Aim/ Kidney transplant recipients (KTR) require lifelong immunosuppression with tacrolimus (TAC), a narrow therapeutic index drug with high intra- and inter-patient pharmacokinetic (PK) variability. Evidence suggests the gut microbiome modulates TAC dose requirements. Given the frequent use of antibiotics in KTR, this study investigates their impact on TAC PK to clarify the microbiome’s role in TAC PK variability. Methods/ REFLECT is a retrospective study analysing TAC PK evolution during antibiotherapy in KTR. Routinely collected data were obtained at 4 study occasions: baseline, infection diagnosis, during antibiotherapy (ATB), and 1-month post-ATB stop. Mixed-effects modelling accounted for hierarchical data. Results/ 107 antibiotherapies (760 TAC trough concentrations Ctrough) were analysed. Three PK endpoints were modelled: TAC dose and weight-adjusted Ctrough (Ctrough/(dose kg-1)), TAC Ctrough and TAC dose kg-1. Antibiotic intake influenced all PK endpoints, alongside age, CYP3A5 genotype, haematocrit, creatinine, C-reactive protein, post-transplant period and trimethoprim/sulfamethoxazole prophylaxis. During ATB, mean TAC Ctrough/(dose kg-1) increased by 15.3% (p=0.004) and Ctrough by 16.4% (p<0.001) compared to baseline values, while TAC dosing remained unchanged. At the post-ATB occasion, TAC dose kg-1 decreased by 13.4% (p<0.0001), restoring Ctrough to baseline values. Antibiotics linked to greater Clostridioides difficile infection (CDI) risk and dysbiosis were associated with a larger Ctrough increase (+19.8%, p<0.001). Conclusion/ Antibiotherapy significantly increases TAC exposure without dose adjustment. The greater effect observed with antibiotics associated with an increased risk of CDI supports the hypothesis that gut microbiome contributes to TAC PK variability. These findings underscore the need for close TAC monitoring during and after antibiotherapy.

Living-donor kidney transplantation (KT) offers the best outcomes for patients with kidney failure (KF). However, recurrence of primary kidney disease in the allograft remains a major concern and represents 1 of the leading causes of graft loss, significantly influencing donor and recipient selection. The recurrence risk varies substantially among kidney diseases and must be carefully assessed during pretransplant evaluation. For diseases associated with low-to-intermediate recurrence risk, such as lupus nephritis, antineutrophil cytoplasmic antibodies-associated vasculitis, or IgA nephropathy, living-donor KT is generally safe, although appropriate counseling remains essential. In contrast, diseases such as membranous nephropathy (MN), primary focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), primary hyperoxaluria (PH), and amyloid light-chain (AL) amyloidosis are associated with higher recurrence rates and often require complex, individualized assessment. Recent advances have significantly transformed this field. Biomarkers such as anti-phospholipase A2 receptor (anti-PLA2R) antibodies in MN and antinephrin antibodies in FSGS enable refined risk stratification and tailored pre- and post-transplant strategies. Complement gene analysis and targeted therapies, including eculizumab, have markedly improved outcomes in aHUS, whereas novel complement inhibitors show promise for recurrent C3G. RNA interference therapy has expanded kidney-alone transplantation options in PH, and modern hematologic therapies have improved post-transplant prognosis in AL amyloidosis. These developments are reshaping the decision-making landscape for living-donor KT in diseases with a high risk of recurrence, highlighting the need for multidisciplinary evaluation, individualized strategies, and transparent donor-recipient communication to optimize transplant outcomes.

John Cunningham Virus (JCV) and BK Virus (BKV) are the most extensively studied Human Polyomaviruses (HPyVs), primarily associated with Progressive Multifocal Leukoencephalopathy (PML) and BKV Nephropathy (BKVN), respectively. While co-infection with these viruses has been documented in the same disease, simultaneous manifestation in distinct pathologies has not been previously reported. We present the first documented case of concurrent PML and Polyomavirus Nephropathy (PVN) due to reactivation of two different HPyVs, offering new insights into the clinical spectrum of HPyV-related diseases.

