Omentin reduces venous neointimal hyperplasia in arteriovenous fistula through hypoxia-inducible factor-1 alpha inhibition.

Arteriovenous fistula (AVF) failure often involves venous neointimal hyperplasia (VNH) driven by elevated hypoxia-inducible factor-1 alpha (HIF-1α) in the venous wall. Omentin, known for its anti-inflammatory and anti-hyperplasia properties, has an uncertain role in early AVF failure. This study investigates omentin's impact on VNH using a chronic renal failure (CRF) rabbit model. The CRF rabbit model of AVF received omentin-expressing adenoviral vector or control ß-gal vector to assess omentin's effects on VNH. Human vascular smooth muscle cells (HVSMCs), stimulated with tumor necrosis factor-α (TNF-α), were exposed to recombinant human omentin (Rh-OMT) to study its influence on cell proliferation and migration. The AMP-activated protein kinase (AMPK) inhibitor compound C and the mammalian target of rapamycin (mTOR) activator MHY1485 were employed to explore omentin's mechanisms in VNH reduction through HIF-1α inhibition. Omentin treatment reduced VNH in CRF rabbits, concomitant with HIF-1α down-regulation and the suppression of downstream factors, including vascular endothelial growth factor and matrix metalloproteinases. Rh-OMT inhibited TNF-α-induced HVSMC proliferation and migration by modulating both cell cycle and cell adhesion proteins. Additionally, omentin reduced HIF-1α expression through the AMPK/mTOR pathway activation. Notably, the blockade of AMPK/mTOR signaling reversed omentin-mediated inhibition of VNH, cell proliferation, and migration, both in vivo and in vitro. In conclusion, omentin mitigates VNH post-AVF creation by restraining HIF-1α via AMPK/mTOR signaling. Strategies boosting circulating omentin levels may offer promise in averting AVF failure.

A TMEM16J variant leads to dysregulated cytosolic calcium which may lead to renal disease.

SIGIRR (single immunoglobulin IL-1 related receptor), PKP3 (plakophilin 3), and TMEM16J (anoctamin 9), a putative calcium-activated ion channel and phospholipid scramblase, control the immune response and the extent of inflammation. Variants of SIGIRR/PKP3/TMEM16J lead to severe inflammatory diseases such as pneumonia, enterocolitis, and kidney graft rejection. Meta-analysis of genome-wide association studies identified TMEM16J-T604A as a promotor for chronic kidney disease (CKD), but the disease mechanism and function of TMEM16J remain unknown. Here, we demonstrate TMEM16J as a calcium-activated calcium-permeable channel, which is expressed in the endoplasmic reticulum (ER). TMEM16J controls the intracellular distribution of calcium, and inhibits intracellular receptor-mediated Ca2+ signals and Ca2+ -dependent activation of ion channels, but augments transcription and release of pro-inflammatory cytokines. Renal epithelial cells expressing the variant TMEM16J-T604A show enhanced calcium signals when compared to cells expressing wt-TMEM16J, and demonstrate spontaneous transcription and release of cytokines. This study identifies TMEM16J as an important regulator of intracellular Ca2+ signals, ion channel activity, and cytokine release. TMEM16J may therefore affect immune response in renal tissue and immune cells.

Prevalence, patient burden and physicians' perception of pruritus in haemodialysis patients.

BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is an underrated symptom in patients with impaired kidney function. The present study assessed the prevalence, impact on quality of life (QoL) and risk factors for CKD-aP in a contemporary national cohort of patients on haemodialysis. In addition, we evaluated attending physicians' awareness and approach to therapy. METHODS: Validated patient's and physician's questionnaires on pruritus severity and QoL were used in combination with information obtained by the Austrian Dialysis and Transplant Registry. RESULTS: The prevalence of mild, moderate and severe pruritus in 962 observed patients was 34.4%, 11.4% and 4.3%. Physicians' estimated prevalence values were 25.0 (95% CI 16.8-33.2), 14.4 (11.3-17.6) and 6.3% (4.9-8.3), respectively. The estimated national prevalence estimate extrapolated from the observed patients was 45.0% (95% CI 39.5-51.2) for any, 13.9% (95% CI 10.6-17.2) for moderate and 4.2% (95% CI 2.1-6.2) for severe CKD-aP. CKD-aP severity was significantly associated with impaired QoL. Risk factors for moderate-severe pruritus were higher C-reactive protein [odds ratio (OR) 1.61 (95% CI 1.07-2.43)] and parathyroid hormone (PTH) values [OR 1.50 (95% CI 1.00-2.27)]. Therapy for CKD-aP included changes in the dialysis regimen, topical treatments, antihistamines, gabapentin and pregabalin and phototherapy in a majority of centres. CONCLUSIONS: While the overall prevalence of CKD-aP in our study is similar to that in previously published literature, the prevalence of moderate-severe pruritus is lower. CKD-aP was associated with reduced QoL and elevated markers of inflammation and PTH. The high awareness of CKD-aP in Austrian nephrologists may explain the lower prevalence of more severe pruritus.

The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. METHODS: Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7). CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

A Rare Cause of Hypotension in Routine Hemodialysis: Secondary Adrenal Insufficiency.

Hypotension is a common complication during hemodialysis that develops due to high ultrafiltration rate and sometimes requires intravenous fluid replacement. Intradialytic hypotension may reduce the effectiveness of dialysis and contributes to hemodialysis-related morbidity and mortality. Adrenal insufficiency is one of the causes of hypotension in the community. Our case was diagnosed with end-stage renal failure and was undergoing routine hemodialysis with a central venous catheter 3 days a week. Upon the patient's hypotension attacks during the dialysis sessions and hypoglycemia attacks in the follow-ups, the morning cortisol was 6.2 µg/dL. Adrenocorticotropic hormone was 39 pg/mL, and testosterone was 0.0442 ng/mL. Adrenocorticotropic hormone stimulation test was performed on the patient with 250 mcg tetracosactide. The patient did not show adequate cortisol response, was detected to have partial empty sella on pituitary magnetic resonance imaging, and was diagnosed with secondary adrenal insufficiency, and then the hemodialysis hypotension improved with prednisolone treatment. We present a case of adrenal insufficiency, which is a rare cause of hypotension in patients on routine hemodialysis.

Improvement in Echocardiographic Indexes of Systolic Heart Failure Post-Kidney Transplantation: A Retrospective Analysis.

INTRODUCTION: End-stage renal disease is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered contraindication for kidney transplant, although some patients demonstrate myocardial recovery post-transplant. We aimed to identify and characterize the phenomenon of reverse myocardial remodeling in kidney transplanted patients. METHODS: The study is a retrospective cohort of patients undergoing kidney transplants between 2016 and 2019 (n = 604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. RESULTS: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal to or above 5%, whereas 36 (12%) patients had a LVEF improvement of 10% or more post-transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5%, and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. CONCLUSION: Renal transplantation might lead to improved LV systolic function in some patients.

Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

BACKGROUND: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. METHODS: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. RESULTS: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. CONCLUSION: This study provides data on anticipated renal trajectory following retransplantation.

SAGES peritoneal dialysis access guideline update 2023.

BACKGROUND: Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed. RESULTS: After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction. CONCLUSIONS: In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.

Renal Metabolomics Study and Critical Pathway Validation of Shenkang Injection in the Treatment of Chronic Renal Failure.

