Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats

Wester, Maarten; Gelder, Maaike K. van; Joles, Jaap A.; Simonis, Frank; Hazenbrink, Diënty H. M.; Berkel, Theo W. M. van; Vaessen, Koen R. D.; Boer, Walther H.; Verhaar, Marianne C.; Gerritsen, Karin G.F.

doi:10.1152/ajprenal.00094.2018

Cited by 14 publications

(17 citation statements)

References 34 publications

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“…First, a single intra-arterial blood pressure measurement was performed two months after embolization to evaluate blood pressure during CKD as continuous telemetric blood pressure monitoring was not available. However, for the purpose of monitoring blood pressure during HD, we demonstrated that the placement of a temporary intra-arterial catheter in the auricular artery is technically feasible in goats [ 41 ]. Second, the number of animals in the present study is relatively small compared with that used in previous studies for the development of uremic large-animal models (7–26 animals).…”

Section: Discussionmentioning

confidence: 99%

A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin

Gelder

Vries

Ahmed

et al. 2021

Biology

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A large animal model of (end-stage) kidney disease (ESKD) is needed for the preclinical testing of novel renal replacement therapies. This study aimed to create stable uremia via subtotal renal artery embolization in goats and induce a temporary further decline in kidney function by administration of gentamicin. Renal artery embolization was performed in five Dutch white goats by infusing polyvinyl alcohol particles in branches of the renal artery, aiming for the embolization of ~80% of one kidney and complete embolization of the contralateral kidney. Gentamicin was administered to temporarily further increase the plasma concentrations of uremic toxins. After initial acute kidney injury, urea and creatinine plasma concentrations stabilized 1.5 ± 0.7 months post-embolization and remained elevated (12 ± 1.4 vs. 5.6 ± 0.8 mmol/L and 174 ± 45 vs. 65 ± 5.6 µmol/L, resp.) during follow-up (16 ± 6 months). Gentamicin induced temporary acute-on-chronic kidney injury with a variable increase in plasma concentrations of small solutes (urea 29 ± 15 mmol/L, creatinine 841 ± 584 µmol/L, phosphate 2.2 ± 0.3 mmol/L and potassium 5.0 ± 0.6 mmol/L) and protein-bound uremic toxins representative of patients with ESKD. A uremic goat model characterized by stable moderate uremia was established via subtotal renal artery embolization with the induction of temporary severe acute-on-chronic kidney injury by the administration of gentamicin, allowing preclinical in vivo validation of novel renal replacement technologies.

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Section: Discussionmentioning

confidence: 99%

A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin

Gelder

Vries

Ahmed

et al. 2021

Biology

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“…Although bicarbonate and pH tended to decline with EO‐regenerated hemofiltration, this could be attributed to not‐EO‐related bicarbonate removal during dialysate regeneration. Our group evaluated a miniature dialysis device, identical to the device used in the present study for plasma experiments, with continuous dialysate regeneration using EO in combination with AC and ion exchangers in vitro and healthy goats 9,11 . In vitro, treatment of dialysate or uremic plasma with this device did not affect total antioxidant capacity, intracellular ROS generation, cell viability, or cell proliferation compared to treatment with AC without EO.…”

Section: Discussionmentioning

confidence: 99%

“…We previously demonstrated that clinically relevant urea removal could be achieved in vitro and in vivo when using EO for the regeneration of spent dialysate. 2 , 9 However, a disadvantage of EO is the formation of toxic oxidative by‐products, such as free chlorine (hypochlorous acid and hypochlorite) and bound chlorine (chloramines and chlorinated organic compounds), ammonium (due to hydrolysis of nitrogenous organic compounds), and other (potentially toxic) unknown compounds. We previously showed that free and bound chlorine release could be reduced to levels below the maximum acceptable levels (as defined by the Association for the Advancement of Medical Instrumentation [AAMI] standards for dialysate in HD) by using graphite electrodes combined with AC at a current of 3 A.…”

Section: Introductionmentioning

confidence: 99%

“…We previously showed that free and bound chlorine release could be reduced to levels below the maximum acceptable levels (as defined by the Association for the Advancement of Medical Instrumentation [AAMI] standards for dialysate in HD) by using graphite electrodes combined with AC at a current of 3 A. 9 , 10 Ammonium release could be reduced by the placement of AC and a cation exchanger downstream of the EO unit to capture ammonium. 9 However, it is unknown whether other potentially toxic compounds are formed that are not removed by AC.…”

Section: Introductionmentioning

confidence: 99%

“… 9 , 10 Ammonium release could be reduced by the placement of AC and a cation exchanger downstream of the EO unit to capture ammonium. 9 However, it is unknown whether other potentially toxic compounds are formed that are not removed by AC.…”

Section: Introductionmentioning

confidence: 99%

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Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products

et al. 2021

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A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO‐based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3‐deoxyglucosone) were measured in EO‐ and non‐EO‐treated fluids. Glyoxal and methylglyoxal concentrations increased 26‐ and 11‐fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209‐ and 353‐fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.

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Second Generation Nanoporous Silicon Nitride Membranes for High Toxin Clearance and Small Format Hemodialysis

Hill

Walker

Salminen

et al. 2020

Adv Healthcare Materials

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Conventional hemodialysis (HD) uses floor‐standing instruments and bulky dialysis cartridges containing ≈2 m2 of 10 micrometer thick, tortuous‐path membranes. Portable and wearable HD systems can improve outcomes for patients with end‐stage renal disease by facilitating more frequent, longer dialysis at home, providing more physiological toxin clearance. Developing devices with these benefits requires highly efficient membranes to clear clinically relevant toxins in small formats. Here, the ability of ultrathin (<100 nm) silicon‐nitride‐based membranes to reduce the membrane area required to clear toxins by orders of magnitude is shown. Advanced fabrication methods are introduced that produce nanoporous silicon nitride membranes (NPN‐O) that are two times stronger than the original nanoporous nitride materials (NPN) and feature pore sizes appropriate for middle‐weight serum toxin removal. Single‐pass benchtop studies with NPN‐O (1.4 mm2) demonstrate the extraordinary clearance potential of these membranes (105 mL min−1 m−2), and their intrinsic hemocompatibility. Results of benchtop studies with nanomembranes, and 4 h dialysis of uremic rats, indicate that NPN‐O can reduce the membrane area required for hemodialysis by two orders of magnitude, suggesting the performance and robustness needed to enable small‐format hemodialysis, a milestone in the development of small‐format hemodialysis systems.

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Removal of urea by electro-oxidation in a miniature dialysis device: a study in awake goats

Abstract: In conclusion, clinically relevant urea removal was achieved in vivo by electro-oxidation. Efficacy and safety testing in a large animal model with uremia is now indicated.

Cited by 14 publications

References 34 publications

A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin

A Uremic Goat Model Created by Subtotal Renal Artery Embolization and Gentamicin

Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products

Second Generation Nanoporous Silicon Nitride Membranes for High Toxin Clearance and Small Format Hemodialysis

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