Introduction In kidney transplantation, immunosuppressive therapy is essential to control alloimmune reactions, prevent graft rejection and improve patient survival rates. However, commonly used drugs like tacrolimus (TAC) and mycophenolate mofetil (MMF) have a narrow therapeutic window and exhibit significant inter- and intra-individual variability in pharmacokinetics (PK) and dose-response relationships. Recent pilot studies suggest that the gut microbiome may influence this variability.Methods and analysis ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiome modulations After kidney transplantation (ENIGMA) is a prospective, low-interventional, naturalistic longitudinal trial designed to identify biomarkers of TAC and MMF PK variability by examining gut microbiome changes and modulations after kidney transplantation and their link with TAC and MMF PK. Biological samples from 50 patients will be collected at nine specific timepoints pre- and post-transplantation using a rich PK and biological sampling strategy. This approach will enable the derivation of PK parameters for the investigated drugs and the creation of a biobank for future hypothesis testing.Ethics and dissemination The ENIGMA trial has received ethical approval from the European Medicines Agency (EMA). The reference number of our project is R&D/1325226 and is registered on the Clinical Trial Information System (CTIS) platform with European Union Clinical Trial number 2023–5 08 335-31-00. Results of the trial will be published in scientific journals and presented at different (inter)national conferences.Trial registration number 2023–5 08 335-31-00 EMA.

OBJECTIVE:Integrated interpretation of renal function and natriuretic peptides is essential in ambulatory cardio-renal care. This study evaluated whether a single-capillary dual point-of-care testing (POCT) strategy combining creatinine/eGFR and NT-proBNP could support real-time, integrated clinical decision-making during a single consultation. METHODS:In this exploratory, single-center, real-world study that was designed as a feasibility study focusing on workflow integration and clinical usability, capillary creatinine/eGFR and NT-proBNP were evaluated using a single-fingerstick dual-POCT workflow in two exploratory clinical subgroups recruited according to their respective clinical indications. Analytical agreement was assessed using Passing-Bablok regression (slope, intercept, and 95% confidence intervals) and Bland-Altman analysis. Agreement at guideline-based clinical thresholds (eGFR ≤60 mL/min/1.73m2; NT-proBNP ≥125 ng/L) was evaluated using Cohen's kappa. Workflow feasibility and time-to-result were also documented. RESULTS:Forty-three patients underwent creatinine/eGFR testing, and a separate subgroup of 22 patients underwent NT-proBNP testing, reflecting different clinical indications and real-world recruitment during this exploratory feasibility study. Passing-Bablok regression showed good agreement with slopes close to unity and no significant systematic bias. Bland-Altman analysis demonstrated clinically acceptable limits of agreement. Diagnostic agreement at clinical thresholds was substantial for eGFR (κ=0.71) and perfect for NT-proBNP (κ=1.00), with no clinically relevant misclassification. Dual biomarker results were available within approximately 15 minutes, enabling same-visit clinical decisions. CONCLUSIONS:A single-capillary dual-biomarker POCT workflow enables rapid and reliable cardio-renal assessment within one ambulatory visit. Its primary value lies in integrated, threshold-based clinical interpretation enabled by the simultaneous availability of complementary biomarkers, rather than analytical comparison alone.

Mechanical dysfunction remains a frequent cause of peritoneal dialysis (PD) catheter failure. Fallopian tube entrapment is an uncommon and probably underrecognized mechanism. A 78-year-old woman with end-stage kidney disease secondary to ANCA-associated vasculitis presented early peritoneal dialysis catheter dysfunction after uncomplicated laparoscopic insertion of a Di Paolo catheter. Peritoneal dialysis was successfully initiated 30 days after PD catheter placement and functioned well for 16 days. The patient subsequently experienced slow and incomplete effluent drainage. Clinical examination was normal. Imaging assessment, including abdominal X-ray and CT scan, showed a normally positioned catheter in the right iliac fossa, with the tip positioned in the Douglas pouch. Laparoscopic exploration revealed wrapping of the right Fallopian tube around the catheter tip as primary cause of catheter dysfunction. Following adhesiolysis of the right Fallopian tube, intraoperative functional testing demonstrated persistent catheter dysfunction due to intraluminal fibrin deposits. As these deposits could not be removed by flushing, the catheter was laparoscopically replaced with a new Swan-neck pigtail PD catheter, and the Di Paolo catheter was removed. Postoperative course was uneventful, and PD function was successfully restored three weeks later. This case highlights that normal PD catheter positioning on conventional imaging does not exclude mechanical obstruction. In women presenting with persistent PD catheter dysfunction despite reassuring imaging, uncommon causes, including Fallopian tube entrapment, should be considered, and early diagnostic laparoscopy may provide both diagnosis and definitive treatment.

