Renal Failure Research Articles

Recommendations for European laboratories based on the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease.

The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD) evaluation and management bring important updates, particularly for European laboratories. These guidelines emphasize the need for harmonization in CKD testing, promoting the use of regional equations. In Europe, the European Kidney Function Consortium (EKFC) equation is particularly suited for European populations, particularly compared to the CKD-EPI 2021 race-free equation. A significant focus is placed on the combined use of creatinine and cystatin C to estimate glomerular filtration rate (eGFRcr-cys), improving diagnostic accuracy. In situations where eGFR may be inaccurate or clinically insufficient, the guidelines encourage the use of measured GFR (mGFR) through exogenous markers like iohexol. These guidelines emphasize the need to standardize creatinine and cystatin C measurements, ensure traceability to international reference materials, and adopt harmonized reporting practices. The recommendations also highlight the importance of incorporating risk prediction models, such as the Kidney Failure Risk Equation(KFRE), into routine clinical practice to better tailor patient care. This article provides a European perspective on how these KDIGO updates should beimplemented in clinical laboratories to enhance CKD diagnosis and management, ensuring consistency across the continent.

Renal Resistive Index as A Early Predictor of Renal Dysfunction in Patients with Type 2 Diabetes Mellitus

Background : Type 2 diabetes develops over a long period of time, represents 85–90 per cent of all cases of diabetes . Diabetic nephropathy is a relatively common form of chronic renal disease. It is the most constant microvascular complication in diabetic patients.Conventional ultrasound and colour Doppler provide easily available, affordable and non-invasive follow up method for evaluation of kidneys in diabetic nephropathy. Aim :The purpose of this study is to assess the intrarenal resistivity index by Doppler ultrasonography in a group of diabetics with normal renal function in comparison to non diabetic controls and correlating them with biochemical parameters. Materials And Methods :The study was done over a period of 2 years from October 2020 To October 2022. The study I a case control study we evaluated the intra-renal hemodynamic changes with Doppler sonography in diabetic patients in comparison to non-diabetic controls, All the data was expressed as mean + SD. Differences between the two groups was analysed by t test and chi-square test. Categorical data expressed as frequency and percentages. Results And Observations The mean age in the diabetic group was 58.84 years SD + 15.61 years and age - non diabetic group was 56.66 years SD + 14.09 years . there was a negative correlation between age and diabetes mellitus with nephropathy , p > 0.0784 r -.026 A significant the correlation of the Mean resistivity index RI of the right kidney at the hilum was 0.63 the correlation was positive that is the resistance increased in diabetes mellitus as compared to non diabetic and this was significant with a p value 0 .049 significant . All the resistive indices were higher in the diabetic than the non diabetic individuals , the highest being in the midpole and it was statistically significant at all places in both kidneys with a p value <0.05. Conclusion :The renal Doppler indices are good indices to evaluate the renal dysfunction in the early stages. In this study, the blood sugar levels of all cases were at least moderately controlled, yet the renal indices showed gross anomaly even though the creatinine clearance was well above normal limits.

Obesity, aldosterone excess, and mineralocorticoid receptor activation: Parallel or intersected circumstances?

The obesity pandemic, with its associated comorbidities of hypertension and diabetes, constitutes a global public health issue. Importantly, there is an increasing prevalence of aldosterone excess related to obesity and resultant poor health outcomes. Nevertheless, the association between aldosterone and obesity still needs to be clarified. In this review, the authors discuss the role of white adipose tissue in linking obesity, aldosterone excess, and hypertension. The consequences of aldosterone excess in obesity are presented as genomic, non-genomic, and non-epithelial effects. Moreover, the authors emphasize the value of interference with aldosterone pathophysiology (as with mineralocorticoid antagonists) in obesity, thus reducing the adverse clinical impact of aldosterone in myocardial infarction, heart failure, kidney dysfunction, and associated mortality.

