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Obesity is a growing epidemic that threatens to deplete healthcare resources by increasing the prevalence of diabetes, heart disease, high blood pressure, cancer, and chronic kidney disease. The prevalence of general and central obesity among the rural Black population in Limpopo Province is high; however, few studies have evaluated the association between obesity and its comorbidities among the rural Black population, and, hence, this study aims to determine the relationship between obesity and associated comorbidities. This study was cross-sectional and retrospective in design, using secondary data from the Africa Wits-INDEPTH Partnership for Genomic (AWI-Gen) research phase 1 study. A sample size of 791 participants was collected conveniently. Data were analysed using the Statistical Package for Social Sciences version 27 (SPSS). A chi-square, unpaired Student's t-test, bivariate and partial correlation, and multivariate regression analysis were used for analysis. General obesity correlated positively and significantly with LDL-C/HDL-C ratio and hypertension, while central obesity correlated positively and significantly with diabetes, hypertension, chronic kidney disease, LDL-C/HDL-C ratio, and TC/HDL-C ratio. In the present study, obese participants were more likely to be hypertensive, and have an increased LDL-C/HDL-C ratio. Centrally obese participants were more likely to be diabetic, hypertensive, have dyslipidaemia, and exhibit reduced kidney function. [ABSTRACT FROM AUTHOR]

Left ventricular diastolic dysfunction (LVDD) commonly coexists with kidney dysfunction. In this study, we investigated the presence of abnormalities in echocardiography parameters indicative of LVDD across stages of kidney function. Methods: We selected patients who visited a university hospital and had a serum creatinine and echocardiography reported in their medical records. Participants were categorized based on their kidney function: normal (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2), mildly decreased (eGFR: 60–90), moderately decreased (eGFR: 30–60), and severely decreased (eGFR < 30). The relationship between kidney function and echocardiography parameters was examined using logistic and linear regressions. Results: Among 4022 patients (age: 66.5 years [SD: 12.1], 41% women), 26%, 50%, 20%, and 4% had a normal, mildly, moderately, and severely decreased kidney function, respectively. Compared to patients with normal kidney function, patients with mildly decreased kidney function had higher odds for an abnormal E/e′ ratio (OR: 1.51 [95% CI: 1.13, 2.02]). Patients with moderately decreased kidney function presented a higher risk of abnormal E/e′ (OR: 2.90 [95% CI: 2.08, 4.04]), LAVI (OR: 1.62 [95% CI: 1.13, 2.33]), TR velocity (OR: 2.31 [95% CI: 1.49, 3.57]), and LVMI (OR: 1.70 [95% CI: 1.31, 2.20]), while patients with severely decreased kidney function had higher odds for abnormal E/e′ (OR: 2.95 [95% CI: 1.68, 5.17]) and LVMI > 95 g/m2 in women or >115 g/m2 in men (OR: 2.07 [95% CI: 1.27, 3.38]). The linear regression showed a significant inverse association between eGFR and echocardiography parameters, meaning that with worse kidney function, the parameters for LVDD worsened as well. Conclusions: Abnormal echocardiography parameters of LVDD were present even in patients with mildly decreased kidney function. As the kidney function worsened, there was a gradual increase in the risk of abnormal parameters of LVDD. [ABSTRACT FROM AUTHOR]

