Low skeletal muscle mass index is independently associated with low bone mineral density in kidney transplant recipients: a retrospective observational cohort study.

BACKGROUND: Osteoporosis and osteopenia are more frequent in patients who have received kidney transplants than in healthy individuals. Although osteoporosis and sarcopenia are closely related, only few studies have considered them in the post-transplantation period. We aimed to investigate the relationship between lower bone mineral density and skeletal muscle in kidney transplant recipients. METHODS: We included 371 patients in the maintenance phase of kidney transplantation (> 6 months after transplantation) followed-up at our institution from January to December 2019. The primary endpoint was the association between bone mineral density and skeletal muscle mass index. As secondary endpoints, in addition to skeletal muscle mass index, we investigated other factors associated with low bone mineral density, including kidney function and 25-hydroxy vitamin D (25(OH)D) concentration. Considering the possibility that factors affecting bone mineral density differ between men and women, we explored these factors separately for both sexes. RESULTS: Of the 371 participants, 243 (65.4%) were men. The median age and time after transplantation were 52 and 14 years, respectively. Univariate analysis showed that age, female sex, time since transplantation, cystatin C-based estimated glomerular filtration rate (eGFRcysC), 25(OH)D, and skeletal muscle mass index were associated with bone mineral density. Multivariate analysis showed associations of bone mineral density with eGFRcysC, 25(OH)D, and skeletal muscle mass index. Multivariate analysis by sex showed significant associations with eGFRcysC, hemoglobin, and skeletal muscle mass index in men and with age, eGFRcysC, albumin, and skeletal muscle mass index in women. Bone mineral density was not associated with history of dialysis prior to transplantation or time since transplantation. CONCLUSIONS: In kidney transplant recipients, an independent association between lower bone mineral density and skeletal muscle mass index was observed in both sexes.

Association between Serum 25-Hydroxyvitamin D Levels and Sarcopenia in Patients Undergoing Chronic Haemodialysis.

INTRODUCTION: Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis. METHODS: Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy. RESULTS: Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (ß = 0.145, p = 0.046, and ß = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007). CONCLUSION: Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.

Impact of an angulated aorto-septal relationship on cardio-cerebrovascular outcomes in patients undergoing hemodialysis.

Aortic and valvular calcification are well-known risk factors for cardio-cerebrovascular events in patients undergoing hemodialysis. We investigated the clinical impact of an angulated aorto-septal angle as a result of aortic elongation due to aortic calcification on cardio-cerebrovascular outcomes in patients undergoing hemodialysis. We investigated 306 patients (mean age 65.4 years, 68% male) who underwent pre-scheduled routine echocardiography between April and September 2018. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was quantified. We determined aortic and mitral valve calcification scores based on calcified cardiac changes; the aortic and mitral valve scores ranged between 0-9 and 0-6, respectively. The primary endpoint was a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The mean duration of dialysis among the patients in this analysis was 9.6 years. The primary endpoint was observed in 54 patients during the observational period (median 1095 days). Multivariable Cox proportional hazards analyses identified left ventricular ejection fraction (per 10% increase: hazard ratio [HR] 0.67; 95% confidential interval [CI] 0.53-0.84, P = 0.001), left ventricular mass index (per 10 g/m2 increase: HR 1.14; 95% CI 1.05-1.24, P = 0.001), ASA (per 10 degree increase: HR 0.69; 95% CI 0.54-0.88; P = 0.003), and aortic valve calcification score (HR 1.15; 95% CI 1.04-1.26, P = 0.005) as independent determinants of the primary endpoint. Kaplan-Meier analysis showed a higher incidence of the primary endpoint in patients with ASA <119.4 degrees than those with ASA ≥119.4 degrees (Log-rank P < 0.001). An angulated aorto-septal angle is an independent risk factor for cardio-cerebrovascular events and cardio-cerebrovascular death in patients undergoing hemodialysis.

Coexistence of Low Muscle Mass and Osteoporosis as a Predictor of Fragility Fractures in Long-Term Kidney Transplant Recipients.

INTRODUCTION: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. METHODS: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. RESULTS: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94-3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96-3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29-6.49; p = 0.010) than those without both LMM and osteoporosis. CONCLUSION: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.

