Excess mortality in COVID-19-affected solid organ transplant recipients across the pandemic.

The excess mortality of coronavirus disease 2019 (COVID-19) solid organ transplant recipients (SOTRs) throughout the pandemic remains unclear. This prospective cohort study based on the Japanese nationwide registry included 1632 SOTRs diagnosed with COVID-19 between February 1, 2020, and July 31, 2022, categorized based on dominant phases of variants of concern (VOCs): Waves 1 to 3 (Beta), 4 (Alpha), 5 (Delta), 6 (Omicron BA.1/BA.2), and 7 (Omicron BA.5). Excess mortality of COVID-19-affected SOTRs was analyzed by calculating standardized mortality ratios (SMRs). Overall, 1632 COVID-19-confirmed SOTRs included 1170 kidney, 408 liver, 25 lung, 20 heart, 1 small intestine, and 8 multiorgan recipients. Although disease severity and all-cause mortality decreased as VOCs transitioned, SMRs of SOTRs were consistently higher than those of the general population throughout the pandemic, showing a U-shaped gap that peaked toward the Omicron BA.5 phase; SMR (95% CI): 6.2 (3.1-12.5), 4.0 (1.5-10.6), 3.0 (1.3-6.7), 8.8 (5.3-14.5), and 21.9 (5.5-87.6) for Waves 1 to 3 (Beta), Wave 4 (Alpha), Wave 5 (Delta), Wave 6 (Omicron BA.1/2), and Wave 7 (Omicron BA.5), respectively. In conclusion, COVID-19 SOTRs had greater SMRs than the general population across the pandemic. Vaccine boosters, immunosuppression optimization, and other protective measures, particularly for older SOTRs, are paramount.

Efficacy and safety of the SARS-CoV-2 mRNA vaccine in lung transplant recipients: a possible trigger of rejection.

OBJECTIVE: Solid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown. METHODS: We performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination. RESULTS: There were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9-10.2) vs 2.8 (1.9-4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250-500) vs 1000 (1000-1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients. CONCLUSIONS: The antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination.

Comparison of BNT162b2 and mRNA1273 vaccines in solid organ transplant recipients: Post-Hoc analysis of a Japanese national prospective study.

The coronavirus disease-19 (COVID-19) vaccine efficacy and immunogenicity in the immunocompetent population are well established. However, in solid organ transplant (SOT) recipients, because of their use of immunosuppressive medication, the immunogenicity of these severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines remains suboptimal. Both BNT162b2 and mRNA1273 have been used for some time, but their immunogenicity has not been directly compared in this immunocompromised patient group. We performed a post-hoc analysis of a previous prospective cohort study. The inclusion criteria were adult SOT recipients with active grafts at least 1 month after SOT. After giving consent, participants chose to receive either BNT162b2 or mRNA1273 vaccine. Anti-spike-protein-S antibody against SARS-CoV-2 was measured. Propensity scores were calculated via logistic regression to transform the probability of having received either BNT162b2 or mRNA1273 vaccine, and a model was developed. We enrolled 623 SOT recipients. In the propensity score-matched analysis, 100 recipients were selected for BNT162b2 and 100 for mRNA1273. SARS-CoV-2 anti-spike protein antibody positivity with BNT162b2 versus mRNA1273 at 3 weeks after the first dose, 1 month after the second dose, 3 months after the second dose, and 6 months after the second dose were 10% versus 19% (P = .07), 51% versus 58% (P = .30), 74% versus 88% (P = .01), and 78% versus 87% (P = .13), respectively. We conducted a propensity score-matched comparison of BNT162b2 and mRNA1273 vaccines as the primary series of COVID-19 vaccines in SOT recipients. We found significantly better immunogenicity with the mRNA1273 vaccine than with BNT162b2.

Impact of COVID-19 on living donor liver and kidney transplantation programs in Japan in 2020.

BACKGROUND: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. METHODS: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. RESULTS: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. CONCLUSIONS: THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

Single vs Multiple Arterial Reconstructions in Living Donor Liver Transplant.

