METTL3-Mediated N 6 -Methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis.

Background: Chemical modifications on RNA profoundly affect RNA function and regulation. m6A, the most abundant RNA modification in eukaryotes, plays a pivotal role in diverse cellular processes and disease mechanisms. However, its importance is understudied in human CKD samples regarding its influence on pathological mechanisms. Methods: Liquid chromatography­tandem mass spectrometry and methylated RNA immunoprecipitation sequencing were used to examine alterations in m6A levels and patterns in CKD samples. Overexpression of the m6A writer METTL3 in cultured kidney tubular cells was performed to confirm the effect of m6A in tubular cells and explore the biological functions of m6A modification on target genes. In addition, tubule-specific deletion of Mettl3 (Ksp-Cre Mettl3f/f) mice and antisense oligonucleotides inhibiting Mettl3 expression were used to reduce m6A modification in an animal kidney disease model. Results: By examining 127 human CKD samples, we observed a significant increase in m6A modification and METTL3 expression in diseased kidneys. Epitranscriptomic analysis unveiled an enrichment of m6A modifications in transcripts associated with the activation of inflammatory signaling pathways, particularly the cyclic guanosine monophosphate­AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway. m6A hypermethylation increased mRNA stability in cGAS and STING1 as well as elevated the expression of key proteins within the cGAS-STING pathway. Both the tubule-specific deletion of Mettl3 and the use of antisense oligonucleotides to inhibit Mettl3 expression protected mice from inflammation, reduced cytokine expression, decreased immune cell recruitment, and attenuated kidney fibrosis. Conclusions: Our research revealed heightened METTL3-mediated m6A modification in fibrotic kidneys, particularly enriching the cGAS-STING pathway. This hypermethylation increased mRNA stability for cGAS and STING1, leading to sterile inflammation and fibrosis.

Aldehyde dehydrogenase 2 preserves kidney function by countering acrolein-induced metabolic and mitochondrial dysfunction.

The prevalence of chronic kidney disease (CKD) varies by race because of genetic and environmental factors. The Glu504Lys polymorphism in aldehyde dehydrogenase 2 (ALDH2), commonly observed among East Asian people, alters the enzyme's function in detoxifying alcohol-derived aldehydes, affecting kidney function. This study investigated the association between variations in ALDH2 levels within the kidney and the progression of kidney fibrosis. Our clinical data indicate that diminished ALDH2 levels are linked to worse CKD outcomes, with correlations between ALDH2 expression, estimated glomerular filtration rate, urinary levels of acrolein - an aldehyde metabolized by ALDH2 - and fibrosis severity. In mouse models of unilateral ureteral obstruction and folic acid nephropathy, reduced ALDH2 levels and elevated acrolein were observed in kidneys, especially in ALDH2 Glu504Lys-knockin mice. Mechanistically, acrolein modifies pyruvate kinase M2, leading to its nuclear translocation and coactivation of HIF-1α, shifting cellular metabolism to glycolysis, disrupting mitochondrial function, and contributing to tubular damage and the progression of kidney fibrosis. Enhancing ALDH2 expression through adeno-associated virus vectors reduced acrolein and mitigated fibrosis in both WT and Glu504Lys-knockin mice. These findings underscore the potential therapeutic significance of targeting the dynamic interaction between ALDH2 and acrolein in CKD.

The impact of the COVID-19 pandemic on dyslipidemia in peritoneal dialysis patients.