The Effects of Syphilis Infection on Total Knee Arthroplasty Outcomes: A Retrospective Cohort Study

Objective: This study investigated the impact of recent syphilis infection on postoperative outcomes following total knee arthroplasty (TKA). We hypothesized that patients with a documented history of syphilis infection would experience a higher rate of postoperative complications compared to those without such a history. Methods: We conducted a retrospective cohort analysis using a national insurance claims database. Our study population included 237,360 patients who underwent primary TKA between 2005 and 2024. Patients were classified into two groups based on the presence (+Syph) or absence (−Syph) of a syphilis diagnosis within one year prior to the TKA. We evaluated the rates of several postoperative complications at 30 days postsurgery, including infection, hematologic issues, and cardiac events. Statistical analyses between groups was performed using chi-squared tests and Fisher’s exact tests. Routine demographic data such as age, sex, race, and comorbidities were also analyzed. Results: Among the 237,360 TKA patients, we identified 71 with a history of syphilis within one year of their surgery. The +Syph group exhibited significantly higher rates of periprosthetic infection (4.23% vs. 0.81%, p = 0.001), need for manipulation under anesthesia (MUA) at four months (7.04% vs. 2.82%, p = 0.032), deep venous thrombosis (4.23% vs. 1.27%, p = 0.026), periprosthetic fracture (2.82% vs. 0.23%, p < 0.001), and pneumonia (2.82% vs. 0.62%, p = 0.019) within 30 days postTKA. No significant differences were observed in 30-day mortality, deep or superficial surgical site infections, wound dehiscence, blood loss anemia, or transfusion requirements. Additionally, rates of acute renal failure, pulmonary embolism, and cardiac events did not differ significantly between groups. Demographically, patients in the syphilis cohort had a higher prevalence of smoking and diabetes preoperatively within one year of their surgical date. Conclusions: A documented syphilis diagnosis within one year of TKA significantly affects postoperative outcomes, increasing the rates of prosthetic joint infection, MUA, deep venous thrombosis, periprosthetic fracture, and pneumonia. These findings underscore the need for heightened vigilance in the pre- and postoperative management of patients with a history of syphilis infection undergoing TKA. Further research is warranted to explore the relationship between prior syphilis infection and TKA outcomes, as well as to develop strategies to mitigate this increased risk.

Pregnancy-related acute kidney injury leads to hypertension, reduced kidney function and cognitive impairment in postpartum rats

IntroductionWomen with hypertensive disorders of pregnancy such as HELLP (hemolysis, elevated liver enzyme, low platelet) Syndrome are affected by acute kidney injury during pregnancy (PR-AKI) at higher rates than women without hypertension. Both hypertensive disorders of pregnancy and Acute Kidney Injury (AKI) outside the context of pregnancy have been associated with an increased risk of developing Chronic Kidney Disease (CKD) and cognitive impairment. In our current study, we set out to determine if PR-AKI led to the development of CKD and impaired cognition in the postpartum period and if HELLP syndrome exacerbates the impairments.MethodsUsing timed-pregnant Sprague Dawley rats, on gestational day (GD) 12, mini-osmotic pumps infusing anti-angiogenic factors were surgically placed in the intraperitoneal cavity to induce HELLP. On GD18, AKI was induced via bilateral renal reperfusion ischemia surgery. Mean arterial pressure and birth outcomes were used to assess the global effects of AKI, and liver enzymes were used to assess HELLP. CKD was assessed by measuring glomerular filtration rate (GFR), urinary output, and renal fibrosis. Anxiety-like behaviors, object recognition memory, spatial memory, and avoidance memory were assessed via behavioral experiments.ResultsHELLP + AKI rats demonstrated more evidence of renal injury, hypertension, and behavioral deficits compared to normal pregnant animals. In addition, AKI had a negative impact on birth outcomes and maternal survival.ConclusionHELLP + AKI together led to evidence of persistent hypertension, progressive renal dysfunction, and cognitive impairment, which were exacerbated compared to AKI or HELLP alone. These findings suggest that PR-AKI in the presence of a hypertensive disorder of pregnancy, such as HELLP, leads to the development of CKD, cognitive dysfunction, and hypertension.

