From the Guidelines
Uremic toxins should be managed by interpreting serum levels of urea or creatinine in the context of their rates of change over time, and treatment dose should be based on marker clearance, with a minimum Kt/V of 1.2 delivered three times a week for patients with acute renal failure (ARF) 1.
Key Points
- The exact identity and relative importance of all uremic toxins are unknown, and no single substance or group of substances have been directly related to adverse effects 1.
- Urea is only a marker substance for the clinical condition known as uremia, and absolute levels of urea and creatinine are difficult to interpret 1.
- The rates of change of urea or creatinine levels may better reflect severity of renal failure, with rapid increases suggesting severe renal dysfunction 1.
- Marker clearance should be used as the primary basis for continuous renal replacement therapy (CRRT) dosing, with fractional clearance being an even better measure 1.
- Emerging evidence suggests the importance of using standardized Kt/V or equivalent renal clearance to compare disparate therapies and different frequencies of treatment 1.
Treatment Considerations
- Treatment dose affects outcome for stable patients with end-stage renal disease (ESRD), and recent evidence supports a similar relationship for patients with ARF 1.
- Higher doses of dialysis may be beneficial in critically ill patients with ARF, with an intensity of continuous venovenous hemofiltration (CVVH) of 35 mL/kg/hour associated with improved survival 1.
- A dose-response relationship exists for dialysis in ARF, and the traditional, ESRD-based, dose recommendation may be too low 1.
From the Research
Uremic Toxins Overview
- Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules 2
- The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of chronic kidney disease (CKD) and its co-morbidities, including cardiovascular disease (CVD) 2
Removal of Uremic Toxins
- Conventional dialysis mainly focuses on the removal of water-soluble compounds of low and middle molecular weight, whereas protein-bound uremic toxins (PBUTs) are strongly protein-bound, thus not efficiently eliminated 3
- Adsorption-based extracorporeal techniques, in addition to conventional dialysis treatment, may effectively adsorb a significant amount of PBUTs during the course of the sessions 3
- Protection of residual kidney function (RKF) can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days 4
Uremic Toxins and Disease Progression
- The retention of uremic toxins and their pathological effects occurs in the advanced phases of CKD, mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment 4
- Uremic toxins, such as indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6, have been identified as potential contributors to the progression of CKD and CVD 2
Management of Uremic Toxins
- Reducing the production of uremic toxins, for example by a low or very low-protein diet, and increasing their removal, for example by adsorption-based extracorporeal techniques, may be a feasible strategy to improve toxins removal effectiveness 4, 3
- Lanthanum carbonate and sevelamer carbonate are phosphate binders that can be used to manage hyperphosphatemia in CKD patients, but their efficacy in reducing uremic toxins is not well established 5