Background: Kidney diseases has been recognized as one of the challenging complications in HIV infected people. Hyponatremia and hyperkalemia are the most disturbed electrolytes associated with an increased risk of death both in hospitalized and in ambulatory HIV patients. Aim: The study aimed to assess the association between renal dysfunction and serum electrolytes disorders among HIV infected patients. Method: It was a retrospective study conducted at Muhororo district hospital from May up to July 2023. HIV infected patients were enrolled in the study and their serum creatinine, sodium, potassium and chloride were tested and the results analyzed by using SPSS version 22. A P-value less than 0.05 was considered statistically significance. Result: Among 115 HIV infected patients, 67.8% were females and 32.1% were males. The Mean serum creatinine was elevated among HIV infected patients [1.01(mg/dl) ±0.27, 0.99(mg/dl) ±0.26], and 40.8% had hyponatremia, 8% had hypernatremia, 6% had hypokalemia 7.8% had hyperkalemia 17.3% had hypochloremia and 20% had hyperchloremia Mean serum sodium was slightly decreased [134.1(mmol/l) ±11.8], there was no change in mean of both serum K+ and CL_ [4.4 (mmol/l) SD±1 / 100.7(mmol/l) with SD±14.2 for serum Cl-]. Serum creatinine was significantly associated with Na+ and K+ [P=0.04, r=-0.19/ p=0.01, r= 0.22] however the correlation between Cl- and Serum creatinine was not statistically significant [P=0.3, r=-0.08]. Conclusion: The study found elevated serum creatinine and, the weak correlation between creatinine and electrolytes in HIV infected patients on ART. The present findings need to be confirmed with further studies with large sample size. HIV infected patients should change life style that predispose their health to the development of kidney diseases they must also stick on healthcare provider's counselling. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Diabetes is associated with significant economic burden. Moreover, cardiovascular disease (CVD), including heart failure, and chronic kidney disease (CKD) are common comorbidities, leading to premature mortality. We conducted a systematic review to assess the humanistic and economic burden of cardio-renal-metabolic (CRM) conditions in individuals ≥ 18 years with CVD, CKD, and type 2 diabetes mellitus. METHODS: We searched Embase® and Medline® databases from 2011 to January 10, 2022 for English publications reporting humanistic and economic burden outcomes from observational studies, real-world evidence, and economic model studies. Intervention and validation studies were excluded. Study quality was assessed using the Newcastle-Ottawa Scale. Abstracts/posters were identified from four conferences (2020-2022). RESULTS: Of 1804 studies identified, 22 (including four conference publications) were selected involving 351,296,930 participants (one modeled the US population); eight reported healthcare resource utilization (HCRU), seven only cost data, six HCRU and cost data, one reported quality-of-life data (11/18 and 7/18 had estimated low and medium risk of bias, respectively). Participants were predominantly ≥ 65 years and identified as having White ethnicity. Higher costs and HCRU were observed in patients with all three conditions compared to those with two or none. Urban/metropolitan and insured patients had higher healthcare expenditure and service utilization compared to uninsured and racial/ethnic minority populations. Comorbidities were associated with increased hospitalizations, higher costs, and more emergency department visits. In general, patients identified as having Black ethnicity had low odds of using healthcare services, possibly due to disparities in healthcare access and distrust in the system. Limitations included no adjustment for inflation and a predominance of retrospective studies. CONCLUSIONS: This review showed a greater economic burden for patients with CRM conditions, with a clear trend between increasing numbers of comorbidities and increasing healthcare costs/resource use. Comparisons between countries are complicated and the scarcity of evidence from minority racial and ethnic groups and lack of data from non-US geographies warrant further investigation.

Obesity is a growing epidemic that threatens to deplete healthcare resources by increasing the prevalence of diabetes, heart disease, high blood pressure, cancer, and chronic kidney disease. The prevalence of general and central obesity among the rural Black population in Limpopo Province is high; however, few studies have evaluated the association between obesity and its comorbidities among the rural Black population, and, hence, this study aims to determine the relationship between obesity and associated comorbidities. This study was cross-sectional and retrospective in design, using secondary data from the Africa Wits-INDEPTH Partnership for Genomic (AWI-Gen) research phase 1 study. A sample size of 791 participants was collected conveniently. Data were analysed using the Statistical Package for Social Sciences version 27 (SPSS). A chi-square, unpaired Student’s t-test, bivariate and partial correlation, and multivariate regression analysis were used for analysis. General obesity correlated positively and significantly with LDL-C/HDL-C ratio and hypertension, while central obesity correlated positively and significantly with diabetes, hypertension, chronic kidney disease, LDL-C/HDL-C ratio, and TC/HDL-C ratio. In the present study, obese participants were more likely to be hypertensive, and have an increased LDL-C/HDL-C ratio. Centrally obese participants were more likely to be diabetic, hypertensive, have dyslipidaemia, and exhibit reduced kidney function.

Intermittent hemodialysis (IH) is an important therapy in the context of kidney dysfunction in dogs. However, its impact on pro-inflammatory cytokines is unclear. This study assessed IL-1β, IL-6, and TNF-α serum concentrations in dogs with chronic kidney disease (CKD) undergoing one session of IH without bypass (IH group, n = 4) and with bypass (IH + bypass group, n = 4). The control group (CG) included four healthy dogs. Cytokine levels were measured before, during, and after the first IH session. Comparative analyses of each cytokine within each group and time point were performed, along with a global comparison between groups. No significant changes were observed in cytokines across evaluation times in the IH groups. IL-1β was significantly higher post-session in the IH and IH + bypass groups compared to CG. Globally, IL-1β and TNF-α concentrations were significantly higher in the IH (11.41 pg/mL (10–16.17) and 2 pg/mL (2–88.54), respectively) and IH + bypass groups (10 pg/mL (10–10) and 2 pg/mL (2–215.5), respectively) compared to CG (0.96 pg/mL (0–3.56) and 0 pg/mL (0–0.003), respectively). The IH group also showed elevated IL-6 concentration (0.1 ng/mL (0.1–0.5)) compared to CG (0 ng/mL (0–0.1)). Higher IL-1β and IL-6 concentrations were observed in the IH group (11.41 pg/mL (10–16.17) and 0.1 ng/mL (0.1–0.1), respectively) compared to the IH + bypass group (10 pg/mL (10–10) and 0.1 ng/mL (0.1–0.5), respectively). In conclusion, a single IH session, with or without bypass, did not increase pro-inflammatory cytokines in CKD dogs with uremic syndrome but maintained the inflammatory state. Dogs undergoing IH without bypass may receive a stronger stimulus for cytokine release.

