Morello W, Montelatici E, Lavazza C
… +14 more, Budelli S, Lazzari L, Puccio G, Bulgaro C, Carrino E, La Rosa S, Tamburello C, Nittoli T, Catenacci L, Montemurro T, Ghio L, Edefonti A, Giordano R, Montini G
Clin Kidney J
· 2026 Jul · PMID 42395862
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BACKGROUND: Children with steroid-dependent nephrotic syndrome (SDNS) require long-term immunosuppressive (IS) treatment, significantly impacting their quality of life. Cord-blood-derived mesenchymal stromal cells (CB-MS...BACKGROUND: Children with steroid-dependent nephrotic syndrome (SDNS) require long-term immunosuppressive (IS) treatment, significantly impacting their quality of life. Cord-blood-derived mesenchymal stromal cells (CB-MSCs) are multipotent stem cells with proven immunomodulatory properties. METHODS: We conducted an adaptive, open-label, single-arm, phase II trial with an adaptive second part to evaluate the efficacy of CB-MSCs in children aged 3-18 years with SDNS in remission for ≥6 months on IS therapy. In Part 1, patients received three intravenous infusions of CB-MSCs (1.5 × 10⁶/kg) at 1-2-week intervals, with rapid IS tapering and discontinuation after the third infusion. The primary endpoint was relapse-free survival at 6 months post-IS withdrawal, with a threshold of <4/11 relapsing patients. In the adaptive Part 2, IS was discontinued before the first infusion to enhance CB-MSCs activity, and the dose was increased to 2 × 10⁶/kg, with a booster fourth infusion. A historical cohort of SDNS children tapering IS under standard care served as a post-hoc control. RESULTS: In Part 1, 9 patients were enrolled, and 7/9 (78%) relapsed, failing to meet the prespecified efficacy threshold. In Part 2, 11 patients were enrolled; 9 (82%) were in remission at 2 weeks post-third infusion and received the boosted dose. However, 6/11 (55%) relapsed within 6 months, with no significant difference in relapse-free survival compared to Part 1 ( = .25). Historical controls had significantly better relapse-free survival ( = .0007). CONCLUSION: In children with SDNS, this novel therapy with CB-MSCs was safe but failed to improve relapse-free survival 6 months after IS withdrawal.
Bartram MP, Capasso G, Cornec-Le Gall E
… +14 more, Deesker LJ, van Eerde AM, Figueres L, Perez Gomez MV, Groothoff J, Oubram L, Halbritter J, Hoorn EJ, Nijenhuis T, Sayer JA, Beck BB, Müller RU, PH1 Survey Study Group, PH1 Survey Study Group
Clin Kidney J
· 2026 Jul · PMID 42395860
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BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder leading to the formation of kidney stones, nephrocalcinosis, and kidney failure. Besides, PH1 poses the risk of developing systemic ox...BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare inherited metabolic disorder leading to the formation of kidney stones, nephrocalcinosis, and kidney failure. Besides, PH1 poses the risk of developing systemic oxalosis, a life-threatening condition with oxalate deposits in multiple organ systems. The rarity of the disorder combined with recent major additions to therapeutic options based on small interfering RNA (siRNA) therapeutics make a formal assessment of current practice and implementation of treatment recommendations an important asset. METHODS: An international questionnaire survey was conducted among medical doctors involved in the treatment of patients with chronic kidney disease. The survey included 32 questions addressing demographics, diagnostics and therapeutics, and educational needs related to the care for PH1 patients. RESULTS: 176 participants from 43 countries completed the survey, the majority of them were from Europe. The results indicate clear shortcomings in the availability of recommended diagnostics, especially with regards to plasma oxalate. Genetic testing strategies often do not include patients who may have PH1, e.g. when the underlying cause of kidney failure is unknown or in patients with nephrolithiasis or nephrocalcinosis. Treatment modalities are only partly harmonized and intensified dialysis is not fully implemented across centers. Strategies toward combination of conventional therapeutics such as hyperhydration and pyridoxine with new siRNA therapeutics depend on the treating physician's expertise. The survey identifies clear needs regarding implementation of current treatment recommendations as well as important educational gaps. CONCLUSION: The advent of targeted treatment opportunities for PH1 comes with an increased need to provide guidance to the field. Filling the existing gaps will ensure that a growing number of patients get access to optimal care and novel life-changing therapies.
