Kidney360最新文献

Background: Chronic stress (CS) due to prolonged exposure to negative life events increases the risk of psychiatric illnesses and significantly affects physiological processes. CS has also been linked to sustained systemic inflammation, resulting in dysregulated immune responses and organ function. We hypothesized that CS would lead to kidney inflammation and tested this in mice.

Methods: Male C57BL/6J mice were subjected to CS by pair-housing them with CD-1 retired breeder mice. Kidney immune cells were isolated and evaluated by spectral flow cytometry. Cytokines were measured using a multiplex assay in kidney tissue and serum. Serum creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured.

Results: Mice subjected to CS exhibited greater weight gain than the control group and had reduced fur quality. CS led to a decrease in the percentage of CD4+ T cells (54.26 ± 0.89% vs. 59.88 ± 1.25%, P < 0.001) and an increase in T helper 17 (Th17) (2.3 ± 0.3% vs. 0.83 ± 0.15%, P < 0.001) and regulatory T cells (Tregs) (3.42 ± 0.45% vs. 1.53 ± 0.21%, P < 0.001). There was an increase in the macrophage percentage in CS mice (88.33 ± 1.16% vs. 84.26 ± 0.73%, P < 0.01). TNF-α levels were higher in the kidney of stressed mice (8.53 ± 1.18 vs. 3.15 ± 1.29 pg/mL, P < 0.01). CS led to elevated levels of cystatin C (515.9 ± 16.88 vs. 456.6 ± 14.79 ng/mL, P < 0.05) and NGAL (833.1 ± 282.4 vs. 90.58 ± 5.57 ng/mL, P < 0.0001).

Conclusions: CS in mice led to kidney inflammation and immunologic changes. These could predispose to acute and chronic kidney diseases in which inflammation plays a pathogenic role.

Background: CKD is common, and its prevalence is increasing rapidly worldwide. The aim of this study was to investigate the relationship between CKD and dynamic changes in cerebral oxygenation, which may help explain the link between CKD, cerebrovascular disease, and cognitive impairment.

Methods: This observational study used data from waves three (2014-2015) and six (2020-2023) of The Irish Longitudinal Study on Ageing (TILDA), a nationally representative, population-based cohort of community-dwelling adults aged ≥50 years in Ireland. A total of 2,322 participants (mean age 64.7 ± 7.6 years; 53% female) were included.7.1% had CKD, defined by estimated glomerular filtration rate (eGFR). Cerebral oxygenation, indicated by the Tissue Saturation Index, was continuously measured using near-infrared spectroscopy during and after an orthostatic manoeuvre.

Results: Participants with CKD were older, had lower levels of educational attainment and higher prevalence of cardiovascular and cerebrovascular disease and cognitive impairment. At wave three, cerebral oxygenation was significantly and independently lower at all time points post-standing in those with CKD (30 s:-0.23 [95% CI -0.43 to -0.04], 60 s:-0.31 [-0.51 to -0.11], 90 s -0.34 [-0.54 to -0.14], 120 s: -0.34 [-0.54 to -0.14], 150 s: -0.32 [-0.52 to -0.12] and 180 s: -0.36 [-0.55 to -0.16], p <0.05). The co-existence of orthostatic hypotension amplified this association at later timepoints while systolic hypotension may mitigate it. Lower eGFR was associated with lower cerebral oxygenation, eGFR 45-59 mL/min/1.732 showed the most pronounced decline.

Conclusions: CKD is significantly and independently associated with reduced cerebral oxygenation during orthostatic challenge. This may represent a key mechanism linking CKD to cognitive impairment. Further longitudinal studies are warranted to explore the clinical utility of cerebral oxygenation as a predictive biomarker for cognitive decline in CKD.

Background: Despite progress in research, the mechanobiological mechanisms behind adverse vascular remodeling and failure in arteriovenous fistulae (AVF) for hemodialysis remain unclear. The aim of this investigation is to assess the association between flow-induced vascular wall vibrations and adverse vascular remodeling in AVFs.

Methods: Six end-stage kidney disease patients with native distal radio-cephalic AVF were monitored for 1 year with magnetic resonance imaging and Doppler ultrasound examinations. Patients were divided based on AVF outcomes: two maintained proper AVF patency and four developed complications (two venous stenoses and two excessive dilatations). Patient-specific fluid-structure interaction simulations were performed at different time points.

