Clinical and Experimental Nephrology最新文献

Background: Protein-energy wasting (PEW), a unique weight loss linked to nutritional and metabolic abnormalities, is common in patients undergoing hemodialysis (HD) and associated with adverse outcomes. This study investigated whether extended-hours HD combined with a liberalized diet could overcome PEW and improve survival.

Methods: The body mass index (BMI) and survival outcomes in patients undergoing extended-hours HD were evaluated for up to 8 years using data from the LIBeralized diet Extended-houRs hemodialysis Therapy (LIBERTY) cohort. Extended-hours HD was defined as weekly dialysis length ≥ 18 h.

Results: The LIBERTY cohort included 402 patients who initiated extended-hours HD. An increase in the length and frequency of HD sessions was observed over time, with approximately 70% and 20% of patients undergoing extended-hours HD for > 21 h/week and > 3 sessions/week at 5 years, respectively. The BMI and percentage creatinine generation rate were maintained over time, with no substantial increase in the phosphorus and potassium levels. The estimated BMI initially increased, and thereafter plateaued over time in patients with a baseline BMI < 25 kg/m², whereas it decreased gradually in patients with a baseline BMI ≥ 25 kg/m² after several years from baseline. Ninety-one patients died, and 108 discontinued extended-hours HD during the median follow-up period of 6.2 years (interquartile range, 3.5-8.0), yielding a 5-year survival rate of 85%.

Conclusions: Extended-hours HD with a liberalized diet may help achieve favorable survival outcomes and maintain nutritional status. Thus, it is a promising treatment option for managing PEW in patients undergoing HD.

Background: Although several studies have examined the Kidney Disease Quality of Life (KDQOL) in patients with chronic kidney disease (CKD), the factors associated with kidney-related symptoms have not been fully explored.

Methods: This nationwide multicenter cohort study enrolled 2248 patients. To identify the factors associated with each item or the three KDQOL domains, such as burden of kidney disease, symptoms/problems of kidney disease, and impact of kidney disease on daily life, multiple regression analysis was performed using baseline data.

Results: The study population had a mean age of 69.1 ± 12.6 years, comprised 64.7% men, and had mean estimated glomerular filtration rate (eGFR) of 23.2 ± 10.4 mL/min/1.73 m². Mean serum creatinine levels were 1.4 ± 0.2, 2.3 ± 0.5, and 4.5 ± 1.5 mg/dL for G3b, G4, and G5, respectively. The mean scores in the three KDQOL domains among CKD stages showed significantly decreasing trends. Of all the 11 symptoms assessed, 6 had scores that significantly decreased as the CKD stage progressed and 9 had scores that significantly decreased as the age category group increased. Multiple regression analysis revealed eGFR as a significantly associated factor for 5 of 11 symptoms. Age, body mass index, and comorbidities were also detected as significant factors for some symptoms.

Conclusions: In addition to eGFR, several factors were associated with symptoms in patients with CKD. Nephrologists need to recognize renal dysfunction-specific symptoms and explore other plausible causes of nonspecific symptoms.

This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar features dynamic case-based discussions, some of which are included as self-assessment questions in this series. The second article in this series focuses on treatment of hyponatremia, a common water and electrolyte disorder frequently encountered in clinical practice. Hyponatremia presents diagnostic challenges due to its various etiologies and the presence of co-morbidities that affect water and electrolyte homeostasis. Furthermore, limited evidence, including a lack of robust randomized controlled trials, complicates treatment decisions and increases the risk of poor outcomes from inappropriate management of both acute and chronic hyponatremia. This review provides a comprehensive overview of treatment of hyponatremia for better comprehension and improved clinical practice.

This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar includes lively discussions based on cases, which are also partly included in this series as self-assessment questions. The first article in this series focuses on pathophysiology, symptoms, outcomes, and evaluation of hyponatremia, a common water and electrolyte disorder in clinical practice. Diagnosing the root cause(s) of hyponatremia can be challenging due to various etiologies and co-morbidities that affect water and electrolyte homeostasis, which can result in inappropriate management and worse outcomes in acute and chronic hyponatremia. This review provides an overview of pathophysiology, symptoms, outcomes, and evaluation of hyponatremia for better comprehension and improved clinical practice.