BACKGROUND: The COVID-19 pandemic has had a profound impacted on various aspects of society, including the healthcare system and patient care. In this context, this study aims to evaluate the impact of COVID-19 control strategies on the lipid profile and blood sugar levels of peritoneal dialysis (PD) patients in Taiwan, a crucial focus for understanding the pandemic's influence on individuals with chronic kidney disease (CKD). METHODS: A retrospective cohort study was conducted, analyzing data from the medical records of 170 PD patients who visited the nephrology division of Taipei Veterans General Hospital in 2021. The generalized estimating equations method was used to analyze the longitudinal data and assess the changes in biomarker levels over different periods. Covariates were taken into consideration in the statistical models. The data were analyzed using R 4.3.0. RESULTS: The study enrolled 70 males (41%) and 100 females (59%), with an average age of 56 years old. Over 12 months in 2021, from the first period (January-April: pre-COVID-19) to the second period (May-August: COVID-19 surge), there was a notable decline in both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, and a significant surge in triglyceride (TG) levels. However, total cholesterol (TC) and hemoglobin (HbA1c) levels remained stable. Furthermore, the TG to HDL, TG to LDL, TC to HDL, and TC to LDL ratios were analyzed, revealing a pronounced increase during the second period. CONCLUSION: Our findings underscore the significant impact of COVID-19 pandemic-related disruptions in the healthcare system and the subsequent management strategies on dyslipidemia in PD patients while not affecting dysglycemia. These results provide valuable insights for healthcare professionals to enhance their strategies and interventions for CKD patients undergoing PD during a pandemic.

The impact of photobiomodulation on sleep and life quality in hemodialysis patients: A randomized controlled trial.

The quality of life (QoL) and sleep quality are closely linked to the physical and psychological health of end-stage renal disease (ESRD) patients, especially those underwent hemodialysis (HD) therapy. This study aims to investigate the impact of 830 nm laser treatment on improving QoL and sleep quality in HD patients. Forty ESRD patients participated in this study. 830 nm laser was used to radiate on the palm (at dose of 256.10 J/cm2), ST 36 and KI 1 acupoints (at dose of 109.76 J/cm2) of HD patients, and QoL and sleep quality questionnaires were utilized to assess changes following the treatment. After 830 nm laser radiation, lower global Pittsburgh Sleep Quality Index and Athens Insomnia Scale scores were observed, accompanied by higher physical and mental component summary scores in MOS 36-item short-form health survey version 2 and a global World Health Organization Quality of Life Brief Version score. The laser group also showed significant improvements in QoL and sleep quality indicators. Additionally, pain levels decreased on the third day and after one month according to visual analogue scale. This study revealed the positive effects of 830 nm laser on palm, KI 1 and ST 36 acupoints for improving the QoL and sleep quality in ESRD patients underwent HD treatment. The results suggest that 830 nm laser applied to specific targets could be used as a complementary and alternative approach to increase the QoL and sleep quality in ESRD patients.

METTL3-Mediated N6-methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis.

BACKGROUND: Chemical modifications on RNA profoundly impact RNA function and regulation. m6A, the most abundant RNA modification in eukaryotes, plays a pivotal role in diverse cellular processes and disease mechanisms. However, its importance is understudied in human chronic kidney disease (CKD) samples regarding its influence on pathological mechanisms. METHODS: LC-MS/MS and Methylated RNA Immunoprecipitation (MeRIP) sequencing were utilized to examine alterations in m6A levels and patterns in CKD samples. Overexpression of the m6A writer METTL3 in cultured kidney tubular cells was performed to confirm the impact of m6A in tubular cells and explore the biological functions of m6A modification on target genes. Additionally, tubule-specific deletion of Mettl3 (Ksp-Cre Mettl3f/f) mice and the use of anti-sense oligonucleotides inhibiting Mettl3 expression were utilized to reduce m6A modification in an animal kidney disease model. RESULTS: By examining 127 human CKD samples, we observed a significant increase in m6A modification and METTL3 expression in diseased kidneys. Epitranscriptomic analysis unveiled an enrichment of m6A modifications in transcripts associated with the activation of inflammatory signaling pathways, particularly the cGAS-STING pathway. m6A hypermethylation increased mRNA stability in cGAS and STING1, as well as elevated the expression of key proteins within the cGAS-STING pathway. Both the tubule-specific deletion of Mettl3 and the use of anti-sense oligonucleotides to inhibit Mettl3 expression protected mice from inflammation, reduced cytokine expression, decreased immune cell recruitment, and attenuated kidney fibrosis. CONCLUSIONS: Our research revealed heightened METTL3-mediated m6A modification in fibrotic kidneys, particularly enriching the cGAS-STING pathway. This hypermethylation increased mRNA stability for cGAS and STING1, leading to sterile inflammation and fibrosis.

