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Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to harbor high morbidity and mortality. The main consequence of PH is right-sided heart failure which causes a complex clinical syndrome affecting multiple organ systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal muscle, as well as the endocrine, immune, and autonomic systems. Interorgan crosstalk and interdependent mechanisms include hemodynamic consequences such as reduced organ perfusion and congestion as well as maladaptive neurohormonal activation, oxidative stress, hormonal imbalance, and abnormal immune cell signaling. These mechanisms, which may occur in acute, chronic, or acute-on-chronic settings, are common and precipitate adverse functional and structural changes in multiple organs which contribute to increased morbidity and mortality. While the systemic character of PH and right-sided heart failure is often neglected or underestimated, such consequences place additional burden on patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the current state-of-the-art understanding of the systemic consequences of PH and right-sided heart failure on multiple organ systems, focusing on self-perpetuating pathophysiological mechanisms, aspects of increased susceptibility of organ damage, and their reciprocal impact on the course of the disease. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a multisystem disorder associated with various systemic diseases such as cardiovascular diseases, diabetes mellitus and metabolic syndrome. Renal involvement in patients with psoriasis is sparsely studied and its association is still unclear. Aim: The aim of this article was to study causal attributable renal involvement in patients with psoriasis and factors affecting the same. Methods: Fifty patients with documented psoriasis were recruited after excluding any secondary causes of renal disease. They were subjected to routine investigations along with hs-CRP and specific investigations for kidney function including urine albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). The eGFR and ACR of the patients were compared with 50 age- and sex-matched controls. Association with any disease-related factors such as severity and duration were assessed. Renal biopsy was planned in patient with ACR >500 mg/g creatinine. Results: The mean eGFR (IQR) (ml/min/1.73 m2) of the case group was found to be 80.00 (71.00–95.75) and in the control group was 88.00 (75.25–99.00). This difference was not significant (P = 0.206). However, in the age group of > 30 years, the eGFR of disease group (78.50 ± 17.94) was significantly lower than that in the control group (88.96 ± 17.01, P = 0.023).The mean urine ACR (mg/g) in the disease group was found to be 13.359 ± 26.01 while that in the control group was found to be 5.66 (3.40–8.08), and the difference was not found to be clinically significant. Four patients with psoriasis had microalbuminuria as opposed to none of the controls. Conclusion: Subclinical albuminuria was found in 8 per cent of patients with psoriasis. Glomerular dysfunction with statistically significant reduction in eGFR was seen in psoriasis in age group of more than 30 years and those who had a long-standing disease. The renal involvement had positive correlation with hs-CRP indicating the role of inflammatory milieu. Further large-scale cohort studies would help assess this aspect in further details. Limitation of the Study: Sample size was small. Large-scale studies would be required to further substantiate these observations. [ABSTRACT FROM AUTHOR]

Gum arabic is a polysaccharides obtained from the stems and branches of Acacia senegaltree. In folk medicine Gum arabic has been reported to have anti-oxidant and nephroprotectant effects. This study aimed to evaluate the Gum arabic effect on kidney dysfunction in chickens which induced by cadmium nitrate. Healthy chickens were divided into three groups, 5 chickens in each group; group 1: Normal group fed on basal diet, group 2: Control group feed on basal diet mixed with (100 ml/kg b. w.) cadmium nitrate, Group 3: Treated group, chickens feed on basal diet mixed with cadmium nitrate (100 ml/kg b. w.) then treated with Gum Arabic extract (500 g/kg body weight). Blood samples were collected at the beginning of the experiment (group 1: normal), after 5 days blood samples collected from (group 2: control) and after 10 days of Gum Arabic treatment blood samples collected from (group 3: treated), creatinine and uric acid were estimated as a kidney function parameters. The results demonstrated that oral administration of cadmium nitrate (control group) recorded a significant increase at (p<0.05) in serum creatinine levels and serum uric acid levels compared with those levels of the normal group. The results in this study illustrated that oral administration of Gum Arabic extract (treated group) showed a significant decrease at (p<0.05) in serum creatinine level and serum uric acid level compared with those levels of the normal group Furthermore, the results obtained from this study suggested that oral administration of Gum Arabic extract may be helpful in the prevention of kidney dysfunction and may represent an effective therapy that normalizes serum creatinine and serum uric acid levels in chickens. [ABSTRACT FROM AUTHOR]

We used a mitochondria-penetrating nitroxide, mito-TEMPO, as a contrast probe for imaging of kidney dysfunction in mice, based on the redox-imbalance and oxidative stress in the renal tissues. Kidney dysfunction was triggered by hypercholesterolemia. The mice were divided in three groups: (i) on normal diet (ND; control); (ii) on cholesterol diet (CD); (iii) on cholesterol plus cholestyramine diet (CC). CD mice showed increased plasma levels of total cholesterol and non-HDL-cholesterol, as well as increased serum levels of blood urea nitrogen, uric acid and creatinine, compared to ND mice. CC mice showed slightly increased plasma levels of total cholesterol and HDL-cholesterol, but not non-HDL-cholesterol, compared to ND mice. The serum levels of blood urea nitrogen, uric acid and creatinine in CC mice were equal to those in ND mice. The MRI signal of mito-TEMPO in the kidneys was characterized by: high intensity and long life-time in CD mice, indicating a high oxidative capacity of renal tissues; poor intensity and short life-time in ND mice, indicating a high reducing capacity of renal tissues; moderate intensity and relatively short life-time in CC mice, which shows the protective effect of lipid-lowering agents against oxidative damage. The data suggest that hypercholesterolemia induces redox-imbalance and oxidative stress in kidneys and this process could be visualized using MRI and mito-TEMPO as a redox-sensitive contrast substance. [ABSTRACT FROM AUTHOR]

Apolipoprotein L1 (APOL1) high-risk genotypes (HRG), G1 and G2, increase the risk of various non-diabetic kidney diseases in the African population. To date, the precise mechanisms by which APOL1 risk variants induce injury on podocytes and other kidney cells remain unclear. Trying to unravel these mechanisms, most studies have used animal or cell models created by gene editing. We developed and characterised conditionally immortalised human podocyte cell lines derived from urine of a donor carrying APOL1 HRG G2/G2. Following induction of APOL1 expression by polyinosinic-polycytidylic acid (poly(I:C)), we assessed functional features of APOL1-induced podocyte dysfunction. As control, APOL1 wild type (G0/G0) podocyte cell line previously generated from a Caucasian donor was used. Upon exposure to poly(I:C), G2/G2 and G0/G0 podocytes upregulated APOL1 expression resulting in podocytes detachment, decreased cells viability and increased apoptosis rate in a genotype-independent manner. Nevertheless, G2/G2 podocyte cell lines exhibited altered features, including upregulation of CD2AP, alteration of cytoskeleton, reduction of autophagic flux and increased permeability in an in vitro model under continuous perfusion. The human APOL1 G2/G2 podocyte cell model is a useful tool for unravelling the mechanisms of APOL1-induced podocyte injury and the cellular functions of APOL1.