Clin Kidney J
· 2026 Jul · PMID 42395859
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RATIONALE & OBJECTIVE: The progression of IgA nephropathy (IgAN) involves complement activation and inflammatory infiltration. Lymphatics is reported to connect tissue injury with immunoregulation effect. This study aime...RATIONALE & OBJECTIVE: The progression of IgA nephropathy (IgAN) involves complement activation and inflammatory infiltration. Lymphatics is reported to connect tissue injury with immunoregulation effect. This study aimed to quantify renal lymphatic vessel (LV) density in a Chinese IgAN cohort, assess its correlation with complement and inflammation, and evaluate its long-term prognostic significance. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We enrolled 127 IgAN patients from Tongji Hospital (Wuhan, China) who were treatment-naïve at renal biopsy (no glucocorticoids or immunosuppressants) and had complete, valid follow-up data. EXPOSURE: Renal LVs and inflammatory cells were assessed by histological staining; urinary galactose-deficient IgA1 (Gd-IgA1), complement components, and cytokines were measured by ELISA (Enzyme-Linked Immunosorbent Assay). OUTCOMES: Two independent primary endpoints were defined: (1) Serum creatinine (Scr) doubling and (2) end-stage renal disease (ESRD). ANALYTICAL APPROACH: Cox proportional hazards regression. RESULT: In patients with IgAN, renal LVs density was significantly elevated compared to controls ( = .004). This increase was positively correlated with urinary levels of Gd-IgA1, ( = 0.41), IL-6 ( = 0.37), C5b-9 ( = 0.34), complement factor H (CFH, = 0.50), mannose-binding lectin (MBL, = 0.40), and C4d ( = 0.26). Inflammatory cell infiltration (CD68, DC-SIGN, CD1c, CD4, CD8, CD20) around LVs also was correlated with LVs density. Patients then were stratified by LVs density into LV1-LV3 groups. Those in the LV3 group showed significantly higher proteinuria, Scr, and pathological scores. Over a median follow-up of 93 months, the LV3 group had a significantly increased risk of Scr doubling (HR = 3.67) and progression to ESRD (HR = 19.81) compared to the lower-density groups. LIMITATIONS: Single-center retrospective design; sample size. CONCLUSION: Renal LVs density exhibits a significant correlation with urinary Gd-IgA1 levels, complement activation, inflammatory cell infiltration and renal lesions. Furthermore, a higher renal LVs density is closely associated with poorer renal outcomes.
Clin Kidney J
· 2026 Jul · PMID 42389200
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BACKGROUND: Chronic kidney disease (CKD) is strongly linked to cardiovascular disease (CVD) risk. Although beta-blockers (BBs) are widely used for CVD prevention, their effectiveness and safety in CKD patients without es...BACKGROUND: Chronic kidney disease (CKD) is strongly linked to cardiovascular disease (CVD) risk. Although beta-blockers (BBs) are widely used for CVD prevention, their effectiveness and safety in CKD patients without established CVD remain uncertain. METHODS: We conducted a nationwide cohort study using Korean health insurance data. CKD patients without established CVD between 2012 and 2015 were identified based on an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m on at least two occasions. BB users were defined as those prescribed BBs for ≥6 months. Primary outcomes were all-cause mortality and 4-point major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, stroke, and hospitalization for heart failure. A 1:2 propensity score matching was performed, and Cox proportional hazards models were applied. Subgroup analyses were also conducted by eGFR category and BB agents. RESULTS: After matching, 9067 BB users and 17 094 non-users were included. BB use was associated with increased risks of all-cause mortality (hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.96-2.24) and MACE (HR, 1.33; 95% CI, 1.26-1.41). The increased risks were consistent across individual outcomes, including cardiovascular death (HR, 2.07; 95% CI, 1.66-2.57), myocardial infarction (HR, 1.29; 95% CI, 1.13-1.46), stroke (HR, 1.21; 95% CI 1.13-1.31), and heart failure hospitalization (HR, 1.58; 95% CI, 1.44-1.72). Subgroup analysis showed greater mortality risk at lower eGFR levels and a higher risk of adverse events with carvedilol compared with other BBs. CONCLUSIONS: Among CKD patients without established CVD, BB use was associated with increased mortality and cardiovascular risk. Further studies are needed to clarify whether these associations reflect treatment effects or underlying patient risk.
