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BACKROUND Complement activation may facilitate hypertension through its effects on immune responses. The anaphylatoxin C5a, a major inflammatory effector, binds to the C5a receptors 1 and 2 (C5aR1, C5aR2). We have recently shown that C5aR1−/− mice have reduced hypertensive renal injury. The role of C5aR2 in hypertension is unknown. METHODS For examination of C5aR2 expression on infiltrating and resident renal cells a tandem dye Tomato-C5aR2 knock-in reporter mouse was used. Human C5aR2 expression was analyzed in a single-cell RNAseq data set from the kidneys of hypertensive patients. Finally, we examined the effect of angiotensin II-induced hypertension in C5aR2-deficient mice. RESULTS Flow cytometric analysis of leukocytes isolated from kidneys of the reporter mice showed that dendritic cells are the major C5aR2-expressing population (34%) followed by monocyte/macrophages (30%) and neutrophils (14%). Using confocal microscopy C5aR2 was not detected in resident renal or cardiac cells. In the human kidney, C5aR2 was also mainly found in monocytes, macrophages, and dendritic cells with a significantly higher expression in hypertension (P  < 0.05). Unilateral nephrectomy was performed followed by infusion of Ang II (0.75 ng/g/min) and a high salt diet in wildtype (n  = 18) and C5aR2-deficient mice (n  = 14). Blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), and cardiac injury (cardiac fibrosis, heart weight, gene expression) did not differ between hypertensive wildtype and C5aR2−/− mice. CONCLUSIONS In summary, C5aR2 is mainly expressed in myeloid cells in the kidney in mice and humans but its deficiency has no effect on Ang II-induced hypertensive injury. [ABSTRACT FROM AUTHOR]

Lithium (Li+) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li+ levels are nephrotoxic and can trigger a local immune response. Our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6NJ mice placed on a 0.3% lithium carbonate diet for 28 days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR and proteome profiler arrays to characterize renal tissue damage, infiltrating immune cells and cytokine markers, activation of pyroptotic and apoptotic cascades in the kidneys of mice receiving Li+-containing and regular diets. We found that biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinaseassociated lipocalin, NGAL, were elevated in the renal tissue of Li+-treated mice when compared to controls. This correlated with increased interstitial fibrosis in Li+-treated mice. Administration of Li+ did not activate the proinflammatory NLRP3 inflammasome cascade but promoted apoptosis in the renal tissue. The TUNEL-positive signal and levels of pro-apoptotic proteins, Bax, cleaved caspase-3, and caspase-8, were elevated in the kidneys of Li+- treated mice. We observed a significantly higher abundance of CD93, CCL21, and fractalkine, accumulation of F4.80+ macrophages with reduced M1/ M2 polarization ratio and decreased CD4+ levels in the renal tissue of Li+- treated mice when compared to controls. Therefore, after 28 days of treatment, Li+-induced insult to the kidney manifests in facilitated apoptotic cell death without an evident pro-inflammatory response. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of combining Qingying decoction with Wuling powder in the treatment of renal hematuria. Method: Seventy-six patients diagnosed with renal hematuria in the Emergency General Hospital and Nanmofang Community Health Service Center in Chaoyang District of Beijing, China were randomized equally into study and control groups. Control group received standard Western treatment in addition to Shenyan Rehabilitation tablets while study group received a combination of Qingying decoction and a modified Wuling powder alongside standard treatment for eight weeks. Treatment effectiveness was evaluated using urinary red blood cell count (URBC), urinary albumin-to-creatinine ratio (UACR), urinary ß 2-microglobulin (ß2-MG) and a 1-microglobulin (a1-MG) levels, serum levels of complement components 3 (C3) and 4 (C4), immunoglobulin A (IgA), and Traditional Chinese Medicine (TCM) syndrome scores. Results: There was a significant difference in total therapeutic effectiveness between study and control groups (p < 0.01). Study group showed significantly improved hematuria and total syndrome scores (p < 0.01). The study group showed significantly lower URBC, UACR, ß 2-MG, a 1-MG, IgA, and C3 levels compared to the control group (p < 0.05). Conclusion: Treatment with Qingying decoction and Wuling powder demonstrates efficacy in managing renal hematuria, regulates urinary red blood cell counts, reduces symptoms, and lowers early renal impairment. Future studies in multiple centers using larger number of patients to determine the mechanisms of these drug actions and interactions and other related factors would be required. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectveMaterials and MethodsResultsConclusionMirabegron (MIRG) is a type of β3 adrenoceptor agonist that is considered an alternative therapy for the treatment of overactive bladder (OAB) symptoms. Cilostazol (CITZ) is a selective inhibitor of phosphodiesterase (III) that has various pharmacological effects.The current study aimed to highlight the regulatory effects of CITZ on MIRG-induced toxicity.Male rats were divided into six groups. Blood samples were collected to determine different hepatic and kidney function levels along with serum protein electrophoresis and inflammatory factor levels. Histopathological studies and oxidative stress (OS) were also assessed. Kidney and hepatic damage were detected following the administration of MIRG, especially at high doses, due to elevated OS, inflammation, and apoptotic marker levels.Rats receiving CITZ exhibited significant improvements in both hepatic and kidney functions, with decreased inflammation and OS.CITZ administration plays a beneficial role in alleviating hepatic and nephrotoxicity induced by MIRG by inhibiting OS and inflammation. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression levels of platelet microparticles(PMPs) in patients with diabetic nephropathy (DN) and their relationship with renal injury. Methods Thirty DN patients, 30 T2DM patients without DN and 30 healthy controls were enrolled. Flow cytometry was used to detect the quantity and phenotype of PMPs, and ELISA was used to measure the levels of plasma renin, angiotensin Ⅱ (angiotoninⅡ, AngⅡ), vascular endothelial growth factor (vascular endothelial growth factor, VEGF) and transforming growth factor-β1(transforming growth factor-β1, TGF-β1). Kidney function was determined by blood biochemistry. Results The quantity of PMPs in the DN group was (1 564±346) particles/μL, which was significantly higher than that in the non-DN group (1 246±312) particles/μL and the control group (1 223±299) particles/μL (P

