Three cases of BRAF-mutant melanoma with divergent differentiation masquerading as sarcoma.

Melanoma is an important cause of skin cancer related death throughout the world, particularly in Europe, the United States, and Australia. Rarely melanoma undergoes divergent differentiation to simulate the full morphologic and immunohistochemical features of other malignancies, notably sarcoma. However, such cases retain the molecular signatures of melanoma, including BRAF gene mutations. Gene mutation analysis of tumour DNA, now standard practice for all melanomas of stage III or above, may establish the diagnosis of melanoma in some advanced malignancies of unknown lineage. A prior history of melanoma or risk factors for melanoma may be the first clue that an advanced malignancy represents metastatic melanoma. Recognition of this presentation of melanoma can allow a patient to access well-tolerated life-prolonging therapies such as targeted therapy, inhibiting the BRAF/MEK pathway, and immune checkpoint inhibitor therapy.

Atypical Pleural Effusion in an Immunocompetent Patient With Valley Fever: A Case Study and Review of the Literature.

Valley fever is a fungal infection, commonly of the lungs, caused by Coccidioides immitis or Coccidioides posadasii. This disease is endemic to the southwestern United States, Central America, and South America. Infected individuals are typically asymptomatic but may develop community-acquired pneumonia. On rare occasions, coccidioidomycosis can present with severe complications in addition to the pulmonary manifestation. In this study, a 58-year-old immunocompetent male presented to the Emergency Department with a cough, night sweats, and pleuritic chest pain. Despite the administration of broad-spectrum antimicrobials, he developed a large right pleural effusion that did not resolve following thoracentesis. Serology was positive for Coccidioides, and the patient was referred to a thoracic surgeon due to persistent effusion. It is rare for patients with coccidiomycosis to develop a large pleural effusion requiring surgical intervention, especially in immunocompetent individuals. This case highlights the importance of monitoring patients with unresolved acute pneumonia in endemic areas and considering Coccidioides as a possible etiology.

First Asia-Pacific experience of trans-bronchial core biopsy with a Franseen needle.

Background: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is the standard for evaluating mediastinal and hilar lesions. EBUS-TBNA is limited by small volume of material obtained for immunohistochemistry (IHC) and ancillary studies important for oncological therapies. The Franseen AcquireTM needle is designed for EBUS-transbronchial needle core biopsy (TBNB) allowing larger core sizes with evidence in gastroenterology literature but little in pulmonology. This study reports the first Asia-Pacific experience of EBUS-TBNB and adequacy of samples for diagnosis and ancillary studies. Methods: A retrospective cohort study of EBUS-TBNB at the Royal Adelaide Hospital was conducted between December 2019 and May 2021. Diagnostic rate, adequacy for ancillary studies and complications were evaluated. Samples were flushed into formalin for histological processing with no rapid on-site cytological evaluation (ROSE). For suspected lymphoma, samples were flushed into HANKS for flow cytometry. Cases performed with the Olympus VizishotTM during the same 18-month were similarly analysed. Results: One hundred and eighty-nine patients were sampled with the AcquireTM needle. Diagnostic rate was 174/189 (92.1%). Where reported [146/189 (77.2%)], average core aggregate sample size was 13.4 mm × 10.7 mm × 1.7 mm. For non-small cell lung cancer (NSCLC) cases, 45/49 (91.8%) had adequate tissue for programmed cell death-ligand 1 (PD-L1). 32/35 (91.4%) adenocarcinoma cases had sufficient tissue for ancillary studies. There was one false negative malignant lymph node at the first AcquireTM procedure. There were no major complications. One hundred and one patients were sampled with the VizishotTM needle. Diagnostic rate was 86/101 (85.1%) with only 25/101 (24.8%) having reported tissue cores (P<0.0001 of VizishotTM) with the remaining samples processed via cell block. Conclusions: AcquireTM EBUS-TBNB diagnostic rate is comparable to historical data with >90% of cases having sufficient core material for ancillary studies. There appears to be a role for the AcquireTM alongside the standard of care for the work up of lymphadenopathy and particularly for lung cancer.

Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs.