Background/Purpose: Tenofovir disoproxil fumarate (TDF) is associated with kidney tubular dysfunction, for which the risk may vary among patients of different ethnicities. Data are limited, however, on the association between renal function changes and TDF exposure in human immunodeficiency virus (HIV)-infected Taiwanese patients. Methods: Medical records of HIV-infected Taiwanese patients seeking HIV care at a university hospital from 2011 to 2014 were reviewed. The change of estimated glomerular filtration rate (eGFR) was compared between patients not receiving combination antiretroviral therapy (cART) and those starting cART with or without TDF. The determinants of annual eGFR changes and factors associated with greater annual eGFR decline in TDF-exposed patients were explored. Results: A total of 775 patients were included: 140 were cART-naïve, 393 received TDF-containing cART, and 242 received cART without TDF. Compared with cART-naïve patients, the annual eGFR decline was greater in TDF-exposed patients (0.57 ± 8.6 mL/min/1.73 m2 and 2.7 ± 8.9 mL/min/1.73 m2, p = 0.012). The annual eGFR decline between patients receiving cART with or without TDF was similar (2.7 ± 8.9 mL/min/1.73 m2 and 1.8 ± 8.3 mL/min/1.73 m2, p = 0.567). Diabetes was associated with worsening eGFR decline in all studied patients. TDF exposure correlated with an additional annual eGFR decline of 2.73 mL/min/1.73 m2 (95% confidence interval 0.139–5.326, p = 0.039) in patients with CD4 count 3 mL/min/1.73 m2 were higher baseline eGFR and lower CD4 counts. Conclusion: Among HIV-infected Taiwanese patients, cART exposure correlated with the decline of renal function. However, TDF-exposed patients are more likely to have prominent eGFR decline, especially those with higher baseline eGFR, advanced HIV disease, and diabetes.

The aim of this study was to evaluate the effect of l-carnitine (L-CAR) treatment on isoprenaline (ISO) administered kidney and heart impairment in male Long Evans rats. Four groups of rats were engaged in this study such as control, ISO, control + L-CAR, and ISO + L-CAR, where n = 6 in each group. The rats were also provided with chow food and water ad libitum. At the end of the study, all rats were sacrificed, and blood and tissue samples were collected for bio-chemical analysis. Oxidative stress parameters and antioxidant enzyme activities were determined in plasma and tissues. Antioxidant and inflammatory genes expression were analyzed in the kidney cortex, and histopathological studies of kidney tissues were performed. This study showed that creatinine and uric acid in plasma were significantly increased in ISO-administered rats. l-carnitine treatment lowered the uric acid and creatinine level. ISO-administered rats showed increased lipid peroxidation and declined levels of antioxidant enzymes activities in kidneys and heart. l-carnitine treatment restored antioxidant enzymes activities and protect against oxidative stress in kidney and heart. This effect is correlated with the restoration of Nrf-2-HO-1 genes expression followed by increased SOD and catalase genes expression in the kidney. l-carnitine treatment also prevented the TNF-α, IL-6, and NF-кB expression in kidneys of ISO administered rats. Histopathology staining showed that l-carnitine treatment prevented kidney damage and collagen deposition in ISO administered rats. The result of this study exhibited that l-carnitine treatment reduced oxidative stress and increased antioxidant enzyme activities by enhancing antioxidant genes expression in ISO administered rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

A growing life expectancy may result in a chronic medical condition and multimorbidity because the aging process leads to a decrease in cognitive and physiological function. These risks may affect the quality of life of geriatrics. The present study aims to determine the correlation between cognitive status (in terms of SIRT1, a nicotinamide adenine dinucleotide (NAD + )-dependent class III deacetylase) and metabolic function (in terms of the lipid profile, kidney function, and blood glucose) in geriatric patients. The differences in the parameters of metabolic function in the participants' cognitive status were determined by using the Indonesian version of the Montreal Cognitive Assessments (MoCA-Ina). The elderly participants (n = 120) were recruited at three sites in Indonesia from March to October 2022. Our study demonstrated a negative correlation between the cognitive status of geriatric patients and their metabolic function, represented by the MoCA-Ina score with a linear regression equation of y = 0.27 - 2.4 ×10 -3 x . Higher levels of LDL-C, cystatin C, and HbA1c were found in the Severe-Moderate Cognitive Impairment group. Determining the SIRT1 levels may be beneficial in predicting both the cognitive and metabolic status of geriatrics because this protein is among numerous metabolic sensors in the hypothalamus.

In stroke patients, the development of acute kidney injury (AKI) is closely linked with worse outcomes and increased mortality. In this study, the interplay between post-stroke and AKI and treatment options was investigated in a rodent model of hemorrhagic stroke. Intrastriatal collagenase injection for 24 h caused neurological deficits, hematoma formation, brain edema, apoptosis, blood–brain barrier disruption, oxidative stress, and neuroinflammation in Sprague Dawley rats. Elevation of serum blood urea nitrogen, serum creatinine, urine cytokine-induced neutrophil chemoattractant-1, and urine Malondialdehyde, as well as moderate histological abnormality in the kidney near the glomerulus, indicated evidence of kidney dysfunction. The accumulation of podocalyxin DNA in urine further suggested a detachment of podocytes and structural deterioration of the glomerulus. Circulating levels of stress hormones, such as epinephrine, norepinephrine, corticosterone, and angiotensin II were elevated in rats with intracerebral hemorrhage. Osmotic agent glycerol held promising effects in alleviating post-stroke brain injury and kidney dysfunction. Although the detailed protective mechanisms of glycerol have yet to be determined, the intrastriatal collagenase injection hemorrhagic stroke model in rats allowed us to demonstrate the functional and structural integrity of glomerulus are targets that are vulnerable to post-stroke injury and stress hormones could be surrogates of remote communications.