Abstract This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non‐dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24‐h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24‐h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone‐renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24‐h wSD of systolic BP (β = 0.383).The study also found significant correlations between the 24‐h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24‐h urinary microalbumin, underscoring the critical role of the 24‐h wSD of systolic BP (β = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Abstract Background Although renal damage is increasingly reported among the most undernourished patients with Anorexia Nervosa (AN), it remains underestimated in current practice, and often associated with acute dehydration. The purpose of our study was to evaluate the frequency, the extent, and the risk factors of renal involvement among adolescents and adults hospitalized in specialized units for AN. Methods In this multi-center study, 197 consecutive participants were included, aged 13–65, from 11 inpatient eating disorder psychiatric units. Information on the course of AN, clinical characteristics, biological data, and medication were collected. Results At admission, mean BMI was 13.1 (± 1.6) kg/m2 for a mean age of 20.74 (± 6.5) years and the z-score was − 3.6 (± 1.33). Six participants (3.0%) had hyponatremia, four (2.0%) had hypokalemia, and nine (4.5%) had hypochloremia. The Blood Urea Nitrogen/Creatinine ratio was over 20 for 21 (10.6%) participants. The mean plasma creatinine was 65.22 (± 12.8) µmol/L, and the mean eGFR was 74.74 (± 18.9) ml/min. Thirty- five participants (17.8%) had an eGFR > 90 ml/min, 123 (62.4%) from 60 to 90 ml/min, 35 (17.8%) from 45 to 60 ml/min, and 4 (2%) under 45 ml/min. In multivariate analysis, only BMI on admission was a determinant of renal impairment. The lower the BMI the more severe was the renal impairment. Conclusion When eGFR is calculated, it highlights renal dysfunction found in severe AN requiring hospitalisation in specialized units. The severity of undernutrition is an independent associated factor. Kidney functionality tests using eGFR, in addition to creatinine alone, should be part of routine care for patients with AN to detect underlying renal dysfunction.

Abstract Background Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. Methods CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. Results The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. Conclusions ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage. Graphical Abstract ILK content in circulating mononuclear cells reflects renal and vascular damage in a CKD experimental model.

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]

Objective: Hypoxia is one of the principal causes of renal diseases. This study aimed to evaluate the effects of Nigella sativa on dinitrophenol (DNP)-induced hypoxia renal damage in rats. Methods: Forty adult male rats were incorporated in this study. The rats were divided into four groups: control group, N. sativa group, DNP hypoxic group, and DNP + N. sativa group receiving N. sativa (400 mg/kg body weight). Serum and renal tissue erythropoietin (EPO) hormone and hypoxia-inducible factor-2α (HIF-2α) levels were measured. Renal oxidative stress biomarkers, inflammatory biomarkers, renal hemodynamics, and histopathological examination were evaluated. Results: Administration of N. sativa highly significantly normalized serum EPO level, HIF-2α (P < 0.001 for each) in DNP + N. sativa treated rats as compared to DNP hypoxic rats. Furthermore, it highly significantly improved renal oxidative stress evident by decreased renal tissues malondialdehyde and increased superoxide dismutase, total thiol, and catalase activity (P < 0.001 for each). Furthermore, a highly significant decline of renal intercellular adhesion molecule-1, myeloperoxidase, and interleukin-6 was observed in DNP + N. sativa rats (P < 0.001 for each). Improvements in renal hemodynamics and kidney functions were also found after N. sativa administration (with P < 0.001 for all parameters). In addition, N. sativa treatment reduced renal histopathological changes of the DNP + N. sativa group. Our results were statistically analyzed using the Prism software package (GraphPad version 8.0). Conclusion: N. sativa has an alleviating effect on DNP-induced hypoxia renal damage and can restore kidney functions in rats’ animal models. These effects were through antioxidant, anti-inflammatory, and hemodynamic mechanisms. [ABSTRACT FROM AUTHOR]

This study explored the mitigating properties of hyperin (HYP) on renotoxicity induced by cadmium chloride (CdCl2). Four groups of seven male albino mice each were used in this experiment. Group 1 served as the control, receiving no treatment. Group 2 received daily oral gavage of CdCl2 at 0.3 mg/kg body weight for 28 d. Group 3 received both CdCl2 (0.3 mg/kg) and HYP (100 mg/kg) daily using the same administration method. Finally, Group 4 received only HYP (100 mg/kg) daily. Cd exposure significantly increased kidney dysfunction markers (blood urea nitrogen and creatinine) and oxidative stress (reactive oxygen species [ROS] and malondialdehyde [MDA]). Conversely, it decreased antioxidant enzyme activities (glutathione peroxidase (GPx] and catalase [CAT]) and glutathione (GSH) levels. Nuclear factor erythroid 2-related factor 2 (Nrf-2) and antioxidant gene expression decreased, while Kelch-like ECH-associated protein 1 expression increased. Additionally, Cd exposure increased inflammatory mediators (nuclear factor kappa B, tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and cyclooxygenase-2) and apoptotic markers (Bax and caspase-3), alongside decreased Bcl-2 expression and renal tissue abnormalities. Mitochondrial dysfunction manifested with diminished activities of Krebs cycle and respiratory chain enzymes, and reduced mitochondrial membrane potential. Co-treatment with HYP significantly attenuated these detrimental effects through its anti-apoptotic, antioxidant, and anti-inflammatory properties. HYP co-treatment significantly attenuated CdCl2-induced renal damage in mice, suggesting its potential as a protective agent against Cd-induced kidney toxicity. [ABSTRACT FROM AUTHOR]

This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non‐dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24‐h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24‐h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone‐renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24‐h wSD of systolic BP (β = 0.383).The study also found significant correlations between the 24‐h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24‐h urinary microalbumin, underscoring the critical role of the 24‐h wSD of systolic BP (β = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes. [ABSTRACT FROM AUTHOR]