Nirmatrelvir/ritonavir is a protease inhibitor antiviral drug indicated in the treatment of severe acute respiratory syndrome coronavirus-2 infections in high-risk patients for a severe disease. Unfortunately, ritonavir, used to boost nirmatrelvir pharmacokinetics, can also inhibit or induce the metabolism of other co-administered drugs substrates. This may lead to a subsequent risk of adverse drug reaction and lack of efficacy. In this study, we aimed at describing the expert advices provided by the biological pharmacology network of the SFPT (i.e. the therapeutic drug monitoring specialists working in the laboratories of the pharmacology departments in France/Belgium). From February to August 2022, we collected all specialized advices provided by the biological pharmacology network of the SFPT. Seven pharmacology departments actively participated in the study (Brussels Saint-Luc Hospital in Belgium, Caen, Dijon, Nantes, Nancy, Rennes and Toulouse in France). We collected the following data: patient’s age, date of nirmatrelvir/ritonavir initiation, clinical department requiring the expert advice, patient’s treatments, and advice provided. One hundred and six expert advice on 753 drugs were provided during the seven months of data collection. Two centers provided 83% of all the expert advice (around 8/month). Patients originated form a transplantation department in 65% of the cases. The most common request were for cardiac drugs (28%), immunosuppressive drugs (24%) and endocrine drugs (18%). The advice were distributed as follows: treatment continuation, treatment discontinuation during the antiviral course, dosage adjustment, and treatment switch in 59%, 28%, 11%, and 1.6% of the cases, respectively. Only 2 pieces of advice (0.3%) constituted treatment contra-indications. Drug monitoring was proposed in 10% of prescription lines.Expert advice provided by the biological pharmacology network of the SFPT allows securing the combination of nirmatrelvir/ritonavir with other concomitant drugs. Most of eligible patients to the antiviral drug can benefit from it despite the risk of drug-drug interaction.

Mortality in patients with kidney failure on maintenance haemodialysis (HD) is higher after the long inter-dialytic interval, probably from fluid overload and electrolyte disturbances. In HD patients, the optimal timing of a HD session before surgery is unknown. Surgery induces cardiovascular stress and may trigger cardiac events in fluid overloaded or hyperkalemic patients if the interval between the last HD and the intervention is too long. However, a shorter interval might on the contrary increase bleeding risk due to recent anticoagulation. Whether a shorter or longer interval between the last HD session and surgery impacts early post-transplant outcomes has not been investigated yet. In this study, we evaluate the effect of the timing of the last HD session on the occurrence of delayed graft function and the need for early surgical revision in chronic haemodialysis patients receiving a kidney allograft. In this retrospective monocentric study, we included all adult patients on maintenance HD who received a deceased donor kidney transplant in our centre between 01/01/2015 and 31/12/2022. Patients with no retrievable information regarding the last HD session and multiorgan transplants were excluded. Baseline characteristics (Table 1), data regarding the last dialysis session before transplant surgery (anticoagulation regimen, ultrafiltration volume, haemodialysis modality, dry weight) and transplantation data (date of transplantation, ischemia time, induction therapy) were collected. The timing between the last dialysis and transplantation was defined as the time between the start of the last HD session and anaesthetic induction for kidney transplant. Patients were divided into a “short” (<24h) and “long" (≥24h) interval based on this delay. The primary outcome was a composite of the occurrence of delayed graft function (as defined by the need for dialysis within the first 7 days after kidney transplantation) or surgical revision within the same hospital stay. 202 patients were included, 87 in the “short” and 115 in the “long” group. Baseline characteristics were similar with a median age at transplantation of 55 y. Data regarding transplantation (cold ischemia time (11.4 vs 12.5 hours), donor type (DBD = 71 vs 72%), induction regimen (including plasmapheresis = 21% in both groups), mean peak historic virtual PRA, cardiovascular (25% vs 31%) and diabetes history (20 vs 22%) were similar between the two groups. The median time between the last HD session and transplant surgery was 9 and 35 hours in the “short” and “long” group respectively. In the “short” group, anticoagulation regimen consisted mainly of unfractionated heparin (57%) while some patients did not receive any anticoagulant (13%). Low molecular weight heparin was used in the majority of patients in the “long” group (87%). There was no primary non function in both groups. The primary outcome occurred in 38% of patients in the “short" versus 23% in the “long” group (p-value = 0.02). This was mainly driven by the need for surgical revision (18% vs 8%; p-value = 0.03). The difference in DGF between the two groups was not significant (28% vs 20%; p-value = 0.18) (Fig. 1). In maintenance HD patients, the timing between the last HD session and transplant surgery may impact postoperative outcomes. Patients dialyzed within the last 24 hours were at an increased risk of surgical revision compared to those dialyzed ≥24h before surgery, despite similar characteristics and the use of unfractionated heparin.

