia, including MD involvement and ID referral. Intermittent/premature stop of VGC may have led to VGC-resistant CMV,and stop of MMF may have led to a trend of higher cellular rejection at 1 yr. There is critical need for new CMV agents with a better safety profile.DisclosuresAmit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder) Cornelius J. Clancy, MD, Merck (Grant/Research Support) Minh-Hong Nguyen, MD, Merck (Grant/Research Support)

BACKGROUND AND AIMS Various COVID-19 vaccines have been developed across a range of platforms and have been deployed among immunocompetent individuals, but data have been lacking regarding the effects of these vaccines among kidney transplant recipients. While it is true that there is high immunogenicity after COVID vaccination among immunocompetent individuals, disappointing results in the humoral response were seen among kidney transplant recipients. There are studies that undermine the over-all immunogenicity among end-stage renal disease on renal replacement therapy, but little is known regarding data among kidney transplant recipients. Hence, this meta-analysis would like to investigate the over-all immunogenicity rate among kidney transplant recipient after COVID vaccination. METHOD A systematic search of relevant articles was performed on two English databases (Pubmed, Cochrane Library) published between January 2020 to November 2021 and we included studies on kidney transplant recipient who reported on antibody response rate after COVID vaccination. RESULTS Thirteen studies were included in this meta-analysis with a total of 2231 participants, analyzing immunogenicity rates among kidney transplant recipients towards the following vaccines: [mRNA-1273 SARS-CoV-2 Vaccine (Moderna), Inactivated whole-virus SARS-CoV-2 vaccine, CoronaVac® (Sinovac), mRNA BNT162b2 vaccine (Pfizer-BioNTech), and Oxford–AstraZeneca COVID-19]. The over-all immunogenicity rate among kidney transplant recipient was 43% (95% CI: 36–52%) with I2 = 80%. Compared with controls, kidney transplant recipient had a 53% reduced likelihood of attaining seroconversion after a standard 2 doses of COVID vaccine (RR: 0.47, 95% CI: 0.34–0.65). CONCLUSION The overall immunogenicity among Kidney Transplant (KT) recipient was 43% and compared with transplant-naïve group, KT recipients have a 53% reduced likelihood of attaining seroconversion. Moreover, KT recipients whom had prior COVID-19 infection, and received mRNA-1273 COVID-19 Vaccine (Moderna) as their COVID vaccine has higher antibody response rate. The addition of booster dose of vaccine showed a slight increase in immunogenicity compared with those whom had two doses only. Lastly, old age and high levels of anti-metabolite might have cause low level of immunogenicity among kidney transplant recipient after COVID vaccination.

While a great deal of literature has been published in recent years on infections in kidney transplant (KT) recipients, there is a relative paucity of literature on infections and their impact on the graft and overall health of older KT recipients. We reviewed the most recent literature and guidelines in the field of kidney transplantation and summarized the current recommendations for physicians caring for older KT recipients at risk for infections. Older KT recipients are at an increased risk of infections during the first year post-KT resulting in readmission or other poor outcomes, compared to younger KT recipients. Immune senescence and frailty likely increase the risk for infections in older KT recipients during the first year post-KT when KT recipients are receiving a higher degree of immune suppressive therapy. Most common infections include urinary tract infections, bloodstream infections, cytomegalovirus reactivation or primary infection, and BK virus. A majority of older KT recipients survive and have a functioning graft at 1 year. KT can be a successful treatment for older adults on dialysis if post-transplant complications, including rejection and infection, can be appropriately managed. Despite this increased risk for infections, older KT recipients have a lower risk for all-cause mortality and death secondary to infections compared with patients on dialysis. Further studies on modification of immune suppression and prophylactic strategies are much needed in this high-risk KT population.