Purpose: This study seeks to investigate the fundamental molecular processes through which histone deacetylase 9 (HDAC9) governs the proliferation of glomerular mesangial cells in the context of immunoglobulin A nephropathy (IgAN) and to identify novel targets for clinical research on IgAN.

Methods: Data from high-throughput RNA sequencing for IgAN were procured from the Gene Expression Omnibus database to assess the expression profiles and clinical diagnostic significance of histone deacetylase family proteins (HDACs). Blood samples from 20 IgAN patients were employed in RT-qPCR analysis, and the spearman linear regression method was utilized to analyze the clinical correlation. The proliferation of glomerular mesangial cells (GMCs) under the influence of HDAC9 was examined using the 5-ethynyl-2'-deoxyuridine (EdU) assay. Proteins interacting with HDAC9 were predicted utilizing the STRING database. Immunoprecipitation and protein immunoblotting employing anti-acetylated lysine antibodies were conducted to determine the acetylation status of calmodulin-like protein 6 (CALML6).

Results: Analysis of the GSE141295 dataset revealed a significant upregulation of HDAC9 expression in IgAN and the results of RT-qPCR demonstrated a substantial increase in HDAC9 expression in IgAN patients. Receiver operating characteristic (ROC) analysis indicated that the area under the curve (AUC) value for HDAC9 were 0.845 and Spearman correlation analysis showed that HDAC9 expression was positively correlated with blood levels of blood urea nitrogen (BUN) and serum creatinine (Crea). The EdU cell proliferation assay indicated that HDAC9 facilitated the excessive proliferation of GMCs. The STRING database and recovery experiments identified CALML6 as a downstream effector of HDAC9 in controlling abnormal GMC multiplication. Co-immunoprecipitation assays demonstrated that HDAC9 modulates CALML6 expression through acetylation modification.

Conclusion: HDAC9 is markedly upregulated in IgAN, and it mediates the excessive proliferation of GMCs by regulating the deacetylation of CALML6.

Background: Several clinical trials showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors have protective effects against chronic kidney disease (CKD) in both patients with and those without type 2 diabetes mellitus. Since one of the renoprotective mechanisms of SGLT2 inhibitors is thought to be amelioration of glomerular hyperfiltration, we hypothesized that an enlarged glomerular diameter, which suggests increased single-nephron glomerular filtration rate, is associated with a reduction in urinary protein after treatment with an SGLT2 inhibitor.

Methods: This study was a retrospective multicentered study including 28 adult patients with CKD who underwent kidney biopsy and were then treated with dapagliflozin, an SGLT2 inhibitor. The association of glomerular diameter with changes in urinary protein 4-8 weeks after the initiation of treatment with dapagliflozin was investigated.

Results: Maximum glomerular diameter was significantly and positively correlated with change in urinary protein-to-creatinine ratio (UPCR) (R² = 0.44; P < 0.001). Maximum glomerular diameter was significantly larger in patients who achieved ≥ 30% reduction in UPCR after the initiation of treatment with dapagliflozin than in patients who achieved < 30% reduction in UPCR (219.4 ± 23.9 vs. 188.0 ± 29.0; P = 0.005). After adjustment of age, sex and estimated glomerular filtration rate, maximum glomerular diameter was independently associated with change in UPCR (β = 0.645, P < 0.001). Furthermore, maximum glomerular diameter was independently associated with ≥ 30% reduction in UPCR (odds ratio: 1.07, 95% confidential interval: 1.01-1.14).

Conclusion: Glomerular diameter is independently associated with an early change in UPCR after the initiation of treatment with dapagliflozin in patients with CKD.

