Kidney360最新文献

Background: CKD is a risk factor for adverse pregnancy outcomes (APOs) in singleton pregnancies. Little is known about multifetal pregnancies in women with CKD. Due to higher maternal age and the wider use of medically assisted fertilization, multifetal pregnancies are increasing. We aimed to review pregnancy outcomes in the largest multicentre series of multifetal pregnancies in women affected by CKD.

Methods: This retrospective study gathered data from three Italian units with long-standing experience in the follow-up of pregnancy in women with CKD (2000-2023). Propensity-score matched (age, parity, BMI, year of delivery) multifetal low-risk pregnancies and singleton pregnancies served as controls; multifetal pregnancies were also matched for chorionicity, amnionicity and mode of conception. Intrauterine death of at least one fetus, given the low number of events, was explored in the overall multifetal cohorts.

Results: In this propensity score matched-cohort study, 52 multifetal pregnancies in women with CKD were associated with a significantly lower gestational age compared to 104 low-risk non-CKD controls (median 34.0 vs 36.0 gestational weeks - GW) and with lower term-delivery rate (9.6% vs 28.8%). NICU admission was more frequent in multifetal pregnancies with CKD (50.9% vs 25.2%, p=0.003).Cox regression and Kaplan-Meier analyses confirmed the independent impact of CKD on gestation duration. In women with CKD, multifetal pregnancies had a markedly shorter gestation than singletons (median 34 vs 39 GW, p< 0.00001), with significantly higher risk of preterm birth <34 GW (OR 9.733), SGA (OR 5.155), and NICU admission (OR 8.033). The difference was sharper than in low-risk non-CKD pregnancies (35 and 39 GW respectively).

Conclusions: This study, the largest assessing the risks of APOs in women with CKD carrying more than one fetus, suggests that multifetal gestation is a strong additional risk. These findings highlight the need for further investigation and demonstrate the importance of careful counselling, particularly in medically assisted reproduction.

Background: Acute or chronic kidney disease (CKD) affects 20-40% of multiple myeloma (MM) patients. While the negative prognostic effect of kidney involvement is established, the specific impact of different histological patterns remains poorly understood. We aimed to characterize the clinical outcomes associated with distinct kidney histologies in MM patients.

Methods: We retrospectively analyzed 193 MM patients who underwent kidney biopsy, comparing outcomes with 62 MM patients without kidney disease. Patients were categorized by histological findings: cast nephropathy (CN, n=120), AL amyloidosis (n=19), monoclonal immunoglobulin deposition disease (MIDD, n=8), and other renal diseases (ORD, n=46). We evaluated kidney function, dialysis requirements, treatment responses, and survival across histological subtypes and treatment modalities (conventional therapy vs. modern agents including proteasome inhibitors, CD38 antibodies, and autologous stem cell transplantation).

Results: The CN and MIDD groups had the lowest median eGFR at biopsy (13.0 and 25.5 ml/min/1.73 m2, respectively). Nephrotic-range proteinuria (>3.5 g/24h per KDIGO) was observed in the AL amyloidosis group (median 3910 mg/24h). Kidney replacement therapy (KRT) was initiated in 42.5% of patients. The proportion achieving KRT independence was 42.4% in the CN group and 50% in the ORD group, whereas none in the AL amyloidosis or MIDD groups recovered sufficient native kidney function. Modern combination therapy significantly improved renal outcomes, with 100% of patients receiving triple therapy showing renal response. KRT dependency was the strongest predictor of mortality: patients remaining on KRT had significantly shorter survival compared to those never requiring KRT (12.7 vs 56.2 months, p<0.001). The extent of improvement in kidney function did not influence survival; only dialysis status was prognostically relevant.

Conclusions: Kidney histology determines distinct clinical trajectories in MM patients, with CN showing potential for dialysis reversibility. Modern combination therapies significantly improve renal outcomes. The requirement for ongoing KRT, was the primary predictor of overall survival.

Background: Persistent somatic symptoms (PSS) in individuals with chronic kidney disease (CKD) occur across all stages and impact patients' quality of life, morbidity and mortality. We aimed to unravel associations between biopsychosocial factors and symptom burden in individuals with CKD.

Methods: This cross-sectional study analysed individuals with CKD (eGFR <60 mL/min/1.73m2) from the first 10,000 participants of the population-based Hamburg City Health Study (HCHS). Somatic symptom burden (PHQ-15) was the primary outcome. Its association with potential biological (e.g., eGFR), psychological (e.g., depressive symptoms), and sociodemographic correlates was analysed in a multivariate prediction model. Correlates were compared to healthy controls and individuals with coronary heart disease (CHD).

Results: Somatic symptom burden in patients with non-dialysis CKD (n = 582, mean age: 69.58 years; 44.7% women; mean baseline eGFR: 52 mL/min/1.73m2) increased with lower eGFR (r = -.161, p < .001). However, in a stepwise multiple linear regression model, eGFR was not correlated with symptom burden. In contrast, female sex, coronary heart disease, self-reported general health, proneness to illness, and depressive symptoms were associated with somatic symptom burden. Correlates of somatic symptom burden were compared to those in patients with CHD (n = 618, mean age: 67.13 years; 24.1% women; mean baseline eGFR: 81 mL/min/1.73m2) and matched healthy controls (n = 582, mean age: 69.58 years; 44.7% women; mean baseline eGFR: 81 mL/min/1.73m2). Self-reported general health and depression were associated with somatic symptom burden in all groups, while there were specific correlates in the CHD (e.g. age) and the healthy control group (e.g. expectancy of deterioration of health status).

Conclusions: Somatic symptom burden in CKD was only marginally related to the eGFR but rather to biopsychosocial factors. Therefore, taking a biopsychosocial perspective on PSS in CKD is important.

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.