Merz LM, Stopp S, Krey I
… +17 more, Baalmann F, Marczak E, Liebmann N, Hempel O, Krüger BM, Engesser M, Teichmann AC, Schnabel F, Jamra RA, Lemke J, Bergmann C, Lindner TH, de Fallois J, Münch J, Halbritter J, Dittrich K, Petzold F
Clin Kidney J
· 2026 Jul · PMID 42389199
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BACKGROUND: Inherited kidney diseases (IKDs) and congenital anomalies of the kidney and urinary tract (CAKUT) are a clinically heterogeneous subset of chronic kidney disease and rank among the leading causes of kidney fa...BACKGROUND: Inherited kidney diseases (IKDs) and congenital anomalies of the kidney and urinary tract (CAKUT) are a clinically heterogeneous subset of chronic kidney disease and rank among the leading causes of kidney failure (KF), especially in younger patients. Although next-generation sequencing has expanded diagnostic opportunities, data linking genetic findings to clinical outcomes across both adults and children remain limited. METHODS: We enrolled 256 patients with suspected IKD (175 adults, 81 children) at a single tertiary center between 2020 and 2023. Genetic testing was performed using targeted panels or exome sequencing, including copy number variant (CNV) and analyses. Clinical data, including family history, proteinuria, hematuria, extrarenal manifestations, and kidney survival, were systematically assessed. RESULTS: Pathogenic variants were identified in 38.7% of patients. Five genes (, and ) accounted for 62.6% of solved cases. Diagnostic yield was highest in cystic kidney diseases (72.0%), followed by tubulopathies (34.3%), glomerulopathies (25.8%), and CAKUT (19.2%). Multivariable regression identified positive family history, extrarenal manifestations, and arterial hypertension as predictors of a genetic diagnosis, with tubular proteinuria serving as an additional predictor in children. Kidney survival varied substantially across genetic subgroups: patients with variants and tubulopathies showed more favorable outcomes, whereas individuals with -associated Alport syndrome and glomerulopathies progressed rapidly. In the overall cohort, females reached 50% KF significantly later than males. Genetically solved men had the poorest outcomes, with a significant difference compared with solved women; however, this difference was reduced to a nonsignificant trend after excluding X-linked disorders. CONCLUSIONS: Genetic testing provided clinically relevant diagnoses in nearly 40% of patients with suspected IKD, enabling more accurate prognostication and patient stratification. High yield in cystic disease and pediatric tubular proteinuria, sex-specific survival differences, and CNV analysis highlight the value of integrating genetics into routine nephrology care to guide diagnosis, management, and family counselling.
