Effectiveness and safety of nirmatrelvir-ritonavir in kidney transplant recipients with severe kidney dysfunction infected with COVID-19.

Transplant patients face an elevated risk of coronavirus disease 2019 (COVID-19) morbidity and mortality and commonly encounter renal dysfunction. Nirmatrelvir is primarily excreted through the kidneys. The dosage of nirmatrelvir/ritonavir (NR) needs to be adjusted according to the degree of renal function impairment. Nevertheless, NR is not recommended for patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min) due to a dearth of associated research. In this study, we focus on kidney transplant patients and document and analyze the experiences of using NR in individuals with severe kidney dysfunction. This was a retrospective multicenter study that included transplant recipients hospitalized for COVID-19 in five major tertiary hospitals in China from December 2022 to June 2023. The outcomes consisted of the disease progression rate by day 28, individual disease progression events, safety outcomes, information on adverse events (AEs), and the blood drug concentrations of immunosuppressants. Data were presented with descriptive statistics. All analyses were performed using SPSS version 22. In total, 40 patients were included in the analysis. Considering the potential interaction between drugs, all patients temporarily discontinued their immunosuppressants during the NR treatment. None of the 32 moderate patients experienced disease progression. However, among the eight patients with critical COVID-19, unfortunately, two of them died. During the medication period, four patients experienced a total of six AEs associated with NR. None of them experienced AEs with a maximum grade of ≥3. Blood drug concentrations of immunosuppressants were monitored in 22 of 40 patients, and the blood drug concentrations of immunosuppressants did not show a significant increase, but some patients experienced lower blood drug concentrations. Our findings supported the use of NR therapy for the treatment of COVID-19 in transplant patients with severe renal insufficiency. A modified dose of NR was well-tolerated.

Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.

INTRODUCTION: Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride. OBJECTIVE: To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water. METHODS: A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs. RESULTS: The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions. CONCLUSION: The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

The Association between Urinary Sodium-Potassium Ratio, Kidney Function, and Blood Pressure in a Cohort from the General Population.

INTRODUCTION: Subclinical kidney dysfunction may contribute to salt-sensitive hypertension. We assessed the association between the urinary sodium-potassium ratio (Na/K ratio) and blood pressure (BP) in a general population cohort without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension. We investigated whether any such association was mediated by the kidney function markers measured glomerular filtration rate (mGFR), urinary albumin-creatinine ratio (ACR), and urinary epidermal growth factor-creatinine ratio (EGF-Cr). METHODS: The Tromsø Study is a population-based study of inhabitants of the municipality of Tromsø, Northern Norway. Participants aged 50-62 years, without diabetes, chronic kidney disease, or cardiovascular disease, were invited to the substudy Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6; 2007-09). For the present study, we excluded participants reporting the use of 1 or more antihypertensive agents, leaving 1,311 RENIS-T6 participants for a cross-sectional analysis. We measured office BP, 24-h ambulatory blood pressure (ABP), and mGFR using iohexol clearance. Na/K ratio, ACR, and EGF-Cr were measured in morning urine samples. RESULTS: Urinary Na/K ratio was significantly associated with systolic office BP and ABP independently of cardiovascular risk factors and kidney function markers. A one-standard deviation unit increase in the Na/K ratio was associated with increased systolic ABP by 1.0 (0.3-1.6) mm Hg. Urinary Na/K ratio showed a stronger association with office BP than ABP. EGF-Cr, ACR, and mGFR did not mediate the relationship between urinary Na/K ratio and systolic BP. CONCLUSIONS: In a representative sample of the middle-aged North-European population without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension, there was a consistent association between urinary Na/K ratio and BP. The association with BP was not mediated through kidney function measures, suggesting a relationship between a diet with high sodium and low potassium and higher BP regardless of kidney function.

The management of non-culprit vessel(s) in patients with unstable angina/non-ST elevation myocardial infarction and chronic kidney dysfunction.

BACKGROUND AND AIMS: The clinical effects of multivessel interventions in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non-culprit lession(s) among this cohort. METHODS: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48-month overall mortality between those undergoing multivessel PCI (MV-PCI) through a single-procedure or staged-procedure approach and culprit vessel-only PCI (CV-PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast-induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. RESULTS: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV-PCI had reduced all-cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48-0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 ) could not benefit from MV-PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (P interaction < 0.01; HR = 0.95, 95% CI = 0.65-1.45). Although the staged-procedure approach (N = 157) failed to bring additional survival benefits compared to single-procedure MV-PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV-PCI and CV-PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94-2.73). CONCLUSION: Among patients with UA/NSTEMI and non-diabetic CKD and an eGFR > 30 mL/min/1.73 m2 , MV-PCI was associated with a reduced risk of long-term death but did not increase the incidence of CIN during the management of MVD compared to CV-PCI. And staged procedures might be a preferable option over single-procedure MV-PCI.