The Impact of Liver Chemistries on Respiratory Failure among Hemodialysis Patients with COVID-19 during the Omicron Wave.

Objective Although the coronavirus disease 2019 (COVID-19) Omicron variant causes less severe symptoms than previous variants, early indicators for respiratory failure are needed in hemodialysis patients, who have a higher mortality rate than the general population. Liver chemistries are known to reflect the severity of COVID-19 in the general population. This study explored the early indicators for worsened respiratory failure based on patient characteristics, including liver chemistries. Methods This retrospective study included 117 patients admitted for COVID-19 during the Omicron wave. Respiratory failure was defined as oxygen requirement during treatment. Information on the symptoms and clinical characteristics, including liver chemistries [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], at admission was collected. Results Thirty-five patients (29.9%) required oxygen supply during treatment. In the multivariate logistic regression analyses, AST [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.00-1.13, p=0.029], ALT (OR 1.09, 95% CI 1.02-1.18, p=0.009), and moderate COVID-19 illness (Model including AST, OR 6.95, 95% CI 2.23-23.17, p<0.001; Model including ALT, OR 7.19, 95% CI 2.21-25.22, p=0.001) were independent predictors for respiratory failure. Based on the cutoff values determined by the receiver operating characteristic curve, higher AST (≥23 IU/L) and ALT levels (≥14 IU/L) were also independently associated with respiratory failure (higher AST: 64.3% vs. 18.8%, OR 3.44, 95% CI 1.08-11.10, p=0.035; higher ALT: 48.8% vs. 19.7%, OR 4.23, 95% CI 1.34-14.52, p=0.013, respectively). Conclusion The measurement of AST and ALT levels at baseline may help predict oxygen requirement in hemodialysis patients with COVID-19.

Non-A Blood Type Is a Risk Factor for Poor Cardio-Cerebrovascular Outcomes in Patients Undergoing Dialysis.

The clinical impact of ABO blood type on cardio-cerebrovascular outcomes in patients undergoing dialysis has not been clarified. A total of 365 hemodialysis patients participated in the current study. The primary endpoint was defined as a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The primary endpoint was observed in 73 patients during a median follow-up period of 1182 days, including 16/149 (11%) with blood type A, 22/81 (27%) with blood type B, 26/99 (26%) with blood type O, and 9/36 (25%) with blood type AB. At baseline, no difference was found in the echocardiographic parameters. Multivariable Cox regression analyses revealed that blood type (type A vs. non-A type; hazard ratio (HR): 0.46, 95% confidence interval (95% CI): 0.26-0.81, p = 0.007), age (per 10-year increase; HR: 1.47, 95% CI: 1.18-1.84), antiplatelet or anticoagulation therapy (HR: 1.91, 95% CI: 1.07-3.41), LVEF (per 10% increase; HR: 0.78, 95% CI: 0.63-0.96), and LV mass index (per 10 g/m2 increase; HR: 1.07, 95% CI: 1.01-1.13) were the independent determinants of the primary endpoint. Kaplan-Meier curves also showed a higher incidence of the primary endpoint in the non-A type than type A (Log-rank p = 0.001). Dialysis patients with blood type A developed cardio-cerebrovascular events more frequently than non-A type patients.

Serological and histopathological assessment of galactose-deficient immunoglobulin A1 deposition in kidney allografts: A multicenter prospective observational study.

BACKGROUND: Recurrent immunoglobulin A (IgA) nephropathy is an important risk factor for kidney allograft loss. However, there is no classification system for IgA deposition in kidney allografts based on serological and histopathological evaluation of galactose-deficient IgA1 (Gd-IgA1). This study aimed to establish a classification system for IgA deposition in kidney allografts based on serological and histological evaluation of Gd-IgA1. METHODS: This multicenter prospective study included 106 adult kidney transplant recipients in whom an allograft biopsy was performed. Serum and urinary Gd-IgA1 levels were investigated in 46 transplant recipients who were IgA-positive and classified into four subgroups according to the presence or absence of mesangial Gd-IgA1 (KM55 antibody) deposits and C3. RESULTS: Minor histological changes without an acute lesion were observed in recipients with IgA deposition. Fourteen (30%) of the 46 IgA-positive recipients were KM55-positive and 18 (39%) were C3-positive. The C3 positivity rate was higher in the KM55-positive group. Serum and urinary Gd-IgA1 levels were significantly higher in KM55-positive/C3-positive recipients than in the other three groups with IgA deposition. Disappearance of IgA deposits was confirmed in 10 of 15 IgA-positive recipients in whom a further allograft biopsy was performed. The serum Gd-IgA1 level at the time of enrollment was significantly higher in recipients in whom IgA deposition continued than in those in whom it disappeared (p = 0.02). CONCLUSIONS: The population with IgA deposition after kidney transplantation is serologically and pathologically heterogeneous. Serological and histological assessment of Gd-IgA1 is useful for identifying cases that should be carefully observed.

Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis.

BACKGROUND: Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS: This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS: Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS: The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

CMV specific T cell immune response in hepatitis C negative kidney transplant recipients receiving transplant from hepatitis C viremic donors and hepatitis C aviremic donors.

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521-2.623; for CD4+: HR = 1.208, 95%CI: 0.543-2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458-2.507; for CD4+: HR = 1.210, 95%CI: 0.526-2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort.

Lateral spine dual-energy X-ray absorptiometry and the risk of fragility fractures in long-term kidney graft recipients.

BACKGROUND: Although the prevalence of osteoporosis and fractures in the first 6-12 months post-renal transplantation is high, little is known about the utility of bone mineral density (BMD) to predict fractures in long-term kidney graft recipients. Lateral spine dual-energy X-ray absorptiometry (DXA) scanning is a reliable tool for measuring glucocorticoid-induced and age-related bone loss in the elderly population. However, little is known about the utility of lateral spine DXA for patients with chronic kidney diseases. This study aimed to analyze the utility of lateral spine BMD for fragility fractures in long-term kidney graft recipients. METHODS: A total of 357 stable kidney transplant recipients for a minimum of 1 year after kidney transplantation underwent DXA measurements at several sites, including the lateral spine between January 2017 and December 2018. We collected data on new incident fractures from the patients' medical records. RESULTS: The median post-transplantation time at baseline DXA measurement was 12.6 years. During the median follow-up period of 3.5 years, 41 (11.4%) fractures occurred. The lateral spine BMDs were independently associated with fractures (adjusted hazard ratio 0.076; 95% confidence interval 0.012-0.42, p = 0.003). The cumulative incidence rate of fractures was significantly higher in the lower lateral spine BMD group (< 0.471 g/cm2, optimal cut-off value by receiver operating characteristic curve) than in the higher lateral spine BMD group (23.4 vs. 7.4%, adjusted hazard ratio 4.92; 95% confidence interval 2.33-10.74, p < 0.001). CONCLUSION: Lateral lumbar spine BMD can be used to predict the risk of fragility fractures in long-term kidney graft recipients.

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).

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).

Association between ezetimibe usage and hepatitis C RNA levels in uninfected kidney transplant recipients who received hepatitis C infected kidneys.

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.

The effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study.

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single-center randomized, double-blind, placebo-controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1-month posttransplant. The primary endpoint was the change in eGFR from baseline to 12-month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12-month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m2 (95% CI; -0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m2 (95% CI, -0.02 to 3.7) in the placebo group, with no significant between-group difference (-0.7 mL/min/1.73 m2 [95% CI; -3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR <45 mL/min/1.73 m2 (Pinteraction <0.05, between-group difference; -4.3 mL/min/1.73 m2 [95% CI; -7.3 to -1.3]). The degree of IFTA, changes in urine albumin-to-creatinine ratio, or adverse events including hypercalcemia and infections requiring hospitalization did not differ between groups. In conclusion, cholecalciferol supplementation did not affect eGFR change compared to placebo among incident KTRs. These findings do not support cholecalciferol supplementation for improving allograft function in incident KTRs. Clinical trial registry: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000020597 (please refer to the links below). UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023776.

The importance of kidney volume as a marker in the assessment of living-donor kidney transplantation in Japan.

