Kidney360最新文献

Background: Tolerant kidney transplant recipients without immunosuppression have a high frequency of circulating granzyme B (GZMB)-expressing regulatory B cells (Breg). Since the precursors of these Bregs remain unknown and IgA-secreting B cells have been shown to have regulatory properties in different situations, we investigated the association between IgA- and GZMB-expressing B cells in a case-control study.

Methods: 45 healthy volunteers and 31 kidney transplant recipients with either stable graft function under immunosuppression (n=10), antibody-mediated rejection (n=7) or tolerant patients (n=14) were included. Serum immunoglobulin concentrations as glycosylation were measured by ELISA, forms of IgA were examined by Western blot. Regulatory B cells were analyzed by single-cell RNA sequencing and multiparameter spectral flow cytometry. Their function was assessed in co-cultured with T cells.

Results: Serum IgA concentration was elevated in tolerant patients compared to other transplanted patients, especially the non inflammatory IgA1 subclass, without changes in IgA size or glycosylation. Single cell transcriptomic analysis revealed higher IgA gene expression in GZMB expressing B cells and conversely higher GZMB gene expression in IgA expressing B cells. Phenotyping analysis by spectral multiparameter flow cytometry showed that IgA+ B cells were memory B cells and that IgA+ B cells from tolerant patients tended to express more GZMB compared to antibody-mediated rejection patients. In functional assays, IgA+ B cells exhibited high regulatory functions that were partially prevented by the presence of GZMB inhibitor.

Conclusions: These data show a strong association between IgA+ and GZMB+ Bregs, particularly in tolerant kidney transplant recipients with higher GZMB and IgA expression and greater suppressive properties.

Background: During AKI, iron deficiency may contribute to worse clinical outcome by interfering cellular repair. Correcting iron deficiency with intravenous (IV) dextran iron may reduce the risk of major adverse kidney events (MAKE). We aimed to assess if IV iron was more efficacious than conventional management for reducing MAKE in AKI- iron deficiency patients.

Methods: In a phase 2 randomized controlled trial, from July 2022 to September 2024, patients with AKI and iron deficiency (iron levels <13 μmol/L or a transferrin saturation <20%) were eligible. We randomly assigned 120 patients to the control (N=62) and intervention groups (single 1,200 mg IV dextran iron infusion; N=58). Primary outcome was the risk of MAKE at 90 days (MAKE90). MAKE were defined as death, kidney replacement therapy (KRT), or worsening kidney function. Each component of MAKE and hemoglobin were secondary outcomes.

Results: The primary outcome MAKE90 occurred in 48 patients in the IV iron group and 47 in the control group (82% versus 75%; P=0.37). Individual components of MAKE were similar in both groups, 36 (62.1%) versus 38 (61.3%) had worsened kidney function; 14 (24.1%) versus 13 (21%) initiated KRT, and mortality was 43.1% and 38.7% in the IV iron and control groups, respectively (p=>0.05 for all). Hemoglobin values and adverse events did not differ between groups during the study.

Conclusions: In patients with AKI and iron deficiency, a single dose of IV iron, compared to usual care, did not improve clinical outcomes evaluated by MAKE90, the hemoglobin value, but was safe.

Background: Energy metabolism is fundamental to organ development, yet its role in determining nephron formation remains poorly understood. Disturbances in the intrauterine environment are known to affect nephron endowment and increased risk of hypertension and chronic kidney disease later in life. However, very little is known about the mechanisms that determine nephron number and metabolic status during nephrogenesis.

Methods: We focused on cytosolic adenosine 5-triphosphate (ATP) levels to examine energy metabolism in embryonic kidneys. To explore the spatiotemporal dynamics of the cytosolic ATP level, we used transgenic mice expressing a cytosolic ATP-FRET biosensor, GO-ATeam2, which enabled ex vivo live imaging of metanephric kidneys at single-cell resolution.