Dotinurad restores exacerbated kidney dysfunction in hyperuricemic patients with chronic kidney disease.

BACKGROUND: In this study, we aimed to clarify the beneficial effects of urate-lowering treatment with the novel agent dotinurad on renal function in patients with chronic kidney disease (CKD) and hyperuricemia (HUA). METHODS: Thirty-five patients with CKD (mean age 65.4 ± 14.8 years, 23 men) diagnosed with HUA were recruited. Changes in eGFR before and after dotinurad administration were assessed. Patients first underwent a 3-month observation period and then 3 months treatment with dotinurad. RESULTS: During the observation period, mean eGFR (mL/min/1.73 m2) declined significantly. The baseline eGFR was 31.8 ± 16.4 and the serum urate level (sUA, mg/dL) was 8.1 ± 1.7. During the treatment period, eGFR recovered to 36.5 ± 17.5 and sUA decreased to 6.7 ± 1.0. The increase in eGFR after dotinurad administration was correlated with a decrease in sUA (R = 0.375, p = 0.0263). CONCLUSION: Dotinurad administration to patients with CKD and HUA appears to be beneficial in restoring kidney function. Dotinurad may represent a potential medication for the prevention of kidney function decline caused by HUA.

A systematic evaluation of population pharmacokinetic models for polymyxin B in patients with liver and/or kidney dysfunction.

Polymyxin B (PMB) is considered a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections. Model-informed precision dosing with population pharmacokinetics (PopPK) models could help to individualize PMB dosing regimens and improve therapy. However, the external prediction ability of the established PopPK models has not been fully elaborated. This study aimed to systemically evaluate eleven PMB PopPK models from ten published literature based on a new independent population, which was divided into four different populations, patients with liver dysfunction, kidney dysfunction, liver and kidney dysfunction, and normal liver and kidney function. The whole data set consisted of 146 patients with 391 PMB concentrations. The prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. In the overall evaluation process, none of the models exhibited satisfactory predictive ability in both prediction- and simulation-based diagnostic simultaneously. However, the evaluation of the models in the subgroup of patients with normal liver and kidney function revealed improved predictive performance compared to those with liver and/or kidney dysfunction. Bayesian forecasting demonstrated enhanced predictability with the incorporation of two to three prior observations. The external evaluation highlighted a lack of consistency between the prediction results of published models and the external validation dataset. Nonetheless, Bayesian forecasting holds promise in improving the predictive performance of the models, and feedback from therapeutic drug monitoring is crucial in optimizing individual dosing regimens.

Platelet-Rich Plasma (PRP) Mitigates Kidney Dysfunction in Alloxan-Induced Diabetic Mice via Modulation of Renal Iron Regulatory Genes.

Kidney dysfunction is a prevalent complication of diabetes mellitus, contributing significantly to diabetes-related morbidity and mortality. We aim to explore whether platelet-rich plasma administration can modulate iron regulation mechanism within the kidney, thereby mitigating renal dysfunction associated with diabetes. Albino mice with an average body weight of 20 ± 5 g were randomly divided into five groups (N = 50; n = 10): Control Group, PRP Group, diabetic group (DG), treated group A (TA), and treated group B (TB). A single intraperitoneal dose of alloxan (160 mg/kg of body weight) was administered to mice in the DG and in both treated groups. Upon confirmation of diabetes, the DG was left untreated, while PRP treatment (0.5 ml/kg of body weight) was administered to the TA and TB groups for two and four weeks, respectively. Histological examinations of kidney tissues revealed notable signs of damage in DG, which were subsequently improved upon PRP treatment. Likewise, PRP treatment restored the changes in liver enzymes, oxidative stress biomarkers and serum electrolytes in both treated groups. Furthermore, there was an observed upregulation of iron regulatory genes, such as Renin, Epo, Hepc, Kim1, and Hfe, in the DG, accompanied by a downregulation of Tfr1 and Fpn; however, Dmt1 and Dcytb1 expression remained unaltered. Treatment with PRP restored the expression of iron regulatory genes in both treated groups. This study concluded that PRP treatment effectively restored the renal histochemistry and the expression of renal iron regulatory genes in an alloxan-induced diabetic mice model.