Weijian Liu,&ast; Liangzi Yang,&ast; Hongjuan Qin, Peize Zhang Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peize Zhang, Email 82880246@qq.comAbstract: Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.Keywords: tuberculosis, contezolid, kidney dysfunction, kidney transplantation, tuberculous peritonitis

Background: Pulmonary hypertension (PH) is a global health issue that has profound medical and research implications. Methods: This retrospective study examined changes in renal and liver function, as well as lipid metabolism, over a 12-month period in 49 adult patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). All cases were admitted, managed, and followed up with in the PH Center, County Emergency Clinical Hospital of Targu Mures, Romania. Results: Kidney dysfunction was observed in 12.24% of cases at baseline, decreasing to 8.16% at 12 months, and CTEPH patients were more affected. In particular, CTEPH patients exhibited an improvement in renal function, confirmed by an increase in their glomerular filtration rates. Hepatic impairment was present in 57.14% of subjects at baseline, declining to 42.86% at 12 months, with significant improvements noted in the PAH group. Lipid metabolic dysregulations were experienced by 22.45% of all patients at baseline, decreasing to 16.33% at 6 months, with a slow elevation to 24.49% at 12 months, but with no statistically significant differences. Pharmacological regimens were adjusted in accordance with the PH groups, a patient's functional and clinical response, and laboratory tests. Conclusions: Our results demonstrate the multi-organ damage in PH and the importance of individualized treatment approaches. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 estimated glomerular filtration rate 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) 1.12–1.19; HR 1.29, 95% CI 1.20–1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR 1.61, 95% CI 1.52–1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI 0.05–0.29). 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Kidney dysfunction is increasing worldwide and is exacerbated by exposure to toxic metals. Also, pregnancy poses an overload on kidney function. We investigated how blood lead (PbB) and cadmium (CdB) levels were associated with kidney function in pregnant women from Recôncavo Baiano, Brazil, during their second trimester. In this cross-sectional study, the estimated glomerular filtration rate (eGFR) was calculated from serum creatinine and whole blood metal levels were measured by graphite furnace atomic absorption spectrophotometry in 136 volunteers. Sociodemographic data were collected using semi-structured questionnaires. The medians (IQR) of PbB, CdB, and eGFR were 0.85 µg/dL (0.45–1.75), 0.55 µg/L (0.08–0.91), and 121.8 mL/min/1.73 m2 (106.0–127.9), respectively. PbB medians were significantly higher in the eGFR < 90 group at 2.00 µg/dL (0.83, 3.10). After age-adjusted logistic regression, pregnant women with elevated PbB levels had decreased eGFR (OR = 1.82; 95%-CI, 1.14–3.14). However, the participants with elevated PbB levels who reported consuming alcohol during pregnancy or had CdB in the highest tertile had higher odds of reduced eGFR (OR = 2.44; 95%-CI, 1.30–5.47) and (OR = 11.22; 95% CI, 2.53–103.51), respectively. These results suggest that low Pb exposure may affect kidney function in pregnant women and calls for further investigation into toxic metal co-exposures on kidney function during pregnancy in at-risk communities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Currently, there is little and inconsistent evidence regarding the possible adverse effects of circulating levels of non-esterified fatty acids (NEFA) on kidney function decline in patients with type 2 diabetes mellitus (T2DM). Methods: We followed for a median of 4.6 years 85 post-menopausal women with non-insulin-treated T2DM and preserved kidney function at baseline. Serum NEFA concentrations were measured using an enzymatic colorimetric method. Glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: Enrolled patients had a baseline mean eGFRCKD-EPI of 83 ± 12 mL/min/1.73 m2 and a median serum NEFA concentration of 662 uEq/L (interquartile range 524–842 uEq/L). During the follow-up period, 13 patients developed kidney function decline at follow-up (defined as an eGFRCKD-EPI decline ≥ 30% from baseline). In Cox proportional hazards regression analyses, higher serum NEFA levels were significantly associated with an increased risk of developing kidney function decline (adjusted-hazard ratio 3.67, 95% CI 1.64–8.22, p < 0.001; for each 1-SD increment, i.e., 262 uEq/L), even after adjustment for waist circumference, hemoglobin A1c, C-reactive protein, HOMA-estimated insulin resistance, hypertension, dyslipidemia, microalbuminuria, baseline eGFRCKD-EPI, as well as temporal changes in HbA1c levels or the use of renin-angiotensin system inhibitors over the follow-up. Conclusions: The findings of this exploratory prospective study show that in post-menopausal women with T2DM and preserved kidney function at baseline, higher circulating levels of NEFA were strongly associated with a faster kidney function decline, even after adjustment for established renal risk factors and potential confounders. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common after lung transplant and may increase risk of chronic kidney disease (CKD). Calcineurin inhibitors (CNIs) such as tacrolimus contribute to AKI risk. This study evaluated outcomes among lung transplant recipients administered enteral or oral versus intravenous (IV) tacrolimus immediately post-lung transplant. Methods: We performed a single-center retrospective study of lung transplant recipients from 2011 to 2019. Tacrolimus concentrations, rates of perioperative AKI, CKD, and one-year survival were compared between those that received IV versus oral tacrolimus post-LT. Results: A total of 153 patients were included; 110 and 43 received IV tacrolimus and enteral or oral tacrolimus, respectively. AKI within 14 days post-LT occurred more frequently in patients that received IV tacrolimus versus enteral administration (84.5 vs 44.1 %, p =

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.

Abstract Aims We aim to investigate the association between kidney dysfunction and left ventricular diastolic dysfunction parameters and heart failure with preserved ejection fraction (HFpEF) and whether this is sex‐specific. Methods and results We included participants from the HELPFul observational study. Outpatient clinical care data, including echocardiography, and an expert panel judgement on HFpEF was collected. Estimated glomerular filtration rate (eGFR) was calculated by creatinine and cystatin C without race. The association between eGFR with E/e′, left ventricular mass index, relative wall thickness, and stage C/D heart failure was tested by multivariable adjusted regression models, stratified by sex, reporting odds ratios and 95% confidence intervals (95% confidence interval). We analysed 880 participants, mean age 62.9 (standard deviation: 9.3) years, 69% female. Four hundred six participants had mild (37.6%) kidney dysfunction (eGFR: 60–89 mL/min/1.73 m2) or moderate (8.5%) kidney dysfunction (eGFR: 30–59 mL/min/1.73 m2). HFpEF was significantly more prevalent in participants with mild and moderate kidney dysfunction (10.3% and 16.0%, respectively) than participants with normal kidney function (3.4%). A lower kidney function was associated with higher E/e′ and higher relative wall thickness values. Participants with moderate kidney dysfunction had a higher likelihood of American College of Cardiology/American Heart Association stage C/D HF (odds ratio: 2.07, 95% confidence interval: 1.23, 3.49) than participants with normal kidney functions. Conclusions Both mild and moderate kidney dysfunction are independently associated with left ventricular diastolic dysfunction parameters and HFpEF. This association is independent of sex and strongest for moderate kidney dysfunction. Considering mild‐to‐moderate kidney dysfunction as risk factor for HFpEF may help identify high‐risk groups benefiting most from early intervention.

Abstract Background Kidney dysfunction is a common, progressive condition that is increasingly becoming a global public health issue. Because the kidneys are the major route for drug excretion, impaired renal function can change the pharmacokinetics and pharmacodynamics of drugs that are renally excreted. Additionally, patients with kidney dysfunction often have co-morbidities and the associated use of multiple medications which increases the risk of drug-related problem (DRP) occurrence. This study aimed to determine the prevalence, types, and factors associated with DRPs in patients with kidney dysfunction. Method We conducted a prospective observational study over 3 months among hospitalized patients diagnosed with acute kidney injury or chronic kidney disease who were hospitalized in the medical ward, and patients attending the renal outpatient clinic at Mbarara Regional Referral Hospital. A total of 183 participants were enrolled through the use of a consecutive sampling technique. DRPs were classified according to the PCNE classification version 9.1. Data analysis was carried out using SPSS version 25. Results A total of 174 patients with kidney dysfunction were included in the study with a mean ± SD age of 50.34 ± 18.13 years. A total of 219 DRPs were incurred by 138 (79.3%) study participants. The most common DRPs were ‘Untreated symptoms or indication’ (35.6%) followed by ‘adverse event (possibly) occurring’ (28.3%), and ‘effect of drug treatment not optimal’ (23.3%). Antimicrobials were the most involved drugs in suboptimal drug treatment (31.3%) and unnecessary drug treatment (32.1%). The study showed that length of hospital stay ≥ 5 days (AOR = 6.39, 95% CI: 1.75–23.27; p-value = 0.005) significantly increased the risk of DRP occurrence. Conclusion The current results, in agreement with previous literature, showed a high burden of DRPs among patients with kidney dysfunction. Antimicrobials were the most involved drugs in suboptimal as well as in unnecessary drug treatment. Longer hospital stay significantly increased the risk of DRPs. The high prevalence of DRPs in patients with kidney dysfunction and the potential impact on antimicrobial resistance underscores the importance of regular medication reviews and close monitoring of patients with renal dysfunction.

