Impact of Age 70 years or Older on Donors for Living-Donor Kidney Transplantation.

Introduction: Kidney transplantation (KT) involving elderly living kidney donors (LKDs) is becoming more frequent because of a profound organ shortage. The efficacy of KT involving grafts obtained from LKDs aged 70 years or older has been reported. However, the safety of donor nephrectomy in LKDs aged 70 years or older, including that associated with changes in the estimated glomerular filtration rate (eGFR), has not been investigated. This study investigated the outcomes of LKDs aged 70 years or older after donor nephrectomy. Methods: This single-center, retrospective cohort study included 1226 LKDs who underwent donor nephrectomy between January 2008 and December 2020. LKDs were stratified into the following age groups: 30 to 49 years (244 LKDs), 50 to 69 years (803 LKDs), and 70 to 89 years (179 LKDs). Surgical outcomes, postoperative eGFR changes, end-stage renal disease (ESRD) rates, and mortality rates were compared among these groups. Results: No significant difference in surgical outcomes was identified among the groups. LKDs aged 70 to 89 years experienced the lowest eGFR changes at all time points and the lowest eGFR improvement; however, ESRD was not identified in any group during the observation period. Mortality was the highest among LKDs aged 70 to 89 years compared to the other age groups. Conclusion: Surgical outcomes, eGFR changes, and ESRD incidences can support the safety of donor nephrectomy in LKDs aged 70 years or older. Considering the advanced age, the high mortality rates in LKDs aged 70 years or older could be considered acceptable.

Lung cancer after kidney transplantation: a 50-year experience at a single institution.

PURPOSE: To investigate the clinical characteristics of lung cancer that develops after kidney transplantation. METHODS: The clinical data of patients with lung cancer diagnosed after kidney transplantation were collected retrospectively. The medical records were extracted from our database. All patients underwent routine chest examination after kidney transplantation. RESULTS: In total, 17 lung tumors were detected in 15 (0.6%) of 2593 patients who underwent kidney transplantation at our institution. Eleven lung tumors were completely resected from a collective 10 patients (surgical group). The remaining five patients did not receive surgical treatment (nonsurgical group). The surgical group underwent wedge resection (n = 5), segmentectomy (n = 1), lobectomy (n = 3), and bilobectomy (n = 1). The pathological stages were 0 (n = 1), IA1 (n = 2), IA2 (n = 4), IA3 (n = 2), and IB (n = 1). The surgical group had a significantly better prognosis than the nonsurgical group. There were no perioperative complications related to kidney transplantation in either group. CONCLUSIONS: Routine chest examination would be useful for the early diagnosis and treatment of lung cancer after kidney transplantation. Moreover, surgical resection for early-stage lung cancer was associated with a better prognosis for kidney transplantation patients.

Prediction models for the recipients' ideal perioperative estimated glomerular filtration rates for predicting graft survival after adult living-donor kidney transplantation.

Introduction: The impact of the perioperative estimated glomerular filtration rate (eGFR) on graft survival in kidney transplant recipients is yet to be evaluated. In this study, we developed prediction models for the ideal perioperative eGFRs in recipients. Methods: We evaluated the impact of perioperative predicted ideal and actual eGFRs on graft survival by including 1,174 consecutive adult patients who underwent living-donor kidney transplantation (LDKT) between January 2008 and December 2020. Prediction models for the ideal perioperative eGFR were developed for 676 recipients who were randomly assigned to the training and validation sets (ratio: 7:3). The prediction models for the ideal best eGFR within 3 weeks and those at 1, 2, and 3 weeks after LDKT in 474 recipients were developed using 10-fold validation and stepwise multiple regression model analyzes. The developed prediction models were validated in 202 recipients. Finally, the impact of perioperative predicted ideal eGFRs/actual eGFRs on graft survival was investigated using Fine-Gray regression analysis. Results: The correlation coefficients of the predicted ideal best eGFR within 3 weeks and the predicted ideal eGFRs at 1, 2, and 3 weeks after LDKT were 0.651, 0.600, 0.598, and 0.617, respectively. Multivariate analyzes for graft loss demonstrated significant differences in the predicted ideal best eGFR/actual best eGFR within 3 weeks and the predicted ideal eGFRs/actual eGFRs at 1, 2, and 3 weeks after LDKT. Discussion: The predicted ideal best eGFR/actual best eGFR within 3 weeks and the predicted ideal eGFRs/actual eGFRs at 1, 2, and 3 weeks after LDKT were independent prognostic factors for graft loss. Therefore, the perioperative predicted ideal eGFR/actual eGFR may be useful for predicting graft survival after adult LDKT.