Numerous studies have characterized the existence of cell subtypes, along with their corresponding transcriptional profiles, within the developing mouse pancreas. The upstream mechanisms that initiate and maintain gene expression programs across cell states, however, remain largely unknown. Here, we generate single-nucleus ATAC-Sequencing data of developing murine pancreas and perform an integrated, multi-omic analysis of both chromatin accessibility and RNA expression to describe the chromatin landscape of the developing pancreas at both E14.5 and E17.5 at single-cell resolution. We identify candidate transcription factors regulating cell fate and construct gene regulatory networks of active transcription factor binding to regulatory regions of downstream target genes. This work serves as a valuable resource for the field of pancreatic biology in general and contributes to our understanding of lineage plasticity among endocrine cell types. In addition, these data identify which epigenetic states should be represented in the differentiation of stem cells to the pancreatic beta cell fate to best recapitulate in vitro the gene regulatory networks that are critical for progression along the beta cell lineage in vivo.

Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia.

Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme and then mesothelium during early development, then subsequently by both mesothelium and rare epithelial cells by E12.5 and onwards. Global knockout of the Fgf9 gene resulted in the reduction of pancreas and stomach size, as well as complete asplenia. The number of early Pdx1+ pancreatic progenitors was reduced at E10.5, as was proliferation of mesenchyme at E11.5. Although loss of Fgf9 did not interfere with differentiation of later epithelial lineages, single-cell RNA-Sequencing identified transcriptional programs perturbed upon loss of Fgf9 during pancreatic development, including loss of the transcription factor Barx1. Lastly, we identified conserved expression patterns of FGF9 and receptors in human fetal pancreas, suggesting that FGF9 expressed by pancreatic mesenchyme may similarly affect the development of the human pancreas.

Metastatic Infiltrating Lobular Breast Cancer to the Colon Diagnosed Through Routine Bowel Screening in a 67-Year-Old Female.

Breast cancer most commonly metastasizes to the bone, lung, liver, and brain. The colon is an uncommon site for metastases and its symptoms are variable. A 67-year-old female with a history of breast cancer was referred for colonoscopy following a positive fecal occult blood test (FOBT); there were no discrete lesions concerning for primary colonic cancers or metastasis; however, a random biopsy revealed metastatic breast cancer. The possibility of colonic metastases must be considered when assessing positive FOBT in a patient with previous breast cancer.

Relationship of Retinal Vessel Caliber with Age-Related Macular Degeneration.

Purpose: Evaluate the relationship between retinal vascular caliber and age-related macular degeneration (AMD) severity or progression. Methods: A retrospective secondary analysis of 1172 fundus photographs and clinical data from the prospective Age-Related Eye Disease Study (AREDS). Central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were measured using the Parr-Hubbard-Knudtson formula. Univariate and multivariate regressions were used to determine the association of CRAE, CRVE, and AVR with age, sex, smoking status, presence of cilioretinal artery, and AMD severity at baseline and 5 years using the 9-step AMD severity score. Results: Only CRAE and CRVE were higher in men (P < 0.001), current smokers (P < 0.001), and the eyes with a cilioretinal artery (P=0.009 - 0.043). AMD severity was greater in older patients (P=0.001), current smokers (P=0.012), the eyes without a cilioretinal artery (P=0.001), and lower AVR (P=0.034) on multivariate regression but was not influenced by CRAE or CRVE (P=0.240 - 0.500). Choroidal neovascularization (CNV) presence was associated with older age (P=0.003) and absence of a cilioretinal artery (P=0.009), while central geographic atrophy (CGA) was associated with narrower CRAE (P=0.002) and possibly AVR (P=0.046). None of the retinal vessel parameters were predictive of AMD severity score or new onset of CNV or CGA at 5 years. Conclusion: A lower arteriole-to-venule ratio may be associated with AMD severity, with narrower arterioles seen in the eyes with geographic atrophy, suggesting a role of the retinal vasculature in AMD pathophysiology. This trial is registered with ClinicalTrials.gov Identifier: NCT00000145.

Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations.

Within the Asian populations, Indian patients had been reported to require higher warfarin dose compared with the Chinese and Malay patients, and this could not entirely be explained by cytochrome P450 (CYP)2C9 gene variants. Genetic variants of vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1) has been well established as one of key determinants in the different responses of warfarin amongst patients. Adult patients who attended an anticoagulation clinic with stable INR were recruited. VKORC1 and CYP2C9 genotype were sequenced, and clinical characteristics were assessed. A total of 91 Malays, 96 Chinese, and 46 Indian patients were recruited. The mean age was 55 years and 51.5% were males. The mean dose of warfarin for all patients was 3.7 mg, and the mean daily dose of warfarin was significantly higher in Indians compared with the Chinese and Malay patients, 4.9 versus 3.5 and 3.3 mg, respectively (p < 0.001). VKORC1 GG genotype was more commonly seen in Indian patients. The mean warfarin dose in patients with GG genotype required a significant higher warfarin dose compared with those with AG and AA genotype (4.9 vs. 3.7 vs. 3.1 mg, respectively; p < 0.001). CYP2C9*2 and *3 is associated with a lower maintenance dose, 2.9 versus 3.7 mg in CYP2C9*1; p < 0.01. In multivariate analysis, age, ethnic groups, and genotypes had a significant influence on the required warfarin dose. In conclusion, VKORC1 and CYP2C9 polymorphism contribute to the difference dose requirement amongst the patients but other additional possible factors may play a role in the Indian race.

Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder.

OBJECTIVES: Several magnetic resonance imaging studies have found changes in amygdala volumes in adults with mood disorders. The cellular basis for these changes has not been explored in detail. Specifically, it is not known whether differences in the density and/or volume of neurons or glial cells contribute to tissue volume changes seen on magnetic resonance images. METHODS: Postmortem amygdala samples were obtained from the Stanley Foundation Neuropathology Consortium from subjects diagnosed with bipolar disorder (n = 10), major depressive disorder (n = 11), and schizophrenia (n = 9), and from normal controls (n = 14). Samples were first stained with glial fibrillary acidic protein (GFAP) and counter-stained with hematoxylin to ascertain neuron and glia (astrocyte) densities. RESULTS: No significant differences in neuronal densities were found between groups. However, a reduction in the density of GFAP immunoreactive astrocytes was observed in the amygdala of subjects with major depressive disorder compared to the bipolar disorder, schizophrenia, and normal control postmortem samples. CONCLUSIONS: A decrease in density of GFAP immunoreactive astrocytes in the amygdala of depressed subjects is consistent with prior histologic reports and might contribute to amygdala volume reductions reported in several in vivo neuroimaging studies.

Donor-recipient age matching improves years of graft function in deceased-donor kidney transplantation.

BACKGROUND: Donor and recipient age in kidney transplantation are known to affect graft and patient survival. In deceased-donor (DD) transplantation, donor and recipient age matching are being increasingly accepted as part of the kidney allocation programme. The aims of this study are to evaluate the effect of donor and recipient age on transplant outcomes and to determine the effect of changing existing allocation criteria to allocation based on age matching of donors and recipients on total graft years of function. METHODS: Using the Australia and New Zealand Dialysis and Transplant Registry, all DD kidney transplant recipients in Australia and New Zealand between 1991 and 2006 were analysed (n = 4616). Outcomes analysed were overall graft failure, death with functioning graft and serum creatinine. We calculated the mean time to graft loss ('years of graft function') for donor and recipient age cut-offs as 60 and 55 years, respectively, over up to 16 years follow-up. We then examined the gain in graft years if all older kidneys were allocated to older recipients. RESULTS: Older donors were associated with higher risk of overall graft failure [adjusted hazard ratio (HR) = 1.79, 95% confidence interval (95% CI) = 1.45, 2.21 and HR = 1.29, 95% CI = 1.09, 1.53, respectively] at 1-8 years post-transplant and higher serum creatinine at 1 and 5 years post-transplant (mean differences 32.74 micromol/L, 95% CI 27.60, 37.89 and 38.17 micromol/L, 95% CI 27.58, 48.77, respectively). Overall, young and old recipients with young donor kidneys have an additional two to three mean graft years compared to those receiving older donor kidneys. CONCLUSION: Donor and recipient age matching is an effective method of organ allocation to improve total graft years.

Pregnancy and maternal outcomes among kidney transplant recipients.

Fertility rates, pregnancy, and maternal outcomes are not well described among women with a functioning kidney transplant. Using data from the Australian and New Zealand Dialysis and Transplant Registry, we analyzed 40 yr of pregnancy-related outcomes for transplant recipients. This analysis included 444 live births reported from 577 pregnancies; the absolute but not relative fertility rate fell during these four decades. Of pregnancies achieved, 97% were beyond the first year after transplantation. The mean age at the time of pregnancy was 29 +/- 5 yr. Compared with previous decades, the mean age during the last decade increased significantly to 32 yr (P < 0.001). The proportion of live births doubled during the last decade, whereas surgical terminations declined (P < 0.001). The fertility rate (or live-birth rate) for this cohort of women was 0.19 (95% confidence interval 0.17 to 0.21) relative to the Australian background population. We also matched 120 parous with 120 nulliparous women by year of transplantation, duration of transplant, age at transplantation +/-5 yr, and predelivery creatinine for parous women or serum creatinine for nulliparous women; a first live birth was not associated with a poorer 20-yr graft or patient survival. Maternal complications included preeclampsia in 27% and gestational diabetes in 1%. Taken together, these data confirm that a live birth in women with a functioning graft does not have an adverse impact on graft and patient survival.

