Treatment of Chronic Active Antibody-mediated Rejection With Pulse Steroids, IVIG, With or Without Rituximab is Associated With Increased Risk of Pneumonia.

BACKGROUND: The risk of infection associated with specific treatments of chronic active antibody-mediated rejection (cAMR) after kidney transplantation remains unknown. METHODS: This was a single-center study of kidney transplant recipients treated with pulse steroids, intravenous immunoglobulin (IVIG) ± rituximab for biopsy-confirmed cAMR. The control group consisted of age- and race-matched patients who underwent donor-specific antibody-based protocol biopsies but had no rejection. We collected data on BK virus (BKV), cytomegalovirus (CMV), urinary tract infection (UTI), and pneumonia postbiopsy. RESULTS: There were 49 patients in each group. In those with cAMR, 21 (43%) were treated with steroids, IVIG, and rituximab; the remaining received steroids and IVIG only. The risk of graft failure was greater in the cAMR group [22 (45%) vs. 3 (6%), P < 0.001]. Kaplan-Meier analyses demonstrated a significantly greater risk of pneumonia in the cAMR group (P = 0.02). This was confirmed by multivariable Cox regression analyses [Hazard ratio (HR) = 6.04, P = 0.027, 95% CI, 1.22-29.75]. None of the patients with pneumonia were affected by opportunistic pathogens. Additionally, the risk of CMV, UTI, and BKV was not increased. Rituximab was not independently associated with any of the infections studied. CONCLUSIONS: Treatment of cAMR, but not rituximab, was associated with a 6-fold increased risk of pneumonia. Additional studies are needed to determine the safety and efficacy of prolonged antimicrobial prophylaxis and monitoring strategies, including for hypogammaglobulinemia, to reduce the risk of pneumonia following the treatment of cAMR.

GalliForm, a database of Galliformes occurrence records from the Indo-Malay and Palaearctic, 1800-2008.

Historical as well as current species distribution data are needed to track changes in biodiversity. Species distribution data are found in a variety of sources, each of which has its own distinct bias toward certain taxa, time periods or places. We present GalliForm, a database that comprises 186687 galliform occurrence records linked to 118907 localities in Europe and Asia. Records were derived from museums, peer-reviewed and grey literature, unpublished field notes, diaries and correspondence, banding records, atlas records and online birding trip reports. We describe data collection processes, georeferencing methods and quality-control procedures. This database has underpinned several peer-reviewed studies, investigating spatial and temporal bias in biodiversity data, species' geographic range changes and local extirpation patterns. In our rapidly changing world, an understanding of long-term change in species' distributions is key to predicting future impacts of threatening processes such as land use change, over-exploitation of species and climate change. This database, its historical aspect in particular, provides a valuable source of information for further studies in macroecology and biodiversity conservation.

Incidence and Outcomes of Significant Weight Changes After Pancreas Transplant Alone.

BACKGROUND: Weight change, primarily weight gain, is a common problem among solid organ transplant recipients. The incidence of weight gain or loss after successful pancreas transplant alone (PTA) and the effect on graft survival is unknown. METHODS: This was a single-center observational study among PTA recipients, transplanted at our center between January 1, 2005, and July 31, 2017, who had a functional pancreas graft for at least 1 year and documented weight change at the 1-year clinic visit. RESULTS: In this cohort study of 105 PTA recipients, 28 had significant weight gain, 27 had significant weight loss, and the remaining 50 did not have significant weight change at 1-year posttransplant. When comparing the weight gain and no weight change groups, the weight gain cohort started to gain weight at 3 months posttransplant to 5 years or last follow up. Similarly, the weight loss group lost weight at 3 months posttransplant up to last follow up. Clinically significant weight gain or weight loss were not associated with uncensored or death censored graft failure in univariate regression and Kaplan-Meier survival analysis. Also, there were no significant differences between the groups in the glycated hemoglobin at last follow up. CONCLUSIONS: Approximately 50% of PTA recipients had a significant weight change at 1-year posttransplant, of which 25% gained significant weight and 25% loss. There was no significant difference in graft survival due to the significant weight changes. Further research is needed in this field.

Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression.

BACKGROUND: The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy. AIM: To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications. METHODS: In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy. RESULTS: We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy (IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy (TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR (40%), TG (17%), and IFTA (13%). Most grafts failed within two years of post-transplant (36%). Subsequently, approximately 10%-15% of grafts failed every two years: > 2-4 years (16%), > 4-6 years (13%), > 6-8 years (11%), > 8-10 years (9%) and > 10 years (16%). AR was the most common cause of graft failure in the first six years (48%), whereas TG was the most prevalent cause of graft failure after 6 years (32%) of transplant. CONCLUSION: In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

Outcomes of malignant melanoma in kidney transplant recipients
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Kidney transplant recipients (KTRs) have an increased risk of skin cancer. We analyzed the outcomes of KTRs transplanted at our center between January 1, 1994, and December 31, 2015, who reported pretransplant melanoma or had post-transplant de novo melanoma. Of 6,522 kidney or kidney with pancreas transplant recipients, 37 had pretransplant melanoma. After adjustment of multiple variables, pretransplant melanoma was associated with overall increased risk of death (HR: 1.75, 95% CI 1.02 - 3.03, p = 0.04) but not for death-censored graft failure (DCGF). A total of 46 patients developed post-transplant de novo melanoma. After adjustment of multiple variables, post-transplant de novo melanoma was associated with significant risk for death within the first year of the diagnosis of melanoma (HR: 4.40, 95% CI 2.21 - 8.74, p < 0.001), and DCGF after the first year (HR: 1.93, 95% CI 1.13 - 3.64, p = 0.04). Similarly, among all pretransplant candidates (including those with history of melanoma) in Cox regression multivariate analysis, older age (HR: 1.32, 95% CI 0.31 - 1.14, p = 0.04) and a history of pretransplant melanoma (HR: 9.27, 95% CI 2.81 - 30.53, p < 0.001) were significantly associated with the risk for development of post-transplant melanoma. Proper risk stratification and early diagnosis may improve patient and graft survival.

Donor-Specific Antibodies in the Absence of Rejection Are Not a Risk Factor for Allograft Failure.

INTRODUCTION: Donor-specific antibodies (DSAs) are considered an important risk factor for graft injury and failure. However, there is limited information on long-term outcomes for kidney transplant recipients with positive DSAs in the absence of rejection on biopsy. METHODS: We evaluated all patients at the University of Wisconsin who underwent a kidney allograft biopsy between January 1, 2013, and December 31, 2016. All patients with clinical indication or protocol biopsies that were negative for acute rejection and lacked significant acute pathological features were included in the study and divided into 2 groups based on DSAs at the time of biopsy. There were a total of 1102 kidney biopsies during the study period of which 587 fulfilled our selection criteria (DSA+, n = 192, and DSA-, n = 395). The incidence of subsequent rejection and death-censored graft failure (DCGF) were outcomes of interest. RESULTS: There was no difference in acute (i + t + v + c4d + ptc + g = 0 in both groups) or chronic (ci + ct + cv + cg = 2.4 ± 2.2 vs. 2.7 ± 2.4; cg = 0.12 ± 0.48 vs. 0.13 ± 0.48) Banff scores in the index biopsy. Patients were followed for a mean of 33.1 ± 16.8 months. Kaplan-Meier analyses demonstrated a higher incidence of DCGF in DSA- group (n = 83) but this was not observed for subsequent rejection (n = 76). In multivariate Cox regression analyses, the interval from transplant to biopsy, de novo DSA, and younger age remained independently associated with increased risk of subsequent rejection. Notably, there was no association between subsequent rejection or DSA (pretransplant, de novo, persistant, Class I/II, MFIsum, or MFImax) and graft failure. CONCLUSION: This study suggests that in the absence of biopsy-proven rejection and acute inflammation, human leukocyte antigen (HLA) DSAs are not associated with increased risk of graft failure.

Glomerular C3 Deposition Is an Independent Risk Factor for Allograft Failure in Kidney Transplant Recipients With Transplant Glomerulopathy.