Left ventricular assist devices (LVADs) are increasingly used for the management of patients with advanced heart failure (AHF) due to their established salutary impact on hemodynamic status and survival benefit. Impairment in kidney function is common in the setting of AHF and is associated with adverse impact on the outcomes. Cardiorenal interactions represent a complex pattern in these patients rendering their care a challenge that needs to be addressed by multidisciplinary approaches. Following LVAD implantation, AHF patients have the potential to achieve marked improvement in kidney function due to increased cardiac output and kidney perfusion as well as reduction in renal venous congestion. However, a subset of these patients is also at risk for acute kidney injury and resurgence of kidney dysfunction on continued mechanical circulatory support. Herein, we provide an overview of various aspects of changes in kidney function pre- and post-LVAD implantation, review potential underlying pathophysiologic mechanisms, and the impact on the outcomes. Moreover, the currently available data on renal replacement therapy of LVAD-treated patients, whether in the acute setting or as a maintenance therapy, are discussed in detail along with areas of high clinical relevance where a clear gap in knowledge exists. [ABSTRACT FROM AUTHOR]

Real‐time imaging of kidney function is important to assess the nephrotoxicity of drugs and monitor the progression of renal diseases; however, it remains challenging because of the lack of optical agents with high renal clearance and high signal‐to‐background ratio (SBR). Herein, a second near‐infrared (NIR‐II) fluorescent molecular semiconductor (CDIR2) is synthesized for real‐time imaging of kidney dysfunction in living mice. CDIR2 not only has a high renal clearance efficiency (≈90 % injection dosage at 24 h post‐injection), but also solely undergoes glomerular filtration into urine without being reabsorbed and secreted in renal tubules. Such a unidirectional renal clearance pathway of CDIR2 permits real‐time monitoring of kidney dysfunction in living mice upon nephrotoxic exposure. Thus, this study not only introduces a molecular renal probe but also provides useful molecular guidelines to increase the renal clearance efficiency of NIR‐II fluorescent agents. [ABSTRACT FROM AUTHOR]

Formaldehyde is a volatile chemical compound that is commonly used in the chemical industry. Formaldehyde inhalation exposure has been associated with cancer, respiratory diseases, digestive and neurological disorders. Oxidative stress is one of the potential mechanisms by which formaldehyde inhalation induces toxicity. Curcumin is a natural compound endowed with antioxidant properties and my thus prevent formaldehyde-induced toxicity. This study aimed to examine the effects of formaldehyde inhalation on renal function and kidney structure of mice; the potential protective effects of curcumin administration against kidney dysfunction, renal damage and oxidative stress were also investigated. Formaldehyde inhalation induced renal dysfunction and damage, as shown by the increase of serum creatinine and blood urea nitrogen levels, and caused histological damage associated with proteinaceous and granular cast formation in renal tubular lumen. The activity of antioxidant enzymes remained unchanged and malondialdehyde levels increased in a discrete and statistically non-significant way. Curcumin treatment prevented the above-described alterations by preventing an increase in renal dysfunction and changes in the kidney structure of mice. Therefore, curcumin can be a potentially useful treatment against the effects induced by exposure to gaseous pollutants such as formaldehyde in distal organs. [ABSTRACT FROM AUTHOR]

Study Objective: Several methods are available to predict unbound (free) phenytoin concentrations in patients with hypoalbuminemia; however, predictive methods have not been evaluated in patients with concurrent hypoalbuminemia and kidney dysfunction or in patients with mild to moderate (estimated glomerular filtration rate [eGFR] 30‐90 ml/min/1.73 m2) kidney dysfunction alone. Thus the objective was to evaluate the accuracy and precision of predictive methods to estimate free phenytoin concentrations in patients with varying albumin concentrations and/or kidney dysfunction. Design: Retrospective chart review. Setting: Large academic medical center. Patients: A total of 344 patients with free and total phenytoin, albumin, and serum creatinine concentrations obtained between November 2012 and May 2017. Measurements and Main Results: Free phenytoin concentrations were estimated in patients without kidney dysfunction using the Winter‐Tozer, Anderson, Kane, and Cheng equations. For the analysis in patients with eGFR lower than 90 ml/min/1.73 m2, free phenytoin concentrations were estimated using the Shiner‐Tozer derivation with adjusted affinity coefficients (C = 0.15, 0.20, 0.25, and 0.30). For both analyses, accuracy of predictive methods was evaluated by P20, the proportion of estimations within 20% of the measured free phenytoin concentration. In 158 patients with normal kidney function/normal albumin concentrations, 73 with normal kidney function/hypoalbuminemia, or 47 with mild kidney dysfunction/normal albumin concentrations, the Anderson method had the highest accuracy (86%, 82%, and 92%, respectively) and highest precision compared with the other methods. In 47 patients with normal albumin concentrations and mild kidney dysfunction or 13 with moderate kidney dysfunction, the free fraction was unchanged, and total phenytoin concentrations accurately reflected free concentrations. In 17 patients with hypoalbuminemia and mild or 17 with moderate kidney dysfunction, the Winter‐Tozer (67% and 50%, respectively) and the Anderson (56% and 67%, respectively) methods had the highest accuracy compared with other methods with significantly lower accuracy compared with patients with normal kidney function. In the 14 patients with severe kidney dysfunction and hypoalbuminemia, none of the coefficients had a P20 accuracy greater than 45%. Conclusion: In patients with normal albumin concentrations, with or without mild or moderate kidney dysfunction and not receiving a protein‐binding displacer, the free fraction of phenytoin is unchanged, and it is not necessary to measure a free phenytoin concentration. Free phenytoin concentrations should be measured directly in patients with hypoalbuminemia and kidney dysfunction. [ABSTRACT FROM AUTHOR]

Background: Congestive heart failure (CHF) entails a complex interaction between the heart and the kidney that represents a clinical entity called cardiorenal syndrome (CRS). One of the mechanisms underlying CRS includes increased intra-abdominal pressure (IAP). We examined the effect of elevated IAP on kidney function in rats with low- and high-output CHF.Methods and Results: Rats with compensated and decompensated CHF induced by means of aortocaval fistula, rats with myocardial infraction (MI) induced by means of left anterior descending artery ligation, and sham control rats were subjected to either 10 or 14 mm Hg IAP. Urine flow (V), Na+ excretion (UNaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. The effects of pretreatment with tadalafil (10 mg/kg orally for 4 days) on the adverse renal effects of IAP were examined in decompensated CHF and MI. Basal V and GFR were significantly lower in rats with decompensated CHF compared with sham control rats. Decompensated CHF rats and MI rats subjected to 10 and 14 mm Hg IAP exhibited more significant declines in V, UNaV, GFR and RPF than compensated and sham controls. Elevated IAP also induced tubular injury, as evidenced by significantly increased absolute urinary excretion of neutrophil gelatinase-associated lipocalin. In addition, in a nonquantitative histologic analysis, elevated IAP was associated with increase in necrosis and cell shedding to the tubule lumens, especially in the decompensated CHF subgroup. Pretreatment of decompensated CHF rats and MI rats with tadalafil ameliorated the adverse renal effects of high IAP.Conclusions: Elevated IAP contributes to kidney dysfunction in high- and low-cardiac output CHF. IAP induces both hemodynamic alterations and renal tubular dysfunction. These deleterious effects are potentially reversible and can be ameliorated with the use of phosphodiesterase-5 inhibition. [ABSTRACT FROM AUTHOR]