Background:Hepatitis E virus (HEV) is the commonest cause of acute viral hepatitis in Western countries. Immunocompromised patients may develop chronic hepatitis. This study aims at determining the seroprevalence and the prevalence of chronic HEV infections in a single tertiary center in Belgium. Methods:From May 2022 to April 2023, we prospectively screened for HEV [immunoglobulin G (IgG), immunoglobulin M (IgM), and polymerase chain reaction (PCR)] all patients transplanted from a solid organ transplantation (SOT) and patients suffering from a lymphoma or followed for a bone marrow transplantation. Results:A total of 740 patients were included: 335 followed for a kidney transplantation (KT), 136 for a heart transplantation (HT), 200 for a liver transplantation (LT), and 69 for a hematological disease (HD). The HEV seroprevalence of the total population is 9.9%. In subgroup analysis, the HEV seroprevalence is 11% for the HT patients, 8.4% for the KT patients, 14% for the LT patients, and 2.9% for the patients followed for HD. There was a significant difference for HEV seroprevalence between HDs and HT group (P=0.046) and between HD and LT group (P=0.01). The identified risk factors for HEV seropositivity were age and being liver transplanted. In the total population, we identified 5 patients with chronic HEV (0.6%), all of them were kidney transplanted patients. HEV clearance was not achieved after decreasing immunosuppression, and a ribavirin treatment was initiated. Conclusions:HEV IgG seroprevalence in our immunosuppressed population is 9.9%. Chronic HEV was found in 0.6% of the patients, all kidney transplanted and having required ribavirin treatment.

Background: Urinary tract infections (UTIs) are a common complication after kidney transplantation. The aim of this study was to evaluate the impact of pre-existing diabetes mellitus and post-transplant diabetes mellitus (PTDM) on the occurrence of pyelonephritis in kidney transplant recipients. Methods: We performed a retrospective analysis which included 299 adult patients transplanted with a kidney between 2018 and 2022. Patients were categorized into pre-transplantation diabetics, PTDM, and non-diabetics. Asymptomatic bacteriuria and lower urinary infections were not included. Results: During a median follow-up time of 31 [17–45] months, 100 UTIs were reported in the total cohort, with a mean time from transplantation to the first UTI episode of 10 ± 11 months. At 48 months, the cumulative incidence of UTIs was 34.9%, 56%, and 47.3% for patients without prior diabetes, pre-transplant diabetes, and PTDM, respectively. Pre-transplant diabetes was independently associated with 79% increased risk of UTIs (adjusted HR = 1.79, 95% CI = 1.14–2.81, p = 0.011). The risk associated with female gender increased to 85%. Patient survival was not significantly affected by the interaction between diabetes and UTI occurrence. Conclusions: Pre-transplant diabetes arises as a significant risk factor for UTIs after kidney transplantation.