Background: Kidney dysfunction (KD) is a main limiting factor of applying guideline‐directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). Hypothesis: We aimed to assess the success of optimization, long‐term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + βB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. Methods: The data of 247 real‐world, consecutive patients were analyzed who were hospitalized in 2019−2021 for HFrEF and then were followed‐up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60−89, 45−59, 30−44, <30 mL/min/1.73 m2). Moreover, 1‐year all‐cause mortality and rehospitalization rates in KD subgroups were investigated. Results: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p <.05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p <.05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One‐year all‐cause mortality (14%, 15%, 16%, 33%, 48%, p <.001), the ratio of all‐cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p =.028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p =.001) were significantly higher in more severe KD categories. Conclusions: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up‐titration of GDMT. [ABSTRACT FROM AUTHOR]

Aims: We aim to investigate the association between kidney dysfunction and left ventricular diastolic dysfunction parameters and heart failure with preserved ejection fraction (HFpEF) and whether this is sex‐specific. Methods and results: We included participants from the HELPFul observational study. Outpatient clinical care data, including echocardiography, and an expert panel judgement on HFpEF was collected. Estimated glomerular filtration rate (eGFR) was calculated by creatinine and cystatin C without race. The association between eGFR with E/e′, left ventricular mass index, relative wall thickness, and stage C/D heart failure was tested by multivariable adjusted regression models, stratified by sex, reporting odds ratios and 95% confidence intervals (95% confidence interval). We analysed 880 participants, mean age 62.9 (standard deviation: 9.3) years, 69% female. Four hundred six participants had mild (37.6%) kidney dysfunction (eGFR: 60–89 mL/min/1.73 m2) or moderate (8.5%) kidney dysfunction (eGFR: 30–59 mL/min/1.73 m2). HFpEF was significantly more prevalent in participants with mild and moderate kidney dysfunction (10.3% and 16.0%, respectively) than participants with normal kidney function (3.4%). A lower kidney function was associated with higher E/e′ and higher relative wall thickness values. Participants with moderate kidney dysfunction had a higher likelihood of American College of Cardiology/American Heart Association stage C/D HF (odds ratio: 2.07, 95% confidence interval: 1.23, 3.49) than participants with normal kidney functions. Conclusions: Both mild and moderate kidney dysfunction are independently associated with left ventricular diastolic dysfunction parameters and HFpEF. This association is independent of sex and strongest for moderate kidney dysfunction. Considering mild‐to‐moderate kidney dysfunction as risk factor for HFpEF may help identify high‐risk groups benefiting most from early intervention. [ABSTRACT FROM AUTHOR]