Cui NX, Zhu SY, Chen RY
… +4 more, Wu S, Lin Q, Zhu Y, Li XZ
Clin Kidney J
· 2026 Jul · PMID 42389198
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BACKGROUND: Rituximab (RTX) is effective for pediatric frequently-relapsing or steroid-dependent nephrotic syndrome (FR/SDNS); however, some patients develop RTX resistance or severe hypersensitivity. Ofatumumab (OFA), a...BACKGROUND: Rituximab (RTX) is effective for pediatric frequently-relapsing or steroid-dependent nephrotic syndrome (FR/SDNS); however, some patients develop RTX resistance or severe hypersensitivity. Ofatumumab (OFA), a fully humanized anti-CD20 monoclonal antibody, represents a potential alternative, yet its use in children remains poorly documented. This study evaluates the feasibility and safety of low-dose subcutaneous (SC) OFA in children with complicated FR/SDNS who are RTX resistant or intolerant. METHODS: We retrospectively analyzed five pediatric patients (median age 14.8 years) with FR/SDNS and a history of RTX resistance or hypersensitivity. Each patient received a standardized SC OFA dose of 20 mg. B-cell depletion (CD19⁺ <1%), serum IgG levels, and adverse events-graded according to the Common Terminology Criteria for Adverse Events (CTCAE)-were monitored throughout follow-up. The primary endpoint was relapse-free remission within 12 months of the last OFA dose. RESULTS: SC OFA achieved peripheral B-cell depletion in all patients, with a median duration of 5 months. Within 12 months, 80% (4/5) of patients maintained remission. One patient with previous severe anti-CD20 hypersensitivity tolerated SC OFA with mild (Grade 2) symptoms after ibuprofen premedication. No severe infections or exacerbations of hypogammaglobulinemia were documented. CONCLUSIONS: Low-dose SC OFA is a feasible preemptive therapy for remission maintenance in pediatric FR/SDNS, particularly for those with RTX resistance or intolerance. This outpatient-compatible route may reduce hypersensitivity risks and healthcare costs. Larger prospective trials are warranted to confirm long-term efficacy.
Bataille S, Seret G, Lavainne F
… +16 more, Giaime P, Serveaux M, Robert T, Bobot M, Vrigneaud L, Jean G, De Laforcade L, Prezelin-Reydit M, Chauveau P, Isnard M, Samson L, Colin A, Boury F, Viton A, Claeys-Bruno M, Pedinielli N
Clin Kidney J
· 2026 Jul · PMID 42389197
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BACKGROUND: Many factors contribute to muscle impairment during chronic kidney disease, among which vitamin D deficiency has been implicated. The aim of this study was to analyze whether cholecalciferol supplementation i...BACKGROUND: Many factors contribute to muscle impairment during chronic kidney disease, among which vitamin D deficiency has been implicated. The aim of this study was to analyze whether cholecalciferol supplementation in hemodialysis patients with low 25-hydroxyvitamin vitamin D (25OHD) concentrations could improve handgrip strength (HGS). METHODS: VITADIAL (Does Correction of 25 OH-VITAmin D With Cholecalciferol Supplementation Increase Muscle Strength in HemoDIALysis Patients?) is a prospective open-labeled French multicenter study in which chronic hemodialysis patients with a 25OHD ≤50 nmol/L were randomized to receive monthly oral 100 000 IU cholecalciferol or no vitamin D treatment during 6 months to assess whether cholecalciferol supplementation in vitamin D-deficient hemodialysis patients improves muscle strength as measured with HGS. The main objective of the study was to analyze whether a 6-month period of oral cholecalciferol improved the muscle strength of hemodialysis patients with low 25OHD levels. RESULTS: Within the 270 hemodialysis patients from 10 hemodialysis centers included in the study, 143 patients with 25OHD ≤50 nmol/L were randomized: 70 were allocated to the cholecalciferol group and 73 to the control group. The two groups were comparable at inclusion. The cholecalciferol supplemented group's 25OHD rose to 89.78 ± 33.43 nmol/L at 6 months and remained ≤50 nmol/L for most patients in the control group, but HGS did not change significantly between randomization and end of the study in both groups (0.07 ± 3.40 kg and -0.19 ± 3.35 kg, respectively, -value .682). No difference was found in terms of either autonomy or frailty. CONCLUSIONS: This highly powered study did not find any effect of cholecalciferol supplementation in muscle strength of hemodialysis patients with low 25OHD.Trial registration: ClinicalTrials, NCT04262934. Registered 10 February 2020. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04262934.
