Donor Characteristics of Pancreas Transplantation in Australia and New Zealand: A Cohort Study 1984-2014

Background The aim of this study was to audit the characteristics of pancreas donors over time in Australia and New Zealand. Pancreas transplantation was introduced in Australian and New Zealand in 1984. Methods We analyzed data from the Australia and New Zealand Islet and Pancreas Transplant Registry, 1984 to 2014. We investigated the variation of donor characteristics of sex, age, body mass index, smoking status, blood group, multiple organ donation, cytomegalovirus status, terminal creatinine, hypertension, and cause of death for pancreas transplantation over time. We used χ2 test (Fisher test when necessary) or analysis of variance to test difference for categorical or continuous characteristics, respectively. Results There were 628 pancreas donors from 1984 to 2014. Donor body mass index (from 21.9 to 24.0, P < 0.001) and age (from 23.9 to 28.5, P = 0.02) have both increased while terminal creatinine has decreased (86.3 to 73.3, P = 0.01) from 1995 to 2014. In the meantime, the proportions of donors with hypertension (from 19% to 1%, P < 0.001) and who were smokers (from 54% to 15%, P < 0.001) have decreased. Profile of cause of donor death has also changed over time (P = 0.06) with increase in cerebral hypoxia/ischemia (from 3% to 17%) and reductions in intracranial hemorrhage (27% to 13%). Conclusions Many donor characteristics have changed over time. The most significant changes appear to reflect changes in the general population, rather than changes in donor selection

Australia and New Zealand Islets and Pancreas Transplant Registry Annual Report 2018—Pancreas Waiting List, Recipients, and Donors

Background This is a synopsis of the registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/. Methods We report data for all solid organ pancreas transplant activity from inception in 1984 to end 2017. Islet-cell transplantation activity is reported elsewhere. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). Results From 1984 to 2017 a total of 809 solid organ pancreas transplants have been performed in Australia and New Zealand, in 790 individuals. In 2017, 52 people received a pancreas transplant. By center, this was; Auckland (4), Monash (17), and Westmead (31). In 2017, 51 transplants were simultaneous pancreas kidney, whereas 1 was pancreas after kidney, and none were pancreas transplant alone. Conclusions The number of pancreas transplants performed in Australia and New Zealand was slightly lower in 2017 but continues to increase over time

Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Communicating projected survival with treatments for chronic kidney disease: patient comprehension and perspectives on visual aids

Abstract Background Mortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD). Methods One hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding. Results We measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002). 87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002). The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment. Conclusion Visual aids, can be beneficial adjuncts to discussing survival in CKD

Time course of upregulation of fibrogenic growth factors in a rodent model of chronic renal allograft rejection

Upregulation of growth factors has been shown in CR but the time point at which this occurs in not known. The aim of this study was to examine the time course of upregulation of growth factors and correlate this with the macrophage and myofibroblast interstitial infiltrate. Methods: Using a rat model of CR (F344 kidney donor to Lewis recipient), infiltration by ED1+ macrophages and proliferation of α-smooth muscle actin (α-SMA) and desmin-expressing cells was examined using immunohistochemistry. In addition, expression of mRNA for interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), basic-fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF) was studied using a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique. Native Lewis rat kidney and Lewis–Lewis isografts were used as controls. Results: Immunohistochemical staining of ED1+ cells showed a marked increase in the macrophage infiltrate of allografts compared to isografts at all time periods (P=0.0002) peaking at weeks 8–12 after transplantation. Expression of α-SMA was also increased in allografts (P=0.002). RT-PCR analysis showed that mRNA for TGF-β was maximally upregulated in allografts in comparison to isografts at week 8 after engraftment (P=0.05) and declined thereafter, although remained at elevated levels compared to controls. IFN-γ and b-FGF gene expression was increased in allografts late in the post-transplantation period. Conclusion: Early infiltration of macrophages and production of TGF-β1 was followed by later upregulation of fibrogenic growth factors and myofibroblasts associated with interstitial fibrosis and organ dysfunction