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Objective The purpose of the current study was to describe the clinico-pathological characteristics and outcomes in patients with lupus nephritis with IgA deposits in the kidneys. Materials and Methods A total of 258 patients with lupus nephritis with complete clinical data and follow-up was enrolled. They were divided into two groups: the IgA deposits group and the non-IgA deposits group. Their clinico-pathological features and outcomes between the two groups were further compared. Results Patients with IgA deposits had significantly lower prevalence of acute kidney failure, higher eGFR, lower plasma levels of C3a, and lower renal pathological chronicity indices scores than those with non-IgA deposits (19.4% vs. 31.8%, 80.9±35.6 vs. 69.1±39.6 ml/min/1.73m2, 1045.48 [559.41, 1796.34] vs. 1920.77 [1155.08, 2986.96]ng/ml, and 2 [1, 3] vs. 2.5 [2, 4], respectively, all P Conclusions Patients with IgA deposits presented with milder renal damage and a good prognosis, which suggested its protective role in lupus nephritis.

Background and Purpose: Drainage of obstructed kidney due to extrinsic ureteral obstruction (EUO), required to prevent renal damage, is often achieved using double-J ureteral stents. But these stents fail frequently, and there is considerable debate regarding what stent size, type and configuration offer the best option for sustained drainage. Here, we examine the impact of stent diameter and choice of single/tandem configuration, subject to EUO and various degrees of stent occlusion, on stent failure. Methods: Computational fluid dynamics (CFD) simulations and an in vitro ureter-stent experiment enabled quantification of flow behavior in stented ureters subject to EUO and stent occlusions. Various single and tandem stents under EUO were considered. In each simulation and experiment, changes in renal pressure were monitored for different degrees of stent lumen occlusion, and onset of stent failure as well as simulated distributions of fluid flow between stent and ureter lumina were determined. Results: For an encircling EUO that completely obstructs the ureter lumen, with or without partial stent occlusion, the choice of stent size/configuration has little effect on renal pressure. The pressure increases significantly for ~90% stent lumen occlusion, with failure at >95% occlusion, independent of stent diameter or a tandem configuration, and with little influence of occlusion length along the stent. Conclusions: Stent failure rate is independent of stent diameter or single/tandem configuration, for the same percentage of stent lumen occlusion, in this model. Stent failure incidence may decrease for larger diameter stents and tandem configurations, because of the larger luminal area.

Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic disease. Renal manifestations have been rarely observed in JIA, although amyloidosis could be a renal complication in systemic JIA (sJIA). To investigate renal damage in JIA children and to establish the relationship with treatment. Blood urea nitrogen (BUN), creatinine, cystatin C (CysC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and renal resistive index (RRI) were assessed in 49 JIA children (9 boys/40 girls, mean age 10.3 ± 3.8 years) and in 49 healthy controls (24 boys/25 girls, mean age 11.3 ± 3.4 years). Twenty-two JIA patients were on methotrexate (MTX) therapy (group A) and 27 on biologic drugs (group B). CysC and BUN (respectively, 0.8 ± 0.1 vs. 0.7 ± 0.1 mg/dl; 13.3 ± 2.9 vs. 11.7 ± 1.4 mg/dl) were higher (p ≤ 0.001) whereas creatinine and eGFR (respectively, 0.5 ± 0.1 vs. 0.6 ± 0.1 mg/dl; 99.2 ± 10.5 vs. 122.5 ± 19.8 ml/min/1.73 m2) were lower in JIA children as compared to controls (p p = 0.003). Mean RRI was higher in JIA children than controls (0.7 ± 0.04 vs. 0.6 ± 0.04; p p p p = 0.003) and eGFR (p = 0.001). JIA children had reduced eGFR, increased UAE and higher RRI values, than controls. RRIs were higher in patients on biologic drugs than MTX group and were associated with inflammation indexes and disease state, suggesting a direct effect of the disease.

Background For long Epstein–Barr virus (EBV) has been suspected to be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to verify the association between EBV, cell-free DNA (cfDNA) and kidney disease in SLE. Methods Blood samples were obtained from 43 SLE patients and 50 healthy individuals. EBV load was measured via real-time PCR assay. Sizing and quantification of plasma cfDNA was performed on Bioanalyzer. We proposed that the uniformity of cfDNA fragmentation can be described using cfDNA fragmentation index. Results SLE patients with chronic kidney disease (CKD +) had higher EBV load compared to CKD(–) patients (P = 0.042). Patients with high cfDNA level had higher EBV load (P = 0.041) and higher cfDNA fragmentation index (P 2 = 0.13), and the correlation was even more pronounced in CKD (+) patients (P 2 = 0.20). Conclusions We showed that EBV load was associated with non-uniform cfDNA fragmentation, higher cfDNA levels, and kidney disease in SLE patients. Although the causality of this relationship could not be determined with the current study, it brings rationale for further investigations on the role of EBV and cfDNA interplay in SLE pathogenesis.

Background Children with β-thalassemia major (β-TM) suffer from tubular dysfunction even before the onset of any renal impairment symptoms and/or clinical signs. Therefore, identifying innovative biomarkers allowing early renal damage detection has focused attention. Aim This study aims to preliminary assess Netrin-1(NTN-1) and clusterin (CLU) in β-TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction. Subjects and methods In this study, 40 β-TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN-1 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real-time PCR. Serum TNF-α, MDA levels and GST activity were measured. Results Urinary NTN-1 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in β-TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in β-TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN-1 and CLU levels are of promising diagnostic performance. Conclusion Our results suggest that NTN-1 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in β-TM children. Moreover, urinary NTN-1 is recommended as a precise one during the clinical practices.