To reveal the mechanism of Shenkang injection (SKI) in the treatment of chronic renal failure, and verify the key pathway. In this work, an untargeted metabolomics approach was performed by LC-MS coupled with multivariate statistical analysis to provide new insights into therapeutic mechanism of SKI. Hematoxylin-eosin (H&E) Staining and Immunohistochemistry were used to evaluate the effects of drug treatment, Western blot was used to verify the critical pathway. Then, a total of 44 potential biomarkers of chronic renal failure (CRF) were identified and reversed regulation, including 2,8-dihydroxypurine, 5-methoxytryptophan, uric acid, acetylcarnitine, taurine, etc. Mainly concerned with arginine and proline metabolism, purine metabolism, histidine metabolism, etc. Pathological examination showed that the renal interstitium of SKI group was significantly improved, with fewer inflammatory cells and thinner vascular walls compared with the model group. Immunohistochemical results showed that the expression of α-smooth muscle actin (α-SMA) was decreased, and the expression of E-cadherin was increased in CRF model group, and the two indicators were reversed regulation in SKI injection, indicating that the degree of fibrosis was relieved. Critical signaling pathway phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and nuclear factor-kappaB (NF-κB) protein expressions were significantly inhibited. This study was the first to employ metabolomics to elucidate the underlying mechanisms of SKI in chronic renal failure. The results would provide some support for clinical application of traditional Chinese medicines in clinic.

Periodontitis and systemic parameters in chronic kidney disease: Systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review with meta-analysis to assess recent scientific evidence on the association between periodontitis and systemic parameters/conditions in individuals with chronic kidney disease (CKD). MATERIALS AND METHODS: The search for studies was performed in MedLine/PubMed, Scopus, Web of Science, and BIREME databases. Reference lists of selected articles were also searched. Studies with different epidemiological designs evaluating the influence of exposure to periodontitis on serum markers and mortality in individuals with CKD were eligible for inclusion. Three independent reviewers performed the article selection and data extraction. The assessment of methodological quality used the adapted Newcastle Ottawa Scale. Random effects meta-analysis was performed to calculate association measurements and 95% confidence intervals. RESULTS: In total, 3053 records were identified in the database search, with only 25 studies meeting the eligibility criteria and, of these, 10 studies contributed data for meta-analysis. Using a random-effects model, periodontitis was associated with hypoalbuminemia (PRunadjusted = 2.47; 95%CI:1.43-4.26), with high levels of C-reactive protein (PRunadjusted = 1.35; 95%CI%:1.12-1.64), death from cardiovascular disease (RRunadjusted = 2.29; 95%CI:1.67-3.15) and death from all causes (RRunadjusted = 1.73; 95%CI:1.32-2.27). CONCLUSIONS: The findings of this review validated a positive association between periodontitis and serum markers and mortality data in individuals with CKD.

Assessment of the hematological profile of children with chronic kidney disease on follow-up at St. Paul's Hospital Millennium Medical College and Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia.

BACKGROUND: Chronic kidney disease (CKD) is a major public health issue with an increasing incidence and prevalence worldwide. In CKD, hematological parameters are influenced, and the effect increases with CKD stage. Thus, the aim of this study was to assess hematological profile of children with CKD on follow up at Tikur Anbessa Specialized Hospital and St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia. METHODS: A cross-sectional study was carried out from March 1 to June 30, 2021 among 238 children with CKD. EDTA tubes were used to collect 4 ml blood samples, which were then examined by Beckman Coulter automated hematology analyzer. SPSS Version 20 was used for statistical analysis, and a bivariate and multivariate regression model were applied to assess correlations. Mean and standard deviation was used to determine hematological profiles. RESULTS: The total number of patients in the study were 238, with 42 (59.7%) of them being men. The majority of the patients (81%) had CKD stage 1. Mean ± standard deviation determined for white blood cell (WBC) parameters in (thousand/µL); WBC, Neutrophil, Lymphocytes, Eosinophil, Monocytes and Basophil were 8.93 ± 3.32, 4.6 ± 8.31, 2.79 ± 1.62, 0.31 ± 0.51, 0.50 ± 3.03 and 0.03 ± 0.24, respectively. For some of red blood cell (RBC) parameters; RBC (million/ µL), Hemoglobin (Hgb) (g/dL), Hematocrit (Hct) (%) and Mean cell volume (fl.) were 4.73 ± 0.87, 12.82 ± 2.76, 38.28 ± 7.53 and 80.32 ± 7.89, respectively. For the platelet count (PLT) (thousand/µL) and Mean Platelet volume (MPV) (fL) 349.34 ± 130.18 and 9.03 ± 4.31 were determined, respectively. This study also found hematologic parameters such as RBC, HGB, HCT and MPV were found to be positively correlated with eGFR with a P-value < 0.05 for all parameters. CONCLUSION: The study found that the majority of study participants were in stages 1 to 3 based on their estimated glomerular filtration rate (eGFR). Some of hematological parameters found to have positive correlation with eGFR. There is a need to improve multiple aspects of CKD management, including routine hematological tests for children with chronic kidney disease.