Traditional Mongolian medicine Wu-Lan thirteen-flavor decoction protects rat from hypertension-induced renal injury via aryl hydrocarbon receptor-mediated pathway

Background Wu-Lan Thirteen-Flavour decoction (WLTd), a traditional Mongolian medicine, has been used for treating hypertension in clinical practice, but the chemical basis and underlying mechanisms remain unknown. Methods The main components of WLTd were identified and quantified using HPLC and UPLC–MS/MS techniques. A compound-target-disease network was constructed using network pharmacology analysis to forecast the potential anti-hypertension targets. In vivo animal and in vitro cellular experiments were performed to validate the efficacy and molecular mechanisms of renal protection of WLTd and its main active components in spontaneous hypertension. Results A total of 136 active compounds in WLTd were collected through relevant databases, and network pharmacology analysis identified that the aryl hydrocarbon receptor (AhR) signaling pathway may serve as a potential anti-hypertension targets. Eight of the active components, including vitexin, kaempferol, toosendanin, ursolic acid, matrine, oxymatrine, gardenoside and quercetin, were identified and quantified by HPLC and UPLC–MS/MS. WLTd effectively lowered the mean blood pressure (159.16 ± 13.91 vs 135 ± 13.37 mmHg), reduced the BUN (391.55 ± 59.96 vs 240.88 ± 51.15 mmol/L) and creatinine (1.78 ± 0.41 vs 0.67 ± 0.34 nmol/L) levels, and reduced hypertension-induced renal damage in SHR. AhR and related key gene expression changes predicted by network pharmacology analysis were validated by immunohistochemistry, RT-qPCR, and Western blot analyses. In vitro, studies also showed that WLTd up-regulated AhR expression in angiotensin II-induced HEK293 cell injury. Conclusions Wu-Lan Thirteen-Flavour decoction effectively protects hypertension-induced renal injury by regulating the Aryl Hydrocarbon Receptor signaling pathway.

Fibronectin type III domain containing protein 5/irisin alleviated sepsis-induced acute kidney injury by abating ferroptosis through the adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid-2-related factor 2 signaling pathway

Objective: Ferroptosis has been described in association with acute kidney injury (AKI)-induced sepsis. Fibronectin type III domain containing protein 5 (FNDC5)/irisin plays a crucial role in renal protection. The objective of this study was to investigate whether FNDC5/irisin is involved in AKI-induced sepsis by modulating ferroptosis, and the molecular mechanisms that may be involved. Material and Methods: A sepsis-induced AKI model was built in vivo and in vitro through lipopolysaccharide (LPS) intervention. FNDC5, adenosine 5'-monophosphate-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 (ACSL4) concentrations in cells and mouse kidney tissues were appraised by Western blot. Pro-inflammatory cytokines concentrations in cell supernatants and mouse kidney tissues were appraised by enzyme-linked immunosorbent assay. Fe2+ concentration in cells and mouse kidney tissue was appraised by kit. The apoptosis rate of cells and mouse kidney tissue was measured by flow cytometry. Automatic biochemical analyzer was to test serum creatinine (SCr) and blood urea nitrogen (BUN). The kidney tissue sections from each groups were observed by hematoxylin and eosin staining. Results: LPS abated FNDC5 concentration in human kidney-2 cells and mouse kidney tissue (P < 0.001). Overexpression of FNDC5 can abated proinflammatory cytokines concentrations in cells and mouse kidney tissue (P < 0.01). Meanwhile, overexpression of FNDC5 can boost GPX4 protein concentration, abate ACSL4 protein, and abate Fe2+ concentration in cells and mouse kidney tissues (P < 0.05). In addition, the overexpression of FNDC5 can reduce the rate of apoptosis (P < 0.01). In vivo experiments showed that FNDC5 overexpression reduced serum BUN and SCr concentrations and alleviated pathological damage in the mouse renal tissues (P < 0.05) and exhibited a certain renal protective effect. FNDC5 overexpression can boost p-AMPK/AMPK, Nrf2, and HO-1 protein concentrations (P < 0.01). Conclusion: FNDC5/irisin improves sepsis-induced acute renal injury by abating ferroptosis through the AMPK/Nrf2 signaling pathway.

