Prediction of acute rejection in renal allografts using shear-wave dispersion slope.

OBJECTIVES: To evaluate the role of shear-wave dispersion slope for predicting renal allograft dysfunction. METHODS: We retrospectively reviewed 128 kidney transplant recipients (median age, 55 years [interquartile range, 43-62 years]; male, 68) who underwent biopsy for allograft evaluation from November 2022 to February 2023. Cortex and renal sinus fat stiffness and shear-wave dispersion slope were obtained at shear-wave elastography (SWE). Cortex-to-sinus stiffness ratio (SR) and dispersion slope ratio (DSR)-related clinical and pathologic factors were evaluated using multivariable linear regression analysis. We conducted univariate and multivariate analyses for multiparametric ultrasound (US) parameters for identifying acute rejection and calculated the area under the receiver operating curve (AUC) values. RESULTS: Of 128 patients, 31 (24.2%) demonstrated acute rejection. The SR value did not differ between patient groups (1.21 vs. 1.20, p = 0.47). Patients with acute rejection demonstrated a higher DSR than those without rejection (1.4 vs. 1.21, p < 0.01). Interstitial fibrosis and tubular atrophy grade (IFTA; coefficient, 0.11/grade; p = 0.04) and renal transplant and biopsy interval (coefficient, 0.00007/day; p = 0.03) were SR determinant factors, whereas only IFTA grade (coefficient, 0.10/grade; p = 0.01) for DSR. Multivariate analysis revealed mean resistive index (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02-1.14, p = 0.01) and DSR value (OR 16.0, 95% CI 3.0-85.8, p = 0.001) as independent factors for predicting acute rejection. An AUC of 0.74 for detecting acute rejection was achieved by combining the resistive index and DSR value. CONCLUSION: Shear-wave dispersion slope obtained at SWE may help identify renal allograft dysfunction. CLINICAL RELEVANCE STATEMENT: Acute rejection in renal allografts is a major cause of allograft failure, but noninvasive diagnosis is a challenge. Shear-wave dispersion slope can identify acute rejection non-invasively. KEY POINTS: • The interstitial fibrosis and tubular atrophy grade was a determinant factor for stiffness ratio and shear-wave dispersion slope ratio between cortex and renal sinus fat. • Shear-wave dispersion slope ratio between cortex and renal sinus fat could identify acute rejection in renal allografts. • A shear-wave dispersion slope has a potential to reduce unnecessary renal biopsy for evaluating renal allografts.

Clinical course of post-kidney transplant Schimke immuno-osseous dysplasia.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare systemic disease characterized by short stature, proteinuria, and recurrent infections. Patients usually have spondyloepiphyseal dysplasia, and progressive steroid-resistant nephropathy that leads to kidney failure. However, their clinical course after kidney transplantation (KT) is not yet well known. Here, we present our experience with cases of SIOD treated at our institute. CASE PRESENTATION: Since 2014, three children have been diagnosed with nephropathy resulting from SIOD. They presented with proteinuria in the nephrotic range at 7, 5, and 3 years of age. Focal segmental glomerulosclerosis was confirmed and progressed to kidney failure approximately 2 years after proteinuria was detected. These patients underwent living-donor KT from their parents. After KT, Case 1 lost his graft within 7 months due to multi-organ failure caused by disseminated adenovirus infection and died. Case 2 experienced graft failure 5 years after KT due to acute rejection from poor compliance. In Case 3, the allograft was still functioning 6 years after KT with low-dose tacrolimus single medication (trough level < 5 ng/mL). Extra-renal manifestations progressed regardless of KT, namely, right renal vein thrombosis and pulmonary hypertension in Case 1, severe bilateral hip dysplasia and Moyamoya syndrome in Case 2, and neutropenia and thrombocytopenia in Case 3, in addition to recurrent infection. CONCLUSION: In SIOD patients, KT is complicated with recurrent infections due to their inherent immune dysfunction. Additionally, extra-renal symptoms may render the patients morbid despite the recovery of kidney function.

Clinical Significances of Anti-Collagen Type I and Type III Antibodies in Antibody-Mediated Rejection.

It is important to determine the clinical significance of non-human leukocyte antigen (HLA) antibodies and their association with antibody-mediated rejection (ABMR) of kidney allografts. We collected post-transplant sera from 68 ABMR patients, 67 T-cell mediated rejection (TCMR) patients, and 83 control subjects without rejection, and determined the titers of 39 non-HLA antibodies including antibodies for angiotensin II receptor type I and MICA. We compared all these non-HLA antibody titers among the study groups. Then, we investigated their association with the risk of death-censored graft failure in ABMR cases. Among the antibodies evaluated, anti-collagen type I (p = 0.001) and type III (p < 0.001) antibody titers were significantly higher in ABMR cases than in both TCMR cases and no-rejection controls. Both anti-collagen type I [per 1 standard deviation (SD), adjusted odds ratio (OR), 11.72 (2.73-76.30)] and type III [per 1 SD, adjusted OR, 6.22 (1.91-31.75)] antibodies were significantly associated with the presence of ABMR. Among ABMR cases, a higher level of anti-collagen type I [per 1 SD, adjusted hazard ratio (HR), 1.90 (1.32-2.75)] or type III per 1 SD, [adjusted HR, 1.57 (1.15-2.16)] antibody was associated with a higher risk of death-censored graft failure. In conclusion, post-transplant anti-collagen type I and type III antibodies may be novel non-HLA antibodies related to ABMR of kidney allografts.

Dominant predictors of early post-transplant outcomes based on the Korean Organ Transplantation Registry (KOTRY).

Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.

Deep Learning-Based Quantification of Visceral Fat Volumes Predicts Posttransplant Diabetes Mellitus in Kidney Transplant Recipients.

Background: Because obesity is associated with the risk of posttransplant diabetes mellitus (PTDM), the precise estimation of visceral fat mass before transplantation may be helpful. Herein, we addressed whether a deep-learning based volumetric fat quantification on pretransplant computed tomographic images predicted the risk of PTDM more precisely than body mass index (BMI). Methods: We retrospectively included a total of 718 nondiabetic kidney recipients who underwent pretransplant abdominal computed tomography. The 2D (waist) and 3D (waist or abdominal) volumes of visceral, subcutaneous, and total fat masses were automatically quantified using the deep neural network. The predictability of the PTDM risk was estimated using a multivariate Cox model and compared among the fat parameters using the areas under the receiver operating characteristic curves (AUROCs). Results: PTDM occurred in 179 patients (24.9%) during the median follow-up period of 5 years (interquartile range, 2.5-8.6 years). All the fat parameters predicted the risk of PTDM, but the visceral and total fat volumes from 2D and 3D evaluations had higher AUROC values than BMI did, and the best predictor of PTDM was the 3D abdominal visceral fat volumes [AUROC, 0.688 (0.636-0.741)]. The addition of the 3D abdominal VF volume to the model with clinical risk factors increased the predictability of PTDM, but BMI did not. Conclusions: A deep-learning based quantification of visceral fat volumes on computed tomographic images better predicts the risk of PTDM after kidney transplantation than BMI.

Presence of a survival benefit of HLA-incompatible living donor kidney transplantation compared to waiting or HLA-compatible deceased donor kidney transplantation with a long waiting time.

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.

Klotho as a potential predictor of deceased donor kidney transplantation outcomes.