Rationale & Objective:Characterize the natural history of advanced primary hyperoxaluria type 1 (PH1) in a multinational patient cohort. Study Design:A retrospective chart review. Setting & Participants:Patients, from participating medical centers in North America, Europe, and the Middle East, had ≥ 4 health care visits related to PH1 spanning ≥ 6 months (except deceased patients) on/after January 1, 2000, and ≥ 2 estimated glomerular filtration rate (eGFR) values ≤ 45 mL/min/1.73m2 (if age < 12 months, 2 serum creatinine values elevated for age) were included. Exposure:None (retrospective observational study). Outcomes:Kidney function, liver and/or kidney transplantation, death, plasma oxalate, systemic oxalosis, emergent clinical events, and abnormal clinical laboratory values. Analytical Approach:Patients were categorized as not on dialysis (Cohort A) and receiving hemodialysis (Cohort B). Patients could be in more than one cohort, but not during the same time. Results:Seventy patients were analyzed (up to 21 years of data; Cohort A, n = 54; Cohort B, n = 53). The median age at entry was 11.8 years (Cohort A) and 12.2 years (Cohort B). The eGFR slope was -2.8 mL/min/1.73m2/year (Cohort A). Patients underwent hemodialysis a median of 6 days/week (range, 3-7; Cohort B). Forty-two patients underwent liver and/or kidney transplantation (median age at first transplant, 15.3 years). Nineteen patients died (median age at death, 3.9 years [range, 2.2-34.9]), including 8 who received liver or liver-kidney transplants. Death occurred in 11 of 28 (39.3%) patients without transplant and 8 of 42 (19.0%) patients with transplant. Improvement in skeletal oxalosis after liver-kidney transplantation generally took > 1 year. Limited plasma oxalate and cardiac oxalosis data were available. The most common emergent clinical events were nephrolithiasis (Cohort A [nondialysis]) and fracture (Cohort B [hemodialysis]). The most commonly reported abnormal clinical laboratory values were bicarbonate, creatinine, and eGFR. Limitations:Minimal follow-up in some patients; small sample for some endpoints. Conclusions:Advanced PH1 is associated with high morbidity and mortality rates.

Serum creatinine (SCr) concentration is a cheap biomarker of kidney function measured globally millions of times every day. It is part of the KDIGO definitions of both chronic kidney disease and acute kidney injury (AKI). However, SCr can be elevated following the introduction of a new medication, unrelated to reduced glomerular filtration rate (GFR) and may lead to medical misjudgment, with clinically significant consequences. Indeed, several antibacterial, antiviral, antifungal or antiparasitic agents, fibrates or corticosteroids have been linked to increases in SCr unrelated to kidney injury (pseudo-AKI). More recently, multiple classes of targeted anti-cancer treatments like tyrosine kinase inhibitors, PARP inhibitors or CDK 4/6 inhibitors have also been associated with pseudo-AKI. The mechanisms responsible are multiple and diverse, ranging from interference with the method of creatinine measurement to inhibition of renal tubular secretion of creatinine via various transporters. Cystatin C measurement can help discern between true and pseudo-AKI but some interactions also exist and data is lacking. In cases where a precise assessment of kidney function is needed, GFR can also be measured through plasma and urinary clearance of an exogenous marker, therefore removing the inaccuracies of the various eGFR equations. Here, we propose a narrative review, exploring for the first time in depth drugs associated with pseudo-AKI. Creatinine and cystatin C metabolism, methods of measurement and derived equations are discussed as well. We also propose a decision-making algorithm to help the clinician in daily practice.

Kidney transplantation (KT) is the best treatment for patients with kidney failure, associated with improved survival and quality of life compared with maintenance dialysis. However, despite constant improvements in the assessment and management of the alloimmune response, KT patients frequently demonstrate a reduced estimated glomerular filtration rate. Therefore, the usual complications of chronic kidney disease (CKD), such as anemia, hypertension, metabolic acidosis, hyperkalemia, or persistent secondary hyperparathyroidism, are highly prevalent after KT. However, their underlying mechanisms are different in the transplant setting (compared with the nontransplanted CKD population), and management recommendations are based on relatively poor-quality data. In recent years, new therapies have emerged, significantly improving kidney and cardiovascular outcomes of non-KT patients with CKD. Whether those new drugs could improve the outcomes of KT patients has largely been under investigated so far. In this review, we will address the challenges of the management of a KT patient with a reduced estimated glomerular filtration rate, cover the published evidence, and highlight the critical knowledge gaps.