This study reports a non-invasive magnetic resonance imaging (MRI) of kidney dysfunction in mice, based on the induction of redox-imbalance and oxidative stress in the renal tissues, using mito-TEMPO as redox-sensitive contrast probe. Kidney dysfunction was triggered by hypercholesterolemia. The mice were divided in three groups: (i) on normal diet (ND); (ii) on cholesterol diet (CD); (iii) on cholesterol plus cholestyramine diet (CC). After 15 weeks feeding, the mice were subjected to the following analyses: plasma cholesterol levels; serum test for renal functionality; nitroxide-enhanced MRI of tissue redox-status in vivo; histochemical staining of tissue section to visualize renal damage; evaluation of total antioxidant capacity and oxidative stress on isolated tissue specimens. MRI signal of mito-TEMPO in the kidney was characterized by: high intensity and long life-time in CD mice, indicating a high oxidative capacity of renal tissues; poor intensity and short life-time in ND mice, indicating a high reducing capacity; moderate intensity and relatively short life-time in CC mice, indicating a protective effect of lipid-lowering drug. The data were confirmed on isolated tissue specimens, using conventional tests. They suggest that hypercholesterolemia induces redox-imbalance in kidney and this process could be visualized using MRI and mito-TEMPO as a redox-sensitive contrast. [ABSTRACT FROM AUTHOR]

Purpose: Obstructive sleep apnea syndrome (OSAS) has been recently proposed as an independent risk factor for chronic kidney disease. Cystatin C (Cyst C) and neutrophil gelatinase-associated lipocalin (NGAL) are novel biomarkers for the earlier detection of latent kidney disease. The aim of the study was to assess serum Cyst C and NGAL levels in otherwise healthy OSAS patients and to explore possible associations with sleep parameters.Methods: Consecutive subjects (n = 96, 79.2% males), without known comorbidities, with symptoms suggestive of OSAS were included. All of them underwent polysomnography (PSG) and blood examination for the measurement of serum Cyst C and NGAL levels.Results: Based on apnea-hypopnea index (AHI), subjects were classified into two groups: 32 controls and 64 OSAS patients, with no significant differences in terms of age (50.1 ± 11.7 vs 51 ± 12.2 years, p = 0.747) and BMI (33.9 ± 8.8 vs 35.9 ± 13.1 kg/m2, p = 0.449). Serum Cyst C and NGAL mean levels were higher in OSAS patients compared to those in controls (1155.2 ± 319.3 vs 966.8 ± 173 ng/ml, p = 0.001, and 43.7 ± 23.2 vs 35.6 ± 13.8 ng/ml, p = 0.035, respectively). After adjustment for age and BMI in OSAS patients, serum NGAL levels were associated with AHI (β = 0.341, p = 0.015) and minimum oxyhemoglobin saturation during sleep (β = − 0.275, p = 0.032), while serum Cyst C levels were associated with percentage of time with oxyhemoglobin saturation < 90% (β = 0.270, p = 0.043), average (β = − 0.308, p = 0.018), and minimum (β = − 0.410, p = 0.001) oxyhemoglobin saturation during sleep.Conclusions: Higher risk for latent kidney disease in otherwise healthy OSAS patients is indicated. Sleep hypoxia seems to be a significant contributor in the pathogenetic process of renal dysfunction in OSAS. [ABSTRACT FROM AUTHOR]

DNA tetrahedron nanostructure (DTN) is one of the simplest DNA nanostructures and has been successfully applied for biosensing, imaging, and treatment of cancer. To facilitate its biomedical applications and potential clinical translation, fundamental understanding of DTN's transportation among major organs in living organisms becomes increasingly important. Here, we describe the efficient renal clearance of DTN in healthy mice by using positron emission tomography (PET) imaging. The kidney elimination of DTN was later applied for renal function evaluation in murine models of unilateral ureteral obstruction (UUO). We further established a mathematical program of DTN to validate its changes of transportation pattern in healthy and UUO mice. We believe the establishment of pharmacokinetic profiles and mathematical model of DTN may provide insight for future optimization of DNA nanostructures for biomedical applications. [ABSTRACT FROM AUTHOR]

The interrelation of the levels of brain natriuretic peptide (BNP) and aldosterone (Al) in serum with the parameters of left ventricular remodeling, the degree of chronic heart failure (CHF) and the parameters of kidney dysfunction in patients with CHF were studied. Revealed a significant increase in neurohumoral factors of BNP and Al associated with functional class (FC) of the CHF, the degree of left ventricular (LV) systolic dysfunction and kidney dysfunction. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Increasing MSG uptake above the safe limit significantly increase the body weight. • Increasing MSG uptake above safe limit produces liver and kidney dysfunctions. • MSG induces oxidative liver and kidney damage. • Vit D and l -Arg suppress the MSG-induced increase in food intake and body weight. • Vit D & l -Arg restore hepatic & renal MSG injury via inhibiting oxidative damage. Abstract Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible MSG-induced injurious effects on some organs have been stated in experimental animal models. Thus, in this study we tried to clarify effect and possible mechanism of action of MSG on liver and kidney, and if this results affected by the addition of l -Arginine or vitamin D to it. Animals divided into; Control, MSG treated, MSG + vitamin D treated, MSG + L-arginine treated group. Serum separated to determine liver and kidney function parameters. Kidneys and livers dissected out for histological examination and for assay of oxidative stress markers. Results MSG increased body weight and produced liver and kidney dysfunctions. The MSG-induced oxidative liver and kidney damage was proved. Vitamin D and l - Arginine have been shown to protect and restore the liver and the kidney capabilities in MSG models injury via inhibiting oxidative damage, vitamin D or l - Arginine suppresses the increased food intake and body weight gain induced by MSG. Conclusions due to injurious effect of MSG, it should be avoided especially in liver or kidney disorders, foods containing excess MSG can be fortified with vitamin D or l - Arginine to overcome its adverse effects. [ABSTRACT FROM AUTHOR]

Abstract Aim We aimed to assess the association between decreasing estimated glomerular filtration rate (eGFR) or abnormal albuminuria and the risk of certain cardiac conduction defects in patients with type 2 diabetes mellitus (T2DM). Methods We examined a hospital-based sample of 923 patients with T2DM discharged from our Division of Endocrinology over the years 2007–2014. Standard electrocardiograms (ECGs) were performed in all patients. eGFR was estimated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria was measured by an immuno-nephelometric method on morning spot urine samples. Results A total of 253 (27.4%) patients had some type of cardiac conduction defects on standard ECGs (defined as at least one heart block among first-degree atrioventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Prevalence of patients with eGFR CKD-EPI < 30 mL/min/1.73 m2, eGFR CKD-EPI 59–30 mL/min/1.73 m2 or abnormal albuminuria (i.e. urinary albumin-to-creatinine ratio ≥ 30 mg/g) were 7.0%, 29.4% and 41.3%, respectively. After adjustment for known cardiovascular risk factors, diabetes-related variables and potential confounders, there was a significant, graded association between decreasing eGFR values and risk of any cardiac conduction defects [adjusted-odds ratios of 2.05 (95% CI: 1.2–3.5), 2.85 (95% CI: 1.6–5.1) and 3.62 (95% CI: 1.6–8.1) for eGFR CKD-EPI 89–60, eGFR CKD-EPI 59–30 and eGFR CKD-EPI < 30 mL/min/1.73 m2, respectively]. Conversely, abnormal albuminuria was not independently associated with an increased risk of any conduction defects (adjusted-odds ratio: 1.09, 95% CI: 0.7–1.6). Conclusion Decreasing eGFR is independently associated with an increased risk of cardiac conduction defects in hospitalized patients with T2DM. [ABSTRACT FROM AUTHOR]

