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We investigated how age affected renal function in healthy subjects in Beijing and compared different estimated glomerular filtration rate (eGFR) equations. Kidney function was evaluated by five equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); the Chinese version of the MDRD (MDRDc); Full Age Spectrum (FAS); and Berlin Initiative Study (BIS). A total of 46,708 subjects were enrolled and followed-up for 3 years. All showed an increase in sCr and a reduction in eGFR with increasing age. Over the 3 years, the eGFR and serum creatinine (sCr) remained unchanged in most subjects. Different equations showed good consistency; the intraclass correlation coefficients (ICC) was 0.849 for males, and 0.817 for females. The CKD-EPI equation yielded higher GFR values than the other equations (according to sCr levels). For subjects aged over 70 years, the BIS equation produced the lowest eGFR values. In summary, we observed that the renal function of individuals was relatively stable with increasing age, although different eGFR equations yielded data that varied across different populations of subjects and sCr levels.

The aim of this study was to investigate associations between age-dependent variations in isolated systolic/diastolic hypertension (ISH/IDH) with target organ damage in chronic kidney disease (CKD). A cross-sectional study was conducted among 2,459 CKD patients with ambulatory blood pressure monitoring. Blood pressure was categorized into four groups: normotension, ISH, IDH, and systolic-diastolic hypertension. The outcome measurements were left ventricular mass index (LVMI), estimated glomerular filtration rate(eGFR), and urinary albumin creatinine ratio (ACR). Older patients (≥60-years-old) had a higher prevalence of ISH and a lower prevalence of IDH than younger patients (

Chronic Kidney Disease (CKD) and neurodegenerative diseases are aging-related diseases. CKD with declined renal function is associated with an elevation of circulating indoxyl sulfate, a metabolite synthesized by gut microbes. We explored the roles of gut microbial metabolites in linking with Central Nervous System (CNS) diseases by administrating indoxyl sulfate intraperitoneally to male C57BL/6 mice with unilateral nephrectomy. Upon exposure, the accumulation of indoxyl sulfate was noted in the blood, prefrontal cortical tissues, and cerebrospinal fluid. Mice showed behavioral signs of mood disorders and neurodegeneration such as anxiety, depression, and cognitive impairment. Those behavioral changes were accompanied by disturbed neuronal survival, neural stem cell activity, expression of Brain-Derived Neurotrophic Factor, serotonin, corticosterone, and Repressor Element-1 Silencing Transcription Factor, and post-receptor intracellular signaling, as well as upregulated oxidative stress and neuroinflammation. Uremic toxin adsorbent AST-120 improved the above mentioned changes. Intriguingly, intracerebroventricular indoxyl sulfate administration only caused limited alterations in the normal mice and the alterations were reversed by aryl hydrocarbon receptor antagonism. The findings suggest pathogenic roles of indoxyl sulfate in the development of CNS diseases, and highlight gut microbiota as alternative targets for intervention with the aim of slowing down the progression of CKD and decreasing CNS complications.

Our study aimed to explore the intercorrelations of brachial‐ankle pulse wave velocity (baPWV), ankle‐brachial index (ABI), ambulatory arterial stiffness index (AASI), 24‐hour mean pulse pressure (24‐h PP), and augmentation index (AIx, AIx@75, the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49‐65) years and 50.5 (35.5‐84.1) ml/min/1.73 m2, respectively. In Pearson correlation analysis, baPWV was significantly associated with 24‐h PP (r = .531, p

The countries of Asia are home to multiple ethnicities. There are ethnic differences in diet, culture, and attitudes towards health screening, access to care, and treatment of chronic diseases. Chronic kidney disease (CKD) and end‐stage kidney disease (ESKD) have rising incidence and prevalence due to increased affliction with non‐communicable diseases of diabetes and hypertension. To prevent the expensive complications of ESKD, one of the most important risk factors to control is hypertension in patients with CKD. We performed a narrative review on the prevalence of CKD in patients with hypertension, the prevalence and control of hypertension in patients with CKD, and the dietary sodium intake in CKD populations.