Deep learning algorithms for predicting renal replacement therapy initiation in CKD patients: a retrospective cohort study.

BACKGROUND: Chronic kidney disease (CKD) requires accurate prediction of renal replacement therapy (RRT) initiation risk. This study developed deep learning algorithms (DLAs) to predict RRT risk in CKD patients by incorporating medical history and prescriptions in addition to biochemical investigations. METHODS: A multi-centre retrospective cohort study was conducted in three major hospitals in Hong Kong. CKD patients with an eGFR < 30ml/min/1.73m2 were included. DLAs of various structures were created and trained using patient data. Using a test set, the DLAs' predictive performance was compared to Kidney Failure Risk Equation (KFRE). RESULTS: DLAs outperformed KFRE in predicting RRT initiation risk (CNN + LSTM + ANN layers ROC-AUC = 0.90; CNN ROC-AUC = 0.91; 4-variable KFRE: ROC-AUC = 0.84; 8-variable KFRE: ROC-AUC = 0.84). DLAs accurately predicted uncoded renal transplants and patients requiring dialysis after 5 years, demonstrating their ability to capture non-linear relationships. CONCLUSIONS: DLAs provide accurate predictions of RRT risk in CKD patients, surpassing traditional methods like KFRE. Incorporating medical history and prescriptions improves prediction performance. While our findings suggest that DLAs hold promise for improving patient care and resource allocation in CKD management, further prospective observational studies and randomized controlled trials are necessary to fully understand their impact, particularly regarding DLA interpretability, bias minimization, and overfitting reduction. Overall, our research underscores the emerging role of DLAs as potentially valuable tools in advancing the management of CKD and predicting RRT initiation risk.

The utilization of renal dialysis: a comprehensive study in Saudi Arabia.

BACKGROUND: Understanding the trend of utilization of renal dialysis in Saudi Arabia (SA) is fundamental as it provides a general overview of renal care. The practice of renal dialysis assists in identifying challenges, opportunities, and potential areas for improvement in the provision of the services. OBJECTIVES: This research investigated the utilization of renal dialysis services in SA by exploring the number of renal dialysis centers, hemodialysis machines (HD), and peritoneodialysis patients. METHODS: The dataset for this study was derived from a collaboration between the General Authority of Statistics (GaStat) and the Ministry of Health (MoH), focusing on indicators for renal dialysis centers and patients across health sectors in 2021. Analysis was conducted using MS Excel 365 and IBM SPSS Version 29, incorporating multiple regression techniques. The health sector was treated as the dependent variable. At the same time, the number of hemodialysis (HD) machines and the counts of HD and peritoneal dialysis patients were considered independent variables. RESULTS: Around 275 renal dialysis centers, over 8000 HD machines, 20,440 HD patients, and 1,861 peritoneal patients were tallied from two resources. The findings revealed a negative relationship between the health sector and several renal dialysis centers and peritoneodialysis patients, as demonstrated by p < 0.05 in multiple regression analysis. CONCLUSION: The number of renal dialysis centers influences the availability of HD machines, affecting the number of HD and peritoneodialysis patients. Most national patients preferred MoH over other semi-governmental and private sectors, and vice versa for non-Saudis.

Aminophylline suppresses chronic renal failure progression by activating SIRT1/AMPK/mTOR-dependent autophagy.

Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

Clinical observation and influence on nutritional status of intensive nutritional nursing combined with 3-day dietary diary intervention in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis is a commonly used treatment for chronic kidney failure patients. Studies have shown that long-term peritoneal dialysis can lead to various degrees of malnutrition. Therefore, it is of great significance to improve the nutritional conditions of patients with peritoneal dialysis. This retrospective cohort study aimed to evaluate the clinical effects of intensive nutritional nursing combined with a 3-day diet diary intervention on the nutritional condition of peritoneal dialysis patients. METHODS: In total, 163 patients were included in this study and, after 6 months of intervention, their nutritional and biochemical indicators, body weight, body mass index (BMI) and intake of dietary ingredients were analysed. RESULTS: After the intervention, patients' serum albumin, haemoglobin, prealbumin, body weight, BMI and cholesterol levels were significantly increased (p < 0.05). Also, the daily energy and protein intake were significantly increased, whereas phosphorus intake was decreased (p < 0.05). Of note, the effective rate of intervention was 63.8%, respectively. We also found that factors such as the patient's age, education degree, income level and peritoneal dialysis age were the risk factors associated with malnutrition. Moreover, patients younger than 55 years old, with dialysis age younger than 5 years, unmarried/divorced and high school graduates, had higher chances of effective intervention, whereas the possibility of effective intervention was lower when the per capita monthly household income was less than 4000 Yuan. CONCLUSIONS: In conclusion, intensive nutritional nursing combined with a 3-day dietary diary intervention can significantly improve the nutritional condition and optimise the diet structure of peritoneal dialysis patients with malnutrition. These findings provide evidence for healthcare providers to develop personalised interventions to address malnutrition in this population.

Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure.

The function of the respiratory chain is closely associated with kidney function, and the dysfunction of the respiratory chain is a primary pathophysiological change in chronic kidney failure. The incidence of chronic kidney failure caused by defects in respiratory-chain-related genes has frequently been overlooked. Correcting abnormal metabolic reprogramming, rescuing the "toxic respiratory chain", and targeting the clearance of mitochondrial reactive oxygen species are potential therapies for treating chronic kidney failure. These treatments have shown promising results in slowing fibrosis and inflammation progression and improving kidney function in various animal models of chronic kidney failure and patients with chronic kidney disease (CKD). The mitochondrial respiratory chain is a key target worthy of attention in the treatment of chronic kidney failure. This review integrated research related to the mitochondrial respiratory chain and chronic kidney failure, primarily elucidating the pathological status of the mitochondrial respiratory chain in chronic kidney failure and potential therapeutic drugs. It provided new ideas for the treatment of kidney failure and promoted the development of drugs targeting the mitochondrial respiratory chain.

Association between intestinal microflora and renal function in patients with chronic renal failure: A case-control analysis.

Objective: To identify the association between the changes in intestinal microflora and renal function in patients with chronic renal failure (CRF). Methods: This retrospective case-control study included 50 patients with CRF (study group), admitted to the Clinical Laboratory Department of Shenzhen People's Hospital from March 2021 to May 2022, and 50 healthy individuals (control group). The association between the distribution of intestinal microflora and the glomerular filtration rate (GFR), levels of serum creatinine (SCr), blood urea nitrogen (BUN), and serum cystatin C (CysC) were analyzed. Results: Intestinal microflora of CRF patients had significantly higher levels of Enterococci compared to the control group (p-Value <0.05), while the levels of Bifidobacterium spp. and Escherichia coli were lower in the study group (p-Value <0.05). GFR was lower, and the levels of BUN, SCr, and CysC were higher in the study group compared to the control group (all p-Value <0.05). GFR, BUN, SCr and CysC levels in the study group negatively correlated with the levels of Bifidobacterium spp. and Lactobacillus spp. (r<0, P<0.05), and positively correlated with the abundance of Enterococcus spp. and Escherichia coli (r>0, P<0.05) in the intestinal microflora. Conclusions: Changes in intestinal microbiota are associated with a significant decrease in GFR and a marked increase in serum levels of renal function indicators, and alterations in the balance of intestinal microbiota may lead to further aggravation of the renal function damage in patients with CRF.