Results: We performed real-time ex vivo ATP imaging of embryonic kidneys of GO-ATeam2 mice. During branching nephrogenesis, ATP levels of ureteric bud (UB) tip cells are significantly lower than those of the UB stalk and cap mesenchyme (CM) cells. Glycolytic inhibition in the early phase of metanephric kidney (embryonic day E12.5) severely suppressed UB branching with a dose-dependent reduction in ATP levels in both UB and CM cells. Time-course observations revealed that the ATP reduction by glycolytic inhibitor was faster and more prominent in UB cells than in CM cells. In addition, glycolytic inhibition significantly reduced the number of branch segments and tips of UB as well as the expression of specific markers in UB and CM cells. Electron microscopy revealed loosening of lateral cell-cell adhesion and disorganized alignment of CM cells, which were accompanied by decreased expression of N-cadherin. These effects were not observed with the inhibition of oxidative phosphorylation.

Conclusions: UB branching was heavily dependent on glycolysis, and UB cells in the early branching phase were more sensitive to glycolytic inhibition than mesenchyme cells are. These results highlight the significance of metabolic regulation in branching nephrogenesis.

Background: Bevacizumab, a monoclonal antibody targeting VEGF-A, is a cornerstone in ovarian cancer. Bevacizumab is associated with renal adverse events, including hypertension, proteinuria, and acute kidney injury. The incidence, risk factors, and prognostic impact of these renal events remain poorly defined. This study aimed to determine the incidence, risk factors, and association with mortality of renal events in patients with ovarian cancer treated with bevacizumab.

Methods: We conducted a retrospective single-center study including 147 patients with ovarian cancer treated with bevacizumab between 2011 and 2023. Renal events were defined as new-onset or worsening hypertension (grade ≥2), proteinuria (grade ≥2), and/or acute kidney injury, as per CTCAE v5.0 and KDIGO guidelines.

Results: Over a median follow-up of 52 months, 34.7% of patients developed a renal event, most commonly hypertension (27.9%), followed by proteinuria (6.8%) and acute kidney injury (6.8%). Only a history of hypertension was identified as an independent risk factor for renal event (p=0.0078). Importantly, patients with renal events had significantly longer survival compared to those who did not (p=0.0243). In the multivariate analysis, the occurrence of a renal event emerged as a protective factor against mortality.

Conclusions: In conclusion, renal events occurred in 34.7% of bevacizumab -treated patients. Hypertension was a risk factor for renal event, but renal events appeared to be a protective factor against mortality. Rather than signaling harm, their presence may reflect effective VEGF pathway inhibition and greater antitumor response. Routine monitoring and early nephrological management of hypertension, proteinuria, and acute kidney injury are essential to optimize treatment continuity and outcomes.

Background: CKD is among the strongest predictors of adverse COVID-19 outcomes, yet how CKD-associated risk evolved across pre-vaccination, roll-out, mass-vaccination, and post-pandemic phases remains incompletely defined in Latin America.

Methods: We performed a nationwide retrospective analysis of Mexico's historical surveillance open datasets, including all laboratory-confirmed cases from January 1, 2020 to June 30, 2025. The primary outcome was death among recorded cases (case-fatality); secondary outcomes were hospitalization, ICU admission, and invasive mechanical ventilation (IMV). Multivariable logistic models were fit overall, by age strata and year/pandemic phase, adjusting for demographics, comorbidities, and symptom-to-care interval; temporal patterns were summarized with LOESS and segmented interrupted time-series analysis. Sensitivity analyses included models restricted to ICU admissions and models additionally adjusted for municipal socioeconomic context.