This study sought to explore the related factors of orthostatic hypotension (OH) in elderly patients with essential hypertension, and analyze the relationship between early renal damage and OH in elderly hypertensive patients.The demographic and clinical data of 511 elderly patients with essential hypertension (EH) were collected from September 2017 to September 2018.These patients were divided into group with OH and group without OH. The data were compared between the two groups to analyze correlations between OH and early renal damage indicators [urine microalbumin (mAlb)30 mg/L].In the study, 118 were in the OH+ group, and 393 were in the OH-group. The proportion of patients with coronary heart disease, atherosclerosis, grade 3 hypertension, persistent rapid atrial fibrillation, left ventricular diastolic dysfunction, and left ventricular hypertrophy in OH+ group was significantly higher than in OH- group (P0.05). Further, logistic regression analysis showed that coronary heart disease, carotid atherosclerosis, and grade 3 hypertension are independent associated factors for OH in elderly EH patients. In the 511 patients, 249 had urine mAlb30 mg/L, and 262 had urine mAlb ≤30 mg/L. The 24-hour systolic blood pressure (SBP)-coefficient of variation (CV), the 24-hour diastolic blood pressure (DBP)-coefficient of variation (CV), the drop difference of both SBP and DBP from supine to standing position in 3-minute were higher in patients with urine mAlb30 mg/L than in patients with urine mAlb ≤30 mg/L (P0.05). The urine mAlb of patients with OH was higher than that of patients without OH, and the urine mAlb of patients with elevated blood pressure variability (BPV) was also higher than that in patients with normal BPV (P0.05). Further groupings revealed that patients with both OH and elevated BPV had the highest urine mAlb levels (P0.05).Coronary heart disease, atherosclerosis, and grade 3 hypertension are independent associated factors of OH in elderly EH patients. In elderly hypertensive patients with both OH and elevated BPV, the urine mAlb is much higher than that in patients with OH or elevated BPV alone. OH is associated with early renal damage.

Background: Acute Kidney Injury is a complication in children with heart disease undergoing cardiac surgery with cardiopulmonary bypass. The aim of this study is to describe the behavior of KIM-1 (Kidney Injury Molecule) and NGAL (Neutrophil Gelatinase Associated Lipocalin) as early predictors of renal damage, comparing them with serum creatinine and creatinine clearance, in neonates undergoing cardiac surgery. Methods: Twenty-one (21) neonates, under 4 kg, with complex congenital heart diseases, RACHS-1 > 3, without preoperative renal failure, were studied. Serum creatinine and creatinine clearance were measured preoperatively and at 24, 48, 72, 96 hours postoperatively. Urinary samples of KIM-1(pg/ml) and NGAL (ng/ml) were collected after induction of anesthesia at 24 and 48 hours post-operatively. Results: nRIFLE criteria were used to divide cohorts in “NO AKI” (12 patients) and “AKI” (nine patients). In the AKI group, serum creatinine increased significantly and creatinine clearance decreased significantly at 24, 48, and 72 hours compared with their respective baseline values. There was no difference in KIM-1 and NGAL values between patients who developed AKI and those who did not at any measured time. Conclusions: The deterioration of renal function continues to be one of the most frequent complications in this population. In our study, biomarkers did not show any correlation with the appearance of AKI. It remains to be seen whether this behavior of the biomarkers is linked with the non-consistent release of these types of molecules in immature kidneys. It is likely that a larger panel of biomarkers together with other glomerular filtration rate assessment methods will provide more information about AKI diagnosis.

Objective Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is an accurate method to document changes in blood pressure (BP) and is more predictive than office and home BP monitoring for cardiovascular outcomes in elderly people. We aimed to determine the relationship between ABPM indices and renal damage in elderly Chinese male patients with essential hypertension. Methods We investigated 998 Chinese men (mean age of 78.44 ± 12.02 years) with essential hypertension. Renal function, laboratory testing, and ABPM, including ABP, BP variability, and BP circadian rhythms were investigated. Data were shown according to BP controlling status. The relationships between ABPM indices and renal damage [expressed by urine protein, urine albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN)] were assessed using multiple regression analysis. Results After adjustments for age, common cardiovascular risk factors, and medications, uACR level was positively associated with 24-h mean systolic blood pressure (SBP), 24-h mean pulse pressure (PP), and 24-h SBP percent time of elevation. eGFR level was negatively associated with the 24-h mean SBP and 24-h mean PP. BUN level was positively correlated with the 24-h mean SBP, 24-h mean PP, and 24-h SBP percent time of elevation, whereas the BUN level was negatively associated with the 24-h DBP SD. Conclusion The ABPM indices associated with renal damage may be regarded as an early predictive marker for renal function impairment in Chinese elderly male patients with hypertension.

Background: Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant.Methods and results: We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00–1.08) and 1.07 (1.03–1.11), respectively], but not with other measures of MVD tested.Conclusion: Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV.

Aims/hypothesis Obesity causes type 2 diabetes leading to vascular dysfunction and finally renal end-organ damage. Vascular smooth muscle (VSM) EGF receptor (EGFR) modulates vascular wall homeostasis in part via serum response factor (SRF), a major regulator of VSM differentiation and a sensor for glucose. We investigated the role of VSM-EGFR during obesity-induced renovascular dysfunction, as well as EGFR–hyperglycaemia crosstalk. Methods The role of VSM-EGFR during high-fat diet (HFD)-induced type 2 diabetes was investigated in a mouse model with inducible, VSM-specific EGFR-knockout (KO). Various structural and functional variables as well as transcriptome changes, in vivo and ex vivo, were assessed. The impact of hyperglycaemia on EGFR-induced signalling and SRF transcriptional activity and the underlying mechanisms were investigated at the cellular level. Results We show that VSM-EGFR mediates obesity/type 2 diabetes-induced vascular dysfunction, remodelling and transcriptome dysregulation preceding renal damage and identify an EGFR–glucose synergism in terms of SRF activation, matrix dysregulation and mitochondrial function. EGFR deletion protects the animals from HFD-induced endothelial dysfunction, creatininaemia and albuminuria. Furthermore, we show that HFD leads to marked changes of the aortic transcriptome in wild-type but not in KO animals, indicative of EGFR-dependent SRF activation, matrix dysregulation and mitochondrial dysfunction, the latter confirmed at the cellular level. Studies at the cellular level revealed that high glucose potentiated EGFR/EGF receptor 2 (ErbB2)-induced stimulation of SRF activity, enhancing the graded signalling responses to EGF, via the EGFR/ErbB2–ROCK–actin–MRTF pathway and promoted mitochondrial dysfunction. Conclusions/interpretation VSM-EGFR contributes to HFD-induced vascular and subsequent renal alterations. We propose that a potentiated EGFR/ErbB2–ROCK–MRTF–SRF signalling axis and mitochondrial dysfunction underlie the role of EGFR. This advanced working hypothesis will be investigated in mechanistic depth in future studies. VSM-EGFR may be a therapeutic target in cases of type 2 diabetes-induced renovascular disease. Data availability The datasets generated during and/or analysed during the current study are available in: (1) share_it, the data repository of the academic libraries of Saxony-Anhalt (10.25673/32049.2); and (2) in the gene expression omnibus database with the study identity GSE144838 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144838).