Background: Although renal damage is increasingly reported among the most undernourished patients with Anorexia Nervosa (AN), it remains underestimated in current practice, and often associated with acute dehydration. The purpose of our study was to evaluate the frequency, the extent, and the risk factors of renal involvement among adolescents and adults hospitalized in specialized units for AN. Methods: In this multi-center study, 197 consecutive participants were included, aged 13–65, from 11 inpatient eating disorder psychiatric units. Information on the course of AN, clinical characteristics, biological data, and medication were collected. Results: At admission, mean BMI was 13.1 (± 1.6) kg/m2 for a mean age of 20.74 (± 6.5) years and the z-score was − 3.6 (± 1.33). Six participants (3.0%) had hyponatremia, four (2.0%) had hypokalemia, and nine (4.5%) had hypochloremia. The Blood Urea Nitrogen/Creatinine ratio was over 20 for 21 (10.6%) participants. The mean plasma creatinine was 65.22 (± 12.8) µmol/L, and the mean eGFR was 74.74 (± 18.9) ml/min. Thirty- five participants (17.8%) had an eGFR > 90 ml/min, 123 (62.4%) from 60 to 90 ml/min, 35 (17.8%) from 45 to 60 ml/min, and 4 (2%) under 45 ml/min. In multivariate analysis, only BMI on admission was a determinant of renal impairment. The lower the BMI the more severe was the renal impairment. Conclusion: When eGFR is calculated, it highlights renal dysfunction found in severe AN requiring hospitalisation in specialized units. The severity of undernutrition is an independent associated factor. Kidney functionality tests using eGFR, in addition to creatinine alone, should be part of routine care for patients with AN to detect underlying renal dysfunction. Plain English summary: AN is a psychiatric illness with organic repercussions that are not always visible nor frequently investigated. Renal damage, if detected, is often attributed to dehydration, and is thought to be rapidly reversible. Assessment of its severity and evolution is therefore not systematic, even in eating disorder units specialised in the care of patients with AN. Our study explored the assessment of renal impairment among adolescents and adults hospitalized in psychiatric units using eGFR calculation. Our results showed that fewer than 18% of the patients hospitalized had normal renal function and that among the various criteria, only BMI on admission was related to the extent of this impairment. Assessment of renal function by eGFR calculation and not only by creatinine measures should be performed routinely in all situations requiring hospitalization in anorexia nervosa, regardless of the reason for hospitalization. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical efficacy of Niaoduqing Granule combined with Febusta in the treatment of renal damage in patients with hyperuricemia (HUA). Methods Eighty-two HUA patients with renal damage in our hospital from March 2020 to March 2022 were divided into observation group (n = 41) and control group (n = 41). The control group was treated with Febusta, while observation group with Niaoduqing granule and Febusta. Two groups were treated for 12 weeks. Blood uric acid, renal function, Cys C and β2-MG level change and adverse reactions in the two groups were compared. Results The total effective rate in the observation group was higher than in the control group (P < 0.05). After treatment, the level of serum uric acid, BUN, Scr, 24h Upro, Cys C and β2-MG decreased in the two groups (P < 0.05), with more significant results in the observation group (P < 0.05). No obvious adverse reactions were observed in the two groups. Conclusion Niaoduqing Granule combined with Febusta has good effect in treating HUA patients with renal impairment. It reduces the level of blood uric acid, Cys C and β2-MG, which protect the renal function of patients [ABSTRACT FROM AUTHOR]

Background: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. Methods: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. Results: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. Conclusions: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage. ILK content in circulating mononuclear cells reflects renal and vascular damage in a CKD experimental model. [ABSTRACT FROM AUTHOR]

Chronic cadmium exposure is known to be a major health concern due to its nephrotoxic effects. Consequently, this study aimed to assess the potential protective effects of date palm fruit extract (DPFE) against cadmium-induced renal toxicity in male albino rats. A total of 48 rats were divided equally into four groups and subjected to specific treatments. Group I (control given 1 ml distal water orally daily), group II (200 mg DPFE /kg b.wt. orally daily), Group III (5 mg CdCl2 /kg b.wt. orally, twice a week), and VI (DPFE and CdCl2). Serum samples were collected after 4 and 8 weeks for biochemical analysis, and kidney tissue specimens were obtained for histopathological examination. The administration of cadmium chloride for 4 and 8 weeks resulted in a significant (p<0.05) increase in the serum creatinine, urea, and uric acid levels, indicating kidney dysfunction. Histopathological changes, including vascular lesions, hemorrhage, edema, periglomerular, perivascular and interstitial fibrosis, mononuclear leucocytic cellular infiltration and excessive glomerular and tubular degeneration and necrosis which further confirmed the nephrotoxic effects of cadmium. However, pre-treatment with DPFE exhibited a substantial ameliorative effect against cadmium-induced nephrotoxicity. DPFE supplementation led to a significant reduction in kidney biochemical parameters toward normal levels and improved renal tissue architecture. Our findings indicate that date palm fruit extract has a time-dependant protective effect on kidney function indices and histopathological alterations induced by cadmium, highlighting its potential as a natural medication to mitigate renal damage caused by chronic cadmium exposure. [ABSTRACT FROM AUTHOR]

Lithium (Li+) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li+ levels are nephrotoxic and can trigger a local immune response. Our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6NJ mice placed on a 0.3% lithium carbonate diet for 28 days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR and proteome profiler arrays to characterize renal tissue damage, infiltrating immune cells and cytokine markers, activation of pyroptotic and apoptotic cascades in the kidneys of mice receiving Li+-containing and regular diets. We found that biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinase-associated lipocalin, NGAL, were elevated in the renal tissue of Li+-treated mice when compared to controls. This correlated with increased interstitial fibrosis in Li+-treated mice. Administration of Li+ did not activate the pro-inflammatory NLRP3 inflammasome cascade but promoted apoptosis in the renal tissue. The TUNEL-positive signal and levels of pro-apoptotic proteins, Bax, cleaved caspase-3, and caspase-8, were elevated in the kidneys of Li+-treated mice. We observed a significantly higher abundance of CD93, CCL21, and fractalkine, accumulation of F4.80+ macrophages with reduced M1/M2 polarization ratio and decreased CD4+ levels in the renal tissue of Li+-treated mice when compared to controls. Therefore, after 28 days of treatment, Li+-induced insult to the kidney manifests in facilitated apoptotic cell death without an evident pro-inflammatory response.

Abstract Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.

Abstract Introduction Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. Methods In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. Results 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726–0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035–1.0041, P = 0.009). Conclusion Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE.

Abstract Background Elabela, a recently discovered hormonal peptide containing 32 amino acids, is a ligand for the apelin receptor. It can lower blood pressure and attenuate renal fibrosis. However, the clinicopathological relationship between Elabela level and renal damage caused by benign hypertension (BHT) and malignant hypertension (MHT) has not been elucidated. Therefore, we investigated the clinicopathological correlation between serum Elabela level and renal damage caused by BHT and MHT. Methods The participants comprised 50 patients and 25 age-matched healthy adults. The 50 patients were separated into two groups: MHT (n = 25) and BHT groups (n = 25). We analyzed their medical histories, demographics, and clinical examinations, including physical and laboratory tests. Results The results showed that serum Elabela level decreased gradually with a continuous increase in blood pressure from the healthy control group, BHT, to MHT. Moreover, Elabela levels negatively correlated with BMI (R = − 0.27, P = 0.02), SBP (r = − 0.64, P

AbstractIt is well-established that Morus alba and its derivatives have been clinically proven to have antioxidant and anti-inflammatory properties. Although several studies have mentioned the beneficial effect of Morus alba on kidney disorders, the role of Morus alba in CKD still needs to be explored. Thus, this study investigated the effect of Morus alba and chlorogenic acid treatment on renal fibrosis in mice induced with unilateral urethral obstruction (UUO). Twenty-five Balb/c mice were randomly divided into five groups: the sham-operated group, the UUO untreated group, and the UUO treated with enalapril (ENA), Morus alba leaves extract (MLE) and chlorogenic acid (CGA) groups. Urine, blood, and organ samples were collected to evaluate urinalysis, haematology, biochemistry, and histopathology. The result indicated that the UUO group had significantly higher levels of creatinine (p

Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies. [ABSTRACT FROM AUTHOR]

