Hypoalbuminemia is a major risk factor for morbidity and mortality in dialysis patients. With increasing interest in highly permeable membranes and convective therapies to improve removal of middle molecules, transmembrane albumin loss increases accordingly. Currently, the acceptable upper limit of albumin loss for extracorporeal renal replacement therapies is unknown. In theory, any additional albumin loss should be minimized because it may contribute to hypoalbuminemia and adversely affect the patient’s prognosis. However, hypoalbuminemia-associated mortality may be a consequence of inflammation and malnutrition, rather than low albumin levels per se. The purpose of this review is to give an overview of albumin handling with different extracorporeal renal replacement strategies. We conclude that the acceptable upper limit of dialysis-related albumin loss remains unknown. Whether enhanced middle molecule removal outweighs the potential adverse effects of increased albumin loss with novel highly permeable membranes and convective therapies is yet to be determined.

Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (−15.3 to 34.6) in patients treated with HDF and increased by 11.9% (−15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients' health. Prolonged hemodialysis (with adequate anticoagulation) could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients' overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, the time that patients' blood is exposed to the dialyzer material is longer during prolonged hemodialysis, and blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers.

Connective tissue growth factor (CTGF) plays a key role in the pathogenesis of tissue fibrosis. The aminoterminal fragment of CTGF is a middle molecule that accumulates in chronic kidney disease. The aims of this study are to explore determinants of plasma CTGF in hemodialysis (HD) patients, investigate whether CTGF relates to all-cause mortality in HD patients, and investigate whether online-hemodiafiltration (HDF) lowers CTGF. Data from 404 patients participating in the CONvective TRAnsport STudy (CONTRAST) were analyzed. Patients were randomized to low-flux HD or HDF. Pre-dialysis CTGF was measured by sandwich ELISA at baseline, after six and 12 months. CTGF was inversely related in multivariable analysis to glomerular filtration rate (GFR) (p < 0.001) and positively to cardiovascular disease (CVD) (p = 0.006), dialysis vintage (p < 0.001), interleukin-6 (p < 0.001), beta-2-microglobulin (p = 0.045), polycystic kidney disease (p < 0.001), tubulointerstitial nephritis (p = 0.002), and renal vascular disease (p = 0.041). Patients in the highest quartile had a higher mortality risk compared to those in the lowest quartile (HR 1.7, 95% CI: 1.02–2.88, p = 0.043). HDF lowered CTGF with 4.8% between baseline and six months, whereas during HD, CTGF increased with 4.9% (p < 0.001). In conclusion, in HD patients, CTGF is related to GFR, CVD and underlying renal disease and increased the risk of all-cause mortality. HDF reduces CTGF.

Improving home haemodialysis: Stability evaluation of routine clinical chemistry analytes in blood samples of haemodialysis patients