Uremia Retention Molecules and Clinical Outcomes

Barreto, Fellype Carvalho; Barreto, Daniela Veit; Canziani, María Eugênia Fernandes

doi:10.1159/000479253

Cited by 14 publications

(9 citation statements)

References 49 publications

(55 reference statements)

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“…Elevated ADMA and SDMA are related with increased all-cause mortality and cardiovascular disease [ 39 ]. Both markers accumulate in chronic kidney disease by increased synthesis, reduced catabolism and reduced renal clearance [ 40 ]. They are small molecules (202 Da) but poorly dialyzed with a substantial rebound occurring at the end of dialysis, which is explained by extended volume of distribution [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children

et al. 2018

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Randomized trials in adults have shown reduced all-cause and cardiovascular mortality on hemodiafiltration (HDF) compared to high-flux hemodialysis (HD), but the mechanisms leading to improved outcomes are not clear. We studied biomarkers of inflammation, oxidative stress, anti-oxidant capacity and endothelial dysfunction in 22 children (13 female, age 8–15 years). All children received HD for at least 3 months, and were then switched to HDF, keeping all dialysis related parameters and dialysis time constant. All the biomarkers of inflammation (ß2-microglobulin, IL-6, IL-10, high sensitive C-reactive protein [hsCRP]), oxidative stress (nitrotyrosine, advanced glycation end-products [AGEs], oxidized low density lipoprotein [ox-LDL] and anti-oxidant capacity) and endothelial dysfunction (asymmetric dimethyl arginine [ADMA], symmetric dimethyl arginine [SDMA]), were comparable between incident and prevalent patients on HD, suggesting that even a short dialysis vintage of 3 months on HD increases inflammation and endothelial stress. After 3 months of HDF therapy there was a significant reduction in ß2-microglobulin (p<0.001), hCRP, ADMA, SDMA, AGEs, ox-LDL (p<0.01 for all) and an increase in total antioxidant capacity (p<0.001) compared to HD. All children were maintained on the same dialyser, dialysis water quality, dialysis time and blood flow speeds suggesting that improved clearances on HDF led to an improved biomarker profile. Even in children with residual renal function there was a significant reduction in ß2 microglobulin, hsCRP, SDMA, ox-LDL and AGEs on HDF compared to HD. Children with a lower blood flow had higher inflammatory status (higher IL-6/IL-10 ratio; p = 0.04, r = -0.43). Children who achieved a higher convective volume (≥median 12.8L/m2) had lower ox-LDL (p = 0.02). In conclusion, we have shown that a significant improvement in inflammation, antioxidant capacity and endothelial risk profile is achieved even within a short time (3 months) on HDF compared to HD treatment.Trial Registration: ClinicalTrials.gov: NCT02063776.

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Section: Discussionmentioning

confidence: 99%

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children

et al. 2018

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“…Such results are partly due to the ever-changing case mix with a continuous increase of older and sicker population. Nevertheless, we may recognize important limitations of current dialysis technology that appears to be incapable of achieving adequate blood purification from several identified uremic toxins [1-6, 34-36]. Continuous innovation and research are therefore needed to improve quality of care and to find solutions for unmet clinical needs [37, 38].…”

Section: Discussionmentioning

confidence: 99%

Quantification of Internal Filtration in Hollow Fiber Hemodialyzers with Medium Cut-Off Membrane

et al. 2018

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Background: Inadequate removal of molecules between 5 and 50 KDa may cause long-term complication in chronic hemodialysis. Medium cut-off (MCO) is a new class of membranes with enhanced sieving properties and negligible albumin loss. MCO membrane makes it possible to perform expanded hemodialysis (HDx), a technique based on high internal filtration (IF).The present study is designed to quantify IF in 2 MCO dialyzers (Theranova 400 and 500, Baxter, Deerfield, USA) using a nuclear imaging technique previously validated. Methods: Blood and dialysate compartment pressure drop along with transmembrane pressure; they were measured in a closed in vitro circuit with human blood (blood flow [Q_B] = 300 and 400 mL/min; dialysate flow 500 mL/min; net ultrafiltration rate 0 mL/min). A non-diffusible marker molecule (albumin macro-aggregates labeled with ⁹⁹Tc metastable) was injected in the blood compartment and nuclear emission was recorded by a gamma camera. Relative variations in the concentration of the marker molecule along the length of the filter were used to calculate local cross filtration. Results: Based on marker concentration profiles, IF was estimated. For Theranova 400, IF were 29.7 and 41.6 mL/min for Q_B of 300 and 400 mL/min. For Theranova 500, IF were 31.6 and 53.1 mL/min for Q_B of 300 and 400 mL/min respectively. Conclusions: MCO membrane provides significant amounts of IF due to the particular combination between hydraulic permeability of the membrane and reduced inner diameter of the fibers. High IF combined with enhanced sieving profile of MCO membrane leads to improved removal of a wider spectrum of uremia retention molecules in HDx, without requiring complex equipment.

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“…In a rat model of chronic renal failure (CRF), the overload of PAH and indoleacetic acid accelerated the loss of kidney function, glomerular sclerosis and tubulointerstitial injury [141]. Numerous studies in patients with CRF showed that uremic toxin accumulation leads to various complications including endothelial senescence [142], atherogenesis [143], cardiovascular diseases [144,145] or increased risk of all-cause mortality [144,146]. In CRF, these toxins accumulate for very long periods, making their toxicity particularly critical.…”

Section: Accumulation Of Toxic Substancesmentioning

confidence: 99%

Effects of Ischemia-Reperfusion on Tubular Cell Membrane Transporters and Consequences in Kidney Transplantation

Faucher

Alarcan

Marquet

et al. 2020

JCM

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Ischemia-reperfusion (IR)-induced acute kidney injury (IRI) is an inevitable event in kidney transplantation. It is a complex pathophysiological process associated with numerous structural and metabolic changes that have a profound influence on the early and the late function of the transplanted kidney. Proximal tubular cells are particularly sensitive to IRI. These cells are involved in renal and whole-body homeostasis, detoxification processes and drugs elimination by a transporter-dependent, transcellular transport system involving Solute Carriers (SLCs) and ATP Binding Cassettes (ABCs) transporters. Numerous studies conducted mainly in animal models suggested that IRI causes decreased expression and activity of some major tubular transporters. This could favor uremic toxins accumulation and renal metabolic alterations or impact the pharmacokinetic/toxicity of drugs used in transplantation. It is of particular importance to understand the underlying mechanisms and effects of IR on tubular transporters in order to improve the mechanistic understanding of IRI pathophysiology, identify biomarkers of graft function or promote the design and development of novel and effective therapies. Modulation of transporters’ activity could thus be a new therapeutic opportunity to attenuate kidney injury during IR.

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Uremia Retention Molecules and Clinical Outcomes

Cited by 14 publications

References 49 publications

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children

Hemodiafiltration is associated with reduced inflammation, oxidative stress and improved endothelial risk profile compared to high-flux hemodialysis in children

Quantification of Internal Filtration in Hollow Fiber Hemodialyzers with Medium Cut-Off Membrane

Effects of Ischemia-Reperfusion on Tubular Cell Membrane Transporters and Consequences in Kidney Transplantation

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