Servan-Schreiber T, Lano G, Giot M
… +6 more, Jehel O, Pelletier M, Sallée M, Brunet P, Burtey S, Robert T
Clin Kidney J
· 2026 Jul · PMID 42389196
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BACKGROUND: Dialysis disequilibrium syndrome (DDS) is a neurological complication occurring during hemodialysis initiation whose pathogenesis remains incompletely understood. Limited prospective adult data exists on DDS...BACKGROUND: Dialysis disequilibrium syndrome (DDS) is a neurological complication occurring during hemodialysis initiation whose pathogenesis remains incompletely understood. Limited prospective adult data exists on DDS incidence and risk factors. METHODS: We conducted a prospective observational study (February 2021-February 2022) including 48 patients initiating hemodialysis. DDS was assessed using a standardized severity score (0-3) before and after each of the first four sessions, defined as any increase in post-session score (). Univariate and multivariate logistic regression identified risk factors. RESULTS: Among 48 patients (70.8% male, median age 67 years), 22.9% developed DDS with two patients experiencing multiple episodes. Univariate analysis identified centrally acting agent use (45.5% vs. 8.1%, = .01), fluid overload (45.4% vs. 13.5%, = .03), lower pre-dialysis pH (7.28 vs. 7.37, = .04), and higher chloride (100 vs. 94 mmol/l, = .01) as significant associations. Pre-dialysis urea was not associated with DDS ( = .15). Multivariate analysis identified intradialytic hypertension as an independent risk factor (Odds ratio = 4.43, 95% confidence interval: 1.38-18.15, = .01) occurring in 78.6% of DDS sessions versus 40.0% of non-DDS sessions. CONCLUSION: DDS is a common complication (22.9% incidence) with intradialytic hypertension as the key independent predictor. Pre-dialysis urea concentration was not predictive. These findings suggest a pathophysiological model involving acid-base dynamics and intracranial pressure regulation rather than solute gradients alone. Future multicenter studies are needed to validate these findings and optimize dialysis initiation strategies.
Vetrano D, Barbuto S, Aguanno F
… +5 more, Mastromauro P, Grandinetti V, Comai G, La Manna G, Cianciolo G
Clin Kidney J
· 2026 Jul · PMID 42389195
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BACKGROUND: Hyperparathyroidism (HPT) is common in chronic kidney disease and may persist after kidney transplantation, but its prognostic significance remains uncertain because of heterogeneous definitions and variable...BACKGROUND: Hyperparathyroidism (HPT) is common in chronic kidney disease and may persist after kidney transplantation, but its prognostic significance remains uncertain because of heterogeneous definitions and variable timing of assessment. METHODS: We performed a systematic review and meta-analysis of observational studies in adult kidney transplant recipients (KTRs) in accordance with PRISMA 2020 (PROSPERO CRD420261293712). PubMed/MEDLINE and Embase were searched from inception to 9 February 2026. Exposures included pre- and post-transplant parathyroid hormone (PTH)/Persistent HPT assessed as categorical or continuous variables. Outcomes were all-cause mortality, overall graft failure, and death-censored graft failure. Random-effects models were applied, with Hartung-Knapp sensitivity analyses; risk of bias was assessed using QUIPS. RESULTS: 23 studies were included in the systematic review, and 19 studies (26 266 KTRs) contributed to the meta-analyses (3 pre-transplant studies = 12 819; 16 post-transplant studies = 13 447). Pre-transplant HPT was not associated with all-cause mortality (HR 0.80) and showed an association with death-censored graft failure (DCGF) in the main analysis (HR 1.42) that lost statistical significance with Hartung-Knapp adjustment. By contrast, categorical Persistent HPT was associated with higher risks of all-cause mortality (HR 1.74), overall graft failure (HR 2.16), and DCGF (HR 1.92), with consistent Hartung-Knapp results. Phenotype-stratified analyses showed a gradient of graft failure risk from normocalcemic HPT (HR 1.66) to hypercalcemic HPT (HR 2.67), with minimal heterogeneity. Continuous PTH analyses showed substantial heterogeneity and were not robust in sensitivity analyses. CONCLUSIONS: Post-transplant Persistent HPT is a consistent risk marker for mortality and adverse graft outcomes, whereas the prognostic significance of pre-transplant HPT remains to be clarified. Standardized definitions and prospective studies are needed to clarify causality and treatment effects.
