Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca2+-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death

Mortality Trends After Transfer From Peritoneal Dialysis to Hemodialysis

Introduction Transition to hemodialysis (HD) is a common outcome in peritoneal dialysis (PD), but the associated mortality risk is poorly understood. This study sought to identify rates of and risk factors for mortality after transitioning from PD to HD. Methods Patients with incident PD (between 2000 and 2014) who transferred to HD for ≥1 day were identified, using data from Australia and New Zealand Dialysis and Transplantation registry (ANZDATA), Canadian Organ Replacement Register (CORR), Europe Renal Association (ERA) Registry, and the United States Renal Dialysis System (USRDS). Crude mortality rates were calculated for the first 180 days after transfer. Separate multivariable Cox models were built for early (180 days) periods after transfer. Results Overall, 6683, 5847, 21,574, and 80,459 patients were included from ANZDATA, CORR, ERA Registry, and USRDS, respectively. In all registries, crude mortality rate was highest during the first 30 days after a transfer to HD declining thereafter to nadir at 4 to 6 months. Crude mortality rates were lower for patients transferring in the most recent years (than earlier). Older age, PD initiation in earlier cohorts, and longer PD vintage were associated with increased risk of death, with the strongest associations during the first 90 days after transfer and attenuating thereafter. Mortality risk was lower for men than women <90 days after transfer, but higher after 180 days. Conclusion In this multinational study, mortality was highest in the first month after a transfer from PD to HD and risk factors varied by time period after transfer. This study highlights the vulnerability of patients at the time of modality transfer and the need to improve transitions

Transition Between Different Renal Replacement Modalities: Gaps in Knowledge and Care-The Integrated Research Initiative

Patients with end-stage kidney disease (ESKD) have different options to replace the function of their failing kidneys. The "integrated care" model considers treatment pathways rather than individual renal replacement therapy (RRT) techniques. In such a paradigm, the optimal strategy to plan and enact transitions between the different modalities is very relevant, but so far, only limited data on transitions have been published. Perspectives of patients, caregivers, and health professionals on the process of transitioning are even less well documented. Available literature suggests that poor coordination causes significant morbidity and mortality.This review briefly provides the background, development, and scope of the INTErnational Group Research Assessing Transition Effects in Dialysis (INTEGRATED) initiative. We summarize the literature on the transition between different RRT modalities. Further, we present an international research plan to quantify the epidemiology and to assess the qualitative aspects of transition between different modalities

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams