Kidney360最新文献

Background: Chronic kidney disease (CKD) counts acute kidney injuries (AKI) as one of its many underlying causes. Lymphatic vessels are important in modulating inflammation post-injury. Manipulating lymphatic vessel expansion thus has the potential to alter CKD progression. Previously, we demonstrated that renal lymphatic expansion prior to injury reduced CKD progression following an AKI. Here we test whether inducing lymphangiogenesis impacts established CKD.

Methods: Following CKD progression, kidney lymphatics were expanded by transgenic induction of kidney-specific overexpression of vascular endothelial growth factor-D (KidVD) in aristolochic acid (AA) nephropathy and cisplatin injury aggravated with chronic high phosphate diet (CisPi) models or by infusion of kidney-targeting nanoparticles (NP) loaded with the VEGFR-3 specific ligand VEGF-C C156S in a progressive proteinuria (POD) model. Renal fibrosis and lymphatic density were determined by picrosirius red staining and immunofluorescence, respectively. Renal function was assessed by creatinine clearance rate, serum creatinine, blood urea nitrogen, urinary protein creatinine ratio and urinary albumin creatinine ratio. Renal pro-inflammatory and fibrotic markers expression were measured by qRT-PCR.

Results: KidVD+ mice demonstrated expanded renal lymphatics while NP treatment minimally expanded lymphatics. In neither the AA nor POD model did lymphangiogenesis improve renal function or fibrosis. AA mice showed decreased Tgfb1 expression and POD mice showed increased Col4a1 expression. Expansion worsened function in CisPi CKD and increased fibrosis. CisPi kidneys also demonstrated increased expression of Mcp-1, Il1b, Col1a1, and Tgfb1 and increased macrophage numbers.

Conclusions: Therapeutically induced lymphatic expansion is ineffective in resolving established CKD and has the potential to further worsen CKD progression.

Background: Patients treated with maintenance hemodialysis (HD) are at high risk of death from a variety of causes.

Methods: To identify markers (i.e., risk phenotypes) that distinguish among causes of death, we used dialysis electronic health record data for a cohort of adults treated with maintenance in-center HD who died between 2003-2016. Patients were linked to the United States Renal Data System (USRDS) Files. We classified USRDS-reported causes of death into five categories: Sudden Cardiac Death (SCD), non-SCD Cardiovascular Death, Infection, Others, and Unknown. A sub-cohort was linked to the National Death Index (NDI) with similar categories defined. We used ensemble classification trees to discriminate among causes using demographics, vital signs, laboratory measures, health service utilization, and comorbidity claims from 30 days prior to death. The area under the receiver operating curves (AUCs) were all between 0.59-0.70, suggesting minimal ability to distinguish among causes using clinical risk markers. We then created nested case-control populations for each cause of death and used ridge logistic regression to evaluate clinical risk markers that associate with distinct causes.

Results: Model coefficients were similar and highly correlated across different cause of death models (i.e., 0.87 - 0.94). This suggests that most clinical risk markers are shared across causes without distinct risk phenotypes.

Conclusions: We conclude that different causes of death may share similar clinical risk markers in the setting of kidney failure or that the causes of death attributed on USRDS or NDI forms are not precise.

Background: The impact of kidney transplantation (KT) on left ventricular (LV) remodeling remains poorly understood. This study aimed to evaluate the effect of KT on LV reverse remodeling, utilizing echocardiographic LV geometric patterns as a key assessment tool.

Methods: In 100 recipients who underwent living KT between 2012 and 2022, we evaluated changes in the distribution of LV geometric patterns (normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy) between baseline and 1 year post-transplantation. These patterns were categorized based on LV mass index (LVMI) and relative wall thickness (RWT) assessed via echocardiography.

Results: Overall, LV geometric patterns improved or remained stable in 81% of recipients, with worsening in 19%. The proportion of normal geometry increased from 15% to 19%, and concentric remodeling from 30% to 45%, while eccentric hypertrophy decreased markedly from 20% to 3%. Concentric hypertrophy remained relatively stable at 33% (p=0.036). Subgroup analysis revealed that 47% of those with pre-KT normal geometry progressed to LV remodeling, while 77% with concentric remodeling remained stable. In contrast, 55% with eccentric hypertrophy experienced reverse remodeling, and 49% with concentric hypertrophy also showed reverse remodeling. These subgroup results suggest an interaction between the effect of KT on LV reverse remodeling and the pre-KT LV geometric patterns. Multivariable analysis identified E/e' > 9.5 (OR 2.01, 95% CI 1.10-3.67, p=0.024) and acute antibody-mediated rejection (OR 2.44, 95% CI 1.01-5.87, p=0.047) as independent predictors of LV remodeling progression.

Conclusions: KT can lead to improvements in even advanced LV geometric patterns, although this effect may be diminished in the presence of pre-KT diastolic dysfunction or the occurrence of acute rejection. Since recipients rarely achieve complete renal recovery, echocardiographic monitoring remains crucial post-KT. Future studies are needed to establish whether these observed improvements in LV reverse remodeling directly translate into long-term reductions in cardiovascular events.