A qualitative case study of health system barriers and facilitators to living donor kidney transplantation in Canada's most populous province

AbstractPatients with kidney failure need dialysis or a kidney transplant to survive. Living donor kidney transplantation (LDKT) is the best therapeutic option, yet global rates of LDKT have minimally increased, and there are disparities in access. The need for a systems approach to improvement has been highlighted. We aimed to understand what elements of a relatively large health system interact to deliver LDKT and act as facilitators or barriers. This was an exploratory case study of Ontario, the most populous province in Canada that conducts 600–700 kidney transplantations annually, of which ~30% are LDKT. Data collection entailed interviews with multiple stakeholders (n = 37), and document review (n = 29) served as a means of triangulating the data. Data were analyzed using inductive thematic analysis. A multicomponent intervention to facilitate kidney transplantation was simultaneously being conducted which allowed us to capture its impact (EnAKT‐LKD). Eight themes were identified, that were separated into facilitators and barriers. Centralized leadership, directed resource deployment, dynamic communities of practice, and informal collaborations between various elements of the health system were found to facilitate LDKT. Barriers were inadequate donor and patient resources to support equitable access, lengthy and poorly coordinated workups for donors and recipients, and issues of jurisdictional control and competition for resources. The EnAKT‐LKD initiative was described as having boosted resource deployment and collaborative capacity and improved strategic alliances by establishing communities of practice. This case study has identified how individual elements in a health system interact to facilitate and impede the delivery of a therapy to patients.

Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria.

Glyoxylate is a toxic metabolite because of its rapid conversion into oxalate, as catalyzed by the ubiquitous enzyme lactate dehydrogenase. This requires the presence of efficient glyoxylate detoxification systems in multiple subcellular compartments, as glyoxylate is produced in peroxisomes, mitochondria, and the cytosol. Alanine glyoxylate aminotransferase (AGT) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR) are the key enzymes involved in glyoxylate detoxification. Bi-allelic mutations in the genes coding for these enzymes cause primary hyperoxaluria type 1 (PH1) and 2 (PH2), respectively. Glyoxylate is derived from various sources, including 4-hydroxyproline, which is degraded in mitochondria, generating pyruvate and glyoxylate, as catalyzed by the mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA); however, counterintuitively, a defect in HOGA1 is the molecular basis of primary hyperoxaluria type 3 (PH3). Irrespective of its underlying cause, hyperoxaluria in humans leads to nephrocalcinosis, recurrent urolithiasis, and kidney damage, which may culminate in kidney failure requiring combined liver-kidney transplantation in severely affected patients. In the past few years, therapeutic options, especially for primary hyperoxaluria type 1 (PH1), have greatly been improved thanks to the introduction of two RNAi-based therapies that inhibit either the production of glycolate oxidase (lumasiran) or lactate dehydrogenase (nedosiran). While lumasiran only targets PH1 patients, nedosiran was specifically developed to target all three subtypes of PH. Inspired by the findings reported in the literature that nedosiran effectively reduced urinary oxalate excretion in PH1 patients but not in PH2 or PH3 patients, we have now revisited glyoxylate metabolism in humans and performed a thorough literature study which revealed that glyoxylate/oxalate metabolism is not confined to the liver but instead involves multiple different organs. This new view on glyoxylate/oxalate metabolism in humans may well explain the disappointing results of nedosiran in PH2 and PH3, and provides new clues for the future generation of new therapeutic strategies for PH2 and PH3.

