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BackgroundChronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS).MethodsWe have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography).ResultsGene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression.ConclusionThese findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to uremic plasma identifies IS as a major, poorly dialyzable, uremic toxin. The signaling pathways initiated by IS and possibly other solutes not effectively removed by dialysis may participate in the pathogenesis of renal scarring and uremic vasculopathy.

Further research on how contextual factors, such as the vocal properties of health care examiners and exposure to background voices, may influence momentary pain perception is necessary for creating more standardized methods for measuring patient pain reports in clinical settings.

This article presents the telehealth version of the Buffalo Concussion Physical Examination (BCPE) (Tele-BCPE). It is a brief, focused telehealth PE for use in the outpatient setting by sports medicine physicians, pediatricians, neurologists, and primary care physicians. It is derived from the BCPE and includes general considerations for providers performing telehealth services and instructions for adapting traditional clinical tests for virtual use. The Tele-BCPE includes an orthostatic intolerance screen, examination of the cranial nerves, and tests of the oculomotor, vestibular, and cervical systems. It is meant to be used at initial and follow-up outpatient visits for patients acutely after concussion and in those with prolonged symptoms. This telehealth PE, when combined with other assessments, can help provide direct treatment to patients at any stage after concussion and reduce barriers to healthcare access posed by the COVID-19 pandemic and for patients living in rural or underserved areas.