ABSTRACT
BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD), most of whom have a mutation in PKD1 or PKD2, abnormally large numbers of macrophages accumulate around kidney cysts and promote their growth. Research by us and others has suggested that monocyte chemoattractant protein-1 (Mcp1) may be a signal for macrophage-mediated cyst growth. METHODS: To define the role of Mcp1 and macrophages in promoting cyst growth, we used mice with inducible knockout of Pkd1 alone (single knockout) or knockout of both Pkd1 and Mcp1 (double knockout) in the murine renal tubule. Levels of Mcp1 RNA expression were measured in single-knockout mice and controls. RESULTS: In single-knockout mice, upregulation of Mcp1 precedes macrophage infiltration. Macrophages accumulating around nascent cysts (0-2 weeks after induction) are initially proinflammatory and induce tubular cell injury with morphologic flattening, oxidative DNA damage, and proliferation-independent cystic dilation. At 2-6 weeks after induction, macrophages switch to an alternative activation phenotype and promote further cyst growth because of an additional three-fold increase in tubular cell proliferative rates. In double-knockout mice, there is a marked reduction in Mcp1 expression and macrophage numbers, resulting in less initial tubular cell injury, slower cyst growth, and improved renal function. Treatment of single-knockout mice with an inhibitor to the Mcp1 receptor Ccr2 partially reproduced the morphologic and functional improvement seen with Mcp1 knockout. CONCLUSIONS: Mcp1 is upregulated after knockout of Pkd1 and promotes macrophage accumulation and cyst growth via both proliferation-independent and proliferation-dependent mechanisms in this orthologous mouse model of ADPKD.
Subject(s)
Chemokine CCL2/genetics , Chemokine CCL2/physiology , Macrophages/physiology , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/pathology , Animals , Chemokine CCL2/deficiency , DNA Damage , Disease Models, Animal , Humans , Kidney Tubules/pathology , Kidney Tubules/physiopathology , Macrophage Activation/drug effects , Macrophage Activation/genetics , Macrophage Activation/physiology , Macrophages/drug effects , Macrophages/pathology , Male , Mice , Mice, Knockout , Polycystic Kidney, Autosomal Dominant/physiopathology , Pyrrolidines/pharmacology , Reactive Oxygen Species/metabolism , Receptors, CCR2/antagonists & inhibitors , TRPP Cation Channels/deficiency , TRPP Cation Channels/genetics , Up-RegulationABSTRACT
CONTEXT: Despite recommendations for shared decision-making and advanced care planning (ACP) for people with chronic kidney disease (CKD), such conversations are infrequent. The MY WAY educational and patient coaching intervention aimed to promote high-quality ACP. OBJECTIVES: This qualitative substudy sought to gain participant feedback on the MY WAY ACP coaching intervention, and how it impacted their wishes, perceptions of kidney care, and factors that helped them reflect on ACP. METHODS: We conducted semi-structured interviews with participants from the intervention arm of the MY WAY study about their prior experience with ACPs in the context of CKD, impressions of the MY WAY intervention, and outcomes of the MY WAY intervention. We conducted a qualitative thematic analysis of transcribed interviews. RESULTS: Among 15 intervention participants, the following major themes emerged: 1) Patients with CKD approach ACP with varied experiences; 2) Patients felt the MY WAY coaching intervention supported ACP by reinforcing values; and 3) Patients found the coaching intervention focused on end of life, but not necessarily on decision making regarding CKD. CONCLUSION: Participants perceived the coaching intervention to have high utility in facilitating ACP, but had a limited impact on CKD-specific decision-making. These findings suggest that the coach plays a crucial role in comfort with ACP conversations and that ACP readiness and engagement may not correlate with treatment preferences or understanding of CKD treatment decisions.
Subject(s)
Advance Care Planning , Qualitative Research , Renal Insufficiency, Chronic , Humans , Male , Female , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/psychology , Aged , Middle Aged , Mentoring/methods , Interviews as Topic , Patient Education as Topic/methods , Decision Making, Shared , Aged, 80 and overABSTRACT
PURPOSE: To review the results of the recent American College of Radiology (ACR) in-training examinations in radiation oncology and to provide information regarding the examination changes in recent years. METHODS AND MATERIALS: A retrospective review of the 2004 to 2007 ACR in-training examination was undertaken. RESULTS: The number of residents taking the in-training examination increased from 2004 to 2007, compatible with the increase in the number of radiation oncology residents in the United States and Canada. The number of questions decreased from approximately 510 in 2004 and 2005, to 405 in 2006 and 360 in 2007, most of these changes were in the clinical oncology section. Although the in-training examination showed construct validity with resident performance improving with each year of additional clinical oncology training, it did so only until Level 3 for biology and physics. Several changes have been made to the examination process, including allowing residents to keep the examination booklet for self-study, posting of the answer key and rationales to questions on the ACR Website, and providing hard copies to residency training directors. In addition, all questions are now A type or multiple choice questions with one best answer, similar to the American Board of Radiology written examination for radiation oncology. CONCLUSION: Several efforts by the ACR have been made in recent years to make the examination an educational tool for radiation oncology residents and residency directors.