Humoral response to SARS-CoV-2 mRNA vaccine on in ABO blood type incompatible kidney transplant recipients treated with low-dose rituximab.

We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.

Maximal parathyroid gland diameter as a predictive factor for autograft-dependent recurrent secondary hyperparathyroidism after total parathyroidectomy.

Introduction: Following total parathyroidectomy (PTx), transcervical thymectomy, and forearm autograft for secondary hyperparathyroidism (SHPT), recurrent SHPT can occur in the autografted forearm. However, few studies have investigated the factors contributing to re-PTx due to autograft-dependent recurrent SHPT before the completion of the initial PTx. Methods: A total of 770 patients who had autografted parathyroid fragments derived from only one of the resected parathyroid glands (PTGs) and who had undergone successful initial total PTx and transcervical thymectomy-defined by serum intact parathyroid hormone level < 60 pg/mL on postoperative day 1-between January 2001 and December 2022 were included in this retrospective cohort study. Factors contributing to re-PTx due to graft-dependent recurrent SHPT before the completion of the initial PTx were investigated using multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to obtain the optimal maximum diameter of PTG for autograft. Results: Univariate analysis showed that dialysis vintage and maximum diameter and weight of the PTG for autograft were significant factors contributing to graft-dependent recurrent SHPT. However, multivariate analysis revealed that dialysis vintage (P=0.010; hazard ratio [HR], 0.995; 95% confidence interval [CI], 0.992-0.999) and the maximum diameter of the PTG for autograft (P=0.046; HR, 1.107; 95% CI, 1.002-1.224) significantly contributed to graft-dependent recurrent SHPT. ROC curve analysis showed that < 14 mm was the optimal maximum diameter of PTG for autograft (area under the curve, 0.628; 95% CI, 0.551-0.705). Conclusions: The dialysis vintage and maximum diameter of PTG for autograft may contribute to re-PTx due to autograft-dependent recurrent SHPT, which can be prevented by using PTGs with a maximum diameter of < 14 mm for autograft.

Persistent hyperparathyroidism after preemptive kidney transplantation.

BACKGROUND: Long-term dialysis vintage is a predictor of persistent hyperparathyroidism (HPT) after kidney transplantation (KTx). Recently, preemptive kidney transplantation (PKT) has increased. However, the incidence, predictors, and clinical implications of HPT after PKT are unclear. Here, we aimed to elucidate these considerations. METHODS: In this retrospective cohort study, we enrolled patients who underwent PKT between 2000 and 2016. Those who lost their graft within 1 year posttransplant were excluded. HPT was defined as an intact parathyroid hormone (PTH) level exceeding 80 pg/mL or hypercalcemia unexplained by causes other than HPT. Patients were divided into two groups based on the presence of HPT 1 year after PKT. The primary outcome was the predictors of HPT after PKT, and the secondary outcome was graft survival. RESULTS: Among the 340 consecutive patients who underwent PKT, 188 did not have HPT (HPT-free group) and 152 had HPT (HPT group). Multivariate logistic regression analysis revealed that pretransplant PTH level (P < 0.001; odds ratio [OR], 5.480; 95% confidence interval [CI], 2.070-14.50) and preoperative donor-estimated glomerular filtration rate (P = 0.033; OR, 0.978; 95% CI, 0.957-0.998) were independent predictors of HPT after PKT. Death-censored graft survival was significantly lower in the HPT group than that in the HPT-free group (90.4% vs. 96.4% at 10 years, P = 0.009). CONCLUSIONS: Pretransplant PTH levels and donor kidney function were independent predictors of HPT after PKT. In addition, HPT was associated with worse graft outcomes even after PKT.

Treatment for secondary hyperparathyroidism focusing on parathyroidectomy.

Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and 99mTc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed via intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.

