Chronic kidney disease (CKD) has been associated with impaired host response and increased susceptibility to infections. Leukocyte recruitment during inflammation must be tightly regulated to protect the host against pathogens. FGF23 levels are increased in blood during CKD, and levels of this hormone have been associated with a variety of adverse effects in CKD patients. Here, we have shown that CKD impairs leukocyte recruitment into inflamed tissue and host defense in mice and humans. FGF23 neutralization during CKD in murine models restored leukocyte recruitment and host defense. Intravital microscopy of animals with chronic kidney failure showed that FGF23 inhibits chemokine-activated leukocyte arrest on the endothelium, and downregulation of FGF receptor 2 (FGFR2) on PMNs rescued host defense in these mice. In vitro, FGF23 inhibited PMN adhesion, arrest under flow, and transendothelial migration. Mechanistically, FGF23 binding to FGFR2 counteracted selectin- and chemokine-triggered β2 integrin activation on PMNs by activating protein kinase A (PKA) and inhibiting activation of the small GTPase Rap1. Moreover, knockdown of PKA abolished the inhibitory effect of FGF23 on integrin activation. Together, our data reveal that FGF23 acts directly on PMNs and dampens host defense by direct interference with chemokine signaling and integrin activation.
Most non-dialysis dependent chronic kidney disease (CKD) patients are cared for by their primary care physicians (PCPs). Studies suggest many CKD patients receive suboptimal care. Recently, CKD clinical practice guidelines were updated with additional emphasis on albuminuria.
19 June 2013 in Nephrology Dialysis Transplantation
The burgeoning population of older dialysis patients presents opportunities to provide personalized care. The older dialysis population has a high burden of chronic health conditions, decrements in quality of life and a high risk of death. In order to address these challenges, this review will recommend routinely establishing prognosis through the use of prediction instruments and communicating these findings to older patients. The challenges to prognosis in adults with end-stage renal disease (ESRD) include the subjective nature of clinical judgment, application of appropriate prognostic tools and communication of findings to patients and caregivers. There are three reasons why we believe these conversations occur infrequently with the dialysis population. First, there have previously been no clinically practical instruments to identify individuals undergoing maintenance hemodialysis (HD) who are at highest risk for death. Second, nephrologists have not been trained to have conversations about prognosis and end-of-life care. Third, other than hospitalizations and accrual of new diagnoses, there are no natural milestone guidelines in place for patients supported by dialysis. The prognosis can be used in shared decision-making to establish goals of care, limits on dialysis support or parameters for withdrawal from dialysis. As older adults with ESRD benefit from kidney transplantation, prognosis can also be used to determine who should be referred for evaluation by a kidney transplant team. The use of prognosis in older adults may determine approaches to optimize well-being and personalize care among older adults ranging from hospice to kidney transplantation.
Many patients on maintenance dialysis experience significant sleepiness and fatigue. However, the influence of the hemodialysis (HD) day and circadian rhythms on patients’ symptoms have not been well characterized. We sought to use ecological momentary assessment to evaluate day-to-day and diurnal variability of fatigue, sleepiness, exhaustion and related symptoms in thrice-weekly maintenance HD patients.
15 April 2016 in Clinical Journal of the American Society of Nephrology
Background and objectives Despite the potential benefits of conservative management, providers rarely discuss it as a viable treatment option for patients with advanced CKD. This survey was to describe the knowledge, attitudes, and practices of nephrologists and primary care providers regarding conservative management for patients with advanced CKD in the United States. Design, setting, participants, & measurements We developed a questionnaire on the basis of a literature review to include items assessing knowledge, attitudes, and self-reported practices of conservative management for patients with advanced CKD. Potential participants were identified using the American Medical Association Physician Masterfile. We then conducted a web-based survey between April and May of 2015. Results In total, 431 (67.6% nephrologists and 32.4% primary care providers) providers completed the survey for a crude response rate of 2.7%. The respondents were generally white, men, and in their 30s and 40s. Most primary care provider (83.5%) and nephrology (78.2%) respondents reported that they were likely to discuss conservative management with their older patients with advanced CKD. Self-reported number of patients managed conservatively was >11 patients for 30.6% of nephrologists and 49.2% of primary care providers. Nephrologists were more likely to endorse difficulty determining whether a patient with CKD would benefit from conservative management (52.8% versus 36.2% of primary care providers), whereas primary care providers were more likely to endorse limited information on effectiveness (49.6% versus 24.5% of nephrologists) and difficulty determining eligibility for conservative management (42.5% versus 14.3% of nephrologists). There were also significant differences in knowledge between the groups, with primary care providers reporting more uncertainty about relative survival rates with conservative management compared with different patient groups. Conclusions Both nephrologists and primary care providers reported being comfortable with discussing conservative management with their patients. However, both provider groups identified lack of United States data on outcomes of conservative management and characteristics of patients who would benefit from conservative management as barriers to recommending conservative management in practice.