Background: Protein-energy wasting, characterized by disordered body protein catabolism resulting from metabolic and nutritional derangements, is associated with adverse clinical outcomes in patients undergoing hemodialysis. Extended-hours hemodialysis (≥6 h per treatment session) offers both enhanced removal of uremic solutes and better fluid management, generally allowing more liberalized dietary protein and calorie intake. This study aimed to evaluate the difference in plasma metabolite profiles among patients receiving in-center daytime extended-hours hemodialysis and those receiving conventional hemodialysis.

Methods: Pre-dialysis plasma samples were obtained from 188 patients on extended-hours hemodialysis (21.9 h/week) and 286 patients on conventional hemodialysis (12.1 h/week) in Japan in 2020 using capillary electrophoresis-mass spectrometry. Group differences were compared for 117 metabolites using Wilcoxon rank-sum tests with multiple comparisons and partial least squares discriminant analysis. Additionally, propensity score-adjusted multiple regression analyses were performed to evaluate group differences for known uremic toxins, branched-chain amino acids, and lactate-to-pyruvate ratio (a possible surrogate marker of mitochondrial dysfunction).

Results: Significant differences were observed in 39 metabolites, largely consistent with the high variable importance for prediction in partial least squares discriminant analysis. Among known uremic toxins, uridine and hypoxanthine levels were significantly higher in the conventional hemodialysis group than in the extended-hours hemodialysis group, whereas trimethylamine N-oxide levels were higher in the extended-hours hemodialysis group than in the conventional hemodialysis group. Patients on extended-hours hemodialysis had higher levels of all branched-chain amino acids and a lower lactate-to-pyruvate ratio than those on conventional hemodialysis (significant difference of -8.6 [95% confidence interval, -9.8 to -7.4]).

Conclusions: Extended-hours hemodialysis was associated with a more favorable plasma metabolic and amino acid profile; however, concentrations of most uremic toxins did not significantly differ from those of conventional hemodialysis.

Background: The prevalence of depression is high in the chronic kidney disease (CKD) (20-40%) and dialysis (30-50%) populations. Less is known about how depressive symptoms change over time in patients with CKD.

Methods: Participants in the Brain in Kidney Disease (BRINK) cohort study completed a depressive symptom questionnaire (PHQ-9) and serum creatinine testing annually. We used linear mixed effects models to examine changes in PHQ-9 scores over time and compared rates of change between participants with different ranges of eGFR impairment and those with normal eGFR.

Results: At baseline, 147 participants had normal eGFR, 424 had impaired eGFR without dialysis dependence, and 31% reported a diagnosis of depression, with a mean baseline PHQ-9 score of 4.3. Participants were followed for up to 5 years. After adjustment for factors associated with depression, mean PHQ-9 scores decreased (improved) by 0.25 points per year (95% confidence interval [CI] 0.07, 0.42) among participants with normal eGFR (>60 ml/min/1.73m2) and by 0.35 points (95% CI 0.14, 0.56), 0.30 points (95% CI 0.13,0.46) and 0.42 points (95% CI 0.06, 0.77) among participants with eGFR of 45 to 59 ml/min/1.73m2, 30 to 44 ml/min/1.73m2, and participants who developed dialysis dependence, respectively. PHQ-9 scores among participants with eGFR <30 ml/min/1.73m2 did not change significantly. We did not observe any statistically significant differences in mean change in PHQ-9 score between participants with any degree of eGFR impairment and those with normal eGFR, nor between participants with dialysis-dependence and those with eGFR of ≤15 ml/min/1.73m2. Participants with a PHQ-9 score ≥5 had 80% greater odds of immediate study attrition than participants with a PHQ-9 score of 0-4."

Conclusions: The mean PHQ-9 scores of participants were largely stable over time, and we observed no differences in the change in PHQ-9 scores between those with impaired eGFR and those with normal eGFR.

Background: Higher β2-Microglobulin (β2-MG) is associated with aging, stroke and cognitive impairment, which are all connected with poor physical fitness. Poor physical function is ascribed to increasing mortality. However, there has been an academic dispute over the association of serum β2-MG with survival rate. Furthermore, diabetes mellitus (DM) has been well linked to poor physical function and a high level of β2-MG. We hypothesized that higher β2-MG could be associated with worse physical performance in hemodialysis (HD) patients, and that association could vary with diabetes.

Methods: We conducted a multicenter cross-sectional study at seven HD centers in Shanghai and Suzhou, respectively, in China, where a collection was made of the clinical characteristics, laboratory indicator, physical performance and DM assessment. The physical function was measured by the Short Physical Performance Battery (SPPB), and SPPB score ≤9 as the cutoff for low physical performance.The patients were divided into two groups of low and high physical performance, before categorized into four subgroups based on the absence of diabetes and SPPB scores. Logistic regression analyses were conducted to explore the association of β2-MG with physical performance.

Results: The final analysis involved a total of 780 patients, 251(32.2%) having diabetes. In the total population, β2-MG was lower in those with low SPPB than in those with high SPPB. Only in non-diabetic patients, β2-MG was lower in the low SPPB group, and positively associated with SPPB and its three compenents scores. Regardless of diabetes status, those who had low SPPB were prone to be older, accompanied by the poor nutritional status. Addtionally, the diabetes patients tended to have shorter HD duration and higher body mass index than the non-diabetic patients. Both before and after the covariates adjusted, β2-MG was significantly associated with physical performance in HD patients without diabetes.

Conclusions: Low level of β2-MG was significantly associated with poor physical performance in Chinese HD patients without DM.