[Display omitted] • DFT study of biosensors for detecting kidney dysfunction biomarker: Uric Acid. • The adsorption of UA onto the metal centers of Ir, Mn, and Re complexes. • UA is chemisorbed by coordinating with the metal centers and ligands. • The adsorption enthalpies are computed to be highest for UA@L 2 Mn complex. • Findings demonstrate that transition metal complexes can act as candidates for biosensing. The potential of isatinic quinolyl Schiff bases transition metal complexes as electronic biosensors for detecting kidney dysfunction biomarker (uric acid) denoted as UA was investigated from first principles computations. The adsorption of UA onto the metal centres of Ir, Mn and Re complexes of (Z)-5-bromo-3-(quinolin-8-ylimino)indolin-2-one and (Z)-5-nitro-3-(quinolin-8-ylimino)indolin-2-one, designated as L 1 and L 2 were studied extensively. Uric acid has been considered an essential biomarker for oxidative stress, human arthritis, cardiomyopathy, and hyperuricemia. Biomarkers perform a pivotal role in the successful diagnosis and treatment of several diseases. Dispersion-corrected DFT calculations were performed, and the results evinced that the modelled transition metal complexes are promising candidates for UA detection. It was found that UA is chemisorbed by coordinating with the metal centers and ligands at a 3.873 Å distance on average with the adsorption enthalpies being −37.11 kcal/mol, –32.95 kcal/mol, and −21.44 for UA@L 2 Mn, UA@L2Re and UA@L 2 Ir complexes respectively. While the computed adsorption enthalpies for L 1 complexes were found to be −24.47 kcal/mol. –22.11 kcal/mol and –22.19 kcal/mol respectively for UA@L1Ir, UA@L1Mn and UA@L 1 Re complexes showing that the L 2 complexes acted as better sensors for UA. The sensitivity of UA by the metal complexes was influenced by the binding conformation of UA and the adsorption sites of the ligands. Overall, the metal complexes demonstrated high sensitivity with high values of work function up to 7.13 eV being recorded and hence making suitable substrates for work-function based sensors. Good stability and excellent conductivity even with the adsorption of UA was maintained and the desorption test-based on the transition state theory was considered and the complexes showed promising results for practical implementation as UA biosensors. [ABSTRACT FROM AUTHOR]

Pre-eclampsia and eclampsia cause unfortunate pregnancies, and currently affect 8% to 10% of pregnancies world-wide, causing ∼ 16% of maternal mortalities. The causations of pre-eclampsia and eclampsia (pre-eclampsia with cerebral seizures and convulsions) are unknown. Several causes have been proposed, including infections of the oral, urinary or genital tracts by certain bacterial or viral pathogens. Pre-eclampsia studies have compiled lists of cytokine signatures to diagnose pre-eclampsia, but these cytokine signatures can also be analyzed to deduce the causations of pre-eclampsia and eclampsia. These cytokines indicate that pre-eclampsia and eclampsia can be caused by certain Gram-negative bacteria or viral pathogen infections boosted by an almost asymptomatic strain of a hemolytic protozoan parasite, such as Trichomonas vaginalis. Such protozoan parasite interactions can provide iron to chronic and/or latent infections by certain Gram-negative bacteria or viral pathogens to reactivate them and increase their virulence to cause pre-eclampsia and/or eclampsia. In summary, the hypothesis of this paper is that one event reactivating pathogens to cause pre-eclampsia is the reappearance of nutrients including iron, provided by a second pathogen. The second pathogen is believed to be the hemolytic protozoan parasite T. vaginalis , a commonly transmitted pathogen which disrupts blood cells to obtain iron for itself and which can enable the reactivation of the first pathogen which was suppressed by iron deprivation. The released iron boosts pathogen infections, impairs important immune cells, and even a small amount of free iron can be repeatedly recycled by reduction–oxidation reactions to cause oxidative stress damage to major organs, including the kidneys. [ABSTRACT FROM AUTHOR]

The presence of metabolic syndrome (MS) in a patient allows him to be assigned to a group at high risk for atherosclerosis, cardiovascular events, coronary heart disease, and type 2 diabetes mellitus. In addition, MS negatively affects not only the heart and vessels, but also kidney function, which leads to chronic kidney disease (CKD). MS is pathogenetically associated with CKD and is an independent prognostic factor of the development of the latter, namely, the involvement of the kidney frequently determines prognosis and quality of life in these patients. The paper gives a modern view on the concept of MS and CKD and considers its main diagnostic criteria, etiology, and pathogenesis. The study of the relationships between MS and CKD may suggest that the high prevalence of kidney dysfunction in the general population is largely determined by metabolic nephropathies, including obesity-related nephropathy. The identification of risk factors and poor prognostic markers in this category of patients seems to be extremely important for the early diagnosis of the disease and their timely elimination is one of the main approaches to the comprehensive prevention of CKD in these patients.

Aim. To evaluate the prognostic impact of chronic kidney disease (CKD) during hospital stay in patients with ST-segment elevation myocardial infarction (STEMI) and to specify factors showing a negative impact of CKD. Subjects and methods. 954 patients with STEMI were examined. The diagnosis of CKD was verified in 338 (35.4%). In all the patients, glomerular filtration rate (GFR) was calculated using the CKD-EPI formula with regard to serum creatinine levels on admission and before discharge (on days 10—12). In the patients who had undergone X-ray contrast intervention, serum creatinine levels were additionally determined on days 2—3 of this procedure in order to identify contrast-induced nephropathy (CIN). Cardiovascular events were assessed in the hospital period. Results. Endovascular interventions into the coronary vessels were made much more rarely in the patients with CHD; but CIN cases were twice more commonly recorded. Nonfatal cardiovascular events were 1.5 times more frequently observed in the CKD patients in the hospital period. The odds of fatal outcomes in both the total sample of STEMI patients and in those with CKD increased by 3.5 and 3.1 times, respectively, in the over 60 age group and by 7.9 and 5.8 times in the presence of Killip Classes II—IV clinically relevant acute heart failure (AHF). In the total sample, the independent predictors for a fatal outcome were a decreased admission GFR less than 60 ml/min/1.73 m2, CIN, and Killip II—IV AHF. The hospital nonfatal complications were also associated with a decreased admission GFR less than 60 ml/min/1.73 m2. Conclusion. The independent predictor of a poor hospital period of STEMI, including fatal outcomes, was a decreased admission GFR less than 60 ml/min/1.73 m2; the presence of CKD was of no independent value.

