Who has influence in multistakeholder governance systems?

As multistakeholder governance has emerged as an important feature in development, new governance structures that foster the participation of multiple stakeholders from the public sector, civil society, and the private sector have emerged in various fields, ranging from the management of natural resources to the provision of public services. To make such governance structures work, it is essential to understand how different stakeholders influence decisionmaking and what determines their influence. This paper uses Net-Map, an innovative participatory method, to analyze how networking influences decisionmaking in multistakeholder governance structures, using the case of the governance board of the White Volta River Basin in northern Ghana as an example. The method visualizes both the relations between all stakeholders in watershed management as perceived by the 17 members on the board and their influence on development outcomes. The study suggests that significant effects of social networking are at play beyond the formal lines of command and funding as stakeholders in watershed management make decisions. Stakeholders are more influential if they participate more prominently in information exchange and provide more advice to others. This counterbalances the overrepresentation of government actors on the board. Meanwhile some government organizations have a low level of influence, even though they are central in giving funding and command. These findings may be interesting for program leaders and policymakers in watershed management: when designing governance structures they need to take into account the importance of social networking to attain main objectives of watershed development; it is important to provide space that allows the exchange of information and advice among stakeholders. Meanwhile, policymakers and program leaders as well must consider overrepresentation of social network champions in multistakeholder governance structures and the limited capacity of government bodies in social networking. The paper serves to introduce not only the specific findings concerning this case study but also the participatory research method (Net-Map) that was used.decisionmaking, multistakeholder governance, Natural resource management, Social networks,

Renal Involvement in Preeclampsia: Similarities to VEGF Ablation Therapy

Glomerular VEGF expression is critical for the maintenance and function of an intact filtration barrier. Alterations in glomerular VEGF bioavailability result in endothelial as well as in podocyte damage. Renal involvement in preeclampsia includes proteinuria, podocyturia, elevated blood pressure, edema, glomerular capillary endotheliosis, and thrombotic microangiopathy. At least the renal signs, symptoms, and other evidence can sufficiently be explained by reduced VEGF levels. The aim of this paper was to summarize our pathophysiological understanding of the renal involvement of preeclampsia and point out similarities to the renal side effects of VEGF-ablation therapy

The Podocyte Power-Plant Disaster and Its Contribution to Glomerulopathy

Proper podocyte function within the glomerulus demands a high and continuous energy supply that is mainly derived from the respiratory chain of the inner mitochondrial membrane. Dysregulations in the metabolic homoeostasis of podocytes may result in podocyte damage and glomerular disease. This article highlights the current knowledge about podocyte energy supply by the respiratory chain. We review the regulation of mitochondrial oxidative metabolism with regard to podocytopathy and discuss the latest understanding of different mitochondrial dysfunctions of the podocyte in diabetic nephropathy and focal segmental glomerulosclerosis (FSGS). We discuss genetic forms of mitochondriopathy of the podocyte and end with recent knowledge about crosstalk between NADH and NADPH and potential therapeutic options for podocyte mitochondriopathy. We aim to raise awareness for the complex and interesting mechanisms of podocyte damage by impaired energy supply that, despite of novel findings in recent years, is poorly understood so far

The ADF/Cofilin-Pathway and Actin Dynamics in Podocyte Injury

ADF/cofilins are the major regulators of actin dynamics in mammalian cells. The activation of ADF/cofilins is controlled by a variety of regulatory mechanisms. Dysregulation of ADF/cofilin may result in loss of a precisely organized actin cytoskeletal architecture and can reduce podocyte migration and motility. Recent studies suggest that cofilin-1 can be regulated through several extracellular signals and slit diaphragm proteins. Cofilin knockdown and knockout animal models show dysfunction of glomerular barrier and filtration with foot process effacement and loss of secondary foot processes. This indicates that cofilin-1 is necessary for modulating actin dynamics in podocytes. Podocyte alterations in actin architecture may initiate or aid the progression of a large variety of glomerular diseases, and cofilin activity is required for reorganization of an intact filtration barrier. Since almost all proteinuric diseases result from a similar phenotype with effacement of the foot processes, we propose that cofilin-1 is at the centre stage of the development of proteinuria and thus may be an attractive drug target for antiproteinuric treatment strategies

