Kidney360最新文献

Background: Little is known regarding whether renal function during pregnancy among healthy women is associated with pregnancy outcomes. Evidence based on the universal screening of maternal eGFR is lacking. We investigated the association of maternal eGFR during the second trimester with fetal birthweight.

Methods: This prospective birth cohort study includes 1,666 singleton pregnant women (median age 36 years, median BMI 20.0) who had universal screening of eGFR during the second trimester. Participants were categorized into the quartile of eGFR. The 1st quartile group was defined as low eGFR, the 4th quartile group as high eGFR, and the 2nd and 3rd quartile group as reference. The primary outcomes are low birthweight (LBW) and small for gestational age (SGA). Multivariable logistic regression models were used to investigate the association of maternal eGFR and pregnancy outcomes.

Results: As compared to the reference group, the adjusted odds ratios (95% Confidence Intervals [CI]) for LBW and SGA in the low eGFR group were 2.25 (1.48-3.40) and 2.51 (1.63-3.87), respectively, and in the high eGFR group were 0.69 (0.40-1.19) and 0.55 (0.30-1.02), respectively. The adjusted odds ratios of eGFR per SD decrease (95% CI) for LBW and SGA were 1.92 (1.50-2.45) (p=0.013) and 2.07 (1.60-2.68) (p<.001). The prediction models were improved by adding eGFR to the models including covariates; for LBW (C statistics difference, +0.018; 95% CI, -0.004-0.040, net reclassification index (NRI), 0.377; 95% CI, 0.208-0.545, and integrated discrimination improvement (IDI), 0.0135; 95% CI, 0.005-0.022) and for SGA (C statistics difference, +0.041; 95% CI, 0.003-0.080, NRI, 0.408; 95% CI, 0.226-0.591, and IDI, 0.017; 95% CI, 0.009-0.025).

Conclusions: The lower maternal midterm eGFR is associated with LBW and SGA, while the higher eGFR is not. Evaluating midterm eGFR may help identify healthy women at risk of adverse birth outcomes.

Background: Dialysis may deplete the body of valuable solutes. We previously found that the diet-derived antioxidant ergothioneine was markedly depleted in hemodialysis (HD) patients. Standard peritoneal dialysis (PD) prescriptions provide lower clearances of small molecules than standard HD prescriptions. We therefore tested whether ergothioneine would be depleted in PD patients but to a lesser degree than in HD patients.

Methods: Blood levels of ergothioneine were compared in 16 PD patients, 16 HD patients, and 15 controls with normal kidney function. Levels were measured using liquid chromatography mass spectrometry in plasma and also in erythrocytes in which ergothioneine is normally highly concentrated. Ergothioneine clearances by PD and HD were also compared.

Results: Erythrocyte ergothioneine levels were much lower in both PD and HD patients than controls. The erythrocyte ergothioneine levels, however, were less depleted in PD patients than in HD patients. The erythrocyte levels in PD patients averaged 34% those of controls while levels in HD patients averaged only 10% those of controls. Plasma ergothioneine levels in dialysis patients were also lower than controls. The time-averaged clearance of ergothioneine was lower with PD than with HD, so that a standard PD regimen would remove less ergothioneine daily than a standard HD regimen at a given plasma level.

Conclusions: The antioxidant ergothioneine is depleted in PD patients but to a lesser extent than in HD patients. Benefits of ergothioneine repletion in dialysis patients remains to be assessed.

Background: Patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) develop progressive symptoms which impact quality of life. We distributed the Kidney Disease Symptom Survey (KDSS), an electronic patient-reported outcome measure (PROM), partially based on the Kidney Disease Quality of Life 36 (KDQoL-36) instrument, to patients with NDD-CKD. We aimed to evaluate the measurement properties of the KDSS when used in usual clinical care.

Methods: We conducted a retrospective analysis of electronic health record (EHR) data for patients with NDD-CKD who completed the KDSS as part of their routine nephrology care. We evaluated temporal stability of KDSS scores for individuals with stable kidney function, responsiveness of KDSS scores for individuals with worsening kidney function, and convergent construct validity of the KDSS with Medicare Annual Wellness Visit (AWV) assessments of patient-reported outcomes.

Results: Among 147 patients with stable NDD-CKD, there were strong correlations between sequential KDSS assessments of general health [Spearman's rank correlation (rho) 0.76], QoL (rho 0.63), physical symptoms (rho 0.74), and mental health (rho 0.71). For 35 individuals with worsening kidney function, the KDSS detecting a clinically important difference in physical symptom and mental health scores in ∼40% of respondents. There were moderate to strong correlations between KDSS and AWV assessments of general health (rho 0.64) and depressive symptoms (rho 0.50).

Conclusions: When used by diverse individuals with NDD-CKD, the KDSS had temporal stability for patients with stable kidney function, as well as moderate convergent construct validity for measuring general health and depressive symptoms. Responsiveness of the KDSS for physical symptoms and mental health was seen in only some individuals with kidney disease. Additional data demonstrating responsiveness to changes in kidney function, as well as interventions such as symptom management strategies, are needed to determine the clinical utility of the KDSS when used in usual care of patients with NDD-CKD.

