Home Dialysis in Patients with Cardiovascular Diseases.

Kidney failure with replacement therapy and cardiovascular disease are frequently comorbid. In patients with kidney failure with replacement therapy, cardiovascular disease is a major contributor to morbidity and mortality. Conventional thrice-weekly in-center dialysis confers risk factors for cardiovascular disease, including acute hemodynamic fluctuations and rapid shifts in volume and solute concentration. Home hemodialysis and peritoneal dialysis (PD) may offer benefits in attenuation of cardiovascular disease risk factors primarily through improved volume and BP control, reduction (or slowing progression) of left ventricular mass, decreased myocardial stunning, and improved bone and mineral metabolism. Importantly, although trial data are available for several of these risk factors for home hemodialysis, evidence for PD is limited. Among patients with prevalent cardiovascular disease, home hemodialysis and PD may also have potential benefits. PD may offer particular advantages in heart failure given it removes volume directly from the splanchnic circulation, thus offering an efficient method of relieving intravascular congestion. PD also avoids the risk of blood stream infections in patients with cardiac devices or venous wires. We recognize that both home hemodialysis and PD are also associated with potential risks, and these are described in more detail. We conclude with a discussion of barriers to home dialysis and the critical importance of interdisciplinary care models as one component of advancing health equity with respect to home dialysis.

Inclusion of Participants with CKD and Other Kidney-Related Considerations during Clinical Drug Development: Landscape Analysis of Anticancer Agents Approved from 2015 to 2019.

BACKGROUND: The US Food and Drug Administration has prioritized efforts to expand availability of therapies, including anticancer agents, for patients with CKD. US Food and Drug Administration Guidance recommends inclusion of study participants with CKD in clinical trials, improving pharmacokinetic characterization in people with decreased GFR, and using contemporary GFR assessment methods during drug development. We performed a landscape analysis of anticancer agents approved from 2015 to 2019 to evaluate inclusion of study participants with CKD and GFR assessment methods used during drug development and subsequent translation to kidney-related safety and dosing data in product labeling. METHODS: Oncology drugs approved from 2015 to 2019 and associated pivotal trials were identified. We evaluated inclusion of study participants with CKD in pivotal trials and pharmacokinetic analyses, investigated GFR assessment methods used for pivotal trial eligibility and renal pharmacokinetic analyses, and identified kidney-related adverse drug event and dosing information. RESULTS: A total of 55 drugs and 74 pivotal trials were included. Of the pivotal trials, 95% contained kidney-related eligibility criteria, including 68% with GFR-based eligibility. The median lower limit of GFR required for inclusion was 45 ml/min or ml/min per 1.73 m 2 . Pharmacokinetic analyses were performed in CKD stages 4-5 and hemodialysis for only 29% and 6% of drugs, respectively. Estimated creatinine clearance was used in over 60% and 80% of pivotal trials and pharmacokinetic analyses, respectively. Reporting of kidney-related adverse drug events was highly variable. Product labeling for 49% of drugs contained no kidney dosing information. CONCLUSIONS: Study participants with CKD continue to be excluded from anticancer drug development, and GFR estimation in pivotal trials and renal pharmacokinetic analyses remains imprecise and heterogeneous. Furthermore, kidney-related safety and dosing information is scarcely and inconsistently presented.