Clinical Impact of Malnutrition According to the Global Leadership Initiative on Malnutrition Criteria Combined With Kidney Dysfunction to Determine Mortality in Inpatients.

OBJECTIVE: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). METHODS: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and the incidence of all-cause mortality was evaluated using a multivariate Cox proportional hazards model. Malnutrition was defined as at least one phenotype (weight loss, low body mass index, or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). RESULTS: Multivariate Cox proportional hazards model showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. CONCLUSION: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

Cyclic Nitroxide 4-Methoxy-Tempo May Decrease Serum Amyloid A-Mediated Renal Fibrosis and Reorganise Collagen Networks in Aortic Plaque.

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3',5'-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ-iNOS-p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes.

Elevated Serum KIM-1 in Sepsis Correlates with Kidney Dysfunction and the Severity of Multi-Organ Critical Illness.

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, p < 0.001) and thrombocytopenia (<150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.

Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.

Typical hemolytic uremic syndrome (HUS) can occur as a severe systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli. Its pathology can be induced by Stx types, resulting in toxin-mediated damage to renal barriers, inflammation, and the development of acute kidney injury (AKI). Two sphingosine kinase (SphK) isozymes, SphK1 and SphK2, have been shown to be involved in barrier maintenance and renal inflammatory diseases. Therefore, we sought to determine their role in the pathogenesis of HUS. Experimental HUS was induced by the repeated administration of Stx2 in wild-type (WT) and SphK1 (SphK1-/-) or SphK2 (SphK2-/-) null mutant mice. Disease severity was evaluated by assessing clinical symptoms, renal injury and dysfunction, inflammatory status and sphingolipid levels on day 5 of HUS development. Renal inflammation and injury were found to be attenuated in the SphK2-/- mice, but exacerbated in the SphK1-/- mice compared to the WT mice. The divergent outcome appeared to be associated with oppositely altered sphingolipid levels. This study represents the first description of the distinct roles of SphK1-/- and SphK2-/- in the pathogenesis of HUS. The identification of sphingolipid metabolism as a potential target for HUS therapy represents a significant advance in the field of HUS research.

Prevalence of Kidney Dysfunction and Associated Risk Factors in a Southwestern City in Nigeria: A Cross-Sectional Study.

BACKGROUND: The burden of chronic kidney disease (CKD) is huge, especially in countries such as Nigeria where majority of patients succumb to the disease early due to inability to afford care. Early diagnosis through regular screening of at-risk population is pivotal to stemming the scourge of the disease. AIM: To determine the prevalence of kidney dysfunction and associated risk factors in a community screening program. METHODS: This cross-sectional study assessed kidney dysfunction and associated risk factors among adults in Ondo City, Nigeria. Information about socio-demographic characteristics and some risk factors for kidney dysfunction was sought. Blood pressure, weight and height were measured. Blood samples were collected for random blood glucose check and serum creatinine while urine sample was collected for urinalysis. Kidney dysfunction was defined by estimated glomerular filtration rate (eGFR) below 60mls/min/1.73m2. Prevalence of kidney dysfunction and associated factors were determined. P value<0.05 was taken as significant. RESULTS: There were 410 participants with a mean age of 58.96±13.78 years. Majority (75.1%) were female. One hundred and forty-seven (35.9%) participants had kidney dysfunction. Identified risk factors for kidney dysfunction were hypertension (72.7%), diabetes mellitus (18.0%), alcohol intake (13.2%), tobacco smoking (2%), analgesic use (82.7%), use of herbal preparations (81.7%), proteinuria (6.1%), overweight (27.8%), generalized obesity (28.5%), and central obesity (33.9%). Significant factors associated with kidney dysfunction were older age (p=<0.001), lower level of education (p=<0.001), and being hypertensive (p=0.019). On binary logistic regression, older age (AOR: 9.14; CI: 3.68-22.7; p=<0.001) was the only significant factor associated with kidney dysfunction. CONCLUSION: The prevalence of kidney dysfunction and that of associated risk factors were relatively high in the screened population. Regular assessment of kidney function should be done in those with higher risk of kidney dysfunction, especially older patients with hypertension.