Objective: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is more effective at estimating glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) equation, particularly in patients with mildly impaired renal function. Recent studies have demonstrated, using the Cockroft-Gault and MDRD formulas, a significant correlation between slow coronary flow (SCF) and normal to mildly impaired renal function. However, these studies had some limitations. The aim of the present study was to investigate the relationship between SCF and normal to mildly impaired renal function using the CKD-EPI equation. Methods: A total of 370 patients were included, 172 with normal coronary flow (NCF) and 198 with SCF. All participants had normal to mildly impaired renal function. Both the CKDEPI and MDRD formulas were used to calculated estimated glomerular filtration rate (eGFR), which was compared between groups. Results: No significant difference in mean values of eGFR was found between the NCF and SCF groups (CKD-EPI: 92.9+-14.7 vs 92.7+-14.2, p=0.72; MDRD: 89.5+-19.5 vs 88.2+-17.0, p=0.70, respectively). Among patients with eGFR(MDRD) ≥90 mL/ min/1.73 m2, mean eGFR levels were lower among patients with SCF (107.0+-12.7 vs 102.7+-10.0, p=0.02). Conclusion: No correlation was found between SCF and normal to mildly impaired renal function.

The article discusses galactosialidosis (GS), a rare autosomal recessive multisystemic congenital glycoprotein storage disease affecting multiple organs. Topics covered include the several types of GS, the pathology and histological changes of the disease, and therapeutic options for GS patients as well as therapy options that have been investigated in mouse models since the 1990s.

Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes.

Purpose: Corona Virus Disease 2019 (COVID-19) endangers the health and survival of the elderly. We tried to explore factors especially kidney function which affected mortality in elderly hypertensive patients with COVID-19., Methods: We conducted a retrospective research of 748 COVID-19 elderly patients (≥65 years old) at Zhejiang Hospital. This study compared demographic data, laboratory values, comorbidities, treatments, and clinical outcomes of hypertension and non-hypertension participants, and subgroup analysis of age and frailty was conducted in the hypertension population. Survival analysis was used to determine risk factors for death in elderly patients with COVID-19., Results: Our study revealed that the elderly hypertensive patients with COVID-19 had higher blood urea nitrogen (BUN), serum uric acid (UA), serum creatinine (Scr), lower estimated glomerular filtration rate (eGFR), higher incidence of severity, admission to intensive care unit (ICU) and death, and longer in-hospital stay than non-hypertensive patients, which also occurred in the very elderly hypertensive patients compared with younger hypertensive patients and frail hypertensive patients compared with no-frail hypertensive patients. In addition, the prevalence of acute kidney injury (AKI) was higher in the oldest old hypertensive patients and frail hypertensive patients. Multivariate survival analysis indicated that the independent risk factors for death from COVID-19 were age ≥80 years, heart failure, antiviral therapy, calcium channel blocker (CCB) therapy, mechanical ventilation, AKI, and eGFR<60 mL/min per 1.73 m 2 ., Conclusion: The results of the present study suggested that the elderly hypertensive patients with COVID-19 would have more serious kidney injury, more serious disease progression and higher mortality, which also occurred in very elderly and frailty subgroup. Kidney dysfunction was closely related to mortality in elderly patients with COVID-19., Competing Interests: The authors have no conflicts of interest to declare that are relevant to the content of this article., (© 2023 Xu et al.)

Background: The study aimed to estimate the attributable burden to kidney dysfunction as a metabolic risk factor in the North Africa and Middle East (NAME) region and its 21 countries in 1990-2019., Methods: The data used in this study were obtained from the Global Burden of Diseases (GBD) 2019 study, which provided estimated measures of deaths, disability-adjusted life years (DALYs), and other epidemiological indicators of burden. To provide a better insight into the differences in the level of social, cultural, and economic factors, the Socio-Demographic Index (SDI) was used., Results: In the NAME region in 2019, the number of deaths attributed to kidney dysfunction was 296 632 (95% uncertainty interval: 249 965-343 962), which was about 2.5 times higher than in the year 1990. Afghanistan, Egypt, and Saudi Arabia had the highest, and Kuwait, Turkey, and Iran (Islamic Republic of) had the lowest age-standardized rate of DALYs attributed to kidney dysfunction in the region in 2019. Kidney dysfunction was accounted as a risk factor for ischemic heart disease, chronic kidney disease, stroke, and peripheral artery disease with 150 471, 111 812, 34 068, and 281 attributable deaths, respectively, in 2019 in the region. In 2019, both low-SDI and high-SDI countries in the region experienced higher burdens associated with kidney dysfunction compared to other countries., Conclusions: Kidney dysfunction increases the risk of cardiovascular diseases burden and accounted for more deaths attributable to cardiovascular diseases than chronic kidney disease in the region in 2019. Hence, policymakers in the NAME region should prioritize kidney disease prevention and control, recognizing that neglecting its impact on other diseases is a key limitation in its management., Competing Interests: Rajaa M Al-Raddadi reports other support as a co-author on the hypertension paper, ‘Patient Journey for Hypertension and Dyslipidemia in Saudi Arabia: Highlighting the Evidence Gaps’ sponsored by Upjohn, a legacy Pfizer division, now merged with Mylan to be Viatris; all outside the submitted work. The other authors declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Chronic kidney disease (CKD) is emerging as one of the major causes of the increase in mortality rate and is expected to become 5th major cause by 2050. Many studies have shown that it is majorly related to various risk factors, and thus becoming one of the major health issues around the globe. Early detection of renal disease lowers the overall burden of disease by preventing individuals from developing kidney impairment. Therefore, diagnosis and prevention of CKD are becoming the major challenges, and in this situation, biosensors have emerged as one of the best possible solutions. Biosensors are becoming one of the preferred choices for various diseases diagnosis as they provide simpler, cost-effective and precise methods for onsite detection. In this review, we have tried to discuss the globally developed biosensors for the detection of CKD, focusing on their design, pattern, and applicability in real samples. Two major classifications of biosensors based on transduction systems, that is, optical and electrochemical, for kidney disease have been discussed in detail. Also, the major focus is given to clinical biomarkers such as albumin, creatinine, and others related to kidney dysfunction. Furthermore, the globally developed sensors for the detection of CKD are discussed in tabulated form comparing their analytical performance, response time, specificity as well as performance in biological fluids., (© 2023 Wiley Periodicals LLC.)