INTRODUCTION: Transplant glomerulopathy (TG) becomes increasingly prevalent in kidney transplant recipients over time, and it is strongly associated with allograft failure. To date, our prognostic biomarkers and understanding of the processes of immunologic injury in TG are limited. METHODS: This is a retrospective cohort analysis of kidney transplant recipients with TG (double contours of the glomerular basement membrane as defined by the chronic glomerulopathy score). Glomerular deposition of the complement protein C3 was determined, and its association with allograft survival was analyzed by Cox regression analysis. RESULTS: Of the 111 patients with TG, 72 (65%) had allograft failure, with a median follow-up time of 3 years from biopsy diagnosis of TG. C3-positive compared to C3-negative patients did not differ with respect to cause of end-stage renal disease, induction or maintenance immunosuppression, or sensitization. A greater proportion of patients with glomerular C3 deposition developed allograft failure compared to those with no C3 deposition (78% vs. 55%, P = 0.01). C3 deposition was independently associated with allograft failure in multivariate analyses (adjusted hazard ratio [HR] = 1.38, 95% confidence interval [CI] = 1.13-1.69, P = 0.002). There was no association between C4d or C1q deposition and allograft failure. Chronicity score was also associated with allograft failure in multivariate analysis (adjusted HR 1.26, 95% CI 1.12-1.41, P = 0.0001). CONCLUSION: In this cohort of patients with TG, glomerular C3 deposition was independently associated with a higher risk of allograft failure. These findings identify glomerular C3 as a novel prognostic indicator in patients with TG.

Subclinical Antibody-mediated Rejection After Kidney Transplantation: Treatment Outcomes.

BACKGROUND: Antibody-mediated rejection (AMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical AMR based on the donor-specific antibody (DSA) testing may result in better outcomes. METHODS: We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between March 1, 2013 and December 31, 2016. Patients were divided into 3 groups: clinical AMR (n = 118), subclinical AMR (n = 25), or no rejection on protocol biopsy (controls; n = 77). RESULTS: Both clinical and subclinical AMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (P = ns). Mean follow-up after AMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical AMR groups, respectively (P < 0.001). Graft outcomes were similar in the subclinical rejection and control groups. In adjusted Cox regression analysis, only clinical rejection (hazards ratio [HR], 4.31; 95% confidence interval [CI], 1.01-18.94; P = 0.05) and sum chronicity scores (HR, 1.16; 95% CI, 1.01-1.35; P = 0.03) were associated with increased risk of graft failure, while estimated glomerular filtration rate at time of biopsy (HR, 0.98; 95% CI, 0.96-0.99; P = 0.01) was associated with decreased risk of graft failure. CONCLUSIONS: Our study suggests that early diagnosis and treatment of subclinical AMR using DSA monitoring may improve outcomes after kidney transplantation.

Association of Pre-Transplant Dialysis Modality and Post-Transplant Outcomes: A Meta-Analysis.

♦ BACKGROUND: It remains unclear whether post-transplant outcomes differ according to the pre-transplant dialysis modality (peritoneal dialysis [PD] versus hemodialysis [HD]). We performed a meta-analysis of studies that assessed either post-transplant mortality, graft survival, or delayed graft function (DGF) in both PD and HD patients. ♦ METHODS: Two independent authors searched English-language literature from January 1, 1980, through August 31, 2014, national conference proceedings, and reference lists. We used combinations of terms related to dialysis (hemodialysis, peritoneal dialysis, or renal replacement therapy), kidney transplant, and outcomes. Studies were included if they measured any of the 3 post-transplant study outcomes in both pre-transplant HD and PD. ♦ RESULTS: A total of 16 studies were included in the final analysis. Of these, 6 studies reported adjusted hazard ratio for mortality, pooled adjusted risk ratio: 0.89 (95% confidence interval [CI] 0.82 - 0.97) in favor of PD (p = 0.006). The same 6 studies reported adjusted hazard ratio for graft survival, pooled adjusted risk ratio: 0.97 (95% CI 0.92 - 1.01, p = 0.16). A total of 13 studies reported unadjusted DGF. Pooled odds ratio: 0.5 (95% CI 0.41 - 0.63) in favor of PD (p < 0.005). Significant heterogeneity observed for all outcomes: I2 = 72.7%, I2 = 59.9%, and I2 = 66.8%, respectively. ♦ CONCLUSIONS: Based on these results, pre-transplant PD is associated with better post-transplant survival than HD. Pre-transplant PD was also associated with decreased risk for DGF compared with HD, although these results were unadjusted. There was no significant difference in graft survival between pre-transplant HD and PD. These results suggest that PD may be the preferred dialysis modality for patients expected to receive a transplant.