Introduction: Multiple myeloma is a type of plasma cell dyscrasia, which causes clonal proliferation of plasma cells and deposition in various organ systems. At presentation, 50% of patients with multiple myeloma have kidney dysfunction, which is considered a poor prognostic indicator. Data on the histopathological manifestations of multiple myeloma are sparse. Objective: To look at the kidney histopathological lesions in patients with the clinical diagnosis of multiple myeloma. Materials and Methods: A retrospective analysis of all kidney biopsies in patients with the clinical diagnosis of multiple myeloma was performed from June 1, 2020 to May 30, 2022, from three tertiary care nephrology referral centers. Results: A total of 61 patients with multiple myeloma and biopsy-proven kidney involvement were included in the study. The mean age at presentation was 55.39 ± 11.91 years, with male predominance (male to female ratio -1.6:1). The most common lesion on kidney biopsy was myeloma cast nephropathy (72.1%), followed by light chain deposition disease (21.3%) and AL amyloidosis (18%). About 26% of patients had dual lesions on kidney biopsy, 3% had three types of lesions on kidney biopsy In 48% of patients, the diagnosis of multiple myeloma was made only after the kidney biopsy. Conclusion: Patients with multiple myeloma and kidney involvement should be biopsied as the type of histopathological lesion influences the treatment options and prognosis. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and acute kidney injury (AKI) are serious public health burden. Patients with advanced stage CKD and severe AKI require hemodialysis (HD). However, their clinico-etiological profile has not been compared yet. Thus, we compared the clinico-etiological and hematological profile of patients with CKD and AKI undergoing HD. Materials and Methods: This prospective, observational, cross-sectional study involved 425 adult patients with CKD (n=328) and AKI (n=97) that underwent HD, between January 2020 and June 2021, in a tertiary care hospital. Data related to clinico-demographic characteristics, and laboratory investigations were recorded. Results: Hypertension (75.9%) and sepsis (49.48%) were predominant etiological factors of CKD and AKI, respectively. The patients with CKD had significantly greater mean age (p=0.005) and BMI (p<0.0001). Significantly greater proportion of the patients with AKI had anorexia (p=0.003), breathlessness (p=0.018), nausea and vomiting (p=0.019), and icterus (p=0.002). Significantly greater proportion of the patients with CKD had impaired cognition (p=0.043), swollen feet (p=0.008), and edema feet (p=0.012). Significantly greater proportion of the patients with AKI and CKD had hyperkalemia (p=0.034) as well as 3+ proteinuria (p<0.0001); and 2+ proteinuria (p<0.0001) as well as moderate anemia (p=0.045), respectively. Conclusion: Hypertension and sepsis are predominantly implicated in CKD and AKI, respectively. CKD is significantly associated with advancing age and higher BMI. Though AKI is significantly associated with hyperkalemia and high-grade proteinuria, CKD is significantly associated with moderate-grade proteinuria and moderate anemia. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated the impact of the clinical presentation of pyometra on the morbidity and mortality of the affected bitches. The medical records of 47 bitches surgically treated for pyometra between May and December 2017 were evaluated. The admission data were analyzed to classify the animals according to the clinical presentation of pyometra, presence of systemic inflammatory response syndrome (SIRS) and organic dysfunctions (cardiovascular, neurological, renal, and hemostatic). The outcomes were recorded for up to 14 days. The overall mortality rate was 13%. Open and closed pyometra were identified in 62% (n= 29) and 38% (n= 18) of the cases, respectively. The SIRS was present in 44 (94%) bitches, and 27 (57%) had at least one organ dysfunction. The most prevalent dysfunction was hemostatic, followed by neurological, cardiovascular, and renal dysfunction. The clinical presentation of pyometra and the presence of SIRS did not correlate with each other, or with the presence of organ dysfunction and mortality. However, cumulative organ dysfunction (r=0.532, P=<0.001) and the presence of neurological (r= -0.371; P=0.012) and renal dysfunction (r=0.303; P=0.041) were correlated with mortality. Thus, the identification of organ dysfunction through physical examination and routine laboratory analysis proved to be more effective in identifying and predicting the critically ill patients than the SIRS criteria or clinical presentation of the disease. [ABSTRACT FROM AUTHOR]

Background: Kidney dysfunction is a common, progressive condition that is increasingly becoming a global public health issue. Because the kidneys are the major route for drug excretion, impaired renal function can change the pharmacokinetics and pharmacodynamics of drugs that are renally excreted. Additionally, patients with kidney dysfunction often have co-morbidities and the associated use of multiple medications which increases the risk of drug-related problem (DRP) occurrence. This study aimed to determine the prevalence, types, and factors associated with DRPs in patients with kidney dysfunction. Method: We conducted a prospective observational study over 3 months among hospitalized patients diagnosed with acute kidney injury or chronic kidney disease who were hospitalized in the medical ward, and patients attending the renal outpatient clinic at Mbarara Regional Referral Hospital. A total of 183 participants were enrolled through the use of a consecutive sampling technique. DRPs were classified according to the PCNE classification version 9.1. Data analysis was carried out using SPSS version 25. Results: A total of 174 patients with kidney dysfunction were included in the study with a mean ± SD age of 50.34 ± 18.13 years. A total of 219 DRPs were incurred by 138 (79.3%) study participants. The most common DRPs were 'Untreated symptoms or indication' (35.6%) followed by 'adverse event (possibly) occurring' (28.3%), and 'effect of drug treatment not optimal' (23.3%). Antimicrobials were the most involved drugs in suboptimal drug treatment (31.3%) and unnecessary drug treatment (32.1%). The study showed that length of hospital stay ≥ 5 days (AOR = 6.39, 95% CI: 1.75–23.27; p-value = 0.005) significantly increased the risk of DRP occurrence. Conclusion: The current results, in agreement with previous literature, showed a high burden of DRPs among patients with kidney dysfunction. Antimicrobials were the most involved drugs in suboptimal as well as in unnecessary drug treatment. Longer hospital stay significantly increased the risk of DRPs. The high prevalence of DRPs in patients with kidney dysfunction and the potential impact on antimicrobial resistance underscores the importance of regular medication reviews and close monitoring of patients with renal dysfunction. [ABSTRACT FROM AUTHOR]