Post-kidney transplant weight change as marker of poor survival outcomes.

BACKGROUND: There are few studies on the associations of postkidney transplant weight change on survival. Weight change in different posttransplant periods may have different causes and implications. We used the Australian and New Zealand Dialysis and Transplant Registry data to examine these issues. METHODS: All adult white primary kidney transplant recipients from April 1991 to December 2004 were included. The associations of first (year 1, n=3899) and second (year 2, n=3419) year weight change with subsequent graft and patient survival were analyzed using multivariable Cox regression. RESULTS: Weight gain 10% to 19.9% in year 1 and stable weight (0%-4.9% gain) in year 2 were associated with the best outcomes. Weight loss more than 5% was associated with subsequent death (year 1 adjusted hazard ratio [aHR]=1.64 [1.08-2.48], P=0.019; year 2 aHR=2.09 [1.44-3.02], P=0.013) but not death-censored graft loss. Weight gain more than or equal to 20% in year 1 and more than or equal to 10% weight gain in year 2 were also associated with subsequent death (year 1 aHR=1.78 [1.13-2.81], P=0.013; year 2 aHR=1.67 [1.01-2.76], P=0.047). These associations were minimally changed by excluding outcomes within 1 year of the weight change. Deaths were from cardiovascular disease (35%), cancer (35%), infections (15%), and "other" causes (15%). Weight gain more than or equal to 20% in year 1 was associated with infection or "other" deaths, and weight loss more than 5% or weight gain more than or equal to 10% in year 2 with cardiovascular deaths. CONCLUSIONS: Significant posttransplant weight gain or loss was associated with poorer transplant outcomes. Reasons underlying these associations may differ between year 1 and year 2 weight changes.

Trends in adult post-kidney transplant immunosuppressive use in Australia, 1991-2005.

AIM: Kidney transplant outcomes have improved over the past 15 years, partly due to improvements in immunosuppression. We used data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry to examine trends in immunosuppressive use post transplant. METHODS: All adult (recipient age 16+ years) kidney-only transplants performed in Australia from April 1991 to December 2005 were followed to graft loss or December 2005. Immunosuppressive use at induction, 1, 3 and 5 years post transplant were analysed by transplant cohort. RESULTS: Calcineurin-inhibitors (CNI) were used in most recipients for induction and maintenance immunosuppression, with increasing tacrolimus use. Induction cyclosporin dose increased since 2001 (from 5.8 to 7.9 mg/kg per day), but maintenance cyclosporin and tacrolimus dose decreased (from 3.8 to 3.0 mg/kg per day cyclosporin at 1 year post transplant). CNI-free induction increased since 2002 (from 1.4% to 8.4%), while CNI-free maintenance increased throughout the study period. Mycophenolates were the predominant antimetabolite used. Steroid-free maintenance decreased (from 22.7% to 8.7% at 1 year post transplant), as did median prednisolone doses (from 0.12 to 0.09 mg/kg per day at 1 year post transplant). Sirolimus or everolimus are increasingly used for CNI-sparing rather than as antimetabolites substitutes. OKT3 or antithymocyte globulin induction decreased, while anti-CD25 antibody usage increased from 9.5% to 57.1% since 2000. CONCLUSION: There is a trend to more potent induction immunosuppression with tacrolimus, mycophenolates and anti-CD-25 antibodies, but with CNI avoidance or minimization during maintenance phase. While steroid avoidance/cessation decreased, maintenance steroid dose has also decreased. Anti-CD25 antibodies are now used in >50% of recipients.

Parental donors in live-donor kidney transplantation associated with increased rejection rates and reduced glomerular filtration rates.