Objective To assess the predictive abilities of serum and urinary cystatin C levels for glomerular lesions in pregnant women with pre-eclampsia. Methods In this study, kidney function markers were compared between38 pregnant women with pre-eclampsia and 22 healthy pregnant women. Results The serum and urine levels of cystatin C and urea were significantly higher in the pre-eclampsia group than in the control group. Receiver operating characteristic curve analysis demonstrated that the serum cystatin C level (91.7%) had a superior diagnostic accuracy for pre-eclampsia than the other markers. Conclusion Serum cystatin C level maybe a significant marker of pre-eclampsia.

Background Obstructive sleep apnea syndrome (OSAS) is associated with a variety of systemic diseases. Among patients with chronic kidney diseases (CKD), the prevalence of OSAS is high. OSAS can induce progression of CKD. However, whether or not OSAS can cause renal damage in healthy people is not clear. Thus, the purpose of this meta-analysis was to elucidate whether or not there was an association between OSAS and early renal damage. Methods PubMed, Embase Database, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biology Medicine Database, Chinese Scientific Journals Database, and Wanfang Database were searched systematically. The relative risk (RR), weighted mean difference (WMD), and 95% confidence intervals (CI) were used to evaluate the relationship between OSAS and early renal damage. Funnel plot and Egger’s test were used to evaluate publication bias, and trial sequential analysis (TSA) was employed to verify the sufficiency of the research conclusions. Results A total of 18 studies were analyzed comprising 4,567 participants. Compared with the healthy control group, levels of cystatin C (MD = 0.530, 95% CI 0.423, 0.637, P P Conclusion In this meta-analysis, OSAS was associated with a higher risk of early renal damage. Patients with OSAS and comorbid hypertension and/or diabetes appear to suffer from severe renal damage.

Background: Informal electronic waste (e-waste) recycling is an increasingly important industry worldwide. However, few studies have studied the health risks in this group of workers. Objective: To assess the associations between occupational exposures to metals and genetic instability and renal markers among e-waste recycling workers. Methods: We recruited informal e-waste recycling workers from a community in northeastern Thailand. Participants completed a questionnaire, several health measurements, and provided urine and blood samples, which we then analyzed for a number of metals including lead (Pb), cadmium (Cd), and manganese (Mn). Samples were analyzed for a marker of RNA and DNA damage (ie, oxidative stress), 8-hydroxy-2'-deoxyguanosine (8-OHdG). Glomerular filtration rate (GFR) and fractional excretion of calcium (FECa%) were measured as markers of renal function. Correlations and regression models were used to assess associations between these various factors. Results: We found significantly higher levels of Cd and Pb in blood of men compared with those in women. Men who worked >48 hours/week had significantly higher levels of 8-OHdG compared with men who worked ≤48 hours/week. Smoking was significantly associated with higher blood Pb and Cd concentrations among men. Conclusion: Our results suggest gender differences in both blood concentrations of metals associated with e-waste recycling and smoking and highlight potentially elevated oxidative stress associated with longer work hours. Health promotion efforts are needed among informal e-waste recyclers to reduce possible risks of renal damage and cancer

Background Patients with primary hyperoxaluria (PH) often develop kidney stones and chronic kidney disease. Noninvasive urine markers reflective of active kidney injury could be useful to gauge the effectiveness of ongoing treatments. Methods A panel of biomarkers that reflect different nephron sites and potential mechanisms of injury (clusterin, neutrophil gelatinase-associated lipocalin (NGAL), 8-isoprostane (8IP), monocyte-chemoattractant protein 1(MCP-1), liver-type fatty acid binding protein (L-FABP), heart-type fatty acid binding protein (H-FABP), and osteopontin (OPN)) were measured in 114 urine specimens from 30 PH patients over multiple visits. Generalized estimating equations were used to assess associations between biomarkers and 24 h urine excretions, calculated proximal tubular oxalate concentration (PTOx), and eGFR. Results Mean (±SD) age at first visit was 19.5 ± 16.6 years with an estimated glomerular filtration rate (eGFR) of 68.4 ± 21.0 ml/min/1.73m2. After adjustment for age, sex, and eGFR, a higher urine MCP-1 concentration and MCP-1/creatinine ratio was positively associated with CaOx supersaturation (SS). Higher urine NGAL and NGAL/creatinine as well as OPN and OPN/creatinine were associated with higher eGFR. 8IP was negatively associated with PTOx and urinary Ox, but positively associated with CaOx SS. Conclusion In PH patients greater urine MCP-1 and 8IP excretion might reflect ongoing collecting tubule crystallization, while greater NGAL and OPN excretion may reflect preservation of kidney mass and function. CaOx crystals, rather than oxalate ion may mediate oxidative stress in hyperoxaluric conditions. Further studies are warranted to determine whether urine MCP-1 excretion predicts long term outcome or is altered in response to treatment.

Background Our aim was to investigate the clinical efficacy and complications of antibiotic treatment regimens for patients with bone infection. Methods We retrospectively analysed patients with bone infection admitted to our hospital between March 2013 and October 2018. After surgical debridement was performed, the patients were divided into three groups: IV group (intravenous antibiotics for 2 weeks); oral group (intravenous antibiotics for 2 weeks followed by oral antibiotics for 4 weeks); and rifampicin group (intravenous antibiotics for 2 weeks followed by oral antibiotics plus rifampicin for 4 weeks). The infection control rate and complications were compared among the three groups. Results A total of 902 patients were enrolled. The infection sites included 509 tibias, 228 femurs, 32 humeri, 23 radii and ulnae, 40 calcanei, and 47 miscellaneous sites, as well as 23 multiple-site infections. After at least 6 months of follow-up, 148 (16.4%) patients had an infection recurrence. The recurrence rate of the IV group was 17.9%, which was not significantly higher than the recurrence rates of the oral group (10.1%) and rifampicin group (10.5%), P = 0.051. The incidence of abnormal alanine aminotransferase (ALT) levels in the IV group was 15.1%, which was lower than that in the oral group (18.0%) and rifampicin group (27.4%), P = 0.026. The rates of proteinuria in the three groups were 3.2, 4.5, and 9.3%, respectively, P = 0.020. Conclusions After debridement of bone infection, short-term antibiotic treatment regimens might offer similar rates of infection eradication while avoiding the risk of renal and hepatic damage associated with prolonged antibiotic use. The level of clinical relevance Stage III.