Evaluating the safety and effectiveness of tolvaptan in patients with heart failure and renal impairment: a systematic review and meta-analysis.

Patients with heart failure and concomitant renal impairment are often prescribed loop diuretics, such as furosemide, as the primary treatment. The present meta-analysis is focused on analyzing the safety and efficacy of the implementation of tolvaptan as a novel approach in patients with renal impairment and heart failure. Two reviewers conducted a screening of articles using online databases, including PubMed, Google Scholar, and Embase. Following a comprehensive literature search, seven articles that met all inclusion criteria (patients with heart failure and renal impairment) were selected for analysis. Subsequently, various primary and secondary outcomes were evaluated. The primary outcomes of our study included urine volume, worsening renal function, blood urea nitrogen (BUN) levels, and creatinine levels. Tolvaptan demonstrated superior efficacy in increasing urine output with a standardized mean difference of 2.18 (95% CI 0.62-3.75, p = 0.006) and resulted in a lower incidence of worsening renal function with odds ratio 0.41 (95% CI 0.22-0.77, p = 0.006). Additionally, there was no significant difference in the tolvaptan and conventional treatment groups in changing serum creatinine levels with a standardized mean difference of - 0.37 (95% CI - 0.86 to 0.12, p = 0.135), but tolvaptan tends to decrease blood urea nitrogen levels with a standardized mean difference - 0.18 (95% CI - 0.30 to - 0.06, p = 0.004) in comparison to conventional treatment group. While tolvaptan administration was related to better renal outcomes, unresolved heterogeneities and various factors could have influenced our findings. Further research is needed to evaluate the role of tolvaptan in the treatment of this patient population.

Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as "cardiorenal syndrome," where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure-chronic heart failure (CRF-CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a "two-step surgical method"), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF-CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF-CHF groups showed significant increases in LVEDP and LVW/BW (P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Compared to the CRF and CHF groups, the CRF-CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Rats with CRF-CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

Comprehensive Documentation and Critiques on Pashanabhedadi Kwatha: Exploring its Potential in Chronic Kidney Disease (CKD)

In Ayurveda, the treatment of Chronic Kidney Disease (CKD) is approached through a holistic lens, where the focus lies not just on alleviating symptoms but also on restoring balance to the body’s intricate systems. Pashanabhedadi Kwatha, a revered polyherbal formulation, exemplifies this Ayurvedic approach by combining a unique blend of herbs (such as Pashanabheda, Yastimadhu, Vasa, Gokshura, Eranda, Aragwadha phala majja, Pippali, Ela, Shilajit, Souvarchala lavana, and Mishri), each chosen for its specific role in supporting kidney health, also known for their diuretic, anti-inflammatory, and detoxifying properties. When combined, they work synergistically to enhance renal function, regulate fluid balance, and reduce inflammation, which are crucial factors in managing CKD. In Ayurveda, kidney dysfunction is often attributed to imbalances in the doshas, accumulation of ama and disturbances in agni and srotas. Pashanabhedadi Kwatha is formulated to address these imbalances, with its herbs targeting specific physiological processes that support renal and metabolic health. The present study aims to evaluate the effects of Pashanabhedadi Kwatha on CKD through the lens of Ayurvedic principles like Rasa Panchaka, and to explore its influence on doshic imbalances, ama, agni, srotas, and the specific phytochemical constituents responsible for its therapeutic benefits. By reviewing both classical and modern literature, this study seeks to shed light on the potential mechanisms behind its beneficial effects in CKD and offer insights into its clinical applications.