BACKGROUND: Living unrelated and related kidney transplantation has been shown to have similar allograft survival. However, the effect of donor-recipient relatedness in living-related and unrelated kidney transplantation on graft and patient survival remains uncertain. METHODS: Using Australia and New Zealand Dialysis and Transplant Registry, primary living renal transplant recipients in Australia between 1995 and 2004 were studied (n=1989). Donors were categorized according to their relationship with recipients: parent (n=606), child (n=103), spouse (n=358), sibling (n=656), other living-related donors (n=81), and other living-unrelated donors (n=185). Outcomes analyzed included the presence of rejection at 6 months, estimated glomerular filtration rate (eGFR) at 1 and 3 years, graft survival, and patient survival. RESULTS: A greater proportion of renal transplant recipients from parental and spousal donors were transplanted preemptively. Donor groups had no relationship with graft or patient survival. Parental donors were associated with an increased relative odds of acute rejection (odds ratio 1.69, 95% confidence interval 1.13-2.53, P=0.009) and a lower eGFR at both 1 and 3 years (coefficient -2.99 and -5.68, respectively; P<0.0001) compared to other donor groups (reference sibling donor group). CONCLUSIONS: This study has established that donor-recipient relatedness in both related and unrelated living kidney transplantation had no significant effect on graft and patient survival. Parental donors were associated with a higher relative risk of rejection and lower eGFR in the transplant recipients, although these findings did not translate to a worse graft outcome.

Effects of body mass index at transplant on outcomes of kidney transplantation.

BACKGROUND: While obesity increases postoperative complications and cardiovascular risks, its effects on long-term kidney transplant outcomes are less clear. METHODS: We used data from the Australian and New Zealand Dialysis and Transplant (ANZDATA) Registry to examine the relationships between body mass index (BMI, classified according to World Health Organization criteria) at transplant and transplant outcome. Patients starting renal replacement therapy from April 1991 and who received a single-organ, primary kidney transplant (when aged > or =16 years) from April 1991 to December 2004 were included, and followed up to death or December 2005. Survival outcomes adjusted for important covariates were analyzed using Cox models, and cause-specific failures by competing risks analysis. Analysis using BMI at various times posttransplant was also performed. Intermediate outcomes were delayed graft function (DGF) and any acute rejection at 6 months. RESULTS: In all, 5684 patients were included. Obese patients had worse graft and patient survival only in univariate analyses, not in multivariate analyses (adjusted hazard ratio [HR] for graft loss: 1.10 [0.94-1.259], P=0.25; for patient death: 1.02 [0.83-1.25], P=0.87). Underweight patients had greater late (> or =5 years) death-censored graft loss (adjusted HR: 1.70 [1.10-2.64], P=0.02), mainly due to chronic allograft nephropathy. Obesity was associated with greater odds for DGF (adjusted OR: 1.56 [1.23-1.97], P<0.001) and 6-month risk of acute rejection (adjusted OR: 1.25 [1.01-1.54], P=0.04). CONCLUSIONS: Obesity per se was not associated with poorer kidney transplant outcomes, although it was associated with factors that led to poorer graft and patient survival. Underweight was associated with late graft failure, mainly due to chronic allograft nephropathy.

Trends in kidney transplantation in Australia and New Zealand, 1993-2004.

BACKGROUND: We hypothesize that transplant outcome in Australia and New Zealand has improved despite more unfavorable transplant characteristics. Data from the Australia and New Zealand Dialysis and Transplant registry was used to examine this hypothesis. METHODS: All adult kidney-only transplants from January 1993 to December 2004 in Australia or New Zealand were followed-up until death or December 2005. Outcomes were adjusted for covariates in multivariate models, with transplant year modeled as a continuous variable. RESULTS: Altogether 6764 patients were included. There were proportionately more live donor and primary transplants, older donors and recipients, and higher recipient body mass index, waiting time, and human leukocyte antigen mismatch in recent cohorts. Death-censored graft loss decreased (adjusted hazard ratio: 0.92 [0.90-0.95] per year, P<0.001). This trend was seen at both 0-1 and 1-5 years posttransplant, and was mainly for immune-mediated graft losses. Patient survival improved only in New Zealand, and only for the first posttransplant year (adjusted odds ratio: 0.88 [0.82-0.95] per year, P=0.001). Cardiovascular deaths decreased while infection or cancer deaths were unchanged. Adjusted delayed graft function rates were unchanged. The acute rejection incidence at 6 months decreased (adjusted odds ratio: 0.88 [0.85-0.90] per year, P<0.001). One and 3-year graft function significantly improved, even after adjusting for rejection. All outcomes did not vary by expanded donor criteria status. CONCLUSIONS: Graft survival and function have improved in recent years, but long-term patient survival remains unchanged. With longer follow-up, the improvement in rejection rates and graft function may lead to further improvements in long-term graft survival and potentially better patient survival.

Trends in hemodialysis vascular access from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) 2000 to 2005.