Aims: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes. Methods: We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30 mL/min/1.73 m2. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline. Results: Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent. Conclusions: High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs. [ABSTRACT FROM AUTHOR]

Qun Xu,1 Fangzhou Li,2 Xujiao Chen2,3 1School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Geriatrics, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Zhejiang Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xujiao Chen, Department of Geriatrics, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, 310003, Email lily197459@163.comPurpose: 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 m2.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.Keywords: mortality, kidney dysfunction, frailty, elderly, hypertensive hospitalized patients with COVID-19

Abstract 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 (

Abstract 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.

Background: Pulmonary hypertension (PH) is a global health issue that has profound medical and research implications. Methods: This retrospective study examined changes in renal and liver function, as well as lipid metabolism, over a 12-month period in 49 adult patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). All cases were admitted, managed, and followed up with in the PH Center, County Emergency Clinical Hospital of Targu Mures, Romania. Results: Kidney dysfunction was observed in 12.24% of cases at baseline, decreasing to 8.16% at 12 months, and CTEPH patients were more affected. In particular, CTEPH patients exhibited an improvement in renal function, confirmed by an increase in their glomerular filtration rates. Hepatic impairment was present in 57.14% of subjects at baseline, declining to 42.86% at 12 months, with significant improvements noted in the PAH group. Lipid metabolic dysregulations were experienced by 22.45% of all patients at baseline, decreasing to 16.33% at 6 months, with a slow elevation to 24.49% at 12 months, but with no statistically significant differences. Pharmacological regimens were adjusted in accordance with the PH groups, a patient’s functional and clinical response, and laboratory tests. Conclusions: Our results demonstrate the multi-organ damage in PH and the importance of individualized treatment approaches.

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.

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.

Abstract Objective We aim to explore the prevalence and temporal trends of the burden of kidney dysfunction (KD) in global, regional and national level, since a lack of related studies. Design Cross-sectional study. Materials The data of this research was obtained from Global Burden of Diseases Study 2019. The estimation of the prevalence, which was measured by the summary exposure value (SEV), and attributable burden of KD was performed by DisMod-MR 2.1, a Bayesian meta-regression tool. The Spearman rank order correlation method was adopted to perform correlation analysis. The temporal trends were represented by the estimated annual percentage change (EAPC). Results In 2019, there were total 3.16 million deaths and 76.5 million disability-adjusted life years (DALYs) attributable to KD, increased by 101.1% and 81.7% compared with that in 1990, respectively. From 1990 to 2019, the prevalence of KD has increased in worldwide, but decreased in High-income Asia Pacific. Nearly 48.5% of countries globally, such as South Africa, Egypt and Mexico had increased mortality rates of KD from 1990 to 2019 while 44.6% for disability rate. Countries with lower socio-demographic index (SDI) are facing a higher prevalence as well as mortality and disability rate compared with those with higher SDI. Compared with females, the prevalence of KD was lower in males, however the attributable mortality and disability rate were higher in all years from 1990 to 2019. Conclusion With the progress of senescent, we will face more severe challenges of reducing the prevalence and attributable burden of KD, especially in regions with lower SDI. Effective measures are urgently required to alleviate the prevalence and burden of KD.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a significant impact on the world’s demographics, resulting in over 6 million deaths globally. COVID-19 has been associated with a variety of disease manifestations in various organ systems, including kidney disease, in addition to pulmonary manifestations. Infection with SARS-CoV-2 can not only cause new kidney damage but also make treatment and care more difficult, as well as increase mortality in people who already have kidney problems. COVID-19 is indeed associated with a variety of renal pathologies, such as acute tubular necrosis, proteinuria, hematuria, and thrombosis complications. Cytokine storms, hypoxemia, direct viral invasion via angiotensin-converting enzyme 2 and cathepsin L, electrolyte imbalance, and fever are among the pathophysiological mechanisms underlying these clinical symptoms. Over the last two years, many COVID-19 vaccines have been discovered. However, there have been a few case reports of AKI, AKD, proteinuria, edema, gross hematuria, and other renal side effects that necessitated hospitalization after receiving COVID-19 vaccinations. Thus, the current review aimed to evaluate COVID-19-induced kidney dysfunction in terms of clinical features, pathogenesis, long-term outcomes, and vaccine harms based on the most up-to-date findings.