Cross-Sectional Study on Hematological Variation Associated with Advance Chronic Kidney Disease (CKD) in a CKDu Endemic Area in Sri Lanka

A cross-sectional study was undertaken to investigate the etiology and disease progression in terms of CKD (chronic kidney disease)-initiation risk factors (IRF) and hematology in Nachchaduwa, a CKDu (CKD of unknown etiology)-endemic area in North Central Province of Sri Lanka. Whole blood, spot urine and risk factor history were obtained following informed consent from all medically confirmed CKD/CKDu cases in the area. CKDu was substantiated when medically accepted IRFs did not exist prior to CKD diagnosis. The disease progression stage (G1-G5) was established by kidney dysfunction markers, eGFR (MDRD, and CKD-EPI-sCr) and UACR using serum creatinine (sCr), urine creatinine (uCr) and urine (uAlb) measured in the study. Hematology variables were compared between early (G2-G3b) and advance (G4-G5) stages to reveal changes over disease progression and assessed for linear associations to disease progression in terms of kidney dysfunction markers and renal outcomes. Multivariate dendrogram and principal component analyses were utilized to study inter-variable relations. The results showed that advance disease (G4-G5) in Nachchaduwa had significantly declined RBC counts and RDW-CV, amid unchanged MCV, MCH, MCHC, hematocrit and total hemoglobin suggesting predominantly normocytic anemia. RBC depletion was further evident in its positive associations to eGFRs, and negative association to sCr (p&lt;0.05, rho stronger than ±0.45). Multivariate analyses revealed that RDW-CV was following the decreasing eGFRs and uCr over disease progression. Results showed the potential utility of erythrocyte count and RDW-CV as markers of advance disease in CKDu endemic areas of Sri Lanka. IRF distribution in Nachchaduwa pointed to a minor fraction of unknown etiology among total CKD, and the major IRFs that led to chronic renal failure did not include Diabetes Mellitus.

Factors that Facilitate Informal Advance Care Planning Conversations With Family: A Cross-Sectional Survey of Black Adults With Kidney Failure.

Background: Advance care planning in adults with kidney failure has been understudied and limited to written advance directives. Many Black adults prefer informal conversations with family, and yet this form of advance care planning is underexplored in research. In this study, we aimed to identify the multilevel factors that facilitate informal advance care planning with family among Black adults with kidney failure. Methods: Black adults with kidney failure were recruited using the electronic health record to identify prospective participants who met inclusion criteria from a metropolitan hospital in the Mid-Atlantic region of the United States from June 2021 to June 2022. Participants completed a survey capturing the personal, interpersonal, and structural level factors that facilitate informal advance care planning conversations with family, and sociodemographic characteristics. Results: The study included 301 respondents, 66% engaged in informal advance care planning and 37% completed an advance directive. Mean age was 56 years, 52% were female, 25% received a high school education or less. Illness acceptance (OR 1.07, P = 0.04) and emotional support (OR 1.44, P = 0.02) facilitated Informal advance care planning, as did having master's or doctoral level education (OR 2.37, P = 0.04). A recent hospitalization (OR 1.79, P = 0.04) and experience as a surrogate decision maker (OR = 1.76, P = 0.05) also facilitated Informal advance care planning. Conclusions: Informal advance care planning conversations occur more frequently than written directives among Black adults with kidney failure. Future interventions should consider cultural preferences by developing interventions that facilitate informal advance care planning conversations with family.

The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration.