Background: Immunoglobulin A nephropathy is the most prevalent primary glomerular disease worldwide; however, its heterogenous clinical course complicates prognostic prediction. Podometrics, a quantitative assessment of podocytes based on the recently proposed "podocyte depletion hypothesis," has been suggested as a potential predictor of renal outcomes in various glomerular diseases. Nevertheless, its correlation with the Oxford classification or the pre-biopsy estimated glomerular filtration rate slope remains unclear. This study aimed to investigate the association between podometrics and MEST-C scores and identify podometric parameters associated with the pre-biopsy estimated glomerular filtration rate slope.

Methods: Kidney biopsy specimens from 101 patients diagnosed with immunoglobulin A nephropathy at our institution between 2019 and 2022 were evaluated using the Oxford classification and podometrics. Patients were categorized into "decline" and "non-decline" groups based on their pre-biopsy estimated glomerular filtration rate slope. Urinary mRNA levels of podocyte markers (NPHS1 and NPHS2) were measured in 94 patients. Independent factors associated with the "decline" group were identified via multivariate nominal logistic regression analysis.

Results: Patients with stage S1 or T1/2 exhibited significantly lower podocyte densities and numbers compared with those with stage S0 or T0, respectively. Elevated urinary podocyte marker levels were associated with E1 and C1/C2 lesions. The "decline" group exhibited significantly lower podocyte density and number and larger mean podocyte volume compared with the "non-decline" group. In the multivariate analysis, a lower podocyte number was the only independent factor associated with the "decline" group.

Conclusions: The podocyte number at the time of kidney biopsy was associated with the pre-biopsy estimated glomerular filtration rate decline slope in patients with immunoglobulin A nephropathy. Furthermore, elevated urinary podocyte mRNA levels suggested the presence of E and C lesions. Podometrics may serve as a potentially less invasive marker for monitoring disease activity and guiding treatment strategies.

Background: Kidney disease contributes to both cognitive and physical decline; whether kidney health biomarkers relate to declining cognitive and physical performance separately and/or together is unknown.

Methods: Among 1,902 participants (26% Black; 53% female) in the Health, Aging and Body Composition Study with intact baseline gait speed (≥0.8 m/s) and cognition (modified Mini-Mental State [3MS] score≥90), we assessed baseline kidney-related biomarkers (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [UACR], serum 25-hydroxyvitamin D, plasma intact parathyroid hormone [iPTH], plasma alpha-klotho, serum intact fibroblast growth factor 23 [FGF23], and vitamin D metabolites) with joint trajectories of cognitive and physical performance. Grouped-based trajectory analysis of 3MS and 20-meter usual gait speed up to 10 years yielded three groups: Group 1 (n=660), superior longitudinal cognitive-physical performance; Group 2 (n=744), high sustained cognition and initially lower, declining gait; and Group 3 (n=498), lower initial cognitive-physical performance, both steeply declining. Three sequential multinomial regression models were built with covariate adjustment.

Results: In Model 1 (M1; kidney function), higher eGFR (per 10 ml/min/1.73m2) was associated with lower odds of being in Group 3 versus Group 1 (odds ratio[OR]=0.84, 95%confidence interval[CI]: 0.75-0.94, p=0.003) after covariate adjustment. Additionally, each doubling of UACR related to higher odds of being in Group 2 (OR=1.13, 95%CI: 1.04-1.23, p=0.006) and Group 3 (OR=1.23, 95%CI: 1.12-1.36, p<0.001) versus Group 1. Log2 25-hydroxyvitamin D and log2 iPTH, added in Model 2 (M2; clinical biomarkers), were not significantly associated with cognitive-physical trajectory (p=0.63, M2 versus M1). However, Model 3 (M3; research biomarkers adding alpha-klotho and FGF23) showed higher log-2 alpha-klotho associated with lower odds of being in Group 3 versus 1 (OR=0.70, 95%CI: 0.52-0.94, p=0.019).

Conclusions: Kidney health biomarkers are potential factors in dual maintenance/decline in cognitive-physical function. Improving kidney health may contribute to preserved function in older adults.

Background: Trauma is a leading global cause of death, and acute kidney injury (AKI) significantly worsens outcomes. Hemorrhagic shock (HS) and rhabdomyolysis (RM) are major contributors, yet their individual and combined effects on the kidney remain poorly defined.

Methods: Using a clinically relevant rat model that closely mimics human trauma, we performed bulk and spatial transcriptomics to characterize early renal responses to HS, RM, and their combination (RM-HS). Commercial mouse spatial transcriptomics probes were successfully applied to rat kidney tissue, enabling cost-effective and region-specific gene expression profiling.

Results: RM emerged as the dominant driver of transcriptional changes, while RM-HS triggered a synergistic, mortality-associated response. Comparative analyses revealed distinct regional and molecular signatures: HS suppressed metabolic activity, whereas RM induced widespread upregulation of inflammatory and stress-response pathways.