Beyond prevalence: significance and differential impact of echocardiographic abnormalities in dialysis patients.

BACKGROUND: Echocardiography is commonly used to assess hydratation status and cardiac function in kidney failure patients, but the impact of structural or functional abnormalities on the prognosis of kidney failure patients was yet to be investigated. This study aimed to investigate the prevalence and clinical significance of echocardiographic abnormalities in kidney failure patients. METHODS: This study included 857 kidney failure patients who underwent echocardiography at dialysis initiation. Patients were followed up for a median of 4.2 years for the occurrence of major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: Among the 857 patients studied, 77% exhibited at least one echocardiographic abnormality. The most common abnormalities were left ventricular hypertrophy and left atrial enlargement, but they were not significantly correlated with poor outcomes. Instead, the primary predictors of both major adverse cardiovascular events and mortality in kidney failure patients were left ventricular systolic function, right ventricular systolic function, left ventricular volume index, and valvular abnormalities. Although diastolic dysfunction was linked to major adverse cardiovascular events, it was not associated with mortality. Furthermore, the study revealed that increased left ventricular volume index and left ventricular systolic dysfunction had a more significant impact on peritoneal dialysis (PD) patients than on hemodialysis (HD) patients. CONCLUSION: This study provides insights into the echocardiographic abnormalities and their association with adverse outcomes in kidney failure patients, which can help clinicians optimize the management of patients and closely monitor possible high-risk populations.

Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

FHL2 in arterial medial calcification in chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Arterial medial calcification (AMC) is a common complication in individuals with chronic kidney disease (CKD), which can lead to cardiovascular morbidity and mortality. The progression of AMC is controlled by a key transcription factor called runt-related transcription factor 2 (RUNX2), which induces vascular smooth muscle cells (VSMCs) transdifferentiation into a osteogenic phenotype. However, RUNX2 has not been targeted for therapy due to its essential role in bone development. The objective of our study was to discover a RUNX2 coactivator that is highly expressed in arterial VSMCs as a potential therapy for AMC. METHODS: We employed transcriptomic analysis of human data and an animal reporter system to pinpoint FHL2 as a potential target. Subsequently, we investigated the mRNA and protein expression patterns of FHL2 in the aortas of both human and animal subjects with CKD. To examine the role of FHL2 in the RUNX2 transcription machinery, we conducted coimmunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) experiments. Next, we manipulated FHL2 expression in cultured VSMCs to examine its impact on high phosphate-induced transdifferentiation. Finally, we employed FHL2 null mice to confirm the role of FHL2 in the development of AMC in vivo. RESULTS: Among all the potential RUNX2 cofactor, FHL2 displays selective expression within the cardiovascular system. In the context of CKD subjects, FHL2 undergoes upregulation and translocation from the cytosol to the nucleus of arterial VSMCs. Once in the nucleus, FHL2 interacts structurally and functionally with RUNX2, acting as a coactivator of RUNX2. Notably, the inhibition of FHL2 expression averts transdifferentiation of VSMCs into an osteogenic phenotype and mitigates aortic calcification in uremic animals, without causing any detrimental effects on the skeletal system. CONCLUSION: These observations provide evidence that FHL2 is a promising target for treating arterial calcification in patients with CKD.

Comparative analysis of hemodialysis and peritoneal dialysis on the risk of new onset diabetes mellitus.