This investigation was planned to determine the ameliorative potential of robinetin (RN) to counteract the adverse effects of polystyrene microplastics (PSMPs) on renal tissues. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups i.e., control, PSMPs (0.01 mg/kg), PSMPs (0.01 mg/kg) + RN (50 mg/kg) and RN (50 mg/kg) only treated group. The activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSR) were reduced while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were escalated following the PSMPs intoxication. Moreover, PSMPs exposure increased the levels of urea, creatinine, KIM-1 and NGAL while downregulating the levels of creatinine clearance. Furthermore, PSMPs markedly escalated the levels of NF-κB, IL-6, IL-1β, TNF-α and COX-2 activity. Besides, the levels of Caspase-3, Bax and Caspase-9 were elevated while levels of Bcl-2 were reduced after PSMPs intoxication. Additionally, PSMPs administration instigated various histopathological anomalies in renal tissues. Nonetheless, RN supplementation considerably restored aforementioned dysregulations instigated by PSMPs due to its antioxidative, antiapoptotic and anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

Introduction: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. Methods: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. Results: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726–0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035–1.0041, P = 0.009). Conclusion: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE. [ABSTRACT FROM AUTHOR]

Background: Elabela, a recently discovered hormonal peptide containing 32 amino acids, is a ligand for the apelin receptor. It can lower blood pressure and attenuate renal fibrosis. However, the clinicopathological relationship between Elabela level and renal damage caused by benign hypertension (BHT) and malignant hypertension (MHT) has not been elucidated. Therefore, we investigated the clinicopathological correlation between serum Elabela level and renal damage caused by BHT and MHT. Methods: The participants comprised 50 patients and 25 age-matched healthy adults. The 50 patients were separated into two groups: MHT (n = 25) and BHT groups (n = 25). We analyzed their medical histories, demographics, and clinical examinations, including physical and laboratory tests. Results: The results showed that serum Elabela level decreased gradually with a continuous increase in blood pressure from the healthy control group, BHT, to MHT. Moreover, Elabela levels negatively correlated with BMI (R = − 0.27, P = 0.02), SBP (r = − 0.64, P < 0.01), DBP (r = − 0.58, P < 0.01), uric acid (r = − 0.39, P < 0.01), bun (r = − 0.53, P < 0.01), and Scr (r = − 0.53 P < 0.01) but positively correlated with eGFR (r = 0.54, P < 0.01). Stepwise multivariate linear regression analysis showed that SBP was the variable most related to Elabela (t = − 5.592, P < 0.01). Conclusions: Serum Elabela levels decreased in patients with hypertension, especially malignant hypertension, and has the potential to be a marker of hypertension-related kidney damage. [ABSTRACT FROM AUTHOR]

Objective: Acute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia–reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated. Methods: New Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated. Results: After IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted. Conclusion: This study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

Abstract Background It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney diseases. However, there have been few studies with large sample sizes, and their findings were inconsistent. This study aimed to conduct a meta-analysis of MGRS to describe the general characteristics of MGRS and its predictive factors. Methods Cohort or case-control studies published through December 2022 and related to clinicopathological features of MGRS were retrieved from the PubMed, Cochrane Library, Web of Science, Scopus, and Embase databases. Two researchers searched for studies that met the inclusion criteria. In the univariate analysis, fixed- or random- effects models were used to obtain pooled estimates of the weighted mean difference (WMD) and odds ratio (OR) for risk factors. In the multivariate analysis, the ORs of the independent risk factors from each study were pooled after transforming the original estimates. Results The meta-analysis included six studies. Univariate analysis showed that the following variables were statistically significant in MGRS: age (WMD = 1.78, 95%CI 0.21–3.35), hypertension (OR = 0.54, 95%CI 0.4–0.73), diabetes (OR = 0.42, 95%CI 0.29–0.59), albumin (WMD = − 0.26, 95%CI − 0.38–−0.14), urinary protein level (WMD = 0.76, 95%CI 0.31–1.2), urinary protein ≥ 1.5 g/d (OR = 1.98, 95%CI 1.46–2.68), lambda-chain value (WMD = 29.02, 95%CI 16.55–41.49), abnormal free light-chain ratio (OR = 4.16, 95%CI 1.65–10.47), bone marrow puncture rate (OR = 5.11, 95% CI 1.31–19.95), and abnormal bone marrow outcome rate (OR = 9.63, 95%CI 1.98–46.88). Multivariate analysis showed urinary protein ≥ 1.5 g/d (OR = 2.80, 95%CI 1.53–5.15) and an abnormal free light-chain ratio (OR = 6.98, 95%CI 4.10–11.91) were associated with predictors of MGRS. Conclusions Compared with non-MGRS patients with monoclonal gammopathy and concomitant kidney diseases, patients with MGRS were older, had fewer underlying diseases, more urinary protein, more abnormal free light-chain ratio, and more abnormal bone marrow results. Urinary protein ≥ 1.5 g/d and an abnormal free light-chain ratio were independent risk factors for MGRS.

Objective To explore the relevance between neutrophil-to-lymphocyte ratio (NLR) and renal injury in patients with primary Sjogren's syndrome (pSS) and evaluate the clinical application value of NLR in renal injury of pSS. Methods From January 2017 to June 2022, the relevant clinical data were retrospectively reviewed for 134 hospitalized pSS patients. Based upon the presence or absence of renal injury, they were assigned into two groups of pSS with renal injury and pSS without renal injury. NLR and other laboratory parameters were compared between two groups. Through Spearman's rank correlation analysis, the correlations were examined between NLR and renal injury parameters (creatinine, urea nitrogen, uric acid, cystatin C & glomerular filtration rate) and inflammation-related parameters (erythrocyte sedimentation rate & C-reactive protein). The risk factors of renal injury were explored by multivariate Logistic regression. Receiver operating characteristic (ROC) curve was utilized for comparing the diagnostic efficacy of NLR, renal injury parameters and inflammation-related parameters for renal injury in pSS. Results NLR was markedly elevated in renal injury group than that in renal non-injury group (P

This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv. leaves flavonoids (CLF) on hyperuricemia induced by potassium oxonate in mice. The results showed that CLF lowered the serum levels of uric acid (UA), creatinine and blood urea nitrogen, downregulated hepatic mRNA expressions of xanthine oxidase (XO), phosphate ribose pyrophosphate synthetase (PRPS) and adenosine deaminase (ADA) in hyperuricemia mice. In addition, CLF repaired renal injury by significantly down-regulating mRNA and protein expressions of renal UA reabsorption-related proteins and up-regulating the mRNA and protein expressions of UA secretory-related proteins. Finally, CLF inhibited UA synthesis and promoted UA excretion to alleviate hyperuricemia. Besides, CLF supplementation repaired the intestinal barrier function as demonstrated by significant increased mRNA levels of intestinal zonula occludens-1 (ZO-1), Occludin, mucin 2 (MUC2) and mucin 4 (MUC4), as well as decreased mRNA levels of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) in mice. Further research showed that CLF treatment restored intestinal homeostasis mediated by improving the composition of gut microbiota and elevating the abundance of beneficial bacteria like Lactobacillus, Alistipes, Prevotellaceae_UCG-001 and Parasutterella. Overall, our findings revealed a novel function of CLF as a promising therapeutic candidate for the treatment of hyperuricemia.