The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. A large retrospective multicenter cohort of 1381 patients treated with TAVI was analyzed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and 1 year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl ≥ 2.2 was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.09-1.22, p 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (odds ratio: 1.18, 95% CI: 1.08-1.28, p 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01-3.60, p = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21-3.11, p = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. The biomarkers currently used in clinical practice are considered relevant when there is already significant renal impairment compromising the early use of potentially successful therapeutic interventions. More sensitive and specific biomarkers to detect CKD earlier on and improve patients' prognoses are an important unmet medical need. The aim of this review is to summarize the recent literature on new promising early CKD biomarkers of renal function, tubular lesions, endothelial dysfunction and inflammation, and on the auspicious findings from metabolomic studies in this field. Most of the studied biomarkers require further validation in large studies and in a broad range of populations in order to be implemented into routine CKD management. A panel of biomarkers, including earlier biomarkers of renal damage, seems to be a reasonable approach to be applied in clinical practice to allow earlier diagnosis and better disease characterization based on the underlying etiologic process. info:eu-repo/semantics/publishedVersion

The zoonotic parasite Plasmodium knowlesi has emerged as an important cause of human malaria in parts of Southeast Asia. The parasite is indistinguishable by microscopy from the more benign P. malariae, but can result in high parasitaemias with multiorgan failure, and deaths have been reported. Recognition of severe knowlesi malaria, and prompt initiation of effective therapy is therefore essential to prevent adverse outcomes. Here we review all studies reporting treatment of uncomplicated and severe knowlesi malaria. We report that although chloroquine is effective for the treatment of uncomplicated knowlesi malaria, artemisinin combination treatment is associated with faster parasite clearance times and lower rates of anaemia during follow-up, and should be considered the treatment of choice, particularly given the risk of administering chloroquine to drug-resistant P. vivax or P. falciparum misdiagnosed as P. knowlesi malaria in co-endemic areas. For severe knowlesi malaria, intravenous artesunate has been shown to be highly effective and associated with reduced case-fatality rates, and should be commenced without delay. Regular paracetamol may also be considered for patients with severe knowlesi malaria or for those with acute kidney injury, to attenuate the renal damage resulting from haemolysis-induced lipid peroxidation.

Primary vesicoureteral reflux often spontaneously resolves in children. However, in select patients, untreated reflux can contribute to recurrent pyelonephritis leading to irreversible renal damage. Management is therefore based on a given child's likelihood of recurrent urinary tract infections and risk of subsequent renal parenchymal injury. Therapeutic options for urinary reflux are diverse, ranging from observation with or without continuous low-dose antibiotic prophylaxis to a variety of operative interventions.

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.

Background Primary aldosteronism (PA) is highly prevalent in hypertensive population. Adrenal vein sampling (AVS) is the only procedure to assess adrenal aldosterone hypersecretion in PA. PA patients without aldosterone-producing adenomas (APA) frequently have unilateral aldosterone hypersecretion (UAH). These patients could bear inappropriate adrenalectomy without AVS. This study aims to identify which clinical characteristics should be recommended to perform AVS in these PA patients. Methods This study was performed from January 2018 to July 2019 at a center for hypertension and metabolic diseases. Adrenal computed tomography (CT) scan, biochemical evaluation, and AVS were performed. Results Total 141 patients were included in this study. Aldosterone to renin ratio (ARR) after confirmatory test is highly associated with adrenal laterality. The specificity of ARR > 10 (ng/dL)/(mU/L) after confirmatory test is 100%. After confirmatory test, patients with ARR > 10 (ng/dL)/(mU/L) had higher plasma aldosterone concentration and incidences of ischemic heart diseases and renal damage(p Conclusions After confirmatory tests, ARR > 10 (ng/dL)/(mU/L) indicates adrenal laterality, with increasingly cardiorenal damage in PA patients without APA. Thus, AVS should be recommended in these patients before surgery. Trial registration NCT03398785, Date of Registration: December 24, 2017.

There is a need for improved animal models that better translate to human kidney disease to predict outcome of pharmacological effects in the patient. The diabetic BTBR

To compare the serum level of the chemokine, CXCL 16, in preeclamptic and healthy pregnant patients.This prospective case control study was conducted between January and December 2018 in a tertiary level hospital. The study group was formed of 70 pregnant women diagnosed with preeclampsia, and the control group was formed of 70 healthy pregnant women matched to the study group in respect of age, gestational week and body mass index (BMI). The study group was separated into two subgroups of mild preeclampsia (No statistically significant difference was determined between the study and control groups in respect of maternal age, gravida, parity, BMI, and gestational age at sampling. Neonatal birth weight was significantly lower in the study group than in the control group. Mean serum alanine aminotransferase (ALT), aspartate amino transferase (AST) and creatinine levels of the study group were significantly higher than those of the control group (This is the first study in literature to show a significantly higher level of CXCL 16 in patients with severe preeclampsia compared to those with mild preeclampsia. The study can also be considered of value in respect of showing that CXCL 16 could play a role in the etiopathogenesis of preeclampsia and the emergence of renal-hepatic damage. Blocking the CXCL 16/CXCR six axis in preeclampsia treatment could lay the ground for the development of new drugs which could be used in the treatment of preeclampsia.

PURPOSE: The lifetime risk of renal damage among children with spina bifida (SB) is high, but only limited baseline imaging data are available for this population. We therefore queried a large, prospective cohort of infants with SB to define their baseline imaging characteristics. PATIENTS AND METHODS: The Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida (UMPIRE) is an iterative quality-improvement protocol that follows a cohort of newborns at nine US centers. Using descriptive statistics, we described the initial baseline imaging characteristics, specifically renal bladder ultrasound (RBUS), cystogram and DMSA scan. RESULTS: Data on 193 infants from 2015–2018 were analyzed. RBUS was normal in 55.9% of infants, while 40.4% of infants had Society for Fetal Urology (SFU) grade 1–2 hydronephrosis in at least one kidney, 3.7% of infants had SFU grade 3–4 hydronephrosis in either kidney, and 21.8% of infants had bilateral hydronephrosis (SFU grade 1 or higher). There was no vesicoureteral reflux in 84.6% of infants. Of the one third of enrolled infants who had a DMSA renal scan, 92.4% had no renal defects and 93.9% of infants had a difference in differential function of

