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Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a new cystic fibrosis transmembrane conductance regulator (CFTR) modulator that has transformed the respiratory prognosis of people with cystic fibrosis (pwCF). However, its impact on other organs such as the kidneys, where CFTR is expressed, remains unclear. Since pwCF are risk of both kidney disease and urolithiasis, we aimed to study the potential effects of ETI on renal function, volume status, and risk factors for urolithiasis., Methods: This prospective, observational, single-center, before-after cohort study, involved adult pwCF eligible for ETI. The changes in plasma and urinary profiles were assessed by comparing renal function (using 2021 CKD-EPI creatinine and 2021 CKD-EPI creatinine-cystatin C formulas), volume status (using aldosterone/renin ratio and blood pressure), and risk factors for urolithiasis, at the time of ETI introduction (M0) and 7 months after (M7)., Results: Nineteen pwCF were included. No significant change in renal function was observed between M0 and M7 (2021 CKD-EPI creatinine : 105.5 ml/min/1.73 m² at M0 vs. 103.3 ml/min/1.73 m² at M7; P  = .17). There was a significant reduction in aldosterone level (370.3 pmol/l at M0 vs. 232.4 pmol/l at M7; P  = .02) and aldosterone/renin ratio (33.6 at M0 vs. 21.8 at M7; P  = .03). Among the risk factors for urolithiasis, a significant reduction in magnesuria level was found (4.6 mmol/d at M0 vs. 3.8 mmol/d at M7; P  = .01)., Conclusion: These findings suggest that ETI seem to have no short-term impact on the renal function of adult pwCF and appears to correct secondary hyperaldosteronism due to excessive sweat losses. Further investigations are needed to determine the potential impact of decreased magnesuria observed under ETI therapy on the risk of urolithiasis., Competing Interests: D.F. has received speaker fees or travel support from AstraZeneca, Astellas, Lilly and Fresenius Kabi. I.D. declares an activity as a clinical trial investigator for Vertex and acknowledges having received support for conference travel from Viatris. L.K. having received grants from Fresenius Kabi, Nestlé, Lallemand, AstraZeneca and consultancy or speaker fees or travel support from AstraZeneca, Lilly, Baxter, Bayer, and Fresenius Kabi. P.G., E.N.-C., Q.R., R.N.-J., and S.P. declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Competing Interests: V.B. served as a consultant, on advisory boards, and as an invited speaker for Dr Schär and Fresenius Kabi, and as a consultant, and an invited speaker for AstraZeneca. D.F. has received travel support and speaker fees from AstraZeneca, Astellas, GSK, Fresenius-Kabi and Dr Schär.