Possible Advantage of Glucagon-Like Peptide 1 Receptor Agonists for Kidney Transplant Recipients With Type 2 Diabetes.

CONTEXT: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have the potential to improve native kidney function. OBJECTIVE: This work aimed to elucidate the possible protective effects of GLP-1 RAs on kidney graft function after successful kidney transplantation (KTX). METHODS: This retrospective cohort study included all KTX recipients (KTRs) at our facility with type 2 diabetes who were followed up from 1 month post-transplantation for 24 months or longer as of December 31, 2020. We investigated associations between the use of GLP-1 RAs and other antidiabetic medications (non-GLP-1 RAs) and the risk of sustained estimated glomerular filtration rate (eGFR) reduction (40% reduction compared with baseline for 4 months) for KTRs with type 2 diabetes. We calculated the propensity score of initiating GLP-1 RAs compared with that of initiating non-GLP-1 RAs as a function of baseline covariates using logistic regression. The inverse probability of the treatment-weighted odds ratio was estimated to control for baseline confounding variables. Sodium-glucose cotransporter 2 inhibitor use was a competing event. The primary outcome was sustained eGFR reduction of at least 40% from baseline for 4 months post-transplantation. RESULTS: Seventy-three patients were GLP-1 RA users and 73 were non-GLP-1 RA users. Six patients and 1 patient in the non-GLP-1 RA and GLP-1 RA groups had sustained eGFR reduction. GLP-1 RA use after KTX was associated with a lower risk of sustained eGFR reduction. CONCLUSION: GLP-1 RAs resulted in lower eGFR reduction compared with non-GLP-1 RAs and may contribute to better kidney graft survival after KTX.

Optimal dose of rituximab in ABO-incompatible kidney transplantation in patients with low anti-A/B antibody titers: A single-center retrospective cohort study.

BACKGROUND: The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS: ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS: Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION: In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.

Short-term outcomes of second kidney transplantation compared with those of first transplantation in Japanese patients: a single-center, retrospective, observational study.

BACKGROUND: Among patients who undergo kidney transplantation, a subsequent second kidney transplantation (TX2) is often necessary. The TX2 outcomes remain controversial, however, and only limited data are available on clinical outcomes of TX2 in Japanese patients. This study aimed to assess graft and patient survival rates of TX2 and compared these rates with those of first kidney transplantation (TX1) in Japanese patients. METHODS: Of the 898 kidney transplantations performed between 2010 and 2019 at our institution, 33 were TX2. We performed survival analysis using weighted Kaplan-Meier analysis and Cox proportional hazards analysis with propensity score matching, specifically inverse probability of treatment weighting (IPTW). RESULTS: Death-censored graft survival (DCGS) rates at 1, 3, and 5 years for the TX1 versus TX2 groups were 99.3, 97.9, and 95.0% versus 100, 96.0, and 91.2%, respectively. Overall survival (OS) rates at 1, 3, and 5 years for the TX1 versus TX2 groups were 99.4, 98.9, and 97.8% versus 100, 100, and 94.4%, respectively. Using the log-rank test, IPTW-weighted Kaplan-Meier curves showed no significant differences for TX1 versus TX2 in DCGS (p = 0.535) and OS (p = 0.302). On Cox proportional hazards analysis for TX2 versus TX1, the IPTW-adjusted hazard ratio (HR) for DCGS was 1.75 (95% CI, 0.28-10.9; p = 0.550) and for OS was 2.71 (95% CI, 0.40-18.55; p = 0.311). CONCLUSIONS: For patients who require TX2, this treatment is an acceptable option based on the short-term outcomes data for DCGS and OS.

Intraoperative intact parathyroid hormone monitoring and frozen section diagnosis are essential for successful parathyroidectomy in secondary hyperparathyroidism.