Results: Among 7,359,354 cases, 70,144 (1.0%) had CKD; crude case-fatality was 33% in CKD vs 4% without. In adjusted models, CKD was associated with higher case-fatality (aOR 1.20, 95% CI 1.19-1.20) and hospitalization (aOR 1.35, 95% CI 1.35-1.35), but not with ICU admission (aOR 0.98) or IMV (0.99). In the ICU-restricted cohort, CKD independently increased in-ICU case-fatality (aOR 1.38, 95% CI 1.25-1.51), strongest at ages 18-64 (aOR 1.52) and smaller at ≥65 (aOR 1.19). Year-specific models showed attenuation during mass vaccination (2022 aOR 1.13) followed by a resurgence in 2024 (aOR 1.90). LOESS/ITS revealed delayed and incomplete post-vaccination benefit for CKD with trend acceleration in 2023. Findings were robust after adding municipal SES indicators to adult models.

Conclusions: Across five years of nationwide surveillance, CKD remained a dominant, independent correlate of COVID-19 case-fatality and hospitalization, with risk resurging in 2024. Lower ICU/IMV use yet higher in-ICU case-fatality among CKD patients may reflect selection effects and underscore the need for rapid escalation pathways.

Background: The extent to which gestational diabetes mellitus (GDM) influences the risk of kidney disease remains unknown. We investigated the associations between GDM and incidence of kidney disease, including CKD and AKI.

Methods: This nationwide population-based cohort study included 1,441,317 parous women in France during 2012-2013. We used Cox regression to investigate the: 1) association of GDM with incident hospitalization for AKI or CKD, 2) timing to postpartum GDM-related kidney disease, and 3) GDM recurrence and the incidence of kidney disease.

Results: Over a 10-year period, women with a history of GDM (n=103,122 [7.2%]) had a 46% higher risk of CKD (aHR: 1.46, 95% CI: 1.36, 1.55) and a 18% higher risk of AKI (aHR: 1.18, 95% CI: 1.11, 1.25), compared to those without a history of GDM. Accounting for post-partum incident hypertension and type 2 diabetes attenuated effect estimates - 10% for CKD (aHR: 1.10. 95% CI: 1.02, 1.19) and 1% for AKI (aHR: 1.01, 95% CI: 0.95, 1.08). The elevated risk of kidney disease was apparent at one-year post-partum and more pronounced among women with two or more GDM episodes than among those with one GDM episode.

Conclusions: GDM was mainly associated with an increased risk of CKD; which is present early in the post-partum and higher among women with repeated GDM.

Background: Sickle cell disease (SCD) is associated with accelerated kidney function decline, with no proven effective therapies. We examined the associations between treatment with renin-angiotensin system inhibitors (RASi) and eGFR decline in SCD.

Methods: This 2-center observational study used electronic health record data of adult, Black patients with SCD (by hemoglobin electrophoresis) and ≥1 year follow-up between 2010-2024. We compared incident RASi users (exposure) to no treatment (reference). We created 1:1 propensity score-matched cohorts, balancing on demographics, vital signs, comorbidities, medications, and laboratory values. The primary endpoint was the difference in the mean change in eGFR per year, analyzing only chronic slopes (≥90 days post-index date) using linear mixed models on the matched cohorts. Sensitivity analyses were performed excluding patients with missing albuminuria and excluding low-dose RASi. Effect modification by SCD-modifying therapies was also examined.

Results: Matched cohorts identified were primary analysis (358 patients), excluding missing albuminuria data (262 patients), and excluding low dose RASi (270 patients). All cohorts achieved optimal standardized mean differences < 0.2. After multivariable adjustment, there was no significant difference in eGFR decline between RASi and the reference in the primary cohort (-0.15 mL/min/year; 95% confidence interval [CI], -1.67 to +1.36; p = 0.84), the sensitivity analysis cohort excluding missing albuminuria data (+0.89 mL/min/year; 95% CI, -0.86 to +2.63; p = 0.32) and the sensitivity analysis cohort excluding low dose RASi (+0.78 mL/min/year; 95% CI, -1.12 to +2.67; p = 0.42). All p values for interaction terms between RASi and SCD-modifying therapies in all models were > 0.05.