Background: Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients., Methods: The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome., Results: Of the 2406 included patients (median age: 68 years; median eGFR: 25 ml/min/1.73 m 2 ), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)]., Conclusions: Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies., Competing Interests: C.E.C., I.A.L., N.A.D.P., O.L., C.C., D.F., L.F., C.J., M.L., S.La., C.L., J.-C.A. and S.Li. declare no conflict of interest. Z.A.M. reports having received grants for CKD-REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp & Dohme-Chibret, Sanofi- Genzyme, Lilly, Otsuka, AstraZeneca, Vifor and the French government, as well as fees and grants to charities from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. The sponsors had no role in the design, execution, interpretation, or writing of the study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis., Methods: This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels., Results: The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: -1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%., Conclusions: SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Kidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations., Methods: Forty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund-Malmö equations were compared with reference methods (inulin or iohexol clearance)., Results: The mean mGFR was 78 ± 28 mL/min/1.73 m 2 . The annual decline of mGFR was -1.9 mL/min/1.73 m 2 /year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy., Conclusions: Patients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: C-type natriuretic peptide (CNP) and its co-product N-terminal proCNP (NTproCNP) have been associated with beneficial effects on the cardiovascular system. In prevalent dialysis patients, however, a relation between NTproCNP and mortality has not yet been investigated. Furthermore, as a middle molecular weight substance, its concentration might be influenced by dialysis modality., Methods: In a cohort of patients treated with haemodialysis (HD) or haemodiafiltration (HDF), levels of NTproCNP were measured at baseline and 6, 12, 24 and 36 months. The relation between serum NTproCNP and mortality and the relation between the 6-month rate of change of NTproCNP and mortality were analysed using Cox regression models. For the longitudinal analyses, linear mixed models were used., Results: In total, 406 subjects were studied. The median baseline serum NTproCNP was 93 pmol/L and the median follow-up was 2.97 years. No relation between baseline NTproCNP or its rate of change over 6 months and mortality was found. NTproCNP levels remained stable in HD patients, whereas NTproCNP decreased significantly in HDF patients. The relative decline depended on the magnitude of the convection volume., Conclusions: In our study, levels of NTproCNP appear strongly elevated in prevalent dialysis patients. Second, while NTproCNP remains unaltered in HD patients, its levels decline in individuals treated with HDF, with the decline dependent on the magnitude of the convection volume. Third, NTproCNP is not related to mortality in this population. Thus NTproCNP does not seem to be a useful marker for mortality risk in dialysis patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Elderly patients with chronic kidney disease (CKD) are often excluded from clinical trials; this may affect their use of essential drugs for cardiovascular complications. We sought to assess the impact of age on cardiovascular drug use in elderly patients with CKD., Methods: We used baseline data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort including 3033 adult patients with CKD Stages 3 and 4. We studied the use of recommended drugs for coronary artery disease (CAD), stroke and atrial fibrillation by age, after adjusting for socio-demographic and clinical conditions., Results: The patients' mean age was 66.8 years (mean estimated glomerular filtration rate 32.9 mL/min/1.73 m 2 ). The prevalence of CAD was 24.5% [81.3% receiving antiplatelet agents, 75.6% renin-angiotensin system (RAS) blockers, 65.4% β-blockers and 81.3% lipid-lowering therapy], that of stroke 10.0% (88.8% receiving antithrombotic drugs) and that of atrial fibrillation 11.1% (69.5% receiving oral anticoagulants). Compared with patients aged <65 years, older age (≥65 years) was associated with greater use of antithrombotic drugs in stroke [adjusted odds ratio (aOR) (95% confidence interval) = 2.83 (1.04-7.73) for patients aged (75-84 years)] and less use of RAS blockers [aOR = 0.39 (0.16-0.89) for patients aged ≥85 years], β-blockers [aOR = 0.31 (0.19-0.53) for patients aged 75-84 years] and lipid-lowering therapy [aOR = 0.39 (0.15-1.02) for patients aged ≥85 years, P for trend = 0.01] in CAD. Older age was not associated with less use of antiplatelet agents in CAD or oral anticoagulants in atrial fibrillation., Conclusions: In patients with CKD, older age per se was not associated with the underuse of antithrombotic drugs but was for other major drugs, with a potential impact on cardiovascular outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The course of cryoglobulinaemia varies widely, from asymptomatic patients to severe vasculitis syndrome. Renal involvement (RI) is the major prognostic factor, and frequently occurs several years after diagnosis. However, predictive factors for RI are not well known. The aim of our study was to identify RI predictive factors during cryoglobulinaemia., Methods: We retrospectively reviewed the clinical charts of a consecutive series of 153 patients positive for cryoglobulinaemia in the University Hospital of Lyon (France). RI was defined either histologically or biologically if cryoglobulinaemia was the only possible cause of nephropathy., Results: Among the 153 positive patients (mean age 55 years, 37% male), cryoglobulinaemia was associated with RI in 45 (29%) patients. Sixty-five percent of patients had Type II cryoglobulinaemia, 28% had Type III and 7% had Type I. Autoimmune diseases were the most common aetiology (48%), followed by infectious diseases (18%) and lymphoproliferative disorders (13%). Membranoproliferative glomerulonephritis was the main histological pattern (93% of the 14 histological analyses). A multivariable logistic regression showed that Type II cryoglobulinaemia, a high serum cryoglobulin concentration, the presence of an IgG kappa monoclonal component and diabetes were independently associated with the risk for developing RI., Conclusion: We identified several factors predictive of RI in patients with cryoglobulinaemia, which were different from the diagnostic criteria for cryoglobulinaemic vasculitis. This could suggest a specific pathophysiology for RI. We suggest performing an extensive renal monitoring and ensure nephroprotection when a diagnosis of cryoglobulinaemia is made in patients with these predictive factors.

Background: The aim of the third French Phosphorus and Calcium Observatory (Photo-Graphe ® 3) was to assess the achievement of international Kidney Disease: Improving Global Outcomes (KDIGO) recommendations on optimal serum phosphate, calcium and parathyroid hormone (PTH) levels and possible associations with mortality in patients with chronic kidney disease (CKD)., Methods: This was a prospective, observational study conducted with nephrologists in France who were selected using a clustering approach. Adult patients with non-dialysis Stage 4 or 5 CKD and no kidney graft history were eligible. Data about clinical events, serum biochemistry and treatment were collected every 6 months for 2.5 years and 12 months thereafter. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model for identification of factors associated with survival., Results: Overall, 566 CKD Stage 4 patients (men, 56%) and 153 CKD Stage 5 patients (men, 62%) were included. In Stage 4, only 14-15% patients achieved the three main 2009 KDIGO targets during the first 2 years and 22% at 2.5 years. In Stage 5 patients, the proportion remained <6% throughout. The percentages of patients achieving the three main 2017 KDIGO targets were slightly higher at each time point. Overall, 14% of Stage 4 and 10% of Stage 5 patients died in the observation period. Only age and haemoglobin level were significantly associated with risk of all-cause mortality., Conclusions: Few CKD patients achieved KDIGO mineral targets. Increased mortality risk was linked to older age and lower haemoglobin level, but not to serum calcium, phosphate or PTH targets.

Extra-pulmonary tuberculosis is frequently located in the kidneys and, in such cases, could be associated with a granulomatous interstitial nephritis. Granulomas are not always detected, especially in human immunodeficiency virus (HIV)-positive patients. We report here a case of tubulointerstitial nephritis without granulomas in an HIV-negative patient. Since all laboratory tests failed to isolate Mycobacterium tuberculosis in the kidney, a targeted biopsy guided by positron emission tomography-computed tomography was performed on a mediastinal node, revealing a positive culture. After 6 months of treatment, no recovery of the renal injury has been observed.