PURPOSE: Klotho is an antiaging factor mainly produced by renal tubular cells. Klotho is reportedly decreased in an animal model of acute kidney injury and patients with chronic kidney disease. However, information on Klotho expression after kidney transplantation is limited. We analyzed the correlation between donor Klotho expression and clinical outcomes of kidney transplantation. METHODS: Sixty patients who underwent deceased donor kidney transplantation between March 2015 and October 2017 were enrolled. Serum and tissue Klotho expression levels were measured by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Graft function was assessed by estimated glomerular filtration rate (eGFR). RESULTS: Patients were divided into 2 groups according to donor Klotho expression in renal tissues. A greater improvement in eGFR was observed at 1 week after transplantation in patients receiving kidneys with higher Klotho expression (47.5 ± 21.9 mL/min/1.73 m2 vs. 63.9 ± 28.2 mL/min/1.73 m2, P = 0.030). Patients were also classified into 2 groups according to donor serum Klotho level. There was a tendency for a higher eGFR at 12 months after transplantation in patients receiving kidneys from donors with a higher Klotho level (51.0 ± 18.0 mL/min/1.73 m2 vs. 61.2 ± 16.5 mL/min/1.73 m2, P = 0.059). When subgrouped into patients with or without biopsy-proven acute rejection, 12-month eGFR remained higher in patients receiving kidneys from donors with higher serum Klotho. CONCLUSION: Our data demonstrated that donor tissue expression of Klotho correlated with early recovery of eGFR after kidney transplantation. Donor serum Klotho level tended to be associated with posttransplant 12-month eGFR. Donor Klotho expression might be a new predictor for deceased donor kidney transplantation outcome.

Risk of Graft Failure in Kidney Recipients with Cured Post-Transplant Cancer.

BACKGROUND: Post-transplant cancer (PTC) is a critical complication after kidney transplantation. However, whether successfully cured PTC affects the long-term graft outcome remains unclear. METHODS: We retrospectively reviewed 1,629 kidney transplant recipients from 1995 to 2017 after excluding patients with post-transplant hematologic or advanced non-curable cancers and who underwent allograft nephrectomy because of cancer. Cured PTCs were defined as cancers treated with curative methods and/or adjuvant therapy without recurrence during ≥ 2 years. Propensity score matching was performed to match cured PTC patients with cancer-naïve patients (i.e., non-PTC group). RESULTS: During the median period of 7 years (maximum, 23 years), 70 patients (4.3%) had cured PTCs. The PTC group showed significantly higher risks of death-censored graft failure (adjusted hazard ratio [HR], 2.56 [1.05-6.23]), class II donor-specific antibodies (adjusted HRs, 3.37 [1.30-8.71]), estimated glomerular filtration rate < 30 mL/min/1.73 m² (adjusted HR, 2.68 [1.43-5.02]) and random urine protein/creatinine ratio > 1 g (adjusted HR, 3.61 [1.92-6.79]) compared to non-PTC group. However, the risk of mortality was not different between the PTC and non-PTC groups. According to the cancer type, only urogenital cancer had a significant association with graft failure (adjusted HR, 4.26 [1.19-15.22]) and the gastrointestinal cancer showed elevated risk of T cell mediated rejection compared to non-PTC (adjusted HR, 20.44 [6.02-69.39]). CONCLUSION: Appropriate monitoring of graft function is necessary in patients with cured PTCs.

Weaning Immunosuppressant in Patients with Failing Kidney Grafts and The Outcomes: A Single-Center Retrospective Cohort Study.

An immunosuppressant weaning protocol in failing allografts has not yet been established. Maintaining immunosuppressants would preserve residual renal function (RRF) and prevent graft intolerance syndrome and sensitization but would increase the risks of infection and malignancy. In this study, graft failure cases after kidney transplantation in a single center were reviewed retrospectively. The outcome differences in all-cause mortality, infection-related hospitalization, cancer, graft intolerance syndrome, re-transplantation, and RRF duration between the immunosuppressant maintaining and weaning groups 6 months after graft failure were compared. Among the weaning group, the outcome differences according to low-dose steroid use were also compared at 6 and 12 months. In a total of 131 graft failure cases, 18 mortalities, 42 infection-related hospitalizations, 22 cancer cases, 11 graft intolerance syndrome cases, and 28 re-transplantations occurred during the 94-month follow-up. Immunosuppressant maintenance significantly decreased the patient survival rate 6 months after graft failure compared with weaning (log-rank P = 0.008) and was an independent risk factor for mortality, even after adjustments (hazard ratio, 3.01; P = 0.025). Infection-related hospitalization, graft intolerance syndrome development, and re-transplantation were not affected by the immunosuppressant weaning protocol. Among the immunosuppressant weaning group, low-dose steroid maintenance at 6 and 12 months helped preserved RRF (P = 0.008 and P = 0.003, respectively).