Background: Total parathyroidectomy (PTx) is often performed to treat secondary hyperparathyroidism (SHPT). Successful PTx is essential to prevent recurrent and persistent SHPT because remnant parathyroid glands (PTGs) in the neck can be stimulated and may secrete excessive parathyroid hormone (PTH) in end-stage renal disease. However, to date, few studies have investigated factors contributing to successful PTx before the completion of surgery. Materials and methods: Between August 2010 and February 2020, 344 patients underwent total PTx, transcervical thymectomy, and forearm autograft for SHPT at our institute. Factors contributing to successful PTx before the completion of surgery were investigated. Preoperative imaging diagnoses, including computed tomography, ultrasonography, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy, intraoperative intact PTH (IOIPTH) monitoring, and frozen section histologic diagnosis, were performed. Successful PTx was defined as intact PTH level < 60 pg/mL on postoperative day 1. A sufficient decrease in IOIPTH level was defined as > 70% decrease in intact PTH levels measured 10 min after total PTx and transcervical thymectomy compared to intact PTH levels measured before skin incision. Logistic regression analysis was conducted to investigate factors contributing to PTx success. Results: Univariate analysis showed that the number of all PTGs identified preoperatively by imaging modalities and the specimens submitted for frozen section diagnosis, which surgeon presumed to be PTGs, were not significant factors contributing to successful PTx. However, multivariate analysis revealed that the number of PTGs identified by frozen section diagnosis (P < 0.001, odds ratio [OR] 4.356, 95% confidence interval [CI] 2.499-7.592) and sufficient decrease in IOIPTH levels (P = 0.001, OR 7.847, 95% CI 2.443-25.204) significantly contributed to successful PTx. Conclusion: Sufficient intact PTH level decrease observed on IOIPTH monitoring and the number of PTGs identified by frozen section diagnosis contributed to successful PTx for SHPT. IOIPTH monitoring and frozen section diagnosis are essential for achieving successful PTx for SHPT.

Hand port-site infection after hand-assisted laparoscopic donor nephrectomy for living-donor kidney transplantation: a retrospective cohort study.

Background: Hand-assisted laparoscopic donor nephrectomy (HALDN) is widely performed to minimize burden on living kidney donors. However, hand port-site infections after HALDN may occur. This study aimed to assess the impact of donor characteristics including preoperative comorbidities and operative factors on hand port-site infection after HALDN. Methods: In this single-center, retrospective cohort study, 1,260 consecutive HALDNs for living-donor kidney transplantation performed between January 2008 and December 2021 were evaluated. All living donors met the living kidney donor guidelines in Japan. Hand port-site infections were identified in 88 HALDN cases (7.0%). To investigate risk factors for hand port-site infection, donor characteristics including preoperative comorbidities such as hypertension, glucose intolerance, dyslipidemia, obesity, and operative factors such as operative duration, blood loss, preoperative antibiotic prophylaxis, and prophylactic subcutaneous suction drain placement at the hand port-site were analyzed using logistic regression analysis. Results: In the multivariate analysis, significant differences were identified regarding sex (P = 0.021; odds ratio [OR], 1.971; 95% confidence interval [CI], 1.108-3.507), preoperative antibiotic prophylaxis (P < 0.001; OR, 0.037; 95% CI [0.011-0.127]), and prophylactic subcutaneous suction drain placement at the hand port-site (P = 0.041; OR, 2.005; 95% CI [1.029-3.907]). However, a significant difference was not identified regarding glucose intolerance (P = 0.572; OR, 1.148; 95% CI [0.711-1.856]). Preoperative comorbidities may not cause hand port-site infections within the donors who meet the living kidney donor guidelines. Preoperative antibiotic prophylaxis is crucial in preventing hand port-site infection, whereas prophylactic subcutaneous suction drain placement may increase the risk of hand port-site infection.

Risk factors for subchondral insufficiency fracture of the femoral head in renal transplant patients.

INTRODUCTION: Risk factors associated with subchondral insufficiency fracture (SIF) of the femoral head have not been established. The aim of the present study was to determine the incidence and risk factors for SIF of the femoral head following renal transplantation (RT). MATERIALS AND METHODS: We analyzed the cases of 681 RT patients (mean age at surgery: 49.5 ± 13.6 years, 249 women, 432 men) to determine the incidence of SIF. Hip magnetic resonance imaging (MRI) was performed 6 months post-RT. The following potential predictors of SIF were evaluated: (1) patient's condition at RT: bone mineral density (BMD), pre-RT laboratory values including calcium (Ca), phosphorus (P), calcium-phosphorus product (Ca × P), and intact parathyroid hormone; the patient and donor's blood relationship; and mismatching number of human leukocyte antigens (HLAs), and (2) post-RT dosage(s) of steroid(s), the immunosuppressive regimen, and the incidence of acute rejection. RESULTS: SIF was observed in 15 hips (13 patients, 1.9%). We successfully matched 39 patients without SIF. A multivariate logistic regression analysis adjusted for cumulative dosages of steroids, revealed the following were risk factors for SIF: osteoporosis (OR: 11.4, p = 0.046), lumbar BMD (OR: 0.003, p = 0.038), pre-RT serum P (OR 2.68, p = 0.004), and pre-RT serum Ca × P (OR: 1.11, p = 0.005). CONCLUSION: Since osteoporosis, the lumbar BMD, serum P, and serum Ca × P were identified as risk factors for a post-RT SIF, these factors should be evaluated before RT for the prediction of the SIF risk.