Background: Oral nutritional supplements (ONS) are commonly prescribed to provide protein and energy to hemodialysis (HD) patients. There is a debate about the appropriate timing to administer ONS. We aimed to study the effect of different timings of ONS on variable outcomes in HD patients.

Methods: This research is a prospective, randomized, multicentric clinical trial (RCT) that included 120 patients on regular HD. Patients were allocated to receive ONS (25 gm protein powder/HD session) for 8 weeks either predialytic (1 h before the start of the session), intradialytic (2 h after the start of the session), or interdialytic (on non-dialysis days). Laboratory parameters, blood pressure (BP), dialysis adequacy, and nutritional parameters were assessed during the study.

Results: At study end, BP at the end of HD dropped significantly in the intradialytic group compared to the other groups (p < 0.001). Serum albumin improved significantly in the predialytic (p < 0.001) and intradialytic (p = 0.039) groups. The mean subjective global assessment score increased significantly in the interdialytic group (p = 0.040). The Kt/V and urea reduction ratio decreased significantly only in the intradialytic group (p value < 0.001 and 0.001). Serum sodium, potassium, phosphorus, cholesterol, triglycerides, and adverse events did not significantly differ between the different groups.

Conclusions: Predialytic ONS supplementation is a favorable option due to improved serum albumin with minimal effects on hemodynamics and dialysis adequacy compared to intradialytic and interdialytic supplementation.

Clinical trials registration: ClinicalTrials.gov NCT05953636. First registration date: 1/07/2023.

Background: Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.

Methods: The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies. Weighted generalized multivariate linear regression was employed to estimate the association between estradiol and eGFR and ACR, and a restricted cubic spline analysis was utilized to investigate potential nonlinear relationships.

Results: A total of 8932 participants were included. Serum estradiol concentration was positively associated with eGFR after adjusting for potential covariates (β, 0.76; 95% CI 0.24 to 1.27) and with ACR (β, 5.99; 95% CI 1.62 to 10.36). A nonlinear positive association was found between estradiol and eGFR, while an inverse "V"-shaped relationship was seen with ACR. Sensitivity analyses confirmed the stability of the relationship between estradiol and eGFR but indicated a less robust association with ACR. Stratified analysis showed that the association between estradiol and eGFR was particularly significant in populations with CKD and hypertension. All forward MR analyses demonstrated a positive causal relationship between estradiol and eGFR, but no causality was found between estradiol and ACR. No reverse causal association was observed.

Conclusions: Serum estradiol concentration was causally associated with eGFR. Further longitudinal research is needed to validate these findings.

Background: Renal fibrosis is strongly correlated with renal functional outcomes. Therefore, this is a significant finding in determining renal prognosis. There are various reports on the imaging evaluation of renal fibrosis, but these are not well established. Scanning acoustic microscopy (SAM) uses ultra-high-frequency ultrasound to visualize tissues in just over a minute. SAM can simultaneously measure acoustic data such as speed of sound (SOS). SOS indicates the elasticity (stiffness) of a material. In this study, we aimed to compare and evaluate SAM acoustic intensity images and SOS data with light microscopy images of renal lesions, especially renal fibrosis.

Methods: Renal specimens containing fibrosis were selected. The acoustic intensity images were compared to PAS-stained images. SOS data of the tubulointerstitium were compared with Masson's trichrome (MT)-stained images. The blue intensity of MT staining, which indicates fibrosis, was numerically valued using image-processing software. Furthermore, the correlations between it and the SOS values were evaluated.

Results: The acoustic intensity images suggested tubular atrophy and interstitial expansion in the same areas as in the PAS staining. SOS values of interstitial expansion with fibrosis were higher than normal area, interstitial expansion without fibrosis. A weak positive correlation was observed between the SOS values and the blue intensity of MT staining.

Conclusions: SOS data can be used to evaluate renal fibrosis. The combination of SOS data and MT-stained images enables a more detailed evaluation of renal fibrosis. This study can contribute to the evaluation of renal fibrosis and has potential clinical applications in the future.