Author Correction: Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Erratum: Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia.

This corrects the article on e203 in vol. 34, PMID: 31373185.

Recurrent parvovirus B19 infection-associated pure red cell aplasia in a kidney transplant patient.

Posttransplant anemia is a common complication after kidney transplantation. Parvovirus B19 (PVB19) infection can induce pure red cell aplasia (PRCA) in immunosuppressed transplant patients. We herein report a case of recurrent PVB19-associated PRCA in a kidney transplant patient. A 49-year-old woman presented with anemia and normal renal function 1 year after a deceased-donor kidney transplantation for immunoglobulin A nephropathy-related end-stage renal disease. She received desensitization therapy, and 2 years later, she underwent transplantation with thymoglobulin induction. Despite repeated red cell transfusion and erythropoietin therapy, her anemia aggravated progressively. Bone marrow biopsy revealed normocytic normochromic PRCA. Real-time polymerase chain reaction detected a high plasma load of PVB19. Administration of intravenous immunoglobulin (IVIG) at 2 g/kg with adjuvant reduction of tacrolimus and discontinuation of myfortic acid effectively treated the anemia. However, the PVB19 load remained high, and PRCA recurred 7 months after the initial IVIG treatment. Tacrolimus was switched to cyclosporine in the second IVIG treatment, which successfully improved PRCA and reduced the PVB19 load. Our case suggested that PVB19-associated PRCA should be suspected when persistent anemia is observed in kidney transplant patients with heavy immunosuppression and that PVB19-associated PRCA can recur in the presence of persistent PVB19 viremia.

Long-term Mortality Risks Among Living Kidney Donors in Korea.

RATIONALE & OBJECTIVE: Living kidney donors may have a higher risk for death and kidney failure. This study aimed to investigate the long-term mortality experience of living kidney donors compared with members of the general public in Korea who underwent voluntary health examinations. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: We first calculated standardized mortality ratios for 1,292 Korean living kidney donors who underwent donor nephrectomy between 1982 and 2016 and 72,286 individuals who underwent voluntary health examinations between 1995 and 2016. Next we compared survival between the 1,292 living kidney donors and a subgroup of the health examination population (n=33,805) who had no evident contraindications to living kidney donation at the time of their examinations. Last, a matched comparator group was created from the health examination population without apparent contraindication to donation by matching 4,387 of them to donors (n=1,237) on age, sex, body mass index, estimated glomerular filtration rate, urine dipstick albumin excretion, previously diagnosed hypertension and diabetes, and era. EXPOSURES: Donor nephrectomy. OUTCOMES: All-cause mortality and other clinical outcomes after kidney donation. ANALYTICAL APPROACH: First, standardized mortality ratios were calculated separately for living kidney donors and the health examination population standardized to the general population. Second, we used Cox regression analysis to compare mortality between living kidney donors versus the subgroup of the health examination population without evident donation contraindications. Third, we used Cox regression analysis to compare mortality between living kidney donors and matched comparators from the health examination population without apparent contraindication to donation. RESULTS: The living kidney donors and health examination population had excellent survival rates compared with the general population. 52 (4.0%) of 1,292 kidney donors died during a mean follow-up of 12.3±8.1 years and 1,072 (3.2%) of 33,805 in the health examiner subgroup without donation contraindications died during a mean follow-up of 11.4±6.1 years. Donor nephrectomy did not elevate the hazard for mortality after multivariable adjustment in kidney donors and the 33,805 comparators (adjusted HR, 1.01; 95% CI, 0.71-1.44; P=0.9). Moreover, living donors showed a similar mortality rate compared with the group of matched healthy comparators. LIMITATIONS: Donors from a single transplantation center. Residual confounding owing to the observational study design. CONCLUSIONS: Kidney donors experienced long-term rates of death comparable to nondonor comparators with similar health status.

