Víctor Joaquín Escudero-Saiz

BK polyomavirus (BKPyV) infection is a major complication after kidney transplantation, with no approved antiviral therapy and management reliant on immunosuppression reduction, which increases rejection risk. This review outlines the biological rationale for extracorporeal photopheresis (ECP) in infectious settings and critically appraises the current evidence for its use in BKPyV replication and BKPyV-associated nephropathy (BKPyVAN). ECP is an immunomodulatory therapy that induces apoptosis of apheresis-isolated mononuclear cells via ex vivo exposure to a photoactivatable agent and UVA light; reinfusion promotes tolerogenic dendritic cells, regulatory T-cell expansion, and cytokine modulation. Its antiviral potential was first observed in cytomegalovirus, with ECP linked to reduced viral burden in heart, lung, and hematopoietic transplantation. Experience in BKPyV is more limited, restricted to small case series and reports, where ECP combined with immunosuppression reduction was associated with sustained reductions in viremia, reaching >99% in individual series, without increased rejection. These uncontrolled, confounded designs cannot isolate an ECP-specific antiviral effect, and the proposed antiviral mechanism remains hypothetical. ECP may be a promising adjunctive strategy in selected high-risk patients with persistent BKPyV viremia or BKPyVAN, but prospective, controlled studies are needed to confirm efficacy and define optimal use.

Background: Synthetic dialysis membranes, particularly those composed of polysulfone blended with polyvinylpyrrolidone, are commonly used in hemodialysis due to their efficiency. However, hypersensitivity reactions—often atypical and not fitting traditional type A and B classifications—have increasingly been reported. Symptoms include chest tightness, bronchospasm, oxygen desaturation, and hypotension, often without clear etiology. The need for safer alternatives has led to interest in newer dialyzer technologies, such as the hydrophilic helixone membrane which incorporates tocopherol to enhance biocompatibility. Methods: We conducted a multicenter, retrospective observational study in four hemodialysis units in Catalonia (Spain). Thirty‐one stable patients previously diagnosed with hypersensitivity to synthetic membranes and dialyzing with cellulose triacetate were switched to hydrophilic helixone (CorAL) dialyzers. Clinical data, including symptoms before and after the switch, were extracted from medical records. The primary outcome was the occurrence of adverse reactions after the transition. Results: Of the 31 patients (mean age 70.1 ± 13.9 years), the most common symptoms at initial reaction included cutaneous (21, 67.7%), respiratory (13, 41.9%), and cardiovascular (9, 29.0%) manifestations. After switching to hydrophilic helixone, 28 patients (90.3%) had no further hypersensitivity symptoms over a mean follow‐up of 5.8 ± 4.3 months. Three patients experienced mild reactions (two with pruritus, one with hypotension) and reverted to cellulose triacetate. No significant associations were found between relapse and the type of membrane or symptom profile. Conclusions: The hydrophilic helixone membranes appear to be a safe and well‐tolerated alternative for patients with a history of hypersensitivity to synthetic membranes. These findings suggest that hydrophilic helixone dialyzers may allow more patients to continue treatment with synthetic membranes without severe reactions, potentially improving biocompatibility and treatment flexibility in routine clinical practice. While the findings are promising, larger prospective studies are necessary to confirm the safety and long‐term clinical benefits.

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1–3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice.

Background: BK virus–associated nephropathy (BKVAN) remains an important risk factor for kidney graft loss. The current strategy to treat the BKVAN consists in reducing immunosuppressants. However, this strategy increases the risk of graft rejection, especially in highly sensitized patients or those with previous rejection episodes. Extracorporeal photopheresis (ECP) has been used for the treatment of T cell–mediated disorders, such as solid organ rejection in cardiac, lung and hepatic transplantation, due to its immunotolerogenic effect. In addition, some data suggest that ECP might also have an immunogenic effect, generating an immune response against infections. Methods: Herein we present a single-center case series of 13 patients with refractory histological-diagnosed BKVAN, where ECP was used after the failure of standard therapy. The cohort had a median age of 51 years (interquartile range 42–59), with 46% considered low immunological risk (cPRA 0%) and 54% high risk (cPRA >50%). ECP was initiated a median of 21.3 weeks (5.9–49.1) after BKVAN diagnosis, with patients receiving a median of 11 sessions (10–20). Results: After starting ECP, serum BK viral load significantly decreased by 55.3%, 95.9%, 99.7% and 99.9% at 3, 6, 12 and 18 months after ECP, respectively, while kidney function slowly decreased but at a lower rate than the historical group not treated with ECP, and no adverse events were observed. Despite the reduction in immunosuppression, only one patient experienced graft rejection during follow-up, with no major impact on graft function. Conclusion: These findings indicate that ECP may provide potential therapeutic benefits for BKVAN and could warrant further investigation in the context of kidney transplantation.

Accurate quantification of indoxyl sulfate (IndS) and p-cresyl sulfate (pCS) is essential for understanding their role in chronic kidney disease (CKD) progression and for developing strategies to mitigate their harmful effects, including cardiovascular morbidity and renal fibrosis. Advances in liquid chromatography–high-resolution mass spectrometry (LC–HRMS) enable the integration of powerful diagnostic tools into clinical laboratories. Along with accurate quantification, precise mass measurements allow for untargeted compound identification. Methods. An LC–HRMS was validated for quantifying IndS and pCS in human serum, following EMA guidelines. The method involved protein precipitation with methanol, micro-LC for chromatographic separation, and detection based on accurate mass, with simultaneous high-resolution full-scan acquisition. Clinical samples from patients with varying degrees of renal insufficiency and samples obtained before and after hemodiafiltration were analyzed. Results. The method demonstrated acceptable linearity, precision, and accuracy. The measurement range for both analytes was from 100 to 40,000 ng/mL. Serum levels of IndS and pCS correlated with decreased renal function. After hemodiafiltration, there was a significant reduction of IndS (50%) and pCS (43%). Simultaneous untargeted analysis allowed to identify metabolites significantly underexpressed after hemodiafiltration. Conclusions. An accurate LC–HRMS method was validated for the quantification of IndS and pCS serum levels in patients with CKD, providing insights into toxin dynamics and enabling untargeted metabolic evaluation.