Brensocatib is an oral, selective, competitive and reversible dipeptidyl peptidase 1 inhibitor in development for the treatment of bronchiectasis. This study evaluated the pharmacokinetics (PKs), safety and tolerability of brensocatib in participants with varying degrees of renal impairment and normal renal function. In this phase 1, multicentre, open-label study, 28 participants with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] 60 to <90, 30 to <60 and 15 to <30 mL/min/1.73 m2, respectively) or normal renal function (≥90 mL/min/1.73 m2) received a single oral 25-mg dose of brensocatib. Blood samples were collected to measure brensocatib PKs at predetermined time points over the 14-day study period. PK parameters were derived using noncompartmental methods. Demographic and baseline characteristics were similar across groups. There were no significant differences between groups in brensocatib PK parameters. The mean coefficient of variation (CV) of elimination half-life of brensocatib was 37.0 (15.3), 42.8 (21.7), 36.3 (22.9) and 39.1 (17.8) h for mild, moderate, severe and normal renal function groups, respectively. Single-dose brensocatib was quickly absorbed; all groups had a median time to maximum observed plasma concentration of 1h. Regression model analyses indicated no significant relationships between selected brensocatib PK parameters and eGFR. No treatment-emergent adverse events were reported during the study. Single-dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment. NCT05673603.

Causal relationships between uremic metabolites or toxins and heart failure: Univariate and multivariate Mendelian randomization

Studies have shown that uremia, renal failure and heart failure (HF) are closely related. However, whether this association reflects a causal effect is still unclear. The aim of this study was to evaluate the causal effect of uremic metabolites or toxins on HF. Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of 11 uremia-related metabolites on HF risk using single-nucleotide polymorphisms (SNPs) from a genome-wide association study. A protein–protein interaction network was constructed to study the function of SNPs corresponding to HF-related factors. Univariate and multivariate MR analyses demonstrated that lipoprotein A and apolipoprotein B were positively correlated with HF. The SNPs corresponding to these key factors were related mainly to MAP kinase activity and lipid metabolic processes. Overall, we identified 2 uremia-related exposure factors (lipoprotein A and apolipoprotein B) closely related to HF, laying a theoretical foundation for the treatment of HF with renal failure or uremia.

Edaravone mitigates calcium oxalate-induced renal tubular epithelial cell injury by inhibiting autophagy-mediated ferroptosis.

Edaravone (EDA) has been found to exert protective effects on kidney injury. Nevertheless, the functions of EDA in kidney stones as well as the potential mechanism are vague. Calcium oxalate (CaOx) was used to induce kidney stones cell model with human renal tubular epithelial cell line HK-2. CCK-8 assay was employed to detect cell viability injury. Oxidative stress was measured by DCFH-DA staining and detection of MDA, SOD, and GSH. Staining of FerroOrange and western blot were applied for ferroptosis. In addition, autophagy was elucidated by western blot and immunofluorescence staining. The data showed that CaOx treatment aggravated HK-2 cell viability injury, increased the levels of ROS, MDA, and Fe2+ in HK-2 cells, and reduced the contents of SOD and GSH. Additionally, CaOx enhanced the expression of KIM1, TFR1, LC3II/LC31, and BECLIN1 in HK-2 cells, while resulting in a decrease in the expression of GPX4, SLC7A11, and P62. Pretreatment of EDA mitigated CaOx-induced oxidative stress and ferroptosis, as well as autophagy in renal tubular epithelial cells. However, autophagy inducer rapamycin (Rap) reversed the protective role of EDA on renal tubular epithelial cell injury, oxidative stress, and ferroptosis. In conclusion, EDA contributes to suppressing oxidative stress and ferroptosis in CaOx-induced HT22 cells by restraining autophagy, which may be a potential candidate for the treatment of kidney stones caused by renal tubular epithelial cell damage.