Mobile medication manager application to improve adherence with immunosuppressive therapy in renal transplant recipients: A randomized controlled trial.

BACKGROUND: Nonadherence to immunosuppressive therapy after renal transplantation is associated with poor graft outcomes. We aimed to evaluate whether the use of the Adhere4U mobile medication manager application could improve adherence among renal transplant recipients ≥1 year posttransplantation. Adhere4U can provide medication reminders, monitor medication use, and provide information on immunosuppressants. METHODS: We conducted a prospective randomized controlled study to compare the rate of nonadherence to index immunosuppressant (tacrolimus or cyclosporine) in a group using the Adhere4U app (mobile group) and in another group receiving conventional care (control group). The primary outcome was the nonadherence rate, which was evaluated using an electronic medication event monitoring system during the 6-month intervention period. Our secondary outcome included self-reported adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) and the visual analog scale (VAS) based on a 4-week recall on days 28, 90, and 180. Longitudinal data of repeated measures of self-rated adherence were analyzed using generalized estimating equations (GEE) to compare the between-group difference in adherence change over time. RESULTS: Between November 2013 and May 2015, 138 renal transplant recipients were randomly allocated to the control (n = 67) or the mobile group (n = 71). The overall nonadherence rate over the 6-month study period by electronic monitoring was 63.6%, with no between-group difference [mobile group, 65.0% (n = 39/60); control group, 62.1% (n = 36/58); odds ratio 1.14; 95% confidence interval 0.53-2.40; p = 0.89]. Self-rated nonadherence assessed using the BAASIS and VAS at baseline was 53.7% and 51.5%, respectively. Although the self-rated nonadherence by BAASIS of the mobile group was lower than the control group throughout the study period, there was no between-group difference in the change of nonadherence over time (χ2 = 2.82, df = 3, p = 0.42 by logistic GEE). There also was no significant between-group difference in the nonadherence by VAS (χ2 = 1.71, df = 3, p = 0.63 by logistic GEE) over time. The main limitation of this study was the low rate of patient engagement with the app among the mobile group. The rate of app use was 47.6% (31/65) at 28 days, 33.9% (19/56) at 90 days, and 11.5% (6/52) at 180 days. CONCLUSIONS: The Adhere4U application did not improve adherence to immunosuppressive therapy. Our evidence is limited by the high rate of attrition. Further studies on strategies to facilitate patient engagement with mobile interventions are warranted.

Possible beneficial association between renin-angiotensin-aldosterone-system blockade usage and graft prognosis in allograft IgA nephropathy: a retrospective cohort study.

BACKGROUND: Although immunoglobulin A nephropathy (IgAN) is associated with an increased risk of renal allograft failure, evidences for its treatment, including renin-angiotensin-aldosterone system blockade (RAASB) usage, remain limited. METHODS: In this bi-center retrospective cohort study, we included patients who were recently diagnosed with IgAN through allograft biopsies. We identified their 6-month antihypertensive medication prescriptions and investigated the association between the medication types, albuminuria changes, and risk of 5-year death-censored-graft-failure (DCGF). The mixed effect model and cox regression analysis were used. RESULTS: A total of 464 allograft IgAN patients were included: 272, 38, 33, and 121 patients in the no antihypertensive medication, single agent RAASB, single agent beta blocker (BB)/calcium channel blocker (CCB), and combination therapy groups, respectively. High-degree albuminuria after 6 months of allograft IgAN diagnosis was an important prognostic parameter and a partial mediator for the association between the subgroups and 5-year DCGF. The usage of single RAASB was associated with decrement of albuminuria from allograft IgAN diagnosis (P for interaction = 0.03). The single BB/CCB group demonstrated significantly worse prognosis than the single RAASB group (adjusted hazard ratio, 2.76 [1.09-6.98]; P = 0.03). CONCLUSIONS: In conclusion, RAASB may be beneficial for graft prognosis in early allograft IgAN patients who require single antihypertensive medication therapy, by means of reducing albuminuria. Further investigation of treatment strategy in allograft IgAN is warranted.