The dialysis membrane based on a hydrophilic polymer (Hydrolink NV) was designed to enhance the movement of adsorbed water at the blood–membrane interface, aiming to achieve antithrombogenic and antifouling effects. This study aimed to assess the performance and albumin loss of the Hydrolink NV dialyzer in hemodialysis (HD) and post-dilution hemodiafiltration (HDF) with different infusion flows (Qis) and compare it with the hydrophilic FX CorAL dialyzer in post-dilution HDF. A prospective study was carried out in 20 patients. Patients underwent five dialysis sessions with the same routine dialysis parameters: four sessions with the Toraylight NV 2.1 (HD, post-dilution HDF with 50, 75 or auto-substitution Qi) and one with the FX CorAL 800 (post-dilution HDF with auto-substitution Qi). The reduction ratios’ (RRs’) wide range of molecular weight molecules were assessed and the dialysate albumin loss was quantified. The lowest β₂-microglobulin, indoxyl-sulfate, and p-cresyl sulfate RR values were observed with the Toraylight NV 2.1 in HD, and they improved progressively with an increased Qi, without differences being observed between the two dialyzers in auto-substitution. A different removal profile was observed in terms of myoglobin, kFLC, prolactin, α₁-microglobulin, α₁-acid glycoprotein, and λFLC, whose RRs also improved progressively with an increased Qi but were significantly higher with the Toraylight NV than the CorAL in the same convective condition. There were significant differences in the albumin dialysate losses, with the highest value obtained with the Toraylight NV in auto-substitution HDF, with more than 50% of patients surpassing 5 g per session. The Toraylight NV dialyzer has great potential for efficacy but should be used at the optimal convective volume (Qi not exceeding 75 mL/min or FF not exceeding 25%) to avoid excessive albumin loss.

Background: High-volume online hemodiafiltration (OL-HDF) has proven to be the most efficient dialysis modality and to offer better clinical outcomes in patients on hemodialysis. Longer and more frequent dialysis sessions have demonstrated clinical and survival benefits. Methods: A single-center observational study of the first one hundred patients on nocturnal every-other-day OL-HDF was conducted with the aim of reporting the experience with this treatment schedule and evaluating analytical and clinical outcomes as well as the patient and technique survival. Results: Nocturnal OL-HDF on alternate days was highly accepted, with no adverse symptoms, good clinical tolerance, and maintained active work in 62%. Kt, and the convective volume increased from 67.6 ± 12 L to 105.4 ± 11.7 L, and from 27.1 ± 4.6 L to 48.1 ± 6.4 L, respectively, from the baseline to 24 months. An improved calcium–phosphate balance and blood pressure control were observed, as the use of phosphate binders and antihypertensive medications decreased from 76.7% to 3.3% and from 56.7% to 28.3%, respectively. Furthermore, 58.3% of patients required phosphate supplementation in the dialysis fluid to prevent intradialytic hypophosphatemia. Additionally, doses of iron and erythropoiesis-stimulating agents were reduced. The global patient survival was 94% at the end of the follow-up. It was higher in those on the transplant waiting list, with 98.1% survival compared to 84.6% in non-wait-listed patients at 24 months. The main reason for treatment discontinuation was kidney transplantation, accounting for 78.4% of the 88 withdrawals, while death was the leading cause of discontinuation in non-listed patients (41.6%). Conclusions: Nocturnal every-other-day OL-HDF is a well-tolerated dialysis regimen that offers significant clinical benefits, which may positively impact morbidity and mortality. Additionally, it allows patients to integrate the treatment into their social and occupational lives.

Pain is a frequent and disturbing symptom among hemodialysis patients. Protein-bound uremic toxins (PBUTs) are related to cardiovascular and overall mortality, and they are difficult to remove with current hemodialysis treatments. The PBUT displacers, such as furosemide, tryptophan, or ibuprofen, may be promising new strategies for improving their clearance. This study aims to compare ibuprofen versus other analgesic drugs in PBUT removal. A prospective study was carried out in 23 patients. Patients underwent four dialysis sessions with routine dialysis parameters, except for analgesic drugs administered (lysine acetylsalicylic acid, acetaminophen, dexketoprofen, and ibuprofen). The reduction ratios (RRs) of a wide range of molecular weight molecules were assessed, including total p-cresyl sulfate and total indoxyl-sulfate. There were no complications related to the administered drug, and pain was controlled independently of the drug. There were no differences in the RR of small-size and medium-sized molecules between all four study treatments. However, indoxyl sulfate and p-cresyl sulfate RRs when ibuprofen was administered were significantly higher than lysine acetylsalicylic acid, acetaminophen, and dexketoprofen treatments. In conclusion, patients with pain may benefit from treatment with ibuprofen instead of lysine acetylsalicylic acid, paracetamol, or dexketoprofen, since in addition to improving pain, it increases the removal of PBUTs.