Elevated parathyroid hormone one year after kidney transplantation is an independent risk factor for graft loss even without hypercalcemia.

BACKGROUND: Hypercalcemic hyperparathyroidism has been associated with poor outcomes after kidney transplantation (KTx). However, the clinical implications of normocalcemic hyperparathyroidism after KTx are unclear. This retrospective cohort study attempted to identify these implications. METHODS: Normocalcemic recipients who underwent KTx between 2000 and 2016 without a history of parathyroidectomy were included in the study. Those who lost their graft within 1 year posttransplant were excluded. Normocalcemia was defined as total serum calcium levels of 8.5-10.5 mg/dL, while hyperparathyroidism was defined as when intact parathyroid hormone levels exceeded 80 pg/mL. The patients were divided into two groups based on the presence of hyperparathyroidism 1 year after KTx. The primary outcome was the risk of graft loss. RESULTS: Among the 892 consecutive patients, 493 did not have hyperparathyroidism (HPT-free group), and 399 had normocalcemic hyperparathyroidism (NC-HPT group). Ninety-five patients lost their grafts. Death-censored graft survival after KTx was significantly lower in the NC-HPT group than in the HPT-free group (96.7% vs. 99.6% after 5 years, respectively, P < 0.001). Cox hazard analysis revealed that normocalcemic hyperparathyroidism was an independent risk factor for graft loss (P = 0.002; hazard ratio, 1.94; 95% confidence interval, 1.27-2.98). CONCLUSIONS: Normocalcemic hyperparathyroidism 1 year after KTx was an independent risk factor for death-censored graft loss. Early intervention of elevated parathyroid hormone levels may lead to better graft outcomes, even without overt hypercalcemia.

Preservation of the nonrecurrent laryngeal nerve using intraoperative nerve monitoring during endoscopic thyroidectomy.

A 40-year-old woman underwent right lobe thyroidectomy for thyroid nodules that increased in size from 17 mm to 33.5 mm within 1 year. Identification of arteria lusoria using computed tomography suggested the presence of a right nonrecurrent laryngeal nerve (RNRLN). Endoscopic thyroidectomy was performed under general anesthesia. The right vagal nerve was first identified between the common carotid artery and jugular vein. A positive response was confirmed via intraoperative neuromonitoring (IONM), implying that the RNRLN did not branch from the central side of the stimulated point of the vagal nerve. The RNRLN was confirmed using IONM around the middle to lower pole of the right thyroid gland. The right thyroid lobe was successfully removed, with meticulous preservation of the RNRLN. The motion of the vocal cord, examined by an ear-nose-throat doctor postoperatively, was intact. We demonstrated the efficacy of IONM in patients with RNRLN who underwent endoscopic thyroidectomy.

Seroprevalence of SARS-CoV-2 spike IgG antibodies after the second BNT162b2 mRNA vaccine in Japanese kidney transplant recipients.

We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage < 7 years were negatively associated with the rate of anti-SARS-CoV-2 S IgG ≥ 15 U/mL in KT recipients. ABO blood type incompatible KT was not significantly associated with seroprevalence. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.

Two-year outcomes of low-exposure extended-release tacrolimus and mycophenolate mofetil regimen in de novo kidney transplantation: A multi-center randomized controlled trial.