Objective Salt loading induces renal damage independently of blood pressure (BP) elevation via reactive oxygen species and sympathetic activity. Melatonin, a hormone that regulates the circadian rhythm, has multiple functions, including anti-oxidant effects and the inhibition of sympathetic activity. We have shown that impaired melatonin secretion is associated with renal damage in chronic kidney disease (CKD) patients. However, the associations between salt loading, melatonin secretion, and urinary albumin and protein have not been clarified. Methods We recruited 32 CKD patients, conducted 24-hour ambulatory BP monitoring and collected daytime and nighttime urine while the patients were consuming a standard salt (10 g/day) or low salt (6 g/day) diet. The excretion levels of albumin, protein and 6-sulfatoxymelatonin (aMT6s), a metabolite of melatonin, in daytime and nighttime urine were investigated in patients consuming standard salt and low salt diets. Results The urinary aMT6s levels in daytime and nighttime of the patients consuming standard salt and low salt diets did not differ to a statistically significant extent. However, the urinary aMT6s levels in patients consuming a standard salt diet-but not patients consuming a low salt diet-were significantly and negatively correlated with the daytime and nighttime urinary albumin and protein levels. Contrarily, no significant correlations were found between the urinary aMT6s levels and the BP levels, renal function, and plasma angiotensin II levels in patients consuming either a standard salt or low salt diet. A multiple regression analysis adjusted for age, sex, and body mass index revealed that the urinary albumin and protein levels were significantly and negatively associated with the urinary aMT6s levels in patients consuming a standard salt diet, but not in patients consuming a low salt diet. Conclusion Salt loading aggravates the relationship between melatonin secretion and albuminuria or proteinuria.

Objectives: Recent studies have identified triglyceride-glucose index (TyG) as a surrogate of insulin resistance. Since insulin resistance correlates with renal damage, our study aims to investigat...

Objective The intrarenal renin-angiotensin system (RAS) is activated in clinical settings, such as chronic kidney disease (CKD), as well as in CKD animal models, and kidney transplant donors have a greater risk of end-stage renal disease than healthy controls. However, whether or not the intrarenal RAS is activated immediately after kidney donation in kidney transplant donors is unclear, and the mechanism underlying intrarenal RAS activation is unknown. Methods We investigated 10 kidney transplant donors (4 men and 6 women, 58.6±9.0 years of age). Their blood pressure (BP), estimated glomerular filtration rate (eGFR), plasma angiotensinogen (AGT) and plasma angiotensin II (AngII) levels (which reflect circulating RAS activation), urinary albumin excretion, and urinary AGT excretion (which reflects intrarenal RAS activation) were evaluated before kidney donation (-1.2±0.40 days) and after kidney donation (7.5±1.7 days). Results The renal function after kidney donation was significantly lower than before donation. There were no significant differences in the BP during 24-h ambulatory BP monitoring, plasma AngII levels, or urinary albumin excretion after kidney donation. In contrast, the levels of plasma AGT and urinary AGT excretion were significantly increased after kidney donation. The urinary AGT excretion after kidney donation did not show a significant relationship with the systolic BP, plasma AGT, plasma AngII, or urinary albumin excretion. In addition, the percentage change in urinary AGT excretion after kidney donation was not associated with the percentage change in other clinical parameters. Conclusion The intrarenal RAS is activated in kidney transplant donors immediately after kidney donation, independent of the systemic BP and filtration of increased plasma AGT, due to augmented inflammation.

Reduced Na+-K+-ATPase function is reported in various renal diseases. This implies that increase of Na+-K+-ATPase function may be a new target in treatment of renal injury. We previously reported that Na+-K+-ATPase was stabilized by DRm217, a specific antibody against DR region of Na+-K+-ATPase. In this study, we compared the protective effect of DRm217 and ouabain on kidney in a chronic kidney disease rat model and investigated the mechanism under it. We found that DRm217 improved renal function, alleviated glomerulus atrophy, inhibited renal tubular cells apoptosis, tubulointerstitial injury and renal fibrosis in 5/6 nephrectomized rats. Contrary to DRm217, ouabain worsened renal damage. Activated Na+-K+-ATPase /Src signaling pathway, increased oxidant stress and activated inflammasome were responsible for nephrectomized or ouabain-induced renal injury. DRm217 inhibited Na+-K+-ATPase /Src signaling pathway, retarded oxidant stress, suppressed inflammasome activation, and improved renal function, suggesting a novel approach to prevent renal damage.

Background/Aims: Association between cigarette smoke and albuminuria (UA) was already demonstrated in cross-sectional studies and in selected population samples (i.e diabetic patients). This study aims to evaluate, prospectively, the relationship between cigarette smoke and UA in a male adult population sample, with basal normal kidney function, participating in the Olivetti Heart Study (OHS). Methods: Among 994 participants, examined in both 1994-95 and 2002-04, were selected those resulted in both visits smokers (n=221) and non-smokers (n=416) and with basal normal kidney function (GFR> 60 mL/min) and basal albumin/creatinine ratio (ACR< 30 mg/g). Results: At baseline, the prevalence of hypertension was 41%, diabetes affected 6.3% and obesity 17% of the whole sample. Smokers showed statistically significant lower levels of systolic (SBP) and diastolic blood pressure (DBP) and BMI (p< 0.001) compared to non-smokers. There were not basal differences in UA, GFR and metabolic profile. However, at follow-up examination, smokers showed a statistically significant increase in SBP and DBP (p< 0.05), but not in GFR and BMI. Moreover, smokers showed a higher risk compared to non-smokers to be in the higher median levels group of UA (OR: 2.17, C.I.95%: 1.51-3.13; p < 0.001), even after correction for major confounding factors. Further adjustment for basal antihypertensive and hypoglycemic treatment did not change these patterns of association. Conclusion: In a selected male adult population sample, cigarette smoke was independently associated with the development of higher levels of albuminuria over time.