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease, for which estimated glomerular filtration rate (eGFR) trajectories are early markers, is frequent in people living with HIV. Setting: Identify eGFR trajectory patterns according to kidney function and assess associated factors over a 13-year followup period. Methods: We evaluated longitudinal changes and its associated factors in eGFR of 3366 participants according to kidney function with a 2-level, linear, mixed model. Results: Participants with initial kidney dysfunction experienced a slight eGFR increase, whereas others showed a slight decrease. A weak relationship was observed between baseline eGFR and its variation over time. Baseline eGFR was affected by age, CD4+ count, viral load, hypertension, hyperlipidemia, AIDS-defining illness and tenofovir (TDF) with integrase inhibitor (INSTI) or efavirenz. Significant factors for eGFR change included the following: in kidney dysfunction, CD4+ cell count of .350 cells per cubic millimeter and undetectable viral load increased eGFR, whereas TDF + protease inhibitor decreased eGFR; in mildly decreased kidney function, CD4 + cell count of .350 cells per cubic millimeter, AIDS-defining illness, and TDF + efavirenz increased eGFR, whereas age, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR; in normal kidney function, age, CD4+ cell count of . 350 cells per cubic millimeter, undetectable viral load, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR, whereas TDF + efavirenz increased eGFR (all P value for interaction, 0.05). Conclusion: Our findings suggest that eGFR trajectories varied widely between individuals in people living with HIV. In the lower eGFR group, virus-related factors were more relevant, whereas traditional risk factors for renal dysfunction were more prominent in the highest eGFR group. [ABSTRACT FROM AUTHOR]

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 (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.

Kidney dysfunction is increasing worldwide and is exacerbated by exposure to toxic metals. Also, pregnancy poses an overload on kidney function. We investigated how blood lead (PbB) and cadmium (CdB) levels were associated with kidney function in pregnant women from Recôncavo Baiano, Brazil, during their second trimester. In this cross-sectional study, the estimated glomerular filtration rate (eGFR) was calculated from serum creatinine and whole blood metal levels were measured by graphite furnace atomic absorption spectrophotometry in 136 volunteers. Sociodemographic data were collected using semi-structured questionnaires. The medians (IQR) of PbB, CdB, and eGFR were 0.85 µg/dL (0.45–1.75), 0.55 µg/L (0.08–0.91), and 121.8 mL/min/1.73 m2 (106.0–127.9), respectively. PbB medians were significantly higher in the eGFR < 90 group at 2.00 µg/dL (0.83, 3.10). After age-adjusted logistic regression, pregnant women with elevated PbB levels had decreased eGFR (OR = 1.82; 95%-CI, 1.14–3.14). However, the participants with elevated PbB levels who reported consuming alcohol during pregnancy or had CdB in the highest tertile had higher odds of reduced eGFR (OR = 2.44; 95%-CI, 1.30–5.47) and (OR = 11.22; 95% CI, 2.53–103.51), respectively. These results suggest that low Pb exposure may affect kidney function in pregnant women and calls for further investigation into toxic metal co-exposures on kidney function during pregnancy in at-risk communities.

Background: There are data supporting the idea that atherogenic dyslipidemia is a risk factor for CKD and reduced GFR. The aim was to evaluate the associations between adipocytokines and early renal dysfunction in young people with dyslipidemia. Materials and methods: A population study was conducted in IIPM—Branch of IC&G SB RAS, in 2013–2017. Furthermore, 1033 people were included in the study (469 men (45.4%) and 564 women (54.6%)). The study included blood sampling, anthropometric data, and adipokines by multiplex analysis. Results: Among people with reduced kidney function and DLP, men were 3.1 times more common than without DLP, women smoked 2 times less often, arterial hypertension was 7.8 times more common, and abdominal obesity was 2.7 times more common (and women with DLP were 3 times more likely than those without DLP). An increase in the level of resistin by 1 mcg/mL was associated with an increased chance of having renal dysfunction by 0.2%. An increase in the level of GIP was associated with an increased chance of having renal dysfunction by 1.1%. Conclusions: In young people with dyslipidemia, regardless of the presence of abdominal obesity, resistin and GIP are associated with the presence of renal dysfunction. [ABSTRACT FROM AUTHOR]