BACKGROUND: Diabetes mellitus is a significant risk factor for cardiovascular events and mortality in dialysis patients. The impact of different dialysis modalities on the risk of new onset diabetes mellitus (NODM) remains a subject of debate. Previous studies did not adequately account for critical confounding factors such as pre-dialysis glycemic status, medication use, and nutritional status, which may influence the association between dialysis modality and NODM risk. METHODS: We conducted a retrospective cohort study of 1426 non-diabetic end-stage renal disease (ESRD) patients who underwent either hemodialysis (HD) or peritoneal dialysis (PD) at a single medical center. We used different statistical methods, adjusting for potential confounding factors, and accounted for competing risk of death. RESULTS: Over 12 years, 331 patients (23 %) developed NODM. After adjusting for potential confounding factors and mortality, PD patients had a significantly higher risk of NODM compared to HD patients (adjusted HR 1.52, p = 0.001). A propensity-matched cohort sensitivity analysis yielded similar results. Among patients with prediabetes, those receiving PD had a 2.93 times higher risk of developing NODM than those receiving HD (p for interaction <0.001), whereas no significant difference was observed among euglycemic patients. NODM was also associated with a 1.78 times increased risk of major cardiovascular events. CONCLUSION: Our study provides evidence that PD treatment may increase the risk of NODM in ESRD patients, particularly among those with preexisting prediabetes. These findings highlight the importance of personalized treatment approaches, and nephrologists should consider prediabetes when choosing the dialysis modality for their patients.

Systemic vascular resistance predicts high-output cardiac failure in patients with high-flow arteriovenous fistula.

AIMS: Patients with high-flow arteriovenous (AV) access are at risk of developing high-output cardiac failure (HOCF) and subsequent hospitalization. However, diagnosing HOCF is challenging and often requires invasive procedures. The role of systemic vascular resistance (SVR) in diagnosing HOCF is underestimated, and its predictive value is limited. Our study aims to identify non-invasive risk factors for HOCF to facilitate early diagnosis and timely surgical interventions. METHODS AND RESULTS: We included 109 patients with high-flow AV access who underwent serial echocardiography. The retrospective cohort was divided into two groups based on their hospitalization due to HOCF. The two groups were matched for age and gender. After a mean follow-up of 25.1 months, 19 patients (17.4%) were hospitalized due to HOCF. The two groups had similar baseline characteristics. However, the HOCF group had a higher value of vascular access blood flow (Qa) (2168 ± 856 vs. 1828 ± 617 mL/min; P = 0.045). Echocardiographic analysis revealed that the HOCF group had more pronounced left ventricular diastolic dysfunction (E/e': 21.1 ± 7.3 vs. 16.2 ± 5.9; P = 0.002), more severe pulmonary hypertension (right ventricular systolic pressure: 41.4 ± 16.7 vs. 32.2 ± 12.8; P = 0.009), a higher Doppler-derived cardiac index (CI) (4.3 ± 0.8 vs. 3.7 ± 1.1; P = 0.031), and a lower Doppler-derived estimated SVR (eSVR) value (5.5 ± 0.3 vs. 6.9 ± 0.2; P = 0.002) than the non-HOCF group. Using multivariable Cox regression analysis, a low eSVR value (<6) emerged as an independent predictor of HOCF hospitalization with a hazard ratio of 9.084 (95% confidence interval, 2.33-35.39; P = 0.001). Receiver operating characteristic curve analysis indicated that CI/eSVR values more accurately predicted HOCF hospitalization [sensitivity: 94.7%, specificity: 51.0%, area under the curve (AUC): 0.75, P < 0.001] than the Qa/cardiac output ratio (AUC: 0.50, P = 0.955), Qa values ≥ 2000 mL/min (AUC: 0.60, P = 0.181), and Qa values indexed for height in metres (AUC: 0.65, P = 0.040). CONCLUSIONS: In patients with high-flow AV access, low eSVR values obtained through non-invasive Doppler echocardiography were associated with a high rate of HOCF hospitalizations. Therefore, routine eSVR screening in these patients might expedite the diagnosis of HOCF.

Circulating Activin A, Kidney Fibrosis, and Adverse Events.