Background The development of lithium-associated kidney damage is still a matter of controversy. We have addressed this question by investigating the role of somatic comorbidity for developing kidney failure in lithium treated patients. Methods The study group comprised of 1741 adult patients with normal creatinine levels at the start of lithium treatment. Patients who developed severe renal failure (CKD stages 4–5, n = 109), were matched by sex, time on lithium and age at start of lithium, with 109 controls (CKD stages 1–2) that did not develop severe renal failure. Results Patients in CKD 4–5 did not differ significantly from controls (CKD 1–2) in sex (females/males were 76/33 in both groups), time on lithium (mean 9.8 years, SD 6.4; vs. 9.6, SD 6.2) or age at start of lithium (mean 61.6 years, SD 13.4; vs. 60.5 years, SD 12.3), respectively. However, comparisons between groups showed a significantly higher prevalence of somatic comorbidity (p Limitations Patients in our study group were relatively old and the findings are therefore not generalizable to patients starting lithium at an early age. The retrospective design, relying on available charts, did not allow to grade severity of comorbid conditions other than need for hospitalisation or chronic drug treatment. Conclusions Our findings emphasize the role of somatic comorbidity for renal damage in lithium treated patients and especially the role of cardiovascular comorbidity. Monitoring of somatic comorbidity should be taken into account in treatment recommendations and safety routines in long-term prophylactic lithium treatment.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.

As the scale and depth of artificial intelligence network models continue to increase, their accuracy in albumin recognition tasks has increased rapidly. However, today’s small medical datasets are the main reason for the poor recognition of artificial intelligence techniques in this area. The sample size in this article is based on the data analysis and research on urine albumin detection of diabetes in the EI database. It is assumed that the observation group has at least 20 mg UAER difference from the control group, and the standard deviation of the UAER change from baseline to 12 weeks is 30 mg. Therefore, the sample size of the two groups is 77 cases. Assuming that the rate of loss to follow-up during the follow-up period is 20%, at least 92 patients are needed. The final enrollment in this study is 100 patients. Studies have shown that DR is used as an indicator to diagnose NDRD, and its OR value is as high as 28.198, indicating that non-DR can be used as an indicator to distinguish DN from NDRD. The meta-analysis found that DR has a sensitivity of 0.65 and a specificity of 0.75 in distinguishing DN from NDRD in patients with type 2 diabetes, and it is emphasized that PDR is highly specific in the diagnosis of DN. Using a meta-analysis to systematically analyze 45 studies, it was found that the sensitivity of DR to diagnose DN was 0.67, the specificity was 0.78, and the specificity of PDR to predict DN was 0.99, indicating that DR is a good indicator for predicting DN, and the team’s latest research has also verified this point of view. They have established a new model for diagnosing DN. In addition to including traditional proteinuria, glycosylated hemoglobin, FR, blood pressure, and other indicators into the diagnostic model, it will also include the presence or absence of DR. The final external verification accuracy rate of this model is 0.875.

Renal dysfunction is a relevant medical issue for patients undergoing TAVR. Chronic kidney disease and postprocedural acute kidney injury are independent predictors of worse outcome after TAVR procedure. Meticulous preprocedural planning and multidisciplinary heart-team management could mitigate renal damage.

Chronic Interstitial Nephritis in Agricultural Communities (CINAC) continues to attract controversy in the scientific community. It was previously known as Chronic Kidney Disease of Unknown Etiology (CKDu) and is not associated with the common aetiological factors such as diabetes. There is general acceptance that it is an environmentally induced disorder due to a combination of toxicities: heavy metals from food, fluoride in drinking water, hard water, heat stress and pesticides. The recent findings of a lysosomal inclusion body tubulopathy is of great interest to those attempting to find therapeutic agents to slow or eliminate its renal damage. The paper argues that despite these new findings, oxidative stress could play a key role and proposes that anti-oxidants such as Vitamin C and E be repurposed for treatment.

Insufficient fruit and vegetable intake (FVI) and low potassium intake are associated with many non-communicable diseases, but the association with early renal damage in children is uncertain. We aimed to identify the associations of early renal damage with insufficient FVI and daily potassium intake in a general pediatric population. We conducted four waves of urine assays based on our child cohort (PROC) study from October 2018 to November 2019 in Beijing, China. We investigated FVI and other lifestyle status via questionnaire surveys and measured urinary potassium, β2-microglobulin (β2-MG), and microalbumin (MA) excretion to assess daily potassium intake and renal damage among 1914 primary school children. The prevalence of insufficient FVI (

We read with great interest the study by Bajaj et al. highlighting the utility of baseline serum and urinary metabolites for predicting renal outcomes in patients with cirrhosis1 . The study is important as serum creatinine (sCr) rises only late after the kidney injury becomes manifest and its level may not reflect the degree of renal damage.

Previous studies have identified Atherogenic index of plasma (AIP) as a simple measure of atherosclerosis. Because atherosclerosis plays a role in the development of renal damage, our study aims to evaluate the effect of AIP on the risk of reduced eGFR and assess its usefulness to refine the risk stratification of reduced estimated glomerular filtration rate (eGFR).Our study included 15,836 participants from the National Health and Nutritional Survey (NHANES) 2009-2016. Association was investigated by logistic regression. AIP was calculated as log (triglycerides/high-density lipoprotein cholesterol). Reduced eGFR was determined as eGFR60 ml/min per 1.73 m*2.The prevalence of reduced eGFR was 8.01%. In the full model, each SD increase of AIP leaded to 27.4% additional risk for reduced eGFR. After dividing AIP into quartiles, the fourth quartile had a 1.649 times risk than the first quartile. Moreover, smooth curve fitting suggested that the risk of reduced eGFR elevated linearly with the increase of AIP. Subgroup analysis demonstrated that the association between AIP and reduced eGFR was robust in sex, body mass index, hypertension, and diabetes subpopulation, but the association was significantly stronger in black race and people aged less than 50 years old. Additionally, AUC displayed an advancement when introducing AIP into established risk factors (0.875 cs. 0.897, P 0.001), category-free net reclassification index (0.249, 95% CI: 0.192-0.306, P 0.001) and integrated discrimination index (0.007, 95% CI: 0.004-0.009, P 0.001) also suggested the improvement from AIP.The present work suggested a linear association between AIP and reduced eGFR. Furthermore, the results showed that the association was stronger in black race and people aged less than 50 years old. Most importantly, our work implicated the usefulness of AIP to refine the risk stratification of reduced eGFR.

