A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease

BACKGROUND: It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes. This post-hoc sub-group analysis compares platelet function, clot structure and thrombin generation time at baseline, and following enoxaparin exposure in three groups of subjects. METHODS: 30 total subjects were evaluated in the three groups: Group I: normal controls (n = 10), Group II: subjects with renal dysfunction but without diabetes (n = 13), and Group III: subjects with concomitant diabetes and renal dysfunction (n = 7). For each subject, platelet contractile force (PCF), clot elastic modulus (CEM) and thrombin generation time (TGT) were simultaneously measured in whole blood at baseline, and following increasing enoxaparin antifactor Xa activity exposure. The group means for each parameter were determined and compared using one-way analysis of variance, with post-hoc Tukey-Kramer test. RESULTS: At baseline, subjects in Group III (diabetics with concomitant renal dysfunction) display significantly enhanced platelet activity, as measured by PCF (p = 0.003) and CEM (p = 0.03), relative to the non-diabetic Groups I and II. Subjects in Group II (renal dysfunction without diabetes) had significantly prolonged TGT values relative to controls when the antifactor Xa activity concentration reached 0.5 (p = 0.007), 1.0 (p = 0.005) and 3.0 IU/mL (p < 0.0001), respectively. There were no differences between Group II and Group III with respect to TGT at these antifactor Xa activity concentrations. When the antifactor Xa activity concentration reached 3.0 IU/mL, Groups II and III formed significantly less rigid blood clots (CEM p = 0.003) and also trended toward reduced PCF (p = 0.06) relative to Group I. CONCLUSION: This hypothesis-generating sub-group analysis suggests that at baseline, patients with concomitant diabetes and renal dysfunction have significantly enhanced platelet activity (PCF), and form more rigid blood clots (CEM) compared to controls and subjects with renal dysfunction but no diabetes. This may suggest that the presence of renal dysfunction does not ameliorate the hypercoagulable state associated with diabetes. Secondly, it appears that subjects with renal dysfunction but without diabetes have an enhanced response to enoxaparin relative to controls

Multispecies Sustainability

The sustainability concept in its current form suffers from reductionism. The common interpretation of ‘meeting the needs of the present without compromising the ability of future generations to meet their own needs’ fails to explicitly recognize their interdependence with needs of current and future non-human generations. Here, we argue that the focus of sustainability on human well-being – a purely utilitarian view of nature as a resource for humanity – limits its conceptual and analytical power, as well as real-world sustainability transformation efforts. We propose a broadened concept of ‘multispecies sustainability’ by acknowledging interdependent needs of multiple species’ current and future generations. We develop the concept in three steps: (1) discussing normative aspects, fundamental principles underlying the con- cept, and potential visual models, (2) showcasing radically diverging futures emerging from a scenario thought experiment based on the axes sustainable-unsustainable and multispecies-anthropocentric, and (3) exploring how multispecies sustainability can be applied to research and policy-making through two case studies (a multispecies stakeholder framework and the Healthy Urban Microbiome Initiative)

Clinical covariates influencing clinical outcomes in primary membranous nephropathy

Abstract Background Primary membranous nephropathy (PMN) frequently causes nephrotic syndrome and declining kidney function. Disease progression is likely modulated by patient-specific and therapy-associated factors awaiting characterization. These cofactors may facilitate identification of risk groups and could result in more individualized therapy recommendations. Methods In this single-center retrospective observational study, we analyze the effect of patient-specific and therapy-associated covariates on proteinuria, hypoalbuminemia, and estimated glomerular filtration rate (eGFR) in 74 patients diagnosed with antibody positive PMN and nephrotic-range proteinuria (urine-protein-creatinine-ratio [UPCR] ≥ 3.5 g/g), treated at the University of Freiburg Medical Center between January 2000 – November 2022. The primary endpoint was defined as time to proteinuria / serum-albumin response (UPCR ≤ 0.5 g/g or serum-albumin ≥ 3.5 g/dl), the secondary endpoint as time to permanent eGFR decline (≥ 40% relative to baseline). Results The primary endpoint was reached after 167 days. The secondary endpoint was reached after 2413 days. Multivariate time-to-event analyses showed significantly faster proteinuria / serum-albumin response for higher serum-albumin levels (HR 2.7 [95% CI: 1.5 – 4.8]) and cyclophosphamide treatment (HR 3.6 [95% CI: 1.3 – 10.3]). eGFR decline was significantly faster in subjects with old age at baseline (HR 1.04 [95% CI: 1 – 1.1]). Conclusion High serum-albumin levels, and treatment with cyclophosphamide are associated with faster proteinuria reduction and/or serum-albumin normalization. Old age constitutes a risk factor for eGFR decline in subjects with PMN

Multispecies sustainability

The sustainability concept seeks to balance how present and future generations of humans meet their needs. But because nature is viewed only as a resource, sustainability fails to recognize that humans and other living beings depend on each other for their well-being. We therefore argue that true sustainability can only be achieved if the interdependent needs of all species of current and future generations are met, and propose calling this ‘multispecies sustainability’. We explore the concept through visualizations and scenarios, then consider how it might be applied through case studies involving bees and healthy green spaces