Kidney360最新文献

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.

Background: Apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD) is an aggressive form of chronic kidney disease (CKD). This study described characteristics of non-diabetic patients with AMKD and compared their disease progression to non-diabetic patients with other forms of CKD.

Methods: This retrospective study used clinical and biosample data from NashBio (Nashbio contains electronic health records (EHR) generated during clinical encounters at Vanderbilt University Medical Center (VUMC)). Non-diabetic patients with ≥ 1 CKD diagnosis code who were ≥10 years of age at index (date of first CKD diagnosis code in patient's medical record) were included. The AMKD and other forms of CKD cohorts were defined based on the presence of APOL1 risk alleles and then their clinical and demographic characteristics were described. To assess progression patients were matched 1:1 on gender, presence of hypertension, and CKD stage at index and were followed until the last observation in the data. Progression outcomes including time from index to dialysis, kidney transplant, and diagnosis of CKD requiring kidney replacement therapy were assessed using Kaplan-Meier analysis, with log-rank tests used to compare matched cohorts.

Results: The study included 645 patients with AMKD and 6,749 patients with other forms of CKD. AMKD patients were significantly younger than other CKD patients (median 44.0 vs. 61.0 years; p<0.001) and had significantly less comorbidity burden such as cardiovascular diseases (16.9% versus 36.6% p < 0.001). Additionally, AMKD patients had higher rates of CKD requiring kidney replacement therapy at index (59% vs. 24%, p<0.001). After 1:1 matching, AMKD patients reached dialysis and kidney transplant significantly faster than other CKD patients (both p<0.001). Among patients who did not require kidney replacement therapy at index (n=264 per cohort), AMKD patients progressed to CKD requiring kidney replacement therapy significantly faster than other CKD patients (p<0.01).

Conclusions: Non-diabetic patients with AMKD experienced more rapid disease progression than patients with other forms of CKD, despite being younger and having lower comorbidity burden.

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.