Clin Kidney J
· 2026 Jul · PMID 42389194
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BACKGROUND: IgA nephropathy is the most prevalent primary glomerulonephritis globally. Dysregulation of the complement system, specifically the alternative pathway, is a critical driver of its pathogenesis. While genome-...BACKGROUND: IgA nephropathy is the most prevalent primary glomerulonephritis globally. Dysregulation of the complement system, specifically the alternative pathway, is a critical driver of its pathogenesis. While genome-wide association studies consistently map a primary susceptibility locus to the complement factor H gene cluster, extensive linkage disequilibrium and complex structural variations have historically obscured precise causal targets. METHODS: We employed a multi-omics triangulation framework to evaluate the genetic association and potential protective effects of circulating complement proteins in IgA nephropathy. The analytical pipeline integrated large-scale plasma proteomics, blood-derived expression quantitative trait loci, Bayesian colocalization, computational clinical transcriptomics, and phenome-wide association studies. Two-sample, bidirectional, and multivariable Mendelian randomization analyses were performed using summary-level data from global genome-wide association studies. RESULTS: Genetically predicted higher circulating levels of complement factor H were significantly associated with a lower risk of IgA nephropathy. Bayesian colocalization decoupled the complex locus, isolating this protective signal to a single missense variant within the complement factor H gene and demonstrating independence from the adjacent complement factor H-related 1 gene. Spatial profiling and clinical transcriptomics suggested a dual-compartment model: the liver supplies the systemic pool, while intrinsic renal cells mount a hypothesized severity-driven compensatory upregulation of complement factor H during active disease. Furthermore, phenome-wide association studies indicated that enhancing complement factor H offers dual protective benefits against IgA nephropathy and age-related macular degeneration without broad chronic systemic pleiotropy. CONCLUSIONS: This study provides convergent genomic and transcriptomic evidence supporting complement factor H as a genetically supported protective factor in IgA nephropathy. Genetic variation consistent with enhanced complement factor H-mediated regulation is associated with reduced disease susceptibility. These findings provide a theoretical framework for exploring direct recombinant supplementation therapies and offer genetic support for the ongoing clinical development of upstream alternative pathway inhibitors.
Sprangers B, Cohen C, Gnemmi V
… +9 more, Shabaka A, Fernandez-Juarez G, van Midden D, Steenbergen E, Milani P, Vignon M, Wilde B, Hegenbart U, Wetzels JF
Clin Kidney J
· 2026 Jun · PMID 42338690
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We introduce the European Union consensus report on the diagnosis and treatment of monoclonal gammopathy of renal significance (MGRS), a generic term to describe kidney disorders caused by a non-malignant monoclonal immu...We introduce the European Union consensus report on the diagnosis and treatment of monoclonal gammopathy of renal significance (MGRS), a generic term to describe kidney disorders caused by a non-malignant monoclonal immunoglobulin clone. There are many subtypes of MGRS, with AL-amyloidosis being most prevalent. The consensus report aims at providing guidance to clinicians, pathologists and laboratory specialists who take care of patients with a (suspected) diagnosis of MGRS. This executive summary provides a condensed overview of the most important aspects of the diagnosis and management of patients with MGRS. Consultation of expert centers is strongly advised. Although most patients will benefit from hematological, clone-directed therapy, treatment decisions must be individualized, in view of the heterogeneity of patients between and within the MGRS subtypes. The final chapter discusses kidney transplantation in patients with MGRS. The working group acknowledges that most advice is based on low-quality evidence. The full report provides the rationale and a detailed discussion of the available literature. This executive summary is an introduction, and not a substitute for the full consensus report.