Ratio of triglyceride to high-density lipoprotein cholesterol and risk of major cardiovascular events in kidney transplant recipients.

BACKGROUND: Dyslipidemia is common in kidney transplant (KT) recipients. We analyzed the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) in KT recipients to identify risk factors for major cardiovascular events (MACE). METHODS: We retrospectively included KT recipients with a lipid profile performed 1 year after transplantation. We classified patients according to the TG/HDL-C divided into quintiles. Subsequently, we analyzed the association between TG/HDL-C and MACE, defined as heart failure, coronary artery disease, and cerebrovascular disease confirmed by imaging studies. RESULTS: A total of 1301 KT recipients were enrolled. The median follow-up duration was 7.4 years (interquartile range 4.4-11.1 years). During the follow-up period, 80 (6.2%) patients developed MACE, which included 38 of unstable anginas, 9 of MIs, 19 of heart failures, 18 of cerebral infarcts, and 4 of cerebral hemorrhages. The fourth and fifth quintiles of TG/HDL-C showed a significantly increased risk of MACE [fourth quintile: adjusted hazard ratio (aHR), 3.38; 95% confidence interval (CI) 1.44-7.95; p = 0.005, fifth quintile: aHR, 2.67; 95% CI 1.13-6.30; p = 0.02]) compared to the second quintile of TG/HDL-C. This association is particularly evident in subgroups of non-DM, HTN, no history of CVD, and statin users. CONCLUSIONS: Higher TG/HDL-C levels may be associated with MACE risk in KT recipients.

Post-Transplant Lymphoproliferative Diseases in Pediatric Kidney Allograft Recipients with Epstein-Barr Virus Viremia.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4-47.8) months and 8.2 (range, 2.8-98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.

The Use of Antithrombotics Is Not Beneficial for Conservative Management of Spontaneous Isolated Dissection of the Superior Mesenteric Artery: A Meta-analysis.

BACKGROUND: Conservative treatment is feasible in most patients with spontaneous isolated dissection of the superior mesenteric artery (SID-SMA). However, the role of antiplatelet agents and anticoagulants is not well defined in either symptomatic or asymptomatic SID-SMA. This study aimed to conduct a meta-analysis, including a single-arm study, comparing the resolution rate of conservative management with versus without antithrombotics for symptomatic and asymptomatic SID-SMA. METHODS: A systematic search of electronic databases, including PubMed, EMBASE, and Cochrane Library, on August 22nd, 2018, was performed to identify studies concerning SID-SMA. Meta-analyses were conducted to determine the primary resolution rate, long-term aneurysmal change for symptomatic SID-SMA, and any event for asymptomatic SID-SMA. We calculated pooled risk ratios and 95% confidence intervals (CIs) using random-effects model in studies with two arms and in studies with two arms or a single arm. RESULTS: We included data from 35 articles involving 727 patients with SID-SMA (symptomatic 693, asymptomatic 134). No significant differences were observed in the successful resolution rate between conservative management with and without antithrombotics (random-effects model, risk ratio [RR] 0.96; 95% CI, 0.87-1.05]). The pooled resolution rate from combining single-arm studies was 91% (95% CI, 85-95) and 95% (95% CI, 88-100) in conservative management with and without antithrombotic, respectively, which was not statistically significant (RR, 0.97; 95% CI, 0.91-1.02). The pooled morphologic progression rate from combining single-arm studies was 3% (95% CI, 0-8) and 11% (95% CI, 2-26) in conservative management with and without antithrombotics, respectively, which was not statistically significant (RR, 0.44; 95% CI, 0.12-1.64). The adverse event was 0% for both groups for asymptomatic SID-SMA. CONCLUSIONS: Additional antithrombotic therapy for both symptomatic and asymptomatic SID-SMA did not benefit the outcomes. We do not recommend the use of antithrombotics for SID-SMA, unless further evidence shows any beneficial effect.