Short versus long-acting erythropoiesis-stimulating agents for anemia management in Egyptian hemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating agents (ESAs) offer promising solutions for managing anemia in CKD. This study aimed to evaluate and compare the effectiveness, safety profile, and cost-effectiveness of short-acting (Eprex®) and long-acting (Aranesp®) ESAs. METHOD: This comparative prospective cohort cost-effectiveness study was carried out over 6 months among adult Egyptian hemodialysis patients of either gender. Participants were categorized into two groups based on the type of ESA administered: the Eprex group, receiving epoetin alfa, and the Aranesp group, receiving darbepoetin alfa. These two treatment groups' efficacy, safety, and cost were analyzed and compared. RESULTS: Of 127 hemodialysis patients, 60 (47.2%) received Eprex, while 67 (52.8%) were treated with Aranesp. Target hemoglobin (Hb) was achieved by 50.6% of patients in the Eprex group versus 63.4% in the Aranesp group, with a significant difference (P < 0.001). Both treatment groups exhibited a similar safety profile, while Aranesp® was considered the cost-saving protocol. CONCLUSION: In hemodialysis Egyptian patients, Aranesp with extended dosing intervals proved to be more effective in achieving target Hb with comparable adverse effect profiles, a substantial cost-saving strategy, and offered time-saving advantages for medical staff workload compared to Eprex. TRIAL REGISTRATION: The Clinicaltrial.gov registration ID is NCT05699109 (26/01/2023).

Clinical findings and kidney morphology in chronic kidney disease of unknown cause in India.

BACKGROUND: Chronic kidney disease of unknown cause (CKDu) is an emerging health problem in India and other countries worldwide. However, clinical descriptions, including kidney pathology, are scarce. METHODS: This is a descriptive case series of patients with CKDu from an endemic region in India, with a focus on clinical and biochemical characteristics, kidney biopsy findings, and environmental exposure. Patients with suspected CKDu, aged 20-65, and eGFR 30-80 mL/min/1.73 m2 from rural areas with endemic prevalence of CKDu were included. The exclusion criteria were diabetes mellitus, uncontrolled hypertension, proteinuria >1 g/24 h, or other known kidney diseases. The participants underwent kidney biopsies, and blood and urine samples were collected. RESULTS: Fourteen participants (3 females, 11 males) with a mean eGFR of 53 (range 29-78) mL/min/1.73 m2 were included. Kidney biopsies showed a combination of chronic tubulointerstitial damage, glomerulosclerosis, and glomerular hypertrophy, with varying degrees of interstitial inflammation. Eight participants had polyuria (diuresis ≥ 3 L/day). The urinary sediments were bland, with no haematuria. Serum potassium and sodium levels were, in most cases, normal but within the lower reference interval. CONCLUSION: The kidney morphology and clinical characteristics in patients with CKDu in India were similar to those described for CKDu in Central America and Sri Lanka.

Monoallelic Loss-of-Function IFT140 Pathogenic Variants Cause Autosomal Dominant Polycystic Kidney Disease: A Confirmatory Study With Suspicion of an Additional Cardiac Phenotype.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. While biallelic variants affecting IFT140 are responsible for Mainzer-Saldino syndrome (characterized by severe ciliopathy causing skeletal abnormalities, kidney disease, and cysts), monoallelic loss-of-function (LoF) variants have been recently reported as an important cause of ADPKD beyond PKD1/2 genes. Herein, we report 6 non-family-related cases of monoallelic IFT140 LoF variants, identified from 1,340 exomes sequenced for nephrological indications in our local database. Every patient presented with polycystic kidney disease. Furthermore, the mother of a boy diagnosed with Mainzer-Saldino syndrome with a biallelic variant affecting IFT140 presented with several bilateral cysts, revealed after kidney imaging, and was found to carry a pathologic frameshift IFT140 variation. As well as this particular Mainzer-Saldino case, our 6 additional patients confirm that heterozygous IFT140 frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the 6 patients, 2 also exhibited dilated cardiomyopathy, which was of unknown origin, as no genetic cause was found after exome sequencing analysis, suggesting a potential connection between IFT140 and heart disease.