Background: It is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied., Aim: To evaluate the role of the erector spine index (ESI) calculated based on abdominal CT imaging in the progression of acute-on-chronic liver failure related to the hepatitis B virus (HBV-ACLF)., Methods: We performed a retrospective study of 118 HBV-ACLF patients and calculated the ESI (the total erector spine area normalized for height 2 in meters) for each patient through abdominal CT. The findings were analyzed regarding the progression of HBV-ACLF and the ESI at baseline, including mortality and the development of complications., Results: The ESI level was associated with mortality and the development of complications. During the 90-day follow-up period, patients with a low ESI (<12.05 cm 2 /m 2 ) had higher mortality than those with a high ESI (≥ 12.05 cm 2 /m 2 ) (51.7% vs. 26.7%), and the cumulative survival rates were 71.0%±4.6 and 85.8%±3.9, respectively (log-rank P = 0.003). The hazard ratios (HRs) calculated using univariable and multivariable analyses were 2.23(95% confidence interval (CI): 1.25-4.21, P = 0.005) and 2.52 (95% CI: 1.34-9.24, P = 0.011), respectively. Patients with a low ESI (<12.05 cm 2 /m 2 ) had higher incidences of kidney dysfunction (43.5% vs. 23.2%, P = 0.029; log-rank P = 0.017) and hepatic encephalopathy (39.6% vs. 14.0%, P = 0.003; log-rank P = 0.010) than those with a high ESI. A low ESI was an independent risk factor for kidney dysfunction (adjusted HR = 1.36, 95% CI: 1.05-2.93, P = 0.043) and the development of hepatic encephalopathy (adjusted HR = 2.26; 95% CI: 2.05-3.13, P = 0.036). In addition, the presence of hepatic encephalopathy (the odds ratio (OR) = 2.26, 95% CI: 2.05-3.18, P = 0.006), spontaneous bacterial peritonitis (OR = 3.95, 95% CI: 1.01-5.46, P = 0.037), and kidney dysfunction (OR = 4.47, 95% CI: 1.02-9.64, P = 0.032) was independently associated with a low ESI in patients., Conclusion: A low ESI is an independent risk factor for mortality in patients with HBV-ACLF, as well as the development of kidney dysfunction and hepatic encephalopathy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Alport syndrome (AS) is caused by mutations in type IV collagen genes that typically target and compromise the integrity of basement membranes in kidney, ocular, and sensorineural cochlear tissues. Type IV and V collagens are also integral components of arterial walls, and whereas collagenopathies including AS are implicated in aortic disease, the incidence of aortic aneurysm in AS is unknown probably because of underreporting. Consequently, AS is not presently considered an independent risk factor for aortic aneurysm and more detailed case studies including histological evidence of basement membrane abnormalities are needed to determine such a possible linkage., Case Presentation: Here, we present unique histopathological findings of an ascending aortic aneurysm collected at the time of surgery from an AS patient wherein hypertension was the only other known risk factor., Conclusions: The studies reveal classical histological features of aortic aneurysm, including atheroma, lymphocytic infiltration, elastin disruption, and myxoid degeneration with probable AS association., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Several D-amino acids have been shown to be protective against kidney injury in mice. Risperidone, a currently used atypical antipsychotic agent for schizophrenia, is also known to inhibit the activity of D-amino acid oxidase, which degrades certain D-amino acids. Based on the hypothesis that risperidone would prevent kidney disease progression, this study investigated the association between risperidone use and kidney function decline in patients with schizophrenia., Methods: This retrospective cohort study included patients who were diagnosed with schizophrenia and had data available from two or more serum creatinine measurements between April 1, 2010, and March 31, 2020. Patients who used risperidone for at least 30 days were included in the risperidone group, whereas those who had no record of risperidone use were included in the control group. Cox regression models were used to evaluate the risk for 40% decline in estimated glomerular filtration rate (eGFR) in patients treated with risperidone compared to that in the control group., Findings: Overall, 212 patients used risperidone and 1468 patients had no record of risperidone use. The mean age was 55 years, 759 (45%) of the patients were male, and the mean eGFR at baseline was 88 mL/min/1.73 m 2 . The mean age in the risperidone group was less than that in the control group (52 vs 56 years); other baseline characteristics were comparable between the two groups. During a mean follow-up of 1.6 years, 267 patients (16%) had a 40% eGFR decline. The incidence rate of 40% eGFR decline was lower in the risperidone group than in the control group (60 vs 104 per 1000 person-years). After adjustment for baseline age, sex, and eGFR, risperidone use was associated with a decreased risk for 40% eGFR decline (hazard ratio = 0.54; 95% CI, 0.33-0.87; P = 0.01)., Implications: Risperidone use may be associated with decreased risk for kidney function decline in patients with schizophrenia. Further studies are warranted to validate these findings., Competing Interests: Declaration of Competing Interest M.M. is the founder and chief executive officer of Kagami Inc, a startup company working on chiral amino acids analysis and research for medical application. The authors have indicated that they have no other conflicts of interest with regard to the content of this article., (Copyright © 2023. Published by Elsevier Inc.)

The purpose of the present research was to study the comparative influence of lisinopril and losartan on the parameters of cardiac hemodynamics and kidney function state in CHF (Congestive Heart Failure) patients with NYHA Functional Class (FC) I-III. Material and Methods: The study included 92 CHF patients between the ages of 41 and 75 (mean age 66.3±9.8 yrs) with FCI-III of ischemic genesis. The patients were divided into two groups. Group I consisted of 47 CHF patients with FCI-III who had been receiving losartan for 6 months in addition to standard therapy. Group II consisted of 45 CHF patients with FCI-III who had been receiving lisinopril for 6 months in addition to standard therapy. The dose of losartan was 50–100 mg/day, and lisinopril, 5–10 mg/day. The control group included 20 healthy volunteers. NYHA FC was determined by the 6-minute walk test (6MWT) and the Russian scale of evaluation of the clinical condition of the patients. All patients underwent clinical examination, ECG, and echocardiography. Estimated creatinine clearance rate (eCCr) was calculated using the Cockcroft-Gault formula; estimated glomerular filtration rate (eGFR) was calculated using the MDRD (Modification of Diet in Renal Disease) formula. Results: The results obtained show a clear association between maladaptive LV remodeling and kidney dysfunction at CHF. Our analysis revealed the significant direct correlation between EF and eGFR, as well as between 6MWT and eGFR. The 6-month therapy of CHF patients with NYHA FCI-III based on a combination of standard therapy with ACEi/ARB has resulted in a significant improvement in the cardiac hemodynamic, LV myocardial contractility, and renal function, with a more significant effect in the patients treated with losartan.