BACKGROUND: In living kidney transplantation, predicting the risk of end-stage kidney disease in the organ donors though crucial remains to be resolved. Thus, any useful biomarker to predict kidney outcome would be highly desirable to safeguard donors. METHODS: This retrospective study was conducted at Nagoya Daini Red Cross Hospital to confirm whether an increase in preserved kidney volume (PKV) was a predict marker of proteinuria. A change of PKV before and 1 year after kidney donation was measured, and its association with proteinuria 3 years after the donation was analyzed. RESULTS: A total of 119 kidney donors who met the Japanese donor guideline were enrolled. The mean age was 57.4 years, 46.2% were male. The mean values of the variables before kidney donation (baseline) were: BMI levels: 23.4 kg/m2, BSA-adjusted PKV: 132.9 cm3/1.73 m2, and estimated glomerular filtration rate (eGFRave): 82.9 mL/min/1.73 m2. A positive correlation was noted between BSA-adjusted PKV and eGFRave (r = 0.61, p < 0.001). BSA-adjusted PKV increased by 19.5% 1 year after donation, and the median urine protein was 0.04 g/gCre. Linear regression analyses showed that change of PKV and BSA-adjusted PKV before the donation were significantly associated with proteinuria 3 years after donation. CONCLUSION: Change of PKV and BSA-adjusted PKV before donation is important factors for proteinuria after donation under the Japanese donor guidelines. Further studies are needed to confirm whether these factors are associated with renal survival after donation.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes.

RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

A Case of Recurrent Atypical Anti-Glomerular Basement Membrane Nephritis Suspicion after Renal Transplantation.

Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM antibody but show linear glomerular basement membrane staining for immunoglobulin. We present a 69-year-old man who underwent a living-donor kidney transplant. The aetiology of the renal failure was a focal segmental glomerulonephritis-like lesion resistant to immunosuppressive therapy. A renal graft biopsy revealed diffuse endocapillary hypercellularity, and mild mesangiolysis with linear GBM staining for IgG. The patient was diagnosed with atypical anti-GBM nephritis since the patient tested negative for circulating anti-GBM antibodies. Treatment involved intravenous methylprednisolone, plasma exchange, and rituximab administration. Protocol graft biopsy performed 1 year after the renal transplant showed a focal segmental glomerulonephritis-like lesion possibly progressing from endocapillary hypercellularity and mesangiolysis. These findings were similar to his native kidney biopsy findings. Although classical recurrent anti-GBM nephritis is rare when a renal transplant is performed after decreased disease activity, this case was considered as a case of recurrent atypical anti-GBM nephritis after renal transplant.

Donor hepatitis C antibody positivity misclassifies kidney donor profile index in non-hepatitis C-infected donors: time to revise the kidney donor profile index - a retrospective cohort study.

The kidney donor profile index (KDPI) defines an hepatitis C (HCV) positive donor based on HCV antibody (Ab) and/or nucleic acid amplification test (NAT) positivity, with donors who are not actively infected (Ab+/NAT-) also classified as HCV positive. From Scientific Registry of Transplant Recipients dataset, we identified HCV-negative recipients, who received a kidney transplant from HCV Ab+/NAT- (n = 116) and HCV Ab-/NAT- (n = 25 574) donor kidneys. We then compared recipients' estimated glomerular filtration rate (eGFR) at 6 months in matched cohorts, using combined exact matching (based on KDPI) and propensity score matching. We created two separate matched cohorts: for the first cohort, we used the allocation KDPI, while for the second cohort we used an optimal KDPI, where the HCV component of KDPI was considered negative in Ab+/NAT- patients. The mean ± SD age of the allocation KDPI-matched cohort at baseline was 59 ± 10 years, 69% were male, 61% were white. Recipients' eGFR at 6 months after transplantation was significantly higher in the HCV Ab+/NAT- group compared to the HCV Ab-/NAT- group (61.1 ± 17.9 vs. 55.6 ± 18.8 ml/min/1.73 m2 , P = 0.011) in the allocation KDPI-matched cohort, while it was similar (61.8 ± 19.5 vs. 62.1 ± 20.1 ml/min/1.73 m2 , P = 0.9) in the optimal KDPI-matched cohort. Recipients who received HCV Ab positive, but NAT-negative donor kidneys did not experience worse 6-month eGFR than correctly matched HCV Ab-/NAT- recipients.

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.