Background: It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney diseases. However, there have been few studies with large sample sizes, and their findings were inconsistent. This study aimed to conduct a meta-analysis of MGRS to describe the general characteristics of MGRS and its predictive factors. Methods: Cohort or case-control studies published through December 2022 and related to clinicopathological features of MGRS were retrieved from the PubMed, Cochrane Library, Web of Science, Scopus, and Embase databases. Two researchers searched for studies that met the inclusion criteria. In the univariate analysis, fixed- or random- effects models were used to obtain pooled estimates of the weighted mean difference (WMD) and odds ratio (OR) for risk factors. In the multivariate analysis, the ORs of the independent risk factors from each study were pooled after transforming the original estimates. Results: The meta-analysis included six studies. Univariate analysis showed that the following variables were statistically significant in MGRS: age (WMD = 1.78, 95%CI 0.21–3.35), hypertension (OR = 0.54, 95%CI 0.4–0.73), diabetes (OR = 0.42, 95%CI 0.29–0.59), albumin (WMD = − 0.26, 95%CI − 0.38–−0.14), urinary protein level (WMD = 0.76, 95%CI 0.31–1.2), urinary protein ≥ 1.5 g/d (OR = 1.98, 95%CI 1.46–2.68), lambda-chain value (WMD = 29.02, 95%CI 16.55–41.49), abnormal free light-chain ratio (OR = 4.16, 95%CI 1.65–10.47), bone marrow puncture rate (OR = 5.11, 95% CI 1.31–19.95), and abnormal bone marrow outcome rate (OR = 9.63, 95%CI 1.98–46.88). Multivariate analysis showed urinary protein ≥ 1.5 g/d (OR = 2.80, 95%CI 1.53–5.15) and an abnormal free light-chain ratio (OR = 6.98, 95%CI 4.10–11.91) were associated with predictors of MGRS. Conclusions: Compared with non-MGRS patients with monoclonal gammopathy and concomitant kidney diseases, patients with MGRS were older, had fewer underlying diseases, more urinary protein, more abnormal free light-chain ratio, and more abnormal bone marrow results. Urinary protein ≥ 1.5 g/d and an abnormal free light-chain ratio were independent risk factors for MGRS. [ABSTRACT FROM AUTHOR]

A common and efficient analgesic-antipyretic medication for a variety of syndromes is paracetamol (PAR). The use of PAR was associated with acute kidney injury and other side effects, and its hazardous effects were influenced by oxidative stress and inflammation. Black seed oil's primary active ingredient, thymoquinone (TQ), has anti-inflammatory, immunomodulatory, and antioxidant properties. A few animal models for drug-induced nephrotoxicity described promising outcomes of its renoprotective action. The main goal of this work was to evaluate TQ nanoparticles' (TQNP) powerful renoprotective properties in a rat model of nephrotoxicity caused by PAR. Three groups of eight rats each were assigned; group one (the control group, CON) was given gavaged normal saline. Group 2 (PAR group, PAR) received 600 mg/kg of gavaged PAR diluted in regular saline. One hour after PAR delivery, group 3 (the TQNP group) received TQNP 0.5 mg/kg via oral administration. In rat kidney tissues, PAR resulted in renal damage, a rise in blood urea nitrogen (BUN), creatinine, cystatin C (CYC), myeloperoxidase, protein carbonyl (PC), malondialdehyde (MDA), and a decrease in nitric oxide and cellular antioxidants. In rats given PAR, TQNP effectively reduced renal damage, lowered serum levels of creatinine, BUN, and CYC, and improved oxidative stress (MDA, MYO, and PC) and inflammatory markers (TNFα and IFN-γ). TQNP treatment resulted in modestly dilated/congested blood vessels in the renal tissues of PAR. The TQNP's renoprotective action is an effective preventative against PAR-induced nephrotoxicity, primarily by enhancing cellular defense mechanisms and reducing inflammatory and oxidative indicators in a rat model. However, additional research and clinical trials should be needed for testing in future studies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potential of 3 T magnetic resonance diffusion kurtosis imaging (DKI) in assessing the renal damage in early-stage of chronic kidney disease (CKD) patients with normal or slightly changed functional index, using histopathology as reference standard. Methods: 49 CKD patients and 18 healthy volunteers were recruited in this study. CKD patients were divided into two groups based on estimated glomerular filtration rate (eGFR): Study group I (eGFR ≥ 90 ml/min/1.73 m2 [n = 20]) and Study group II (eGFR < 90 ml/min/1.73 m2 [n = 29]). DKI was performed in all participants. The DKI parameters (mean kurtosis [MK], mean diffusivity [MD], fractional anisotropy [FA]) of renal cortex and medulla were measured. The differences of parenchymal MD, MK and FA values among the different groups were compared. The correlations between DKI parameters and clinicopathological characteristics were assessed. Diagnostic performance of DKI to assess renal damage in early-stage of CKD was analyzed. Results: The cortex MD and MK showed significant difference among three groups (P < 0.05): trend of cortex MD: Study group II < Study group I < control group; trend of cortex MK: control group < Study group I < Study group II. The cortex MD and MK and medulla FA were correlated with eGFR and Interstitial fibrosis/Tubular atrophy score (0.3 < r < 0.5). Cortex MD and MK yielded an AUC of 0.752 for differentiating healthy volunteers from CKD patients with eGFR ≥ 90 ml/min/1.73 m2. Conclusion: DKI shows potential in non-invasive and multi-parameter quantitative assessment of renal damage in early-stage of CKD patients and provide additional information for changes in renal function and histopathology. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the nexus between mitochondrial function and kidney injury by using a dietary-induced obese minipig model. Female Lee-Sung minipigs feeding a high-fat diet (HFD) for 6 months exhibited obesity, hyperglycaemia and dyslipidemia. HFD elevated the levels of plasma biomarkers related to renal injury, including symmetric dimethylarginine, creatinine and urea nitrogen. An extensive structural change in tubules and glomeruli was observed in HFD-fed pigs. A great amount of triacylglycerol was accumulated in HFD kidney compared to control kidney, whereas a reduction of ATP level and antioxidant capacity were exhibited in HFD kidney. Moreover, HFD altered the expressions of mitochondrial-related protein in renal cortex. To conclude, long-term HFD feeding to Lee-Sung minipigs induced obesity and kidney injury accompanied by abnormal mitochondrial functions in the renal cortex, suggesting an interrelationship with renal disease progression. [ABSTRACT FROM AUTHOR]