Scientific societies are increasingly seen as central to the advancement of information sharing and collaboration among scientists and clinical investigators for the progress of medical research and the promotion of education, professional competence, integrity and quality studies. To more effectively serve the practicing nephrologists and investigators dedicated to renal science, the Council of the European Renal Association and European Dialysis and Transplantation Association (ERA-EDTA) reorganized and integrated the various activities of the society into two branches, the Clinical Nephrology Governance branch and the Renal Science branch. New affordable initiatives to promote research, education and professional development and to advocate for the recognition of chronic kidney disease as a major public health issue at the European level will be put in place and/or potentiated in the new organizational frame. Educational initiatives will be espoused to Continuous Professional Development and, starting from 2019, 14 Education & Continuous Professional Development courses will be held covering the full range of knowledge areas of modern nephrology. Consolidation and development is the short- and medium-term mantra of the ERA-EDTA. The society has a rich portfolio of successful activities and brilliant, creative scientists among its members. Integrating the various activities of the ERA-EDTA and treasuring the expertise and wisdom of its most accomplished members will facilitate collaborative research, education and its public impact at large.

Background: Abnormal serum phosphate, calcium and parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) undergoing haemodialysis have been associated with poor survival. The French Phosphorus and Calcium Observatory (Photo-Graphe ® 3) aimed to estimate the percentage of CKD patients achieving the three Kidney Disease: Improving Global Outcomes (KDIGO) targets about optimal serum phosphate, calcium and PTH over a 3.5-year follow-up period., Methods: This was a prospective, multicentre, epidemiological observational study conducted with nephrologists in France, selected using a clustering approach. Eligible patients were adults undergoing intermittent haemodialysis or haemodiafiltration therapy started within the preceding 12 months. Data about clinical events, serum biochemistry and treatment were collected once every 6 months for 2.5 years and 12 months thereafter., Results: Overall, 9010 incident patients were included (men, 63%; median age, 71 years) of whom 7515 (83.4%) were treated by haemodialysis and 1495 (16.6%) by haemodiafiltration. None had a history of fracture or revascularization while 89 (1%) patients had a history of parathyroidectomy >6 months. Overall, 874 (10%) patients received a kidney graft, 2183 (24%) died and 1148 (13%) were lost to follow-up. The proportion achieving the three KDIGO targets increased significantly from 11% to 16% (P < 0.0001) until Year 2, but remained stable afterwards. The percentage of incident dialysis patients with normal serum phosphate (P < 0.0001) or normal serum calcium (P < 0.0001) levels increased significantly over time, while no significant change was observed for those with controlled PTH., Conclusion: Less than 20% of patients achieved the KDIGO recommendations although their proportion increased slightly over time.

Inflammation is a multifactorial phenotype that in chronic kidney disease is associated with adverse patient outcomes. Recently, alterations in gut microbiota composition and intestinal barrier have been associated with inflammation and oxidative stress in CKD patients. Vanholder and Glorieux recently critically reviewed [Clin Kidney J (2015) 8 (2): 168-179] the current understanding of the role of gut microbiota in the production of uraemic toxins and the therapeutic implications. Where do we stand now? The basic mechanisms of the gut-kidney crosstalk must still be clarified. In addition, the efficacy and safety of therapeutic strategies to modulate the gut microbiota in order to decrease uraemic toxin production and inflammation in chronic kidney disease should be evaluated. Finally, an impact of such strategies on hard outcomes should be demonstrated before incorporation into routine clinical practice.

Background: The calcimimetic cinacalcet lowers parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) in dialysis patients with secondary hyperparathyroidism (SHPT). We explored serum P changes in dialysis patients treated with cinacalcet, while controlling for vitamin D sterol and phosphate binder (PB) changes, based on data from the pan-European observational study ECHO., Methods: Patients were categorized by serum P change (decreased/unchanged/increased) at 12 months after starting cinacalcet and subcategorized by vitamin D sterol and PB dose changes (decreased/unchanged/increased). The impact of PTH, Ca and P, and vitamin D sterol, PB and cinacalcet doses (absolute values and/or change) was evaluated. Predictors of P change were explored using univariate and multivariate general linear models (GLM) and logistic regression analysis., Results: At Month 12, 661 (41%) of 1607 patients had decreased, 61 (4%) unchanged and 400 (25%) increased serum P, while 485 patients had missing data. In 45% of the patients with serum P reduction, vitamin D was either increased or unchanged and P binders decreased or unchanged. PTH was a key predictor of serum P reduction, with an estimated 3% decrease in P per 10% reduction in PTH. Changes in vitamin D sterol and PB doses were not generally significant factors in GLM and regression analyses., Conclusions: The serum P reduction observed in a significant proportion of dialysis patients after adding cinacalcet to an existing therapeutic regimen for SHPT appears to result mainly from PTH reduction, rather than from changes in vitamin D sterol or PB doses. Financial support for the ECHO study was provided by Amgen.