BACKGROUND: Identification of reliable biomarkers to assess kidney fibrosis severity is necessary for patients with CKD. Activin A, a member of the TGF- ß superfamily, has been suggested as a biomarker for kidney fibrosis. However, its precise utility in this regard remains to be established. METHODS: We investigated the correlation between plasma activin A levels, kidney fibrosis severity, and the incidence of major adverse kidney events in patients who underwent native kidney biopsies at a tertiary medical center. We performed RNA sequencing and histological analyses on kidney biopsy specimens to assess activin A expression. In vitro experiments were also conducted to explore the potential attenuation of TGF- ß -induced fibroblast activation through activin A inhibition. RESULTS: A total of 339 patients with biopsy-confirmed kidney diseases were enrolled. Baseline eGFR was 36 ml/min per 1.73 m 2 , and the urine protein/creatinine ratio was 2.9 mg/mg. Multivariable logistic regression analysis revealed a significant association between plasma activin A levels and the extent of tubulointerstitial fibrosis. Our RNA sequencing data demonstrated a positive correlation between kidney INHBA expression and plasma activin A levels. Furthermore, the histological analysis showed that myofibroblasts were the primary activin A-positive interstitial cells in diseased kidneys. During a median follow-up of 22 months, 113 participants experienced major adverse kidney events. Cox proportional hazards analysis initially found a positive association between plasma activin A levels and kidney event risk, but it became insignificant after adjusting for confounders. In cultured fibroblasts, knockdown of activin A significantly attenuated TGF- ß -induced fibroblast-myofibroblast conversion. CONCLUSIONS: Plasma activin A levels correlate with kidney fibrosis severity and adverse outcomes in various kidney disorders.

Survival benefit of a third dose of the COVID-19 vaccine among hemodialysis patients: A prospective cohort study.

BACKGROUND: Hemodialysis (HD) patients are particularly vulnerable to severe coronavirus disease 2019 (COVID-19) due to their immunocompromised state and comorbid conditions. Timely vaccination could be the most effective strategy to reduce morbidity and mortality. However, data on the survival benefit of the COVID-19 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and death among HD patients are limited, especially during the Omicron-dominant period. METHODS: In this prospective hospital-based cohort study, we identified HD patients from July 1, 2021, to April 29, 2022. The patients were divided into fully vaccinated and partially vaccinated groups. We compared the humoral response, risk of developing SARS-CoV-2 infection, and all-cause mortality between the two groups. RESULTS: Among the 440 HD patients included, 152 patients were fully vaccinated, and 288 patients were partially vaccinated. Patients in the fully vaccinated group exhibited higher anti-spike protein receptor-binding domain (S protein RBD) antibody levels and lower risks of all-cause mortality (adjusted hazard ratio, 0.35; 95% confidence interval, 0.17-0.73; p = 0.005) than the partially vaccinated group. However, the risk for SARS-CoV-2 infection did not significantly differ between the two groups. Irrespective of the number of vaccinations, the risk of all-cause mortality was lower in patients with anti-S protein RBD antibody levels in the higher tertile. CONCLUSION: A third dose of the COVID-19 vaccine was associated with a decreased risk of all-cause mortality among HD patients during the Omicron-dominant period. A higher post-vaccination anti-S protein RBD antibody level was also associated with a lower risk of mortality.

Effect of far-infrared radiation therapy on von Willebrand factor in patients with chronic kidney disease.

Background: Hemostatic abnormality has contributed to vascular access thrombosis in patients with chronic kidney disease (CKD). Previous studies have demonstrated that far-infrared radiation (FIR) therapy can maintain the patency and maturity of arteriovenous fistulas of patients undergoing hemodialysis (HD). However, prolonged access bleeding is observed once FIR is conducted at the end of dialysis. FIR can block the binding of platelet and von Willebrand factor (vWF), a predictor of hemostatic abnormality and vascular access thrombosis. However, clinical studies exploring FIR and vWF are sparse. Methods: We recruited 20 HD patients, 21 CKD patients, and 20 controls to examine the alteration of vWF and a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) following a single 40-min session of FIR therapy. In addition, the alteration of these factors in the HD group was examined following a 40-min FIR session thrice a week for 3 months. Results: A decreasing trend in the vWF activity-antigen ratio of participants in all groups following a single FIR session was observed. In addition, the ratio in the HD group was significantly lower following 3 months of FIR therapy. The subgroup analysis revealed a consistent trend and multiple regression analysis showed that participants not taking hydroxymethylglutaryl-coenzyme A reductase inhibitor, diabetes mellitus, and higher hemoglobin levels were the significant factors. The alteration of the vWF activity-antigen ratio correlated moderately to that of ADAMTS13 antigen and activity. Conclusion: FIR may alter the ratio of ultra-large vWF multimers through ADAMTS13, contributing to inhibiting platelet-endothelium interactions of CKD patients.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

Key pathological features characterize minimal change disease-like IgA nephropathy.