BACKGROUND: Once-daily extended-release tacrolimus (TACER) is commonly administered following kidney transplantation (KTx); however, its optimal dosage remains unknown. METHODS: In this multi-center, randomized controlled trial, 62 living donor KTx recipients were assigned to either standard-exposure (SE; n = 32) or low-exposure (LE; n = 30) TACER (Graceptor®, Astellas Pharm Inc.) groups. All patients received basiliximab and mycophenolate mofetil (MMF). The primary outcomes were acute rejection, graft/patient survival, and the secondary outcomes were incidence of cytomegalovirus infection, and de novo donor-specific antibodies (dnDSA) production. RESULTS: The tacrolimus trough level and estimated area under the blood concentration-time curve (eAUC) were significantly higher in SE than in LE (SE vs. LE; 1 year: 5.0 ± 0.9 ng/ml and 206.9 ± 26.8 ng h/ml vs. 3.4 ± 1.0 ng/ml and 153.9 ± 26.4 ng h/ml; 2 years: 4.8 ± 1.0 ng/ml and 204.9 ± 30.1 ng h/ml vs. 3.8 ± 0.9 ng/ml and 164.4 ± 27.0 ng h/ml). In contrast, the dosage and eAUC of MMF did not differ between groups. Two-year graft and patient survival rates were 100% in both groups, and acute rejection rates were 0% and 10% in the SE and LE, respectively (p = 0.11). The mean estimated glomerular filtration rates did not differ between the groups. Cytomegalovirus infection was slightly lower in the LE (SE: 12.5% and LE: 6.7%, p = 0.37). In the LE, four cases of dnDSA were noted within 2 years of transplantation; no case was observed in the SE (p = 0.034). CONCLUSIONS: Although the LE TACER regimen showed similar rates of acute rejection, as well as graft and patient survival compared with SE after KTx, LE was significantly more associated with dnDSA. Further investigation of its long-term effect on graft survival is warranted. (University Hospital Medical Information Network Clinical Trials Registry ID: UMIN000033089).

Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation.

AIM: Bacterial and fungal infections are serious, life-threatening conditions after kidney transplantation. The development of oral/oesophageal candidiasis after kidney transplantation is not a reported risk factor for subsequent severe infection. This study was performed to investigate the relationship between oral/oesophageal candidiasis after kidney transplantation and the development of subsequent infection requiring hospitalization. METHODS: This retrospective study included 522 consecutive patients who underwent kidney transplantation at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 1 January 2010 to 1 February 2019. Ninety-five percentage of patients were living donor transplant recipients. Visual examination was performed to detect oral candidiasis, beginning immediately after kidney transplantation; upper gastrointestinal endoscopy was performed 8-10 months after kidney transplantation. Twenty-five patients developed candidiasis (Candida-onset group) and 497 did not (non-Candida-onset group). The follow-up periods were 67 (37-86) months in the Candida-onset group and 55 (34-89) months in the non-Candida-onset group. Severe infection was defined as bacterial or fungal infection requiring hospitalization; viral infections were excluded. RESULTS: Severe infection developed in 9/25 (36%) patients in the Candida-onset group and in 77/497 (15%) patients in the non-Candida-onset group (p = .006). Binomial logistic analysis revealed that Candida infection (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.06-6.06; p = .037) and use of rituximab (OR 1.81, 95% CI 1.12-2.93; p = .016) were significant predictors of subsequent severe infection. CONCLUSION: Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation and suggests an over-immunosuppressive state, which should prompt evaluation of immunosuppression.

Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial.

Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post-transplant, we randomized 193 patients to an 11-month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25-hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between-group difference of -15%; 95% confidence interval [CI] -25 to -3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (pint < 0.05). The percent change in lumbar spine (LS) BMD from before KTx to 12 months post-transplant was -0.2% (95% CI -1.4 to 0.9) in the cholecalciferol group and -1.9% (95% CI -3.0 to -0.8) in the placebo group, with a significant between-group difference (1.7%; 95% CI 0.1 to 3.3). The beneficial effect of cholecalciferol on LS BMD was prominent in patients with low bone mass pint < 0.05). Changes in serum calcium, phosphate, bone metabolic markers, and BMD at the distal radius were not different between groups. In mediation analyses, change in whole PTH levels explained 39% of treatment effects on BMD change. In conclusion, 4000 IU/d cholecalciferol significantly reduced PTH levels and attenuated LS BMD loss after KTx. This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).