Abstract
Uremic toxins (UTs) generally accumulate in patients developing end-stage renal disease (ESRD). Although some kinds of UTs cause early death after starting hemodialysis (HD), it remains unknown whether the degree of excessive accumulation of various UTs is associated with worsening of prognosis. We retrospectively conducted this cohort study consisting of adult patients developing ESRD who initiated HD at the National Center for Global Health and Medicine from 2010 to 2019. We created a new uremic score, which was defined as the aggregate score of the following variables reflecting uremic state: elevated blood urea nitrogen, β2-microglobulin, and anion gap before starting HD. The primary outcome was early mortality within 1-year after HD commencement. The hazard ratio (HR) and 95% confidence interval (CI) for a one-point increase in uremic score was calculated with Cox proportional hazard models adjusted by baseline conditions. We included 230 participants, 16 of whom experienced the primary outcome of early mortality after HD commencement. Uremic score was significantly associated with the primary outcome (crude HR: 1.91, 95% CI 1.16–3.14; adjusted HR: 4.19, 95% CI 1.79–9.78). Our novel uremic score, reflecting accumulation of specific UTs, more precisely predicts early mortality after HD commencement.
Highlights
One of the main roles of the kidney is to excrete harmful metabolites and toxins produced by various metabolic activities in the body [1,2]
We found that uremic score, defined as the aggregate score of three variables reflecting the uremic state, i.e., elevated blood urea nitrogen (BUN), β2MG, and anion gap (AG) before HD commencement, was related to 1-year mortality after HD commencement in adult end-stage renal disease (ESRD) patients
Elevated BUN mainly correlated with cardiovascular problems, including blood pressure and comorbid cardiovascular diseases, elevated β2MG levels mainly correlated with malnutrition and inflammation in patients with more advanced impairment of residual kidney function, and elevated AG mainly correlated with inflammation unaccompanied by malnutrition
Summary
One of the main roles of the kidney is to excrete harmful metabolites and toxins produced by various metabolic activities in the body [1,2]. Normal kidney with enough renal function provides efficient excretion of these uremic toxins (UTs), UTs generally accumulate in patients developing chronic kidney disease (CKD) [3]. Many UTs have been proven to perform unfavorable biological activity, resulting in poor prognosis, and causing uremic syndrome in patients developing end-stage renal disease (ESRD) [4]. Dialysis therapy has been established as a practical renal replacement therapy to remove a sufficient amount of small water-soluble and smaller mid-size. Dialysis is generally initiated when subjective symptoms of uremic syndrome appear and are not treatable by other medications regardless of residual kidney function, there are only a few widely established objective indicators to diagnose uremic syndrome despite the variety of UTs. Many UTs have been newly identified using integrative metabolomic and proteomic approaches in the past few years [4]. Blood urea nitrogen (BUN) has been universally regarded as a surrogate for all accruing small water-soluble UTs, and an indicator of the need to start dialysis [6]
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