Background: The underlying pathogenesis of patients with salt-sensitive hypertension expressing higher blood pressure and severer renal damage remains uncertain. Methods: We recruited 329 subjects, 131 in salt-sensitive (SS) group, 148 in nonsalt-sensitive (NSS) group, and 50 healthy people in normal group and tested their renal function, 24-h ambulatory blood pressure, and growth factor series. Results: The SS group showed worse renal function with lower estimated glomerular filtration rate and higher urinary microalbumin, α-microglobulin, urinary protein Cr ratio, and urinary immunoglobulin. Most indicators in 24-h ambulatory blood pressure of the SS group were significantly enhanced than the NSS group, indicating their higher blood pressure. The significantly elevated growth factors in the SS group were AR, BMP-5, EG-VEGF, GH, HGF, IGFBP-2, IGFBP-3, IGFBP-6, MCSFR, NT-4, PDGF-AA, SCF, SCFR, VEGFR2, VEGFR3, and VEGF-D, compared to other 2 groups or one of them. PI3K-AKT pathway was activated in the SS group. Conclusions: Differences in growth factors and pathways may account for the manifestations of the SS group. Activated PI3K-AKT pathway with higher IGFBP-3 and GH can lead to renal damage. Higher MCSFR in the SS group indicates that high blood pressure and severe kidney damage may be associated with the activation of the immune system. EG-VEGF, VEGFR2, VEGFR3, and VEGF-D can also explain the elevated blood pressure due to the dilated lymphatic system which drains excess sodium and water back into circulation. The SS group presented higher AR and HGF which may worsen renal function by regulating cell proliferation and tumor formation. However, due to the potential low awareness rate of hypertension at the very beginning, we cannot ensure the exact occurrence order of blood pressure, renal damage, and salt sensitivity. Therefore, further studies which can track data from the onset of hypertension are needed.

Humans with salt-sensitive (SS) hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Increasing evidence indicates that immune mechanisms play an important role in the full development of SS hypertension and associated renal damage. Recent experimental advances and studies in animal models have permitted a greater understanding of the mechanisms of activation and action of immunity in this disease process. Evidence favors a role of both innate and adaptive immune mechanisms that are triggered by initial, immune-independent alterations in blood pressure, sympathetic activity, or tissue damage. Activation of immunity, which can be enhanced by a high-salt intake or by alterations in other components of the diet, leads to the release of cytokines, free radicals, or other factors that amplify renal damage and hypertension and mediate malignant disease.

Renal replacement lipomatosis is a rare condition characterized by extensive fat deposition in hilum with parenchymal thinning and progressive detoriation of function.1-4 Though uncommon, it should be considered as a possibility in patients with history of intervention for stone disease.5,6 Correct diagnosis can be easily established by cross sectional imaging and is helpful to counsel patients about the possibility of progressive functional detoriation and poor salvageability of the affected kidneys.7-10 Here, we present 2 patients with previous history of intervention for calculus disease who had developed progressive renal damage due to RRL with one patient ultimately needing nephrectomy.

It would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Previous findings have shown renalase not only plays an important role in hypertension but also closely correlates with kidney function. The purpose of this study is to investigate whether urinary renalase could be used as a predictive index of early-stage renal damage in patients with primary hypertension. Urinary albumin to creatinine ratio (UACR) was used to divide subjects with primary hypertension into two groups: a no renal damage (NRD) group (UACR 30 mg/g). Subjects with normal examination results were randomly included in a healthy control (HC) group. Urinary renalase was determined through an enzyme-linked immunosorbent assay (ELISA). Urinary renalase continued to reduce among the HC (n = 81), NRD (n = 84) and RD group (n = 80), while systolic blood pressure (SBP) increased. Urinary renalase was negatively correlated with SBP in all the groups. Among the subjects with stage 1 primary hypertension, urinary renalase in the RD group was lower than the NRD group, while the UACR was higher, and urinary renalase was negatively correlated with the UACR. A multiple linear stepwise regression analysis showed that there was a linear regression relationship between the increase of the UACR and urinary renalase, heart rate (HR), SBP and serum creatinine. In addition, the standardized partial regression coefficient of urinary renalase was the highest. The performance of urinary renalase as a marker for the diagnosis of early-stage renal damage in patients with primary hypertension was 0.968 with a cut off value of 2.01 µg/ml. Taken together, urinary renalase was further decreased in patients with early-stage renal damage and primary hypertension, and consequently, it could be used as a predictive index. Impact statement In patients with early-stage kidney damage of primary hypertension, there are no obvious structural or functional changes, which leads to a high level of diagnostic omissions. Therefore, it would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Urinary albumin to creatinine ratio (UACR) is a classic indicator used in early-stage renal damage, but it is affected by many factors. Renalase, a protein discovered by Xu in 2005, not only plays an important role in hypertension but also closely correlates with kidney function. In our study, we found that urinary renalase was further decreased in patients with early-stage renal damage in primary hypertension, and it could be used as a predictive index. This finding could help to diagnose the early-stage renal damage in primary hypertension much earlier and improve the prognosis of these patients.

This review will highlight recent studies that have investigated the relationship between Na+, renal macrophage polarization, and renal damage. A hyperosmotic environment drives the macrophage toward a proinflammatory phenotype and away from an anti-inflammatory phenotype. Animal models of salt-sensitive hypertension demonstrate a characteristic infiltration of macrophages into the kidney that is greatly reduced when blood pressure is lowered. Because general immunosuppression or macrophage depletion leads to a host of adverse side effects, more recent studies have modulated the interaction of specific signaling molecules, including NOD-like receptor family pyrin domain-containing 3, chemokine (C-X-C motif) ligand 16, and VEGF, to prevent the end-organ renal damage that accumulates in salt-sensitive disease.

Extracellular vesicles released into urine (uEVs) can represent interesting biomarkers of renal cell damage. CD133, a stem/progenitor cell marker expressed by renal progenitor cells, is highly expressed in uEVs of healthy individuals. In the present study, we evaluated the level of CD133 in the uEVs of patients with acute and chronic glomerular damage by cytofluorimetric analysis. The level of CD133+ uEVs was significantly decreased in pediatric patients with acute glomerulonephritis during the acute phase of renal damage, while it was restored after the subsequent recovery. A similar decrease was also observed in patients with chronic glomerulonephritis. Moreover, CD133+ uEVs significantly declined in patients with type 2 diabetes, used as validation group, with the lowest levels in patients with albuminuria with diabetic nephropathy. Indeed, receiver-operating characteristic curve analysis indicates the ability of CD133+ uEV values to discriminate the health condition from that of glomerular disease. In parallel, a significant decrease of CD133 in renal progenitor cells and in their derived EVs was observed in vitro after cell treatment with a combination of glucose and albumin overload, mimicking the diabetic condition. These data indicate that the level of CD133+ uEVs may represent an easily accessible marker of renal normal physiology and could provide information on the “reservoir” of regenerating cells within tubules.