Conclusions: We propose a mechanistic framework linking these traumatic insults to tubular cell injury and death, with mitochondrial dysfunction, dysregulated lipid metabolism, PLIN2 expression, and ferroptosis as central components. This integrative model advances our understanding of trauma-induced renal injury and may enable the identification of novel biomarkers and therapeutic strategies to mitigate AKI severity in trauma patients.

Background: People with kidney failure on chronic hemodialysis (HD) require sustainable vascular access. The AV Access trial is a randomized controlled trial comparing clinical and patient-reported outcomes in adults ≥ 60 years old on HD with a central venous catheter, randomized to receive either a surgical arteriovenous (AV) fistula or graft. Patient enrollment in the trial initially progressed slower than anticipated. We designed a cross-sectional qualitative substudy to identify facilitators and barriers to patient enrollment in the AV Access trial.

Methods: We conducted qualitative focus groups and semi-structured interviews of site investigators and providers, and semi-structured interviews of patients who had been approached for enrollment in the AV Access trial. We performed hybrid inductive-deductive thematic analysis of transcripts.

Results: We analyzed transcripts from two focus groups (one with four vascular surgery physician investigators and one with four nephrology physician investigators) and 44 individual interviews with vascular surgery physician investigators (n=2), nephrology physician investigators (n=2), vascular surgery providers (n=9), nephrology providers (n=10), and patients (n=21). Participants identified themes related to clinical site selection, buy-in from clinical teams, patient referral processes to vascular surgery, and processes to recruit patients to enroll in the trial. Subthemes included barriers related to patients receiving care from providers external to the study team, pervasive biases from the "Fistula First" initiative, limited patient knowledge of the importance of AV access, and a need for additional information provided to patients to support informed decision-making about trial participation.

Conclusions: Enrollment in the AV Access trial was hindered by multi-level barriers. Some of these may be mitigated through collaborative patient education surrounding the importance of access placement, as well as provider-directed education to increase buy-in and enhance engagement. These findings can inform the design and implementation of future randomized controlled trials concerning surgical AV access outcomes.

Background: CKD is a global health issue exacerbated by the rising prevalence of diabetes and obesity. Renal fibrosis, characterized by the accumulation of extracellular matrix proteins, is a critical factor in CKD progression. Transforming growth factor β (TGF-β), a key profibrotic cytokine, plays a pivotal role in this process. However, systemic inhibition of TGF-β has been limited by associated toxicities.

Methods: This study explores the role of αvβ8 integrin in renal fibrosis and its potential as a therapeutic target in CKD. We used various preclinical models of CKD, including humanized αvβ8 mice and the db/db uninephrectomy model, to investigate the role of αvβ8 integrin in renal fibrosis. Gene Set Variation Analysis (GSVA) was employed to assess fibrotic gene signatures in human kidney biopsies. The therapeutic potential of MEDI8367, a monoclonal antibody targeting αvβ8 integrin, was evaluated in vitro and in vivo.

Results: Our findings demonstrate that αvβ8 integrin is upregulated in the tubulointerstitium of CKD kidneys, particularly in diabetic kidney disease (DKD), and correlates with TGF-β activation and renal function decline. MEDI8367 effectively inhibited αvβ8-mediated TGF-β activation in vitro and attenuated murine unilateral ureteral obstruction (UUO)-induced renal fibrosis. Notably, inhibition of αvβ8 reduced kidney damage and improved kidney function in models of DKD and hypertensive nephropathy.

Conclusions: Our study highlights the potential of MEDI8367 to mitigate renal fibrosis and improve kidney function, offering a novel approach to CKD treatment that complements existing therapies.

Cardiovascular outcome trials are challenging to conduct in patients with CKD. Despite this, well-designed randomized controlled trials are critical to inform optimal management strategies and improve clinical care. Unfortunately, many cardiovascular outcome trials in nephrology have not demonstrated a treatment benefit. Contributing to this are the difficulties associated with endpoint selection and the limitations of many traditional endpoints such as resting left ventricular geometric measures and circulating biomarkers in patients with CKD, which are well known to be a major impediment to the conduct of cardiovascular trials in this population. The emergence of state-of-the-art Cardiopulmonary Exercise Testing (CPET) technology in nephrology has taken center stage in this field due to the possibilities and solutions afforded by CPET-derived functional endpoints. CPET is a powerful tool that incorporates ventilatory gas exchange measurements during graded exercise and robustly quantifies VO2Peak, the gold standard index for cardiovascular functional capacity. The use of functional endpoints such as VO2Peak is a critical mechanism to promote patient-centered clinical trials in patients with CKD. Furthermore, the Food and Drug Administration (FDA) has now approved both drugs and devices that have utilized VO2Peak as an endpoint outside of nephrology. With accumulating scientific evidence base supporting the rationale for CPET-derived endpoints in patients with CKD, the potential use of VO2Peak in clinical trials as a basis for regulatory approval creates an exciting opportunity in nephrology.