Results: Before vascular remodeling, stenotic AVFs exhibited two dominant frequency bands, between 45 and 100 Hz, while excessively dilated AVFs exhibited a single band at 50 Hz. Before the onset of remodeling, patients with complications exhibited significantly higher vibration amplitude (22.5 ± 5.8 μm vs. 6.6 ± 2.0 μm, p < 0.01) and high-pass strain ((1.30 ± 0.35)∙10-3 vs. (0.30 ± 0.10)∙10-3, p < 0.01) than those with proper patency. Significant differences in vibration amplitude and high-pass strain were observed between patients with proper patency and those with stenosis (p < 0.001 and p < 0.01, respectively), and in high-pass strain between patients with preserved patency and those with excessive dilatation (p < 0.01).

Conclusions: Specific vibration frequencies and amplitude levels appear to be associated with distinct types of vascular remodeling, indicating they could potentially be biomarkers for AVF surveillance.

Background: Diagnosing heart failure (HF) in dialysis patients is challenging due to overlapping symptoms of volume overload. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a health status questionnaire measuring HF symptoms and functional limitations, with lower scores indicating greater burden.

Methods: We studied 625 Chronic Renal Insufficiency Cohort study (CRIC) participants who developed end-stage kidney disease (ESKD) and had KCCQ scores post-ESKD diagnosis treated with hemodialysis (HD) or peritoneal dialysis (PD). The primary outcomes were rates of HF hospitalization, 30-day HF readmission and all-cause mortality. KCCQ was modeled dichotomously (<75 vs ≥75) and continuously (per 5-point decrement). Poisson regression with robust standard errors was used to test the association of KCCQ score with each outcome.

Results: Among 625 participants (mean age 59 years; 60% male; 87% on HD), median follow-up from KCCQ evaluation was 6.8 (IQR 3.2-12.0) years. Those with KCCQ <75 had nearly twice the rate of HF hospitalizations (15.4 vs 8.4/100 person-years) compared to KCCQ ≥75. Each 5-point decrement in KCCQ was associated with 9% higher adjusted relative risk (aRR) of HF hospitalization (p=0.0003), 7% higher aRR of 30-day HF readmission (p=0.03), and 6% higher aRR of all-cause mortality (p<0.001). Stratified by HF subtype, patients with HFrEF and KCCQ <75 had 81% higher aRR of HF hospitalization vs those with KCCQ ≥75 (p=0.02). Decline in KCCQ by ≥ 5 from pre-ESKD to post-ESKD was associated with >40% increase in aRR of all-cause mortality (p=0.02).

Conclusions: Higher HF symptom burden and functional limitations at dialysis initiation are independently associated with increased risk of HF hospitalization and all-cause mortality, suggesting that the KCCQ score may help predict outcomes early in the course of treatment.

Background: In the Kidney Allocation System (KAS), adult kidney candidates who are a zero Human Leukocyte Antigen (HLA) ABDR-mismatch with a potential donor are given priority in the match run over non-zero HLA ABDR-mismatch candidates. Furthermore, KAS allows for the shunting of kidneys to zero-mismatch candidates across compatible ABO blood types, potentially disadvantaging O candidates who have longer waiting times. This study was undertaken to determine who is receiving zero HLA ABDR-mismatch kidneys, the number of donors shunted to non-identical ABO recipients, the impact on dialysis exposure before transplant, and the current patient and graft outcomes.

Methods: All adult deceased donor kidney recipients since the start of KAS on 12/4/2014 were included in the study. Multi-organ transplants with a kidney, 98-100% Calculated Panel Reactive Antibodies (CPRA), previous living donors, pediatric, medically urgent, and safety net transplants were excluded. Patients were considered a zero-mismatch allocation if they received a zero HLA ABDR-mismatch kidney and had an allocation CPRA less than 98%. 122,951 adult deceased-donor kidney transplants were in the study population. 6228, or 5.1%, were zero HLA ABDR-mismatch recipients.

Results: The zero HLA ABDR-mismatch recipients were predominantly of the White race, female, had lower allocation CPRAs, much shorter dialysis exposure, and were more likely to be retransplant recipients. 1441 blood type O donors were shunted to other ABO groups, or 2.46% of O donors. Cox analysis of graft and patient survival showed that zero HLA ABDR-mismatch recipients had a small graft survival advantage (0.898, 0.834-0.967, p=0.004) and no patient survival advantage (0.947, 0.865-1.037, p=0.239). The adjusted graft survival at 7 years was 67% (zero HLA-ABDR mismatch) versus 65% (non-zero HLA-ABDR mismatch).