Burton JO, Izquierdo MJ, Linde C
… +6 more, Robles NR, Sood MM, Allum AM, Eudicone JM, Dahl M, Amin AN
Clin Kidney J
· 2026 Jun · PMID 42338689
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BACKGROUND AND HYPOTHESIS: Hyperkalaemia is common and potentially life-threatening in individuals with chronic kidney disease (CKD). While sodium zirconium cyclosilicate (SZC) is used in the hospital setting for hyperka...BACKGROUND AND HYPOTHESIS: Hyperkalaemia is common and potentially life-threatening in individuals with chronic kidney disease (CKD). While sodium zirconium cyclosilicate (SZC) is used in the hospital setting for hyperkalaemia management, few patients are discharged with a continuing prescription, leaving them at risk of recurrent hyperkalaemia and rehospitalization. The CONTINUITY study aimed to establish the efficacy of continuing post-hospital discharge treatment with SZC versus standard of care (SOC) in maintaining normokalaemia and reducing all-cause and hyperkalaemia-related hospital admissions and emergency department visits in patients with CKD and hyperkalaemia. METHODS: This phase 4, randomized, controlled, open-label, parallel-group (multicentre study 28 sites; six European countries; 24 March 2022-10 December 2024), included participants aged ≥18 years admitted to hospital with diagnosed CKD (any stage) and hyperkalaemia [serum potassium (sK) >5.0 and ≤6.5 mmol/l] without ongoing K binder treatment. Participants received SZC for 2-21 days to normalize sK. Those with normokalaemia (3.5-5.0 mmol/l) at discharge were randomized to SZC or SOC. The primary objective was occurrence of normokalaemia at 180 days post-discharge [those achieving normokalaemia (responders) vs those who did not (non-responders)]. RESULTS: The difference between arms for normokalaemia responders was not statistically significant: 30.9% (SZC) and 36.2% (SOC) (odds ratio 0.81; 95% CI 0.39-1.66; = .558). High and imbalanced levels of missing sK measurements at 180 days [ = 35 (51.5%) in the SZC arm and = 25 (36.2%) in the SOC arm] led to substantially lower levels of normokalaemia response than the original assumptions in the sample size calculations used to power the study. CONCLUSION: The study did not meet its primary endpoint. Study design limitations may have masked true treatment effects. Post hoc analyses revealed positive trends in SZC use and potential for reducing rehospitalization and enabling renin-angiotensin-aldosterone system inhibitor therapy continuation at optimal doses.
Schermuly K, Weber H, Tschirner A
… +3 more, Rebe T, Haffner D, Leifheit-Nestler M
Clin Kidney J
· 2026 Jun · PMID 42338688
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BACKGROUND: Currently, uniform reference values for parameters of phosphate (Pi) homeostasis-the phosphaturic hormone fibroblast growth factor 23 (FGF23) and its coreceptor, soluble Klotho (sKlotho)-are used for women an...BACKGROUND: Currently, uniform reference values for parameters of phosphate (Pi) homeostasis-the phosphaturic hormone fibroblast growth factor 23 (FGF23) and its coreceptor, soluble Klotho (sKlotho)-are used for women and men regardless of age. This may not be adequate, especially in older subjects. We established Lambda-Mu-Sigma (LMS)-based continuous age- and sex-specific reference values for key parameters of Pi homeostasis, FGF23 and sKlotho. METHODS: The HAnnover Reference values for Adults study included 504 participants (51% women) aged 18-70 years. Main outcome measures were serum Pi, intact (iFGF23) and total FGF23, sKlotho, tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR), fractional tubular reabsorption of phosphate (TRP), and urinary calcium-to-creatinine (Ca/Crea) and phosphate-to-creatinine ratios. RESULTS: All parameters examined showed statistically significant differences between the sexes. There was a constant decrease in renal Pi reabsorption capacity (TmP/GFR, TRP) and serum Pi concentrations in older men, beginning around their sixth decade of life, whereas the parameters of Pi homeostasis in women hardly changed with age. Women had significantly lower iFGF23 but slightly higher total FGF23 concentrations. sKlotho concentrations decreased with age in both sexes, with women generally having higher concentrations than men regardless of the age-related decline in kidney function. Women taking estrogen-containing oral contraceptives had lower sKlotho concentrations than their peers. Women showed higher urine Ca/Crea values than men. CONCLUSION: The presented LMS-based continuous reference values for key parameters of Pi homeostasis enable the calculation of standardized -scores to facilitate test result interpretation in women and men.