Background and Aims: To evaluate the association of Chinese visceral adiposity index (CVAI) and its dynamic trends with risk of renal damage, and to compare its prediction performance with that of other obesity indices. Methods and Results: A community-based population with 23 905 participants from Shantou city was included in the cross-sectional analysis. A total of 9,778 individuals from two separated cohort were included in the longitudinal portion. Five patterns of CVAI change were predefined (low-stable, decreasing, moderate, increasing, and persistent-high). Logistic and Cox regressions were used to evaluate the association between CVAI and renal damage. We explored potential mechanisms using the mediating effect method, and the prediction performance was determined by receiver operating characteristic curve analysis. Results from both cross-sectional and longitudinal data revealed a positive and linear association between CVAI and risk of renal damage. Pooled analysis of the two cohorts showed that per unit increase in Z score of CVAI induced 18% increased risk of renal damage (P = .008). Longitudinal trends of CVAI were also associated with renal damage, and the moderate, increasing, and persistenthigh patterns showing a higher risk. Blood pressure and glucose had a mediating effect on renal damage induced by CVAI. Among several obesity indices, CVAI was the optimal for predicting renal damage. Conclusion: A higher level of immediate CVAI and longitudinal increasing and persistent-high patterns of CVAI were independently associated with increased risk of renal damage. Monitoring immediate level and long-term trend of CVAI may contribute to the prevention of renal damage. [ABSTRACT FROM AUTHOR]

Objectives: To assess the ideal interval between repeated extracorporeal shockwave lithotripsy (SWL) for renal stones. Patient and Methods: Eligible patients with a single renal stone ≤20 mm who required SWL were randomly assigned to one of three groups based on intervals between first and second sessions. Patients underwent the second session after 3, 7, and 14 days in Groups 1, 2, and 3, respectively. Tubular functions were assessed through comparisons of urinary execration of kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), and interleukin-18 (IL-18) with pre-SWL values, whereas glomerular function was assessed by comparisons of protein/creatinine ratio with pre-SWL and changes in ipsilateral renal function on isotope scans. Treatment success was assessed by noncontrast CT after 3 months. Results: All demographics of the 166 patients included in the study were comparable between the three groups. There were significant elevations of tubular biomarkers and protein/creatinine ratio after first and second SWL sessions compared with pre-SWL values (p < 0.0001). All tubular biomarkers returned to pre-SWL values at 7 and 14 days after second session, whereas they remained significantly elevated 3 days after second session (p = 0.027, < 0.001 and <0.001 for KIM-1, NGAL, and IL-18, respectively). SWL success was 73.6% in Group 1, 83.7% in Group 2, and 81% in Group 3. A significant decrease in ipsilateral renal split function was observed in Group 1 at the 3-month follow-up. Conclusions: An interval of 7 days is required between SWL sessions when treating renal stones to allow for complete recovery of kidney functions. Clinical Trial Registration: ID: NCT04575480. [ABSTRACT FROM AUTHOR]

(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins. [ABSTRACT FROM AUTHOR]

Introduction: Two of the most frequent Lupus nephritis (LN) diseases are multiple glomerulonephritis and renal fibrosis. Recent studies have verified that 10-30% of patients with SLE after several years (3-6 years) develop LN and end-stage chronic renal disease (ESRD) when there is a need for chronic intermittent hemodialysis (HD) treatment. [1, 2, 3] The paper aimed to assess renal damage due to LN using the results obtained from the examined parameters in patients with chronic kidney disease (CKD) in the third stage (a and b). Materials and Methods: This prospective cohort research (cross-section ") study included 100 patients with CKD (55 were men with an average age of 57.00±8.50 years old with chronic renal disease, 20 with diabetes mellitus (DM) and nephropathy diabetics, 15 were arterial hypertension (AHT), 11 were with chronic glomerulonephritis (CGN), 3 with Adult polycystic kidney disease (APCKD) and six patients were with undefined renal disease, while 45 were female with an average age of 55.80 ±10.50 years old), with primary kidney disease: 16-with diabetes mellitus and diabetic nephropathy,11 with HTA… Statistical analysis of the examined material: The obtained results from the studied patients with CKD and the control group were statistically processed with arithmetic mean value, standard deviation X ± SD, with student, "t" test, Mann-Whitney and Wilcoxon test. The results were processed with the appropriate state-of-the-art statistical program, SPSS V26. Results: the results obtained at the beginning of the study (for all patients with LN and CKD: women and men) and after 12 months of treatment are presented in tables and graphs 4 and 8. Conclusion: From the results obtained, we can conclude that LES affects the appearance of renal damage; therefore, early detection and treatment of the initial stages of LN seem to influence the reduction of its activity.

Nonylphenol (NP) is potent noxious pollutant which is documented to induce nephrotoxicity via escalating the levels of oxidative stress in renal tissues. Aucubin (AUC) is a novel phytochemical having tremendous pharmacological abilities. This research aimed to estimate the efficacy of AUC against NP intoxicated renal impairment in male albino rats. 48 albino rats were randomly assigned into four different groups viz. control group, NP administered group (50 mg/kg), NP + AUC administrated (50 mg/kg + 40 mg/kg) group and AUC treated (40 mg/kg) group. Our results showed that NP intoxication raised urinary proteins, creatinine, urea, urobilinogen, NGAL and KIM-1 levels. Besides, NP exposure lowered the levels of creatinine clearance and albumin. Furthermore, NP treatment lowered level of total protein, activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GSR) & glutathione (GSH) contents along with the level of total antioxidant status (TAS) however, raising the oxidative stress markers levels Thiobarbituric acid reactive substance (TBARS), reactive oxygen species (ROS), hydrogen peroxide (H2O2) & total oxidant status (TOS). Additionally, following the NP administration, the levels of Bax, caspase-9, & caspase-3 were augmented however the Bcl-2 level was decreased. Furthermore, rats exposed to NP showed various histopathological disruptions. Whereas treatment with AUC showed a palliative effect against NP-induced renal damage, restoring all alterations to normal levels. Taken together, AUC administration convalesced NP-induced kidney impairment.