BACKGROUND: It is true that multiple arterial reconstructions are sometimes required in living donor liver transplant (LDLT). However, the best procedure is still controversial regarding arterial reconstruction in liver grafts with multiple arteries. METHODS: A total of 93 patients, 55 right lobe grafts and 38 left lobe grafts, who underwent LDLT at our university from 2003 to 2017 were enrolled for this study. Regarding arterial reconstruction in grafts with multiple hepatic arteries, the dominant artery was reconstructed first. Subsequently, when both the pulsating arterial flow from the remaining artery stumps and the intra-graft arterial flow by Doppler ultrasonography were confirmed, the remaining arteries were not reconstructed. The patients were divided into the following 3 groups: (1) single artery/single reconstruction (n = 81), (2) selective arterial reconstruction of multiple arterial grafts (n = 7), and (3) multiple arterial reconstructions (n = 5). RESULTS: A total of 12.9% (12/93; right lobe: 2/55; left lobe 10/38) of grafts had multiple arteries. The incidence of multiple arteries was significantly higher in the left lobe grafts (P = .0029). The arterial diameters (SD) of multiple arterial grafts were narrower (2.43 [0.84] mm) than single arterial grafts (3.70 [1.30] mm) (P = .0135). Extra-anatomic arterial reconstruction were frequently required in multiple arterial reconstructions (group 1 and 2 vs 3) (P = .0007). The strategy of selective arterial reconstruction with the above criteria did not negatively affect the rates of biliary complications or the overall patient survival (P = .52). CONCLUSIONS: It can be argued that selective arterial reconstructions demonstrated acceptable outcomes in LDLT, provided that the above criteria were satisfied.

Impact of Donor and Recipient Age on Outcomes After Living Donor Liver Transplant.

BACKGROUND: Living donor liver transplant between elderly donors and recipients has gained popularity, but the effects of their age remain unknown. Our aim is to evaluate the effects of matching by donor and recipient age with special insights into their recovery periods. METHODS: Ninety-five living donor liver transplant pairs, excluding the left lateral segment graft cases, who underwent surgery were enrolled. Median follow-up was 97 months (range, 1-212 months). Elderly recipients were classified as being 51 years or older. Donor-recipient pairs were divided into (1) nonelderly donor/nonelderly recipient (YY) (n = 26), (2) elderly donor/nonelderly recipient (n = 8), (3) nonelderly donor/elderly recipient (n = 38), and (4) elderly donor/elderly recipient (EE) (n = 23). RESULTS: The 1-, 3-, and 5-year survival rates were 92.7%, 92.7%, and 88.9% (YY); 75.0%, 62.5%, and 62.5% (EY); 80.5%, 76.3%, and 67.9% (EY); and 86.9%, 82.6%, and 78.1% (EE) (P = .30), respectively. Perioperative parameters were comparable between the 4 groups. Liver grafts from the elderly population exhibited higher peaks of transaminases post-transplant regardless of recipient age (P ≤ .05). Postoperative recovery of total bilirubin in the EE group was relatively slower (P = .27). Required rates of plasma exchange postoperatively were relatively higher in the EE group (34.8% vs 15.4% in the YY group). CONCLUSIONS: These findings suggest a modest and not statistically significant effect that elderly liver grafts exhibit slower recovery trajectories in the acute phase but finally achieve acceptable outcomes.

Intra-Liver Allograft C3d-Binding Donor-Specific Anti-HLA Antibodies Predict Rejection After Liver Transplantation.

BACKGROUND: There is no doubt that antibody-mediated rejection (AMR) due to donor-specific anti-HLA antibodies (DSA) brings a poor outcome for liver transplant recipients. However, the relationship between intragraft DSA (g-DSA), complement-binding abilities, and AMR remains unknown. MATERIALS AND METHODS: We enrolled a total of 20 liver transplant recipients who underwent protocol or episode graft biopsies in the mid to long term after liver transplant (median 48.5, range 6-198 months), and their status of g-DSA and complement 3d (C3d)-binding abilities was assessed with the graft immunocomplex capture fluorescence analysis (ICFA) technique. RESULTS: The prevalence of g-DSA was 15.0 % in liver transplant recipients (3/20), and serum DSA (s-DSA) also existed in 15.0% of recipients. The number of g-DSA+/s-DSA+, g-DSA+/s-DSA-, g-DSA-/s-DSA+, and g-DSA-/s-DSA- cases are 1, 2, 2, and 15, respectively. The g-DSA+ group demonstrated a significant high rejection activity index: 3.67 ± 1.53, compared with the g-DSA- group: 1.24 ± 1.15 (P = .0045). Moreover, C3d-binding reaction was notably higher in the g-DSA+ group (C3d index: 1.87 ± 0.38 vs 0.76 ± 0.35) (P < .0001). Overall, the g-DSA+ group was more associated with liver allograft rejection-not only AMR, but also T cell-mediated rejection (P = .031). CONCLUSIONS: These results suggest that the existence of g-DSA and intragraft C3d-binding reaction had a negative impact on the liver allografts, but in contrast s-DSA did not have any significant impact.