CONTEXTE: Le fardeau de la maladie rénale chronique (MRC) est énorme, en particulier dans des pays tels que le Nigeria, où la majorité des patients succombent à la maladie tôt en raison de l'incapacité à se permettre des soins. Le diagnostic précoce par le dépistage régulier des populations à risque est crucial pour endiguer le fléau de la maladie. OBJECTIF: Déterminer la prévalence de la dysfonction rénale et des facteurs de risque associés dans le cadre d'un programme de dépistage communautaire. MÉTHODES: Cette étude transversale a évalué la dysfonction rénale et les facteurs de risque associés chez des adultes à Ondo City, au Nigéria. Des informations sur les caractéristiques sociodémographiques et certains facteurs de risque de dysfonction rénale ont été recueillies. La pression artérielle, le poids et la taille ont été mesurés. Un échantillon de sang a été prélevé pour vérifier la glycémie aléatoire et la créatinine sérique, tandis qu'un échantillon d'urine a été collecté pour une analyse d'urine. La dysfonction rénale a été définie par un taux de filtration glomérulaire estimé (TFGe) inférieur à 60 ml/min/1,73 m2. La prévalence de la dysfonction rénale et des facteurs associés a été déterminée. Une valeur de p<0,05 a été considérée comme significative. RÉSULTATS: Il y avait 410 participants avec un âge moyen de 58,96 ± 13,78 ans. La majorité (75,1 %) étaient des femmes. Cent quarante-sept (35,9 %) participants avaient une dysfonction rénale. Les facteurs de risque identifiés pour la dysfonction rénale étaient l'hypertension (72,7 %), le diabète sucré (18,0 %), la consommation d'alcool (13,2 %), le tabagisme (2 %), l'utilisation d'analgésiques (82,7 %), l'utilisation d'herbes médicinales (81,7 %), la protéinurie (6,1 %), le surpoids (27,8 %), l'obésité générale (28,5 %) et l'obésité centrale (33,9 %). Les facteurs significativement associés à la dysfonction rénale étaient l'âge plus avancé (p=<0,001), un niveau d'éducation plus bas (p=<0,001) et l'hypertension (p=0,019). Dans la régression logistique binaire, le seul facteur significatif associé à la dysfonction rénale était l'âge plus avancé (RA : 9,14 ; IC : 3,68-22,7 ; p=<0,001). CONCLUSION: La prévalence de la dysfonction rénale et des facteurs de risque associés était relativement élevée dans la population examinée. Une évaluation régulière de la fonction rénale devrait être réalisée chez ceux présentant un risque élevé de dysfonction rénale, en particulier chez les patients plus âgés souffrant d'hypertension. MOTS-CLÉS: Filtration glomérulaire réduite; Dysfonction rénale; Facteur de risque ; Dépistage communautaire.

123I-MIBG imaging in heart failure: impact of comorbidities on cardiac sympathetic innervation.

PURPOSE: Heart failure (HF) is a primary cause of morbidity and mortality worldwide, with significant impact on life quality and extensive healthcare costs. Assessment of myocardial sympathetic innervation function plays a central role in prognosis assessment in HF patients. The aim of this review is to summarize the most recent evidence regarding the clinical applications of iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging in patients with HF and related comorbidities. METHODS: A comprehensive literature search was conducted on PubMed and Web of Science databases. Articles describing the impact of 123I-MIBG imaging on HF and related comorbidities were considered eligible for the review. RESULTS: We collected several data reporting that 123I-MIBG imaging is a safe and non-invasive tool to evaluate dysfunction of cardiac sympathetic neuronal function and to assess risk stratification in HF patients. HF is frequently associated with comorbidities that may affect cardiac adrenergic innervation. Furthermore, HF is frequently associated with comorbidities and chronic conditions, such as diabetes, obesity, kidney disease and others, that may affect cardiac adrenergic innervation. CONCLUSION: Comorbidities and chronic conditions lead to more severe impairment of sympathetic nervous system in patients with HF, with a negative impact on disease progression and outcome. Cardiac imaging with 123I-MIBG can be a useful tool to reduce morbidity and prevent adverse events in HF patients.

Design and development of opto-electrochemical biosensing devices for diagnosing chronic kidney disease.

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.

Sarcopenia and mild kidney dysfunction and risk of all-cause and cause-specific mortality in older adults.

BACKGROUND: Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain. METHODS: This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as eGFR between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis. RESULTS: During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.12 to 1.19; HR: 1.29, 95% CI: 1.20 to 1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR: 1.61, 95% CI: 1.52 to 1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI: 0.05 to 0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases, and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function. CONCLUSIONS: The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation.