Metabolic Syndrome Nonalcoholic Steatohepatitis Male Mouse With Adeno-Associated Viral Renin as a Novel Model for Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) currently accounts for more than half of patients with HF, with limited approved evidence-based therapies. HFpEF is a complex multifactorial disease associated with hypertension, obesity, diabetes, and renal dysfunction. In addition to our limited understanding of HFpEF pathophysiology, the development of new therapies is partially hindered by the existing translationally relevant preclinical HFpEF models. Here, we report the development of a novel 2-hit HFpEF male mouse model through adding hypertensive stress from the activation of the renin-angiotensin-aldosterone system with adeno-associated viral-renin (AAV-renin), to the metabolic syndrome nonalcoholic steatohepatitis (MSNASH, formerly FATZO) mouse (MSNASH+AAV-renin). To further demonstrate model translatability, MSNASH+AAV-renin mice were then treated with approved HFpEF therapies sacubitril/valsartan or a combination of sacubitril/valsartan and empagliflozin. We found that the MSNASH+AAV-renin mouse model demonstrates clinically relevant features of human HFpEF, including preserved ejection fraction, cardiac hypertrophy, left atrial enlargement, diastolic dysfunction, elevated natriuretic peptides, inflammation, and low exercise capacity. We also demonstrate that treatment with approved HFpEF therapies sacubitril/valsartan and the combination of sacubitril/valsartan with empagliflozin improves the cardiac phenotypes of HFpEF in this model. The MSNASH+AAV-renin model faithfully represents a severe cardiometabolic HFpEF phenogroup that can be used as a new tool for HFpEF preclinical research and drug discovery.

Diagnosis and treatment experience of Chlamydia psittaci pneumonia: A multicenter retrospective study in China

BackgroundIn recent years, clinical cases of Chlamydia psittaci pneumonia have gradually increased. Chlamydia psittaci pneumonia can quickly progress to severe pneumonia, leading to respiratory failure. Chlamydia psittaci cannot be detected by commonly used detection methods, leading to difficulties in clinical diagnosis and treatment, which may eventually develop into severe Chlamydia psittaci pneumonia. Therefore, we should improve our diagnostic and treatment capabilities for this disease.MethodsThis article retrospectively studied 61 cases of pneumonia from 12 different provinces in China, and classified them into severe pneumonia and non-severe pneumonia. Divided into two groups, with 23 cases of severe pneumonia and 38 cases of non-severe pneumonia. We compared the two groups in terms of imaging, laboratory testing, treatment, prognosis, etc., hoping to provide better explanations and help clinical physicians better diagnose the disease.ResultsThere is no difference in age, gender, contact history, smoking history, or basic disease between severe and non-severe Chlamydia psittaci pneumonia. The most prominent symptom is fever, with a median body temperature of 39.7 ℃, and other symptoms similar to common respiratory infections. White blood cells and neutrophils may not show significant elevation, but C-reactive protein (CRP) and procalcitonin (PCT) will both show significant elevation, often accompanied by a decrease in arterial oxygen pressure. Some patients may experience liver and kidney dysfunction, but there is no statistically significant difference between the two groups. Doxycycline remains the preferred drug for severe Chlamydia psittaci pneumonia. The imaging mainly shows consolidation and bronchial inflation sign, and may also present with pleural effusion.ConclusionsThe imaging of Chlamydia psittaci pneumonia usually shows consolidation with bronchial inflation sign, which can also be manifested as ground glass changes or solid masses. Atypical images are prone to misdiagnosis in the early stages. There are some differences in laboratory examination and imaging between severe pneumonia and non-severe pneumonia, which can help identify severe patients in the early stage. Metagenomic next-generation sequencing (mNGS) played an important role in the diagnosis of all cases in this article. Timely treatment has a good prognosis for the disease, and imaging lesions can be completely absorbed.

Approaches to patients with obesity and CKD: focus on nutrition and surgery.

Obesity is recognized as a public health challenge. During the last three decades, the global age-standardized prevalence increased from 8.8% to 18.5% in women and from 4.8% to 14.0% in men, with an absolute current number of 878 million obese subjects. Obesity significantly increases per se the risk of developing disability and chronic diseases, including chronic kidney disease (CKD). Specifically, obesity acts as a major, modifiable cause of CKD onset and progression toward kidney failure; as such, it is considered by the International Society of Nephrology a major health priority. This review analyses the effectiveness, safety and practicability of non-pharmacological anti-obesity interventions in CKD as the different patient phenotypes that may take advantage of personalized approaches.