Conclusions: In this large, real-world cohort of patients with SCD, RASi use was not associated with slowed eGFR decline. These findings underscore the limitations of observational data and highlight the urgent need for prospective trials to identify effective GFR-preserving therapies for this high-risk population.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder caused by mutations in genes encoding ciliary proteins. Increasing evidence suggests that immune cell infiltration, chronic inflammation, and dysregulated immune signalling pathways contribute to cyst growth, fibrosis, and progressive kidney function decline. Notably, features of chronic inflammation are already detectable in early stages of the disease, including infiltration by immune cells, elevated levels of pro-inflammatory cytokines, and immunological crosstalk between immune and epithelial cells. These immune responses promote fibroblast activation and excessive extracellular matrix deposition via key signalling pathways such as NF-κB, JAK-STAT, and TGFβ-SMAD, ultimately driving renal fibrosis and functional deterioration. Conversely, components of the adaptive immune system have been implicated in slowing disease progression. CD8+ T cells have been shown to exert a protective effect by limiting cyst expansion and preserving tubular architecture. Remarkably, cyst-lining epithelial cells themselves can regulate immune cell activity, highlighting a complex and dynamic interplay between ADPKD and the immune system at multiple levels. Beyond direct crosstalk, immune mechanisms may also contribute to the genotype-independent interindividual variability observed in ADPKD progression. In this review, we provide a comprehensive overview on the role of immune cells in ADPKD, offering mechanistic insight into the processes underlying cyst initiation and progression. This perspective underscores the increasing recognition that cystic kidneys share fundamental features with tumor-like microenvironments, including chronic inflammation, immune-driven matrix remodelling, and metabolic dysregulation. We further summarize emerging immune-related biomarkers and therapeutic targets, providing a foundation for future translational approaches.

Background: In the STOP-ACEi trial, patients with advanced CKD were randomised to continue or stop renin-angiotensin system inhibitors (RASi) and showed no difference in kidney outcomes. This post-hoc analysis investigates interactions with loop diuretic use.

Methods: Patients with eGFR<30ml/min/1.73m2 and progressive CKD were randomized, to stop or continue RASi. Primary outcome was eGFR over 3-years using repeated-measures, mixed-effects linear regression, random-slope models. Cox models were used to calculate hazard ratios for time-to-event outcomes, including ESKD and KRT.

Results: At baseline, eGFR, arterial pressure and proteinuria were similar for 133 patients taking loop diuretics and 278 who were not. Those receiving loop diuretics at randomization, least-squares mean (±SE) eGFR at 3-years was 12.3 (±1.1) for those stopping compared to 10.1 (±1.2) for those continuing RASi, trend favouring stopping RASi (+2.2; 95% CI, -0.9 to +5.4), but eGFR slope over 3-years was similar (-7.2 vs -7.7 ml/min/1.73m2). Those not receiving loop diuretics, eGFR at 3-years was 8.8 (±0.8) and 11.6 (±0.8) (discontinue and continue RASi groups), a difference favouring continuing RASi (-2.8; 95% CI, -4.9 to -0.8), and a steeper eGFR slope for those discontinuing RASi (-9.9 vs -7.6 ml/min/1.73m2). The interaction between loop diuretic use and the effect of RASi on eGFR at 3-years and the three-way interaction between diuretic subgroup, effect of RASi and time were both statistically significant (p=0.01 and p=0.04 respectively). Of patients taking loop diuretics, 73 (55%) developed ESKD/KRT, and 23 (17%) died. Of patients not taking loop diuretics, 170 (61%) developed ESKD/KRT and 19 (7%) died.

Conclusions: Withdrawal of RASi was associated with a steeper decline in eGFR over 3-years in those not receiving loop diuretics but this was not observed in those who were taking loop diuretics. Patients receiving loop diuretics had a high mortality. These data support the need for randomised trials investigating the efficacy and safety of loop diuretics in patients with advanced CKD.