Montomoli M, Gil Martins Roxo MI, González-Rico M
… +6 more, Núñez J, Núñez-Marín G, Uriarte BA, De La Espriella R, Puchades MJ, Górriz JL
Clin Kidney J
· 2026 Jun · PMID 42318102
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Diuretic resistance in heart failure and the cardiorenal syndrome is traditionally managed by escalating diuretic doses, yet this approach often fails to address the underlying pathophysiology. Emerging evidence challeng...Diuretic resistance in heart failure and the cardiorenal syndrome is traditionally managed by escalating diuretic doses, yet this approach often fails to address the underlying pathophysiology. Emerging evidence challenges the sodium-centred paradigm and identifies chloride as a key determinant of diuretic responsiveness, tightly interconnected with potassium, magnesium, and acid-base balance. Disturbances in this multi-ionic network promote maladaptive tubular responses, neurohormonal activation, and persistent sodium retention, ultimately leading to diuretic resistance. Clinical and mechanistic data consistently show that hypochloraemia, often accompanied by hypokalaemia and metabolic alkalosis, is associated with impaired natriuretic efficiency and worse outcomes. Through a representative clinical case, we illustrate how a physiology-guided, multi-ionic strategy-focused on identifying and correcting the specific biochemical drivers of resistance rather than intensifying diuretics-can restore diuretic response and achieve effective decongestion. Diuretic resistance should not be viewed as a failure of dose, but as a failure of understanding. A personalized, multi-ionic approach that integrates chloride, potassium, magnesium, and acid-base status offers a more coherent and effective framework for managing congestion in heart failure.
Clin Kidney J
· 2026 Jun · PMID 42318101
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BACKGROUND AND AIMS: Acute kidney injury (AKI) is increasingly recognized as a long-term risk factor for chronic kidney disease and cardiovascular disease (CVD). However, it remains uncertain which patients with AKI are...BACKGROUND AND AIMS: Acute kidney injury (AKI) is increasingly recognized as a long-term risk factor for chronic kidney disease and cardiovascular disease (CVD). However, it remains uncertain which patients with AKI are at greatest CVD risk. We performed a systematic review and meta-analysis to quantify CVD risks post-AKI and to determine whether these risks differ by AKI severity, duration, and clinical setting. METHODS: PubMed and Embase were systematically searched for studies comparing individuals with and without AKI and reporting major adverse cardiovascular events (MACE) or individual outcomes such as myocardial infarction (MI), stroke, heart failure (HF), or cardiovascular mortality. Follow-up was at least 1 year. Relative risks (RRs) were pooled in meta-analyses using random-effect models. Subgroup and metaregression analyses were used to explore heterogeneity across patient and AKI characteristics, and clinical settings. RESULTS: We included 54 studies comprising 1261 090 individuals, of whom 290 648 experienced AKI. Meta-analyses showed that AKI was associated with an RR of 1.97 [95% confidence interval (CI) 1.67-2.27] for MACE (13.9% overall incidence), 1.64 [95% CI 1.38-1.89] for MI (3.5% overall incidence), 1.36 [95% CI 1.13-1.59] for stroke (1.7% overall incidence), 1.92 [95% CI 1.67-2.16] for HF (3.5% overall incidence), and 1.86 [95% CI 1.59-2.13] for cardiovascular mortality (9.4% overall incidence), compared to patients without AKI. Elevated risks were observed across all AKI stages and durations and in patients across all studied clinical settings, including noncardiac care. The highest RRs were shown for more severe AKI stages and longer AKI durations. Older age and lower baseline estimated glomerular filtration rate were associated with even higher risk of MACE compared to patients without AKI. CONCLUSIONS: AKI is followed by an increase in CVD risk, even after AKI with low severity. These findings highlight AKI as a clinically relevant CVD risk marker and support the need for targeted post-AKI care management to prevent future cardiovascular events.