Predisposing Factors and Outcome of Acute Kidney Injury After Blunt Trauma: A 10-Year Study.

INTRODUCTION: Acute kidney injury (AKI) indicates an impairment of the renal function following blunt trauma. It is multifactorial and associated with an increased risk of morbidity and mortality. The incidence and risk factors of AKI in young patients with trauma are not well-described. This study aimed to evaluate the incidence, clinical characteristics, and outcomes of post-traumatic AKI. We hypothesized that AKI is associated with worse outcomes in patients with trauma. METHODS: This was a retrospective study of all adult trauma patients admitted to a level 1 trauma center between 2011 and 2021. AKI was diagnosed on the basis of the Kidney Disease Improving Global Outcomes criteria. Data were collected and analyzed for patients with and without AKI using chi-square test and Student's t-test. Multivariate logistic regression analysis and Kaplan-Meier curves were performed. RESULTS: A total of 17,341 patients with trauma were evaluated, of which 140 (0.8%) developed AKI. Patients with AKI were older (40 ± 20 versus 32 ± 16 y), had more comorbidities, and had a higher injury severity score (ISS) and in-hospital mortality (65% versus 3.2%) than non-AKI patients. Direct trauma to the kidney was reported in only nine (6.4%) patients in the AKI group. Among patients with AKI, nonsurvivors had a higher ISS and were more likely to have hypotension, elevated serum lactate, positive troponin, and a lower platelet-to-lymphocyte ratio than survivors. Multiple logistic regression analyses showed that age, ISS, acute respiratory distress syndrome, blood transfusion, diabetes mellitus, onadmission Glasgow coma scale score, and shock index were predictors of AKI in trauma patients, whereas ISS (odds ratio (OR) = 1.05; 95% confidence interval (CI):1.003-1.100; P = 0.03), serum lactate level (OR = 1.25; 95% CI: 1.019-1.533; P = 0.03), and hypotension (OR = 3.22; 95% CI: 1.044-9.945; P = 0.04) were independent predictors of mortality in patients with posttraumatic AKI. Kaplan-Meier survival analysis showed significant differences in mortality among the three stages of AKI (P = 0.03), with the worst outcome in stage III. However, after adjusting for age, hypotension, and ISS, the Cox regression model showed that only stage I had better survival than stages II and III, whereas no survival difference was noted between stages II and III (P = 0.06). CONCLUSIONS: AKI in young trauma patients is uncommon and associated with a prolonged hospital course and higher mortality. This study identified factors that independently predicted the development of AKI and its outcomes in patients with trauma. However, further prospective and multicenter studies are required to minimize the incidence and complications of posttraumatic AKI.

A novel imaging index for predicting adverse progression in acute-on-chronic liver failure related to hepatitis B virus: the low erector spine index.

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 height2 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 cm2/m2) had higher mortality than those with a high ESI (≥ 12.05 cm2/m2) (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 cm2/m2) 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.

Association between PNPLA3 rs738409 variant and 5-year estimated glomerular filtration rate decline in post-menopausal women with type 2 diabetes: A panel-data analysis.

BACKGROUND AND AIMS: Little is known about the relationship between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 variant and decline in estimated glomerular filtration rate (eGFR) over time in individuals with type 2 diabetes (T2DM). METHODS AND RESULTS: We enrolled an outpatient sample of 46 post-menopausal women with T2DM and preserved kidney function at baseline (in 2017), who were followed through 2022. eGFR and albuminuria were measured annually. Genotyping of PNPLA3 rs738409 was performed by TaqMan-based RT-PCR system. Overall, 25 (54.3%) patients had PNPLA3 rs738409 CC (homozygous wild-type) genotype and 21 had CG or GG genotypes. During the 5-year follow-up, the presence of rs738409 CG/GG genotypes was associated with faster eGFR decline (coefficient: -6.55; 95% CI -11.0 to -2.08; p = 0.004 by random-effects panel data analysis). This association remained significant even after adjustment for 5-year changes in age, hemoglobin A1c, hypertension status, albuminuria and use of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists. CONCLUSIONS: This pilot study suggests that in post-menopausal T2DM women with preserved kidney function at baseline, the risk allele (G) of PNPLA3 rs738409 is associated with a faster eGFR decline during a 5-year follow-up, independent of annual changes in common renal risk factors and use of certain glucose-lowering medications.