Abstract Objective To explore the clinical features of renal damage related to pregnancy and pregnancy after chronic kidney disease (CKD), providing clinical evidence for the relationship between renal damage and pregnancy. Methods A retrospective analysis was performed on patients admitted to our hospital between March 2013 and February 2021 who had both pregnancy and kidney damage. The study collected pathology results from renal biopsies, 24-hour urinary protein quantity, albumin (Alb), serum creatinine (Scr), blood lipids, coagulation function, blood routine, and other indicators during and after pregnancy. Results This study included 82 cases, with 48 cases in the pregnancy-related renal damage group. Thirty-four cases were in the post-CKD pregnancy group. Of the patients, 30 cases (88.24%) had CKD stage 1–2. Results showed better pregnancy and fetal outcomes in the post-CKD pregnancy group compared to the pregnancy-related renal damage group (Ρ was 0.029 and 0.036, respectively). Renal biopsy pathology revealed that 16 cases (33.33%) in the pregnancy-related renal damage group mainly had focal segmental glomerulosclerosis (FSGS), while the post-CKD pregnancy group was dominated by 14 cases (43.75%) of IgA nephropathy. The first blood test indicators revealed that the pregnancy-related renal damage group had lower estimated glomerular filtration (eGFR) and Alb levels compared to the post-CKD pregnancy group (Ρ was 0.003 and 0.000, respectively). Additionally, 24-hour urinary protein quantity, total cholesterol (Tch), triglyceride (TG), and platelet (PLT) counts were higher in the pregnancy-related renal damage group compared to the post-CKD pregnancy group (Ρ was 0.005, 0.001, 0.008, and 0.031, respectively). The abnormal rate of Scr during pregnancy was 41.67% (20/48) in the pregnancy-related renal damage group and 17.39% (4/23) in the post-CKD pregnancy group, with a statistically significant difference (Ρ was 0.043). Conclusion The pregnancy-related renal damage group is mainly associated with FSGS, while the post-CKD pregnancy group is characterized by IgA nephropathy. Patients with CKD1-2 can have a successful pregnancy after achieving good control of eGFR, albumin, 24-hour urinary protein quantity and other indicators, resulting in better pregnancy and fetal outcomes. Abnormal Scr levels during pregnancy of pregnancy-related renal damage can be improved within 3 months after delivery.

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.

Over the past few decades, significant progress has been made in the development of drugs to combat cancer. It is unfortunate that these drugs can also lead to various kidney injuries and imbalances in electrolyte levels. Nephrotoxicity caused by chemotherapy drugs can impact different parts of the kidneys, including the glomeruli, renal tubules, interstitium, or renal microvessels. Despite the existing knowledge, our understanding of the mechanisms underlying the renal damage caused by antitumoral drugs remains incomplete. In this review, we aim to provide a comprehensive overview of the specific types of kidney injury and the mechanisms responsible for the drug-mediated renal damage, and briefly discuss possible prevention and treatment measures. Sensitive blood and urine biomarkers can provide clinicians with more information about kidney injury detection and reference value for subsequent treatment options. In addition, we emphasize that both oncologists and nephrologists have a responsibility to remain vigilant against the potential nephrotoxicity of the drugs. It’s crucial for experts in both fields to collaborate in early detection, monitoring and prevention of kidney damage.

The incidence of diabetes mellitus (DM) is gradually increasing, making it a widespread global health concern. Cadmium (Cd) is a common toxic heavy metal in the environment, and cadmium exposure may be associated with diabetic nephropathy (DN). However, the mechanism of Cd-induced DN remains unclear. In this study, we aimed to determine the effect of cadmium on diabetic kidney injury and the underlying mechanism in diabetic rats and a renal tubular epithelial cell line (NRK-52E cells). Our results could provide novel insights on the nephrotoxic mechanism of cadmium. HE, PAS, and Masson staining were used to observe pathological renal injury. COL-I, COL-IV, CTSB, and CTSD protein levels were detected by immunohistochemistry and western blotting. Immunofluorescence was used to detect the fluorescence intensity of p62 and LC3 proteins in kidney tissue. TEM was used to observe the ultrastructure of mitochondria and number of autophagosomes. After cadmium exposure, DM rats showed a dramatic decrease in body weight compared to the unexposed DM group. Relative kidney weight showed a contrasting trend after cadmium exposure. Urinary microalbumin/creatinine significantly increased in normal and DM rats after cadmium exposure. However, the trend was clearer in the DM groups than in the control groups. Endogenous creatinine clearance exhibited a contrasting trend. After cadmium exposure in DM rats, MDA content significantly increased and GSH, CAT, SOD, and GSH-PX activation reduced compared to normal controls. Pathological damage was more pronounced, and the expression of autophagy related proteins and apoptosis and fibrosis proteins was significantly higher in vivo and vitro in the cadmium-exposed groups than in unexposed controls. Further, lysosomal protein levels were lower, and ROS content and autophagosome count significantly higher in the cadmium exposed groups compared to the unexposed controls. Therefore, Cadmium exposure aggravates diabetic kidney injury via autophagy inhibition.

The present study was designed to evaluate the palliative potential of ginkgetin (GK) against polystyrene microplastics (PS-MPs) instigated renal damage in rats. 24 rats were separated into 4 groups i.e., control, PS-MPs-intoxicated (0.01mgkg-1), PS-MPs (0.01mgkg-1) and GK (25mgkg-1) administrated and GK (25mgkg-1) only treated group. Results of the experiment showed that the activities of anti-oxidant enzymes i.e., glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GSR) & catalase (CAT) were significantly decreased, while the levels of ROS and MDA were increased following PS-MPs treatment. Furthermore, PS-MPs intoxication increased the levels of kidney function markers such as creatinine, urea, NGAL and KIM-1, while a significant reduction was observed in creatinine clearance. Moreover, PS-MPs significantly increased the TNF-α, NF-κB, IL-6, IL-1β levels and COX-2 activity. Furthermore, it reduced the Bcl-2 level, while increased the levels of Caspase-9, Bax and Caspase-3 and induced histological damages in the renal tissues. However, the treatment of GK significantly regulated the biochemical, renal, inflammatory, apoptotic markers and attenuated the PS-MPs induced histopathological damages due to its reno-protective, anti-apoptotic, anti-oxidant and anti-inflammatory nature. [ABSTRACT FROM AUTHOR]