Hand-Assisted Laparoscopic Subtotal Colectomy for Ogilvie Syndrome Associated With Idiopathic Fibrosis of Colon After Simultaneous Pancreas Kidney Transplant.

Ogilvie syndrome (acute colonic pseudo-obstruction) is a rare, acquired, life-threatening disorder for which treatment plans vary from simple observation to surgical intervention. Ogilvie syndrome has been reported in patients after renal or liver transplant, but its occurrence after simultaneous pancreas-kidney transplant is rare. Herein, we present the case of a 45-year-old female recipient of a deceased donor simultaneous pancreas-kidney transplant who developed Ogilvie syndrome 10 days after a previous fecal ileus that had resolved at posttransplant week 3. She demonstrated Ogilvie syndrome with obstructive colitis features (severe abdominal pain and high-grade fever), which we immediately treated with colonic decompensation by placement of a transanal ileus tube. After several screening examinations and discontinuation of unnecessary medicines, we were not able to confirm the cause of Ogilvie syndrome in our patient. After 2 weeks, the patient remained unresponsive to the conservative treatment, and so hand-assisted laparoscopic subtotal colectomy was performed to remove the dilated colon. Her symptoms gradually resolved after surgery. Histologically, we confirmed submucosal fibrotic changes, especially at the distal end of the resected colon, without evidence of amyloidosis, and the number of Auerbach plexus ganglia had decreased. Nevertheless, we observed no degenerated appearance of ganglion cells in the Auerbach plexus or the Meissner plexus. After exclusion of several collagen diseases, including systemic sclerosis, we determined that idiopathic colonic fibrosis was the likely cause of Ogilvie syndrome in our patient. When surgery is indicated in transplant patients with Ogilvie syndrome with obstructive colitis features, colectomy should be considered.

A suspected case of plasma cell-rich acute renal transplant rejection associated with de novo donor-specific antibody.

A kidney transplant case with de novo donor-specific antibody showed monoclonal plasma cell infiltration into the graft with ABO incompatibility. Three years after transplantation, the patient's graft function suddenly deteriorated. Interstitial edema and the predominant infiltration of inflammatory plasma cells with kappa chain monoclonality were observed in biopsy specimens. The in situ hybridization of Epstein-Barr virus was negative and post-transplant lymphoproliferative disorder was not evident from radiological examinations. On laboratory examination, the patient had de novo donor-specific antibody for HLA-DQ. We suspected plasma cell-rich acute rejection for which methylprednisolone pulse therapy, plasma exchange, rituximab, and 15-deoxyspergualin were given. In the ensuing biopsy, the degree of plasma cell infiltration was similar to the first biopsy; however, kappa chain monoclonality relatively weakened. Owing to resistance to these treatments, intravenous immunoglobulin (IVIG) (0.5 g/kg/day) was added. The serum creatinine level gradually declined to 3.1 mg/dL; however, it increased up to 3.6 mg/dL again. In the final biopsy, the infiltrated plasma cells disappeared but severe interstitial fibrosis developed. This case showed difficulty in the diagnosis and treatment of plasma cell-rich acute rejection. A detailed consideration of this case may be helpful in understanding the clinical features and pathogenesis of this condition.

Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy.

BACKGROUND: Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. METHODS: This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. RESULTS: Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. CONCLUSIONS: Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

Significance of renal biopsy in patients with presumed diabetic nephropathy.

AIMS/INTRODUCTION: Patients with diabetic nephropathy (DN) typically show varying degrees of proteinuria and renal impairment. Because these clinical signs are frequently observed in other glomerulopathies, renal biopsy is required to make a definitive diagnosis of DN. We carried out the present study to evaluate the significance of renal biopsy for patients who have been presumptively diagnosed with DN. MATERIALS AND METHODS: A total of 55 patients with type 2 diabetes mellitus (DM), and proteinuria, hematuria and/or renal impairment were enrolled in this study. RESULTS: Renal biopsy showed that just 30 patients (54.5%) were histologically diagnosed with DN. Fasting plasma glucose and glycated hemoglobin levels were associated with the presence of DN, whereas baseline renal function showed no statistically significant relationship to DN. The duration of DM was not associated with the presence of DN. Patients with DN had a higher rate of diabetic retinopathy (DR) than those with non-DN (DN 18 patients vs non-DN three patients, P = 0.00029). DN patients with DR showed a more severe renal histology than those without. CONCLUSIONS: These data suggest that, even for patients with long-term DM, renal biopsy should be carried out in patients with presumed DN. Because treatment options differ between DN and primary glomerulopathies, renal biopsy should especially be considered for presumed DN without DR.