Lower range of serum uric acid level increases risk of rapid decline of kidney function in young and middle-aged adults: the Yuport Medical Checkup Center Study.

BACKGROUND: The effect of low serum uric acid (sUA) levels on kidney function is unclear. This study aimed to clarify the relationship between low sUA levels and the rapid decline in kidney function. METHODS: We examined the relationship between sUA levels and kidney function decline in health check-up examinees. A total of 10,547 participants were enrolled using data from the Yuport Medical Checkup Center Study between 1998 and 2002 for baseline and data from 2002 to 2006 as the follow-up period in Japan. According to sUA level (mg/dL), we classified the participants into the following six groups: (1) 2.0-2.9 (n = 247), (2) 3.0-3.9 (n = 1457), (3) 4.0-4.9 (n = 2883), (4) 5.0-5.9 (n = 2899), (5) 6.0-6.9 (n = 2010), and (6) 7.0-7.9 (n = 1,051). The relationship between sUA level and rapid decline in estimated glomerular filtration rate (ΔeGFR ≥ 3 mL/min/1.73 m2/year) was examined using a logistic regression model. RESULTS: During study period (5.4 ± 1.6 years), the incidence of rapid eGFR decline for the respective sUA groups (2.0-2.9, 3.0-3.9, 4.0-4.9, 5.0-5.9, 6.0-6.9, 7.0-7.9) were as follows: 4.5%, 4.0%, 2.4%, 3.3%, 3.1%, 3.4%. The crude and adjusted odds ratios (OR) for rapid eGFR decline were significantly higher in the 2.0-2.9 (OR:1.93 and 1.86) and 3.0-3.9 (OR:1.72 and 1.73) groups than in the 4.0-4.9 groups (reference). Stratified analysis of age differences revealed that the detrimental effect of low sUA was not evident in older adults (age ≥ 65 years). CONCLUSION: A lower normal sUA level is related to an increased risk for a rapid decline in kidney function.

Kidney dysfunction: prevalence and associated risk factors in a community-based study from the North West Province of South Africa.

BACKGROUND: Globally, the World Health Organization ranks chronic kidney disease (CKD) as one of the top 10 causes of mortality. In South Africa, where noncommunicable diseases have become leading causes of mortality, the true population prevalence of CKD is unknown and associated risk factors remain understudied. This study aimed to describe the prevalence of kidney dysfunction and associated risk factors in a community from the North West province of South Africa. METHODS: This cross-sectional study included 1999 participants older than 30 years. Kidney dysfunction was defined as (i) estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2, or (ii) urine albuminuria-to-creatinine ratio (uACR) ≥ 3.0 mg/mmol, or a combination (i and ii). Risk factors included age, sex, urban/rural locality, body mass index (BMI), blood pressure (BP), lipid profile, haemoglobin A1c (HbA1C), C-reactive protein (CRP), gamma-glutamyl transferase (GGT), tobacco use, and HIV status. RESULTS: Mean age of participants was 48 (42;56) years, and 655/1999 (33%) had eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol. Compared to those with normal kidney function, participants with eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol were older, female, had higher measures of adiposity, systolic, diastolic, and mean arterial blood pressure, serum lipids and C-reactive protein (CRP) (all p ≤ 0.024). In multiple regression analyses eGFR was associated with systolic BP (ß = 0.11) and HIV infection (ß = -0.09), and albuminuria was associated with elevated CRP (ß = 0.12) and HIV infection (ß = 0.11) (all p < 0.026). In both groups (individuals with and without kidney dysfunction respectively), eGFR was associated with age (ß = -0.29, ß = -0.49), male sex (ß = 0.35, ß = 0.28), BMI (ß = -0.12, ß = -0.09), low-density/high-density lipoprotein cholesterol ratio (ß = -0.17, ß = -0.09) and CRP (ß = 0.10, ß = 0.09) (all p < 0.005); and uACR was associated with female sex (ß = 0.10, ß = -0.14), urban locality (ß = -0.11, ß = -0.08), BMI (ß = -0.11, ß-0.11), and systolic BP (ß = 0.27, ß = 0.14) (all p < 0.017). CONCLUSION: In this study from the North West province, South Africa, eGFR < 90 ml/min/1.73m2 and/or uACR ≥ 3.0 mg/mmol was prevalent and associated with modifiable risk factors. The findings may inform screening strategies for kidney disease prevention, focusing on women, obesity, blood pressure control, dyslipidaemia, identifying and treating inflammation, and HIV diagnosis and treatment.