Maternal undernutrition (MUN) during pregnancy leads to low-birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein-restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 mo of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy, and a worse survival rate than LBW females. In contrast, both sexes experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method). Isolated aortas from both LBW sexes demonstrated reduced vasodilation in response to ACh, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and immunofluorescence analysis revealed a significant increase of circulating reactive oxygen species and NADPH oxidase type 4 (NOX4) expression in both LBW sexes, although these increases were more pronounced in males. Although more effective in males, chronic tempol treatment did improve all observed pathologies in both sexes of LBW mice. Chronic NOX4 inhibition with GKT137831 was more effective than tempol in preventing pathologies in LBW males. In conclusion, despite some minor differences, LBW female and male adults have a reduced nephron endowment comparable with progressive renal and vascular dysfunction, which is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults. [ABSTRACT FROM AUTHOR]

Radiolabeled nanoprobes for positron emission tomography (PET) imaging has received special attention over the past decade, allowing for sensitive, non-invasive, and quantitative detection of different diseases. The rapidly renal clearable nanomaterials normally suffer from a low accumulation in the tumor through the enhanced permeability and retention (EPR) effect due to the rapidly reduced concentration in the blood circulation after renal clearance. It is highly important to design radiolabeled nanomaterials which can meet the balance between the rapid renal clearance and strong EPR effect within a suitable timescale. Herein, renal clearable polyoxometalate (POM) clusters of ultra-small size (∼1 nm in diameter) were readily radiolabeled with the oxophilic 89 Zr to obtain 89 Zr-POM clusters, which may allow for efficient staging of kidney dysfunction in a murine model of unilateral ureteral obstruction (UUO). Furthermore, the as-synthesized clusters can accumulate in the tumor through EPR effect and self-assemble into larger nanostructures in the acidic tumor microenvironment for enhanced tumor accumulation, offering an excellent balance between renal clearance and EPR effect. [ABSTRACT FROM AUTHOR]

Background. Considering the fact that subjects with dysglycemia, dyslipidemia or high blood pressure are at high risk for chronic kidney disease (CKD), long-term adherence to the Dietary Approaches to Stop Hypertension (DASH)-style diet may contribute to the prevention of CKD. This study, examined the association between adherence to the low-sodium DASHstyle diet and incident CKD among high-risk adults over 3 years of follow-up. Methods. In this prospective cohort study (followed up for 3 years, 2012-15), we selected 1100 subjects with dysglycemia, 2715 with dyslipidemia and 2089 with high blood pressure, all of whom were free of CKD at baseline (2009-11) in a subgroup of the Tehran Lipid and Glucose Study. The low-sodium DASH-style diet was designed based on eight foods and nutrients using a food frequency questionnaire. Estimated glomerular filtration rate (eGFR) was calculated and CKD was defined as eGFR <60mL/min/1.73m². Results. After 3 years of follow-up, among subjects with dysglycemia, dyslipidemia or high blood pressure, the rate of incident CKD was ~16%. In multivariable-adjusted analyses for participants in the highest compared with the lowest quartile of the low-sodium DASH-style diet score, the odds ratio was 0.58 [95% confidence interval (CI) 0.36-0.92] for subjects with dysglycemia, 0.64 (95% CI 0.48-0.87) for subjects with dyslipidemia and 0.62 (95% CI 0.44-0.87) for subjects with high blood pressure. Conclusions. Higher adherence to the low-sodium DASH-style diet might be associated with a lower risk of incident CKD among high-risk adults, highlighting the importance of adherence to the low-sodium DASH-style diet in substantially reducing both the occurrence of CKD and the burden imposed by it in the future. [ABSTRACT FROM AUTHOR]

Awareness of the uncommon associated clinical manifestations of immunoglobulin G4 (IgG4)-related kidney disease is essential for the early diagnosis and effective treatment of patients. To the best of our knowledge, there have been few reports of patients with IgG4-related kidney disease associated with autoimmune hemolytic anemia. We here report a rare case of IgG4-related kidney disease associated with autoimmune hemolytic anemia. A 70-year-old man with kidney dysfunction and severe anemia had been diagnosed with chronic kidney disease and treated without any improvement. On admission, he had a high serum creatinine level, low hemoglobin level, positive direct Coombs test, and mild proteinuria. Serum IgG and IgG4 were elevated. Kidney biopsy showed marked infiltration of IgG4-positive plasma cells and storiform fibrosis in the interstitial compartment, which confirmed the diagnosis of IgG4-related kidney disease. Corticosteroid therapy was initiated, and subsequently, the kidney dysfunction and anemia dramatically improved. [ABSTRACT FROM AUTHOR]

Background:/Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS), however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1) disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2) urinary markers of renal dysfunction. Methods: Fourteen individuals (7 males and 7 females) with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR) has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR) in a mean follow-up period of 4 years (3-7). Results: 42 proteins were significantly over- or under-represented in BBS patients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN) (r2=0.28; p<0.05), CD44 antigen (r2 =0.35; p<0.03) and lysosomal alfa glucosidase ( r20.27; p<0.05) abundance with the eGFR. In addition, u-FN (r2 =0.2389; p<0.05) was significantly correlated with ΔeGFR. Conclusion: The present study demonstrates that urine proteome of BBS patients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis. [ABSTRACT FROM AUTHOR]

Background: Ceftriaxone (CTRX) is a known cause of biliary pseudolithiasis (BPL) mainly in children. Biliary elimination of CTRX increases in patients with renal dysfunction. However, the influence of renal dysfunction on the incidence of CTRX-associated BPL has not been well investigated. The aim of this study was to investigate the cumulative incidence of CTRX-associated BPL in adults and to assess if renal dysfunction is a risk factor.Methods: We retrospectively analyzed the medical records of 478 patients treated with CTRX to assess the incidence and risk factors of CTRX-associated BPL. We examined age, sex, body weight, dosage, and duration of CTRX therapy, and the concentrations of serum creatinine, estimated glomerular filtration rate (eGFR), albumin, and serum calcium in all the patients. The cumulative incidence of BPL was calculated using a competing risk model. The multivariate analysis of each variable for the development of BPL was assessed by a Cox proportional hazards model.Results: A total of 362 patients (75.7%) had renal dysfunction (eGFR: < 60 mL/min). The cumulative incidence of BPL in patients with renal dysfunction was significantly higher than that in patients with normal kidney function (4.1 vs. 0.6%, p = 0.017). Renal dysfunction (Hazard ratio (HR) 8.14, 95% CI 1.05-63.0, p = 0.045) and female sex (HR 5.35, 95% CI 1.17-24.5, p = 0.031) were independent risk factors of CTRX-associated BPL, which was confirmed using multivariate analysis (renal dysfunction: HR 7.93, 95% CI 1.04-60.5, p = 0.046) (female sex HR 4.65, 95% CI 1.03-21.1, p = 0.046).Conclusions: Renal dysfunction is an independent risk factor of CTRX-associated BPL in adults. [ABSTRACT FROM AUTHOR]