Conclusions: The current zero HLA ABDR-mismatch priority is highly biased against racial minority recipients, shunts a sizable number of O donors to non-O recipients, only makes a small improvement to organ utility, and should be removed from the allocation priority list.

For 25 years, the Brazilian Society of Nephrology has systematically monitored chronic dialysis care through the Brazilian Dialysis Survey (BDS), offering a unique perspective on the evolution of dialysis practices and access to treatment in a large and diverse middle-income country. Analysis of data from 1999 to 2024 reveals that hemodialysis has remained the dominant modality, representing on average 92% of treatments, while peritoneal dialysis accounted for only 8% and showed a steady decline. Regional differences have been marked: the Northeast consistently reported the lowest rates of peritoneal dialysis, while the South maintained above-average use. Funding sources also reflect broader structural dynamics in the health system. The Unified Health System (SUS) has been the backbone of dialysis provision, covering 83% of patients over the period. Yet, the role of private health insurance has expanded, with coverage increasing from 12% in 2006-2009 to 20% in 2019-2024. Interestingly, regional comparisons show contrasting patterns, with private insurance supporting a disproportionately high share of dialysis in the North compared with the general population, while in the Southeast the opposite scenario was observed. Taken together, these findings illustrate a landscape shaped by declining use of peritoneal dialysis, heavy reliance on public financing, and persistent regional inequities. Beyond documenting numbers, the BDS highlights the need for policies that promote equity, strengthen the role of peritoneal dialysis, and ensure sustainable access to kidney replacement therapies for all Brazilians.

Combined inhibition of neprilysin and the angiotensin II receptor through Angiotensin Receptor-Neprilysin inhibitors (ARNI) has transformed heart failure management and is garnering increasing attention in nephrology. This article explores the renal role of neprilysin and critically reviews preclinical and clinical evidence on the use of ARNIs in CKD, following a "bench to bedside" approach. Experimental data show that neprilysin inhibition improves proteinuria, fibrosis, and endothelial function, with enhanced benefits when combined with RAAS blockade. Randomized Clinical Trials (RCTs) in Heart Failure patients (PARADIGM-HF, PARAGON-HF, PARAGLIDE-HF) have demonstrated renal safety and potential benefit emerged in secondary endpoints and prespecified analysis. The only RCT performed with primary kidney outcome, the UK HARP-III trial, confirmed the tolerability of Sac/Val, and reported a significant reduction in proteinuria. No clear nephroprotective effect was observed; however, the trial design may not have been adequately structured to detect such an effect. On the other hand, real-world data indicate that ARNIs have an acceptable risk profile when patients are appropriately monitored, as Renin-Angiotensin-Aldosterone System blockers. Moreover, the benefits of the treatment clearly outweigh the adverse effects. Therefore, Sac/Val may emerge as a promising therapeutic option in nephrology, especially in patients with cardiorenal disease, pending further trials to better define its role in CKD.

Background: Alport syndrome (AS) is a hereditary kidney disease caused by COL4A3/4/5 mutations that lack of effective treatments. Sodium-Glucose Co-Transporter 2 inhibitors (SGLT2i) have demonstrated renal and cardiovascular protective effects in patients with chronic kidney disease (CKD), however their long-term effects in patients with AS and the underlying mechanisms remain to be clarified.

Methods: We conducted a single-arm, prospective study to examine the effect of dapagliflozin in patients with AS. In parallel, Col4a3 p.C1615Y mutant mice (129S2/Sv background) were used as an AS model to investigate the reno-protective mechanisms of dapagliflozin.

Results: A total of twenty-one AS patients were enrolled. After approximately 12 months of follow-up (12.6±1.2 months), the mean 24-hour urinary protein decreased by 29% to 1.25±0.73 g from baseline (1.75±0.90) (p<0.001). The estimated glomerular filtration rate (eGFR) showed no significant difference compared with baseline (76±28 vs.77±29 ml/min/1.73 m2, p=0.057). In the animal studies, dapagliflozin significantly reduced macrophage infiltration and the expression of inflammatory cytokines levels in the renal cortex of Col4a3 mutant mice. Mechanistic studies showed that STING pathway was activated in the renal cortex and tubular epithelial cells from Col4a3 mice, contributing to a pro-inflammatory phenotype. Dapagliflozin effectively inhibited STING activation and suppressed inflammatory cytokines production in mutant tubular epithelial cells.

Conclusions: Dapagliflozin can reduce proteinuria in patients with Alport syndrome and plays an anti-inflammatory role by inhibiting the STING pathway in tubular epithelial cells of AS mice.