AIMS: A subset of IgA nephropathy (IgAN) patients exhibiting minimal change disease (MCD) like features present with nephrotic-range proteinuria and warrants immunosuppressive therapy (IST). However, the diagnosis of MCD-like IgAN varied by reports. We aimed to identify the key pathological features of MCD-like IgAN. METHODS: In this cohort, 228 patients had biopsy-proven IgAN from 2009 to 2021, of which 44 without segmental sclerosis were enrolled. Patients were classified into segmental (< 50% glomerular capillary loop involvement) or global (> 50%) foot process effacement (FPE) groups. We further stratified them according to the usage of immunosuppressant therapy after biopsy. Clinical manifestations, treatment response, and renal outcome were compared. RESULTS: 26 cases (59.1%) were classified as segmental FPE group and 18 cases (40.9%) as global FPE group. The global FPE group had more severe proteinuria (11.48 [2.60, 15.29] vs. 0.97 [0.14, 1.67] g/g, p = 0.001) and had a higher proportion of complete remission (81.8% vs. 20%, p = 0.018). In the global FPE group, patients without IST experienced more rapid downward eGFR change than the IST-treated population (-0.38 [-1.24, 0.06] vs. 1.26 [-0.17, 3.20]mL/min/1.73 m2/month, p = 0.004). CONCLUSIONS: The absence of segmental sclerosis and the presence of global FPE are valuable pathological features that assist in identifying MCD-like IgAN.

Hybrid Method for Peritoneal Dialysis Catheter Insertion: A New Technique for Improved Outcomes and Reduced Costs.

INTRODUCTION: Peritoneal dialysis (PD) is a well-established treatment choice for end-stage kidney disease (ESKD). While there are several methods for PD catheter insertion, they each have limitations. In this study, we present a new hybrid method for PD catheter insertion and compare it to the conventional laparoscopic method. METHODS: This retrospective study included 171 patients who were undergoing their first PD catheter insertion, and a total of 20% of the enrolled patients had a past medical history of abdominal surgery. Out of these, 101 patients underwent the laparoscopic method and 70 underwent a new invented hybrid method. The study aimed to compare the surgical outcomes, incidence of early and late complications, hospital stay, and medical expenses between the two groups. RESULTS: There were no notable differences in basic demographic features and comorbid conditions between the two groups. The results of our data revealed that the hybrid group had a significantly shorter break-in period and did not require temporary hemodialysis. Additionally, length of hospital stay and medical costs were significantly lower in the hybrid group (all p < 0.05). The incidence of early complications was lower in the hybrid group, while the incidence of late complications was comparable between the two groups. CONCLUSION: Our study demonstrates that the hybrid method of PD catheter insertion provides a safe and efficient alternative to the traditional laparoscopic method, enabling urgent-start PD and reducing hospital stays and medical expenses. Our findings support the use of the hybrid method as a new standard of care for ESKD patients undergoing PD catheter insertion.

Pyruvate kinase M2 modification by a lipid peroxidation byproduct acrolein contributes to kidney fibrosis.

