The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997. The 2015 update of the KDOQI Clinical Practice Guideline for Hemodialysis Adequacy is intended to assist practitioners caring for patients in preparation for and during hemodialysis. The literature reviewed for this update includes clinical trials and observational studies published between 2000 and March 2014. New topics include high-frequency hemodialysis and risks; prescription flexibility in initiation timing, frequency, duration, and ultrafiltration rate; and more emphasis on volume and blood pressure control. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.

Rationale Microglial activation in autonomic brain regions is a hallmark of neuroinflammation in neurogenic hypertension (HTN). Despite evidence that an impaired sympathetic nerve activity supplying the bone marrow (BM) increases inflammatory cells and decreases angiogenic cells, little is known about the reciprocal impact of BM-derived inflammatory cells on neuroinflammation in HTN. Objective Test the hypothesis that pro-inflammatory BM cells from hypertensive animals contribute to neuroinflammation and HTN via a brain-BM interaction. Methods and Results Following BM ablation in spontaneously hypertensive rats (SHR), and reconstitution with normotensive Wistar-Kyoto (WKY) rat BM, the resultant chimeric SHR displayed significant reduction in mean arterial pressure (MAP) associated with attenuation of both central and peripheral inflammation. In contrast, an elevated MAP along with increased central and peripheral inflammation was observed in chimeric WKY rats reconstituted with SHR BM. Oral treatment with minocycline, an inhibitor of microglial activation, attenuated HTN in both the SHR and chronic angiotensin II (Ang II)-infused rats. This was accompanied by decreased sympathetic drive and inflammation. Furthermore, in chronic Ang II-infused rats, minocycline prevented extravasation of BM-derived cells to the hypothalamic paraventricular nucleus (PVN), presumably via a mechanism of decreased C-C chemokine ligand 2 levels in the cerebrospinal fluid. Conclusions The BM contributes to HTN by increasing peripheral inflammatory cells and their extravasation into the brain. Minocycline is an effective therapy to modify neurogenic components of HTN. These observations support the hypothesis that BM-derived cells are involved in neuroinflammation, and targeting them may be an innovative strategy for neurogenic resistant HTN therapy.

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