Background and Purpose: Complement activation may drive hypertension through its effects on immunity and tissue integrity. Experimental Approach: We examined expression of C3, the central protein of the complement cascade, in hypertension. Key Results: Increased C3 expression was found in kidney biopsies and micro‐dissected glomeruli of patients with hypertensive nephropathy. Renal single cell RNA sequence data from normotensive and hypertensive patients confirmed expression of C3 in different cellular compartments of the kidney. In angiotensin II (Ang II) induced hypertension renal C3 expression was up‐regulated. C3−/− mice revealed a significant lower albuminuria in the early phase of hypertension. However, no difference was found for blood pressure, renal injury (histology, glomerular filtration rate, inflammation) and cardiac injury (fibrosis, weight, gene expression) between C3−/− and wildtype mice after Ang II infusion. Also, in deoxycorticosterone acetate (DOCA) salt hypertension, a significantly lower albuminuria was found in the first weeks of hypertension in C3 deficient mice but no significant difference in renal and cardiac injury. Down‐regulation of C3 by C3 targeting GalNAc (n‐acetylgalactosamine) small interfering RNA (siRNA) conjugate decreased C3 in the liver by 96% and lowered albuminuria in the early phase but showed no effect on blood pressure and end‐organ damage. Inhibition of complement C5 by siRNA showed no effect on albuminuria. Conclusion and Implications: Increased C3 expression is found in the kidneys of hypertensive mice and men. Genetic and therapeutic knockdown of C3 improved albuminuria in the early phase of hypertension but did not ameliorate arterial blood pressure nor renal and cardiac injury. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical features of renal damage related to pregnancy and pregnancy after chronic kidney disease (CKD), providing clinical evidence for the relationship between renal damage and pregnancy. Methods: A retrospective analysis was performed on patients admitted to our hospital between March 2013 and February 2021 who had both pregnancy and kidney damage. The study collected pathology results from renal biopsies, 24-hour urinary protein quantity, albumin (Alb), serum creatinine (Scr), blood lipids, coagulation function, blood routine, and other indicators during and after pregnancy. Results: This study included 82 cases, with 48 cases in the pregnancy-related renal damage group. Thirty-four cases were in the post-CKD pregnancy group. Of the patients, 30 cases (88.24%) had CKD stage 1–2. Results showed better pregnancy and fetal outcomes in the post-CKD pregnancy group compared to the pregnancy-related renal damage group (Ρ was 0.029 and 0.036, respectively). Renal biopsy pathology revealed that 16 cases (33.33%) in the pregnancy-related renal damage group mainly had focal segmental glomerulosclerosis (FSGS), while the post-CKD pregnancy group was dominated by 14 cases (43.75%) of IgA nephropathy. The first blood test indicators revealed that the pregnancy-related renal damage group had lower estimated glomerular filtration (eGFR) and Alb levels compared to the post-CKD pregnancy group (Ρ was 0.003 and 0.000, respectively). Additionally, 24-hour urinary protein quantity, total cholesterol (Tch), triglyceride (TG), and platelet (PLT) counts were higher in the pregnancy-related renal damage group compared to the post-CKD pregnancy group (Ρ was 0.005, 0.001, 0.008, and 0.031, respectively). The abnormal rate of Scr during pregnancy was 41.67% (20/48) in the pregnancy-related renal damage group and 17.39% (4/23) in the post-CKD pregnancy group, with a statistically significant difference (Ρ was 0.043). Conclusion: The pregnancy-related renal damage group is mainly associated with FSGS, while the post-CKD pregnancy group is characterized by IgA nephropathy. Patients with CKD1-2 can have a successful pregnancy after achieving good control of eGFR, albumin, 24-hour urinary protein quantity and other indicators, resulting in better pregnancy and fetal outcomes. Abnormal Scr levels during pregnancy of pregnancy-related renal damage can be improved within 3 months after delivery. [ABSTRACT FROM AUTHOR]

OBJECTIVE: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARSCoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Infiltrating T cells in the kidney amplify salt-sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells (SSCD247−/−) or of the p67phox subunit of NADPH oxidase 2 (NOX2; SSp67phox−/−) attenuates SS hypertension in the Dahl SS rat. We hypothesized that reactive oxygen species produced by NOX2 in T cells drive the SS phenotype and renal damage. T cells were reconstituted by adoptively transferring splenocytes (∼10 million) from the Dahl SS (SS→CD247) rat, the SSp67phox−/− rat (p67phox→CD247), or only PBS (PBS→CD247) into the SSCD247−/− rat on postnatal day 5. Animals were instrumented with radiotelemeters and studied at 8 wk of age. There were no detectable differences in mean arterial pressure (MAP) or albuminuria between groups when rats were maintained on a low-salt (0.4% NaCl) diet. After 21 days of high-salt diet (4.0% NaCl), MAP and albuminuria were significantly greater in SS→CD247 rats compared with p67phox→CD247 and PBS→CD247 rats. Interestingly, there was no difference between p67phox→CD247 and PBS→CD247 rats in albuminuria or MAP after 21 days. The lack of CD3+ cells in PBS→CD247 rats and the presence of CD3+ cells in rats that received the T cell transfer demonstrated the effectiveness of the adoptive transfer. No differences in the number of CD3+, CD4+, or CD8+ cells were observed in the kidneys of SS→CD247 and p67phox→CD247 rats. These results indicate that reactive oxygen species produced by NOX2 in T cells participates in the amplification of SS hypertension and renal damage. NEW & NOTEWORTHY Our current work used the adoptive transfer of T cells that lack functional NADPH oxidase 2 into a genetically T cell-deficient Dahl salt-sensitive (SS) rat model. The results demonstrated that reactive oxygen species produced by NADPH oxidase 2 in T cells participate in the amplification of SS hypertension and associated renal damage and identifies a potential mechanism that exacerbates the salt-sensitive phenotype. [ABSTRACT FROM AUTHOR]

Cisplatin is clinically proven to combat different cancers, including sarcomas, soft tissue cancers, bones, muscles, and blood. However, renal and cardiovascular toxicities are important limitations in cisplatin therapeutical use. Immunoinflammation could be key factor in cisplatin‐induced toxicity. The aim of the present study was to evaluate the activation of the inflammatory TLR4/NLRP3 pathway as a common mechanism for cardiovascular and renal cisplatin's cycles treatment toxicity. Adult male Wistar rats were treated with saline, cisplatin 2 mg/kg or cisplatin 3 mg/kg (intraperitoneally once a week, for five experimental weeks). After treatments, plasma, cardiac, vascular, and renal tissues were collected. Plasma malondialdehyde (MDA) and inflammatory cytokines were determined. TLR4, MyD88, NF‐κβ p65, NLRP3, and procaspase‐1 tissue expressions were also analyzed. Cisplatin treatment induced a dose‐dependent increase in plasma MDA and IL‐18. In cardiovascular system, an increase in NLRP3 and in cleaved caspase‐1 were observed in cardiac tissue and a moderate increase in TLR4, MyD88 appeared in mesenteric artery. In kidney, a significant dose‐dependent increase in TLR4, MyD88 and NLRP3 and cleaved caspase 1 expressions were observed after cisplatin treatments. In conclusion, cisplatin cycles provoke a low grade pro‐inflammatory systemic state. Kidney was more sensitive than cardiovascular tissues to this pro‐inflammatory state. TLR4 and NLRP3 are key pathways involved in renal tissue damage, NLRP3 is the main pathway involved in cardiac toxicity and TLR4 pathway in resistance vessel toxicity. [ABSTRACT FROM AUTHOR]