Renal fibrosis is a hallmark of diabetic nephropathy (DN) and is characterized by an epithelial-to-mesenchymal transition (EMT) program and aberrant glycolysis. The underlying mechanisms of renal fibrosis are still poorly understood, and existing treatments are only marginally effective. Therefore, it is crucial to comprehend the pathophysiological mechanisms behind the development of renal fibrosis and to generate novel therapeutic approaches. Acrolein, an α-,ß-unsaturated aldehyde, is endogenously produced during lipid peroxidation. Acrolein shows high reactivity with proteins to form acrolein-protein conjugates (Acr-PCs), resulting in alterations in protein function. In previous research, we found elevated levels of Acr-PCs along with kidney injuries in high-fat diet-streptozotocin (HFD-STZ)-induced DN mice. This study used a proteomic approach with an anti-Acr-PC antibody followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify several acrolein-modified protein targets. Among these protein targets, pyruvate kinase M2 (PKM2) was found to be modified by acrolein at Cys358, leading to the inactivation of PKM2 contributing to the pathogenesis of renal fibrosis through HIF1α accumulation, aberrant glycolysis, and upregulation of EMT in HFD-STZ-induced DN mice. Finally, PKM2 activity and renal fibrosis in DN mice can be reduced by acrolein scavengers such as hydralazine and carnosine. These results imply that acrolein-modified PKM2 contributes to renal fibrosis in the pathogenesis of DN.

The Associations between Erythropoietic Response with Inflammation Markers and Perfluorinated Chemicals in Hemodialysis Patients.

Erythropoiesis-stimulating agents (ESA) are used to treat anemia in hemodialysis (HD) patients. We investigated the role of inflammation and accumulation of environmental toxins (perfluorinated chemicals (PFCs), such as perfluorooctanoic acid and perfluorooctane sulfonate) in the erythropoietic response of HD patients who receive a fixed monthly continuous erythropoietin receptor activator (CERA) dosage. Forty-five patients underwent three successive phases of ESA treatment for two months each (phase one: 100 µg CERA once monthly; phase two: 50 µg CERA twice monthly; phase three: 100 µg CERA once monthly). Patient data were collected to determine the association of various factors with erythropoietic response (change in hematocrit). Liquid chromatography-tandem mass spectrometry was used to analyze perfluorinated chemicals. Twenty-eight patients exhibited a poor erythropoietic response that was significantly associated with: age > 80 years, initial hematocrit > 36%, glucose > 200 mg/dL, alanine aminotransferase > 21 U/L, c-reactive protein > 1 mg/dL, interleukin-6 > 10 ng/mL, lactate dehydrogenase ≤ 190 U/L, and chloride ≤ 93 mEq/L. There was also a borderline significant association between inflammation and PFCs, although PFCs failed to show any impact on ESA response. Age, glucose, chloride, liver function, and inflammation may be associated with cost-effective fixed CERA dosage administered at an increased frequency.

Double Filtration Plasmapheresis with Polyvinyl Alcohol-Based Membrane Lowers Serum Inflammation and Toxins in Patients with Hyperlipidemia.

Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.

The Effects of Yoga Exercise on Blood Pressure and Hand Grip Strength in Chronic Stroke Patients: A Pilot Controlled Study.

BACKGROUND: We investigated the beneficial effect of add-on yoga with rehabilitation on blood pressure (BP) and hand grip strength in patients with chronic stroke (more than 90 days). METHODS: The study included patients 30-80 years of age who could stand independently for 1 min. Patients with psychiatric diseases or undergoing other therapies (like acupuncture) were excluded. The yoga group received training (1 h session twice weekly) with standard rehabilitation for 8 weeks. The control group received standard rehabilitation only. There were no differences in age, gender, hand grip strength, or BP between the two groups (16 subjects in each group) at baseline. RESULTS: The systolic BP (p = 0.01) decreased significantly, and the diastolic BP also decreased but not significantly in the yoga group (p = 0.11). For hand grip strength, both the unaffected hand (p = 0.00025) and the affected hand (p = 0.027) improved significantly. The control group showed no significant change in systolic or diastolic BP, nor did the grip strength change in both hands. Gender and age also affected the results of overall rehabilitation in that women benefited more from a decrease in BP, while men and young people (lower than the mean age of 60) benefited from hand grip strength improvement. CONCLUSIONS: Combining yoga with rehabilitation in chronic stroke patients can improve hand grip strength and decrease systolic BP.