BACKGROUND: Australia historically has been recognized for its high fistula use. STUDY DESIGN: Observational study using registry data. SETTING & PARTICIPANTS: Adult patients registered in the Australia and New Zealand Dialysis and Transplant Association Registry on hemodialysis in Australia. PREDICTOR: Cohort year. OUTCOMES & MEASUREMENT: Hemodialysis access trends were examined from 2000 to 2005 for incident patients (within 60 days of hemodialysis therapy start), patients on hemodialysis therapy for 6 to 8 months, and prevalent hemodialysis patients. Multivariate analyses were performed to examine the relationship between access type and cohort year for each group, with adjustment for age, sex, race, body mass index, late referral, smoking status, cause of end-stage renal disease, comorbidities, and dialysis vintage. RESULTS: During 2000 to 2005, catheter use increased from 39% to 53% in incident patients, 10% to 22% in the 6- to 8-month groups, and 6% to 13% in prevalent patients. Fistula use decreased from 56% to 43% in incident patients and 78% to 67% in the 6- to 8-month group and remained at 73% to 75% in prevalent patients. Graft use decreased in all groups. Adjustment for factors associated with access type did not significantly change these results. LIMITATIONS: The registry collects only the access in use at the end of the survey period; thus, it was not possible to determine whether another access had failed or was present, but not in use. The small number of incident numbers prevented separate analysis of arteriovenous fistulas and arteriovenous grafts. CONCLUSION: Incident use of fistulas and grafts decreased, with an unexpected increase in both incident and prevalent catheters between 2000 and 2005. Adjustment for factors associated with access type did not significantly alter the trends. Changes in unidentified practice patterns, attitudes, or preferences are contributing to these trends. Ongoing evaluation of data and investigation into processes of care are required to increase functioning fistulas, together with reevaluation of the role of grafts in patients without a fistula.

Donor human leukocyte antigen specific antibodies predict development and define prognosis in transplant glomerulopathy.

The pathogenesis of transplant glomerulopathy (TG) remains unclear, with evidence of human leukocyte antigen (HLA) antibodies as important contributors to the disease. We studied the risk factors and the associations of HLA antibodies in the development of TG. Sixty-one cases with morphologic features of TG were identified and compared with contemporaneous matched patients (without TG) from a 17-year period, all undergoing renal biopsy in a single center. Univariate risk factors for TG were previous glomerulitis [odds ratio (OR) 3.3, 95% confidence interval (95% CI) [1.2-9.4], p = 0.025), delayed graft function (OR 2.3 [1.0-5.1], p = 0.042), HLA class I presensitization defined by Luminex solid-phase immunoassays (OR 5.0 [2.3-11.0]. p < 0.001), and de novo posttransplant development of donor HLA specific antibody (DSA) (OR 4.7 [1.7-13.2], p = 0.002). Only DSA remained significantly associated with TG after adjustment (OR 3.8 [1.1-12.9], p = 0.032). DSA was detected in >50% of TG patients, suggesting HLA antibodies play a critical role in TG pathogenesis. TG patients with DSA had increased risk of graft loss (median graft survival 4.4-5.2 years), whereas patients with morphologic features of TG without DSA had similar graft survival compared with the non-TG group (median graft survival 15 years). Thus, DSA is a useful predictor for graft failure in TG patients.

Reduction in cardiovascular death after kidney transplantation.

BACKGROUND: Cardiovascular (CVS) disease is the commonest cause of death after kidney transplantation. In the general population, CVS mortality has reduced significantly over the last two decades; however, this trend has not been specifically examined in the kidney transplant population. METHODS: We studied all patients in Australia and New Zealand with a functioning kidney transplant between 1980 and 2007 and examined trends in the cause and timing of all 2195 deaths recorded after kidney transplantation in the Australia and New Zealand Dialysis and Transplant registry. Poisson regression was used to compare death rates over the time periods. RESULTS: CVS events were the commonest cause of death throughout all the time points examined; however, CVS death rates significantly decreased with an adjusted risk ratio of 0.61 (95% confidence interval, 0.38-0.96; P=0.034) for 2005 to 2007 era. In comparison, death rates due to malignancy have increased significantly over this period. Decreased CVS death rates have occurred despite increasing comorbidity at the time of transplantation. Factors associated with CVS death were older recipient age, preexisting CVS disease, and diabetes mellitus. There was a significantly lower CVS death rate in patients with a glomerular filtration rate >48 mL/min compared with those with poor renal function (risk ratio, 0.66; 95% confidence interval, 0.45-0.95; P=0.024). CONCLUSIONS: These trends suggest improvements in CVS risk management and outcomes in the kidney transplant population in Australia and New Zealand.