International audience; Uraemic toxins seem to play an important role in the genesis of cardiovascular and renal damage in chronic kidney disease patients. This short article is divided into two thematic sections. The first part focuses on a selection of `old' toxins for which recent data (published between 2016 and 2018) have provided a better understanding of the associated harmful mechanisms and which, in our opinion, nephrologists should be more aware of. The second part highlights new perspectives for identifying and quantifying these compounds using `omics' techniques.

Background Irradiation-induced kidney damage is inevitable during radiotherapeutic practice, which limits effective radiotherapy doses on tumor treatment. In the present study, the role of mTOR complex 1 (mTORC1) signaling was investigated in irradiation-induced renal injuries. Methods Mice were exposed to 8.0-Gy X-ray of total body irradiation and subsequently treated with rapamycin. Changes of renal morphology were assessed by hematoxylin and eosin staining. Expression of pS6 and CD133 was detected via immunostaining. Cellular apoptosis and proliferation were measured by TUNEL, caspase-3 and BrdU staining. Activation of mTORC1, TGF-β and NF-κB signaling pathways was determined through western blot analysis. Results Our data displayed that irradiation disrupted the structures of renal corpuscles and tubules and decreased the density of CD133+ renal stem-like cells, which were related with increasing cellular apoptosis and decreasing cell proliferation post exposure. Activation of mTORC1, TGF-β and NF-κB signaling pathways was determined in irradiated renal tissues, which were inhibited by rapamycin treatment. Application of rapamycin after irradiation decreased cellular apoptosis and increased autophagy and cell proliferation in renal tissues. The density of CD133+ renal stem-like cells was significantly increased in irradiated kidneys after rapamycin treatment. The morphology of irradiated renal corpuscles and tubules was gradually recovered upon rapamycin treatment. Conclusions These findings indicate that inhibition of mTORC1 signaling by rapamycin ameliorates irradiation-induced renal toxicity mediated by decreasing cellular apoptosis and increasing CD133+ renal stem-like cells. Electronic supplementary material The online version of this article (10.1186/s13287-018-0963-5) contains supplementary material, which is available to authorized users.

BACKGROUND The increased use of herbal remedies particularly in patients with kidney diseases indicated the importance of studies, which focused on nephrotoxic plants. OBJECTIVE The present study aimed to review and assess the kidney-damaging herbs mentioned in the Persian medicine [PM] books. METHOD The main PM books were searched for nephrotoxic herbs and their relevant reformers traditionally proposed for preventing renal damage. PubMed, Scopus and Google Scholar were investigated for evaluation of the scientific evidence relating to the nephrotoxicity of herbs. RESULTS A total of 64 plants with kidney damage potential and their reformer medicaments were recorded in 7 sources included in this review. Allium schoenoprasum and Marrubium vulgare were the most repeated and emphasized nephrotoxic plants in PM books, but there was no relevant scientific evidence. Despite the lack of clinical studies, some evidence was found for 38% of plants that were related to renal damage. The most repeated reformers for reducing the renal side effects mainly consisted of gum tragacanth, gum Arabic, mastic gum, anise, jujube and honey and some evidence was found for their nephroprotective activities. CONCLUSION The present study reviewed and assessed the herbs with adverse renal effects in the main PM books. Some evidence was in line with the potential nephrotoxicity of plants and their .reformers. Despite the lack of clinical research for evaluation of their renal damage, the herbs may be focused in term of their nephrotoxicity; and there is a need for further studies on the scientific basis of their nephrotoxicity.

Lupus nephritis (LN) is a multifactorial event that contributes to the long-term mortality of systemic lupus erythematosus (SLE). Activation of NLRP3 inflammasome has been known to play a role in SLE pathogenesis. We evaluated the renal protection effects of procyanidin B2 (PCB2) and the involvement of NLRP3 in a mouse model involving MRL/lpr and MRL/MpJ mice. Kidney injury was evaluated by measuring the renal clinical and pathological features, renal immune complex deposition, and serum anti-double-stranded (anti-dsDNA) Abs. ELISA and Western blotting were used to detect NLRP3 inflammasome activation and IL-1β/IL-18 production. NLRP3 gene silencing was introduced into MRL/lpr mice by short hairpin RNA, and the renal damage was compared with the treatment of PCB2. PCB2 remarkably reduced renal damage in MRL/lpr mice, reflected by the reduced proteinuria, and serum levels of blood urea nitrogen and creatinine, as well as pathological features with less renal injury. PCB2 significantly reduced renal immune complex deposition and serum anti-dsDNA levels, notably inhibited the NLRP3 inflammasome activation, and reduced the renal and serum levels of IL-1β and IL-18 in MRL/lpr mice compared with those of NLRP3 gene-silenced MRL-lpr mice. PCB2 significantly suppressed LN in MRL-lpr mice by inhibiting the activation of NLRP3 inflammasome and subsequent IL-1β and IL-18 production. This finding explores a novel mechanism by which procyanidin exerts inflammatory suppression effects and its clinical benefits in LN prevention.

Reliable markers for the rapid discrimination of severe renal damage remain a vital concern for lupus nephritis (LN). To determine a better tool for kidney damage detection, the present study compared the evaluation ability of novel urinary cytokines and chemokines (namely urinary monocyte chemoattractant protein 1 (uMCP-1), tumor necrosis factor-like weak inducer of apoptosis (uTWEAK)) with traditional serum or urinary markers (namely urinary alpha 1-microgrobulin (uα1-MG), beta 2-microglobulin (uβ2-MG) and serum complement C3 (C3), complement C4 (C4), creatinine (Cr), blood urea nitrogen (BUN) and cystatin C (Cys C)) in discriminating LN renal damage. Correlations between markers with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) renal SLEDAI scores, biopsy activity index (BAI) and biopsy chronicity index (BCI) scores were evaluated. Receiver operating characteristic (ROC) curves were generated to evaluate a single or combined model in discriminating active renal involvement (rSLEDAI scores 0) and patients with poor pathological outcome (BAI scores ≥ 7). uMCP-1 and uTWEAK possess higher correlation coefficients with renal damage and larger areas under ROC curves (AUCs) than other markers. A combined model of uMCP-1 and uTWEAK showed an AUC of 0.887, sensitivity of 86.67% and specificity of 80.00% to discriminate active LN, and an AUC of 0.778, sensitivity of 75.00% and specificity of 81.82% to discriminate LN with poor outcome, which are better than the utility of any markers individually.