A Meta-analysis of Stent Placement vs. Angioplasty for Dialysis Vascular Access Stenosis.

Dysfunction of arteriovenous fistulas (AVF) and arteriovenous grafts (AVG) contribute significantly to morbidity and hospitalization in the dialysis population. Despite advances in endovascular techniques, the incidence of vascular access stenosis remains problematic. Currently, the role of endovascular stent placement in the treatment of vascular access stenosis is poorly defined. This meta-analysis compares the primary patency rates of stenotic vascular access treated with stent placement vs. angioplasty. We searched Medline for English language publications from 1980 through December 2013, along with national conference proceedings and reference lists of all included publications. Inclusion criteria were a measure of primary patency, secondary patency, or access dysfunction. Studies were excluded if they were not in English or if they included pediatric patients. Ten studies with a total of 860 subjects met the inclusion criteria, including six experimental studies and four observational studies. There was significantly higher overall primary patency in those receiving stent placement than in those treated with angioplasty (pooled relative risk [RR] = 0.79; 95% confidence interval [CI]: 0.65-0.96). The estimate did not differ by study design. The effect of treatment differed significantly (p = 0.001) by the type of stents used, however. In studies including nitinol stents (six studies, 678 patients), 6-month patency was significantly better for stent placement than angioplasty (pooled RR = 0.67; 95% CI: 0.54-0.84), whereas there was no significant differences between stent placement and angioplasty in those studies using bare metal stents exclusively (four studies, 182 patients; pooled RR = 1.09; 95% CI: 0.91-1.32). There was significant heterogeneity between studies (I(2)  = 70.6%; p < 0.0001). Our results suggest that stent placement may confer an advantage over balloon angioplasty in primary patency of dialysis access stenoses.

The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and elevated plasma homocysteine levels in a U.S. pediatric population with incident thromboembolism.

OBJECTIVE: Elevated plasma homocysteine (tHcy) and the MTHFR c.677C>T variant have been postulated to increase the risk of venous thromboembolism (VTE), although mechanisms and implications to pediatrics remain incompletely understood. The objectives of this study were to determine the prevalences of elevated tHcy and MTHFR variant in a pediatric population with VTE or arterial ischemic stroke (AIS), and to determine associations with thrombus outcomes. STUDY DESIGN: Subjects were enrolled in an institution-based prospective cohort of children with VTE or AIS. Inclusion criteria consisted of objectively confirmed thrombus, ≤21years at diagnosis, tHcy measured and MTHFR c.677C>T mutation analysis. Clinical and laboratory data were collected. Frequencies for elevated tHcy and MTHFR variant were compared with NHANES values for healthy US children and also between study groups (VTE vs AIS, provoked vs idiopathic) and by age. RESULTS: The prevalences of hyperhomocysteinemia or MTHFR variant were not increased in comparison to NHANES. tHcy did not differ between those with wild-type MTHFR versus either c.677C>T heterozygotes or homozygotes. There was no association between tHcy or MTHFR variant and thrombus outcomes. CONCLUSION: In this cohort of US children with VTE or AIS, neither the prevalence of hyperhomocysteinemia nor that of MTHFR variant was increased relative to reference values, and adverse thrombus outcomes were not definitively associated with either. While it is important to consider that milder forms of pyridoxine-responsive classical homocystinuria will be detected only by tHcy, we suggest that routine testing of MTHFR c.677C>T genotype as part of a thrombophilia evaluation in children with incident thromboembolism is not warranted until larger studies have been performed in order to establish or refute a link between MTHFR and adverse outcomes.