Higher Incidence of BK Virus Nephropathy in Pediatric Kidney Allograft Recipients with Alport Syndrome.

A retrospective review was performed to assess the risk factors and outcomes of BK virus infection and nephropathy (BKVN), an early complication in pediatric kidney allograft recipients. The study investigated the incidence, risk factors, and clinical outcomes of BK viremia and BKVN in a Korean population of pediatric patients who received renal transplantation from 2001-2015 at the Seoul National University Hospital. BKVN was defined as biopsy-proven BKVN or plasma BK viral loads >10,000 copies/mL for >3 weeks. BK viremia was defined as a BK viral load >100 copies/mL in blood. Among 168 patients assessed for BK virus status, 30 patients (17.9%) tested positive for BK viremia at a median of 12.6 months after transplantation. BKVN was diagnosed in six patients (3.6%) at a median of 13.4 months after transplantation. Three of the six BKVN patients had Alport syndrome (p = 0.003), despite this disease comprising only 6% of the study population. Every patient with BK viremia and Alport syndrome developed BKVN, while only 11.1% of patients with BK viremia progressed to BKVN in the absence of Alport syndrome. Multivariate analysis revealed that Alport syndrome was associated with BKVN development (hazard ratio 13.2, p = 0.002). BKVN treatment included the reduction of immunosuppression, leflunomide, and intravenous immunoglobulin. No allografts were lost in the two years following the diagnosis of BKVN. In summary, the incidence of BKVN in pediatric kidney allograft recipients was similar to findings in previous reports, but was higher in patients with underlying Alport syndrome.

Timing of referral for vascular access for hemodialysis: Analysis of the current status and the barriers to timely referral.

INTRODUCTION: Current guidelines recommend the placement of vascular access 6 months before the anticipated start of hemodialysis therapy; however, many patients start hemodialysis using a central venous catheter. We investigated the timing of referral for vascular access, the vascular access type at hemodialysis initiation, and the barriers to a timely referral. METHODS: The study involved a retrospective review of 237 patients for whom the first vascular access for hemodialysis was created between January and November 2017. RESULTS: Among the 237 patients, 58.2% were referred before hemodialysis initiation, while 41.8% were referred after hemodialysis initiation. Among the 138 patients, 55, 59, and 24 patients were referred more than 6 months, between 2 and 6 months, and within 2 months before hemodialysis initiation, respectively. Within these subgroups, 3.6%, 10.2%, and 75.0% patients underwent hemodialysis initiation with a central venous catheter, respectively. Among the 99 patients referred after hemodialysis initiation, the reasons for late referral were as follows: unexpected rapid progression of kidney disease (n = 23), noncompliance (n = 21), late visit to the nephrologist (initial visit within 2 months of hemodialysis initiation; n = 14), change of treatment strategy from peritoneal dialysis or transplants (n = 9), and unknown reasons (n = 32). CONCLUSION: Only 23% of patients were referred for vascular access 6 months before the anticipated hemodialysis therapy. In addition, 53% of patients initiated hemodialysis with a central venous catheter. Avoidance of catheter insertion was mostly successful in patients referred 2 months before hemodialysis initiation. The most common modifiable barrier to the timely referral was noncompliance.