Role of Protein Kinase C in Podocytes and Development of Glomerular Damage in Diabetic Nephropathy

The early glomerular changes in diabetes include a podocyte phenotype with loss of slit diaphragm proteins, changes in the actin cytoskeleton and foot process architecture. This review focusses on the role of the Protein Kinase C family in podocytes and points out the differential roles of classical, novel and atypical PKCs in podocytes. Some PKC-isoforms are indispensable for proper glomerular development and slit diaphragm maintenance whereas others might be harmful when activated in the diabetic milieu. Therefore some might be interesting treatment targets in the early phase of diabetes

Prevalence and Correlates of Cognitive Impairment in Kidney Transplant Patients Using the DemTect—Results of a KTx360 Substudy

Cognitive impairment in kidney transplantation (KTx) patients is associated with allograft survival and mortality. However, the prevalence of cognitive impairment after KTx is still understudied. Thus, we aimed to assess the prevalence of cognitive impairment in KTx patients and to identify sociodemographic, medical, donation-specific, and psychological variables associated with cognitive impairment. In this cross-sectional two-center study, 583 KTx patients participated in a structured post-transplant care program. The DemTect was used to assess cognition, and cognitive impairment was defined as a score of 30 kg/m2). Using logistic regression analysis, all variables except age remained significant. Our results suggest that cognitive impairment affects a significant number of patients after KTx. Transplant centers may consider screening for cognitive impairment using objective tests, especially in patients with a high-risk profile. Furthermore, studies with longitudinal designs are required in order to assess moderators and mediators for cognitive trajectories

Author Correction: Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease

Dyadic Coping of Kidney Transplant Recipients and Their Partners: Sex and Role Differences

Background: Coping with stressful health issues – e.g., organ transplantation – can affect interpersonal relationships.Objective: The study examines individual and dyadic coping (DC) in kidney transplant recipients and their partners under consideration of sex and role differences. The Dyadic Coping Inventory allows analyzing partners’ perception of their own DC and also of their partner’s behavior and investigating different perspectives with three discrepancy indexes (similarity, perceived similarity, congruence).Methods: Fifty-six kidney transplant recipients and their partners completed self-report questionnaires (N = 112) on DC, depression, anxiety, and relationship satisfaction. The average age of the patients was 58.1 years and of the partners 57.2 years; 64.3% of the patients were male; time since transplantation was on average 9.7 years.Results: (1) Individual and dyadic functioning: In couples with male patients female caregivers showed higher own supportive DC than the males. In couples with female patients, women reported higher own stress communication, supportive DC, total positive DC and total DC as well as depression compared to men. (2) Regarding the discrepancy indexes, in couples with male patients lower levels of similarity in DC reactions of the couple was associated with higher depression of the males as well as higher anxiety of the females. Moreover, lower comparability of the own DC with partner-perception was correlated with higher depression in males. In couples with female patients, higher comparability was associated with higher DC. Higher DC of the males was associated with lower own anxiety and better similarity in DC reactions. Lower levels of similarity of the male spouse showed correlations with higher depression and anxiety of the females. (3) Sex and role differences occurred. No significant differences between male patients and male partners occurred whereas female patients showed higher own stress communication, supportive DC, common DC, total positive DC, total DC and relationship satisfaction compared to female caregivers (role differences). The same differences were found comparing female with male patients. No differences occurred between male and female caregivers (sex differences). (4) Regarding male’s relationship quality, male’s DC total score and similarity index seem to be important predictors in couples with male patients.Discussion: The results demonstrate the relevance of DC in couples with kidney transplantation and show differences between males and females as well as between patients and partners

Novel diagnostic and therapeutic techniques reveal changed metabolic profiles in recurrent focal segmental glomerulosclerosis

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease

Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

BACKGROUND: Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. METHODS/DESIGN: The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. DISCUSSION: It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. TRIAL REGISTRATION: Clinical trials gov. number: NCT0111766