Background Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation. Methods Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years. Results In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD (P P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51–7.38; P P = 0.006), single RV lead (OR 1.67; 95% CI 1.09–2.56; P = 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42–3.05; P P = 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04–1.84; P = 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02–1.77; P = 0.034), heart failure (HR 1.75; 95% CI 1.31–2.33; P P P Conclusions Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival. Graphic abstract

Background: Although associations between low protein diet (LPD) and changes of gut microbiota have been reported; however, systematic discernment of the effects of LPD on diet-microbiome-host interaction in patients with chronic kidney disease (CKD) is lacking. Methods: We searched PUBMED and EMBASE for articles published on changes of gut microbiota associated with implementation of LPD in CKD patients until July 2021. Independent researchers extracted data and assessed risks of bias. We conducted meta-analyses of combine p-value, mean differences and random effects for gut microbiota and related metabolites. Study heterogeneity was measured by Tau2 and I2 statistic. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Five articles met inclusion criteria. The meta-analyses of gut microbiota exhibited enrichments of Lactobacillaceae (meta-p= 0.010), Bacteroidaceae (meta-p= 0.048) and Streptococcus anginosus (meta-p< 0.001), but revealed depletion of Bacteroides eggerthii (p=0.017) and Roseburia faecis (meta-p=0.019) in LPD patients compared to patients undergoing normal protein diet. The serum IS levels (mean difference: 0.68 ug/mL, 95% CI: -8.38-9.68, p= 0.89) and pCS levels (mean difference: -3.85 ug/mL, 95% CI: -15.49-7.78, p < 0.52) did not change between groups. We did not find significant differences on renal function associated with change of microbiota between groups (eGFR, mean difference: -7.21 mL/min/1.73 m2, 95% CI: -33.2-18.79, p= 0.59; blood urea nitrogen, mean difference: -6.8 mg/dL, 95% CI: -46.42-32.82, p= 0.74). Other clinical (sodium, potassium, phosphate, albumin, fasting sugar, uric acid, total cholesterol, triglycerides, C-reactive protein and hemoglobin) and anthropometric estimates (body mass index, systolic blood pressure and diastolic blood pressure) did not differ between the two groups. Conclusions: This systematic review and meta-analysis suggested that the effects of LPD on the microbiota were observed predominantly at the families and species levels but minimal on microbial diversity or richness. In the absence of global compositional microbiota shifts, the species-level changes appear insufficient to alter metabolic or clinical outputs.

Iron metabolism, hepcidin and some blood profiles were investigated in 13 healthy and 31 chronic kidney disease (CKD) dogs. The study consisted of 2 experiments, experiment I included healthy dogs (CONT) and CKD dogs (stage 2, 3 and 4), while experiment II consisted of anemic CKD dogs subjected to 28-day darbepoetin alfa treatment. The response to darbepoetin alfa could divide anemic CKD dogs into responder (RP) and non-responder (NRP) subgroups. The results from experiment I showed that packed cell volume (PCV) and plasma albumin concentration were significantly lower in CKD dogs of all stages while the total iron binding capacity (TIBC) was lower in only CKD stage 3 and 4 compared with dogs in CONT group. The PCV was related to both TIBC and albumin when considering among all dogs or only in CKD dogs. The hepcidin concentration in CKD dogs with anemia was lower than those without anemia (P

Chronic kidney disease (CKD) patients obtained high levels of uremic toxins progressively develop several complications including bone fractures. Protein-bound uremic toxins especially p-cresol and indoxyl sulfate are hardly eliminated due to their high molecular weight. Thus, the abnormality of bone in CKD patient could be potentially resulted from the accumulation of uremic toxins. To determine whether protein-bound uremic toxins have an impact on osteogenesis, mesenchymal stem cells were treated with either p-cresol or indoxyl sulfate under in vitro osteogenic differentiation. The effects of uremic toxins on MSC-osteoblastic differentiation were investigated by evaluation of bone phenotype. The results demonstrated that p-cresol and indoxyl sulfate down-regulated the transcriptional level of collagen type I, deceased alkaline phosphatase activity, and impaired mineralization of MSC-osteoblastic cells. Furthermore, p-cresol and indoxyl sulfate gradually increased senescence-associated beta-galactosidase positive cells while upregulated the expression of p21 which participate in senescent process. Our findings clearly revealed that the presence of uremic toxins dose-dependently influenced a gradual deterioration of osteogenesis. The effects partially mediate through the activation of senescence-associated gene lead to the impairment of osteogenesis. Therefore, the management of cellular senescence triggered by uremic toxins could be considered as an alternative therapeutic approach to prevent bone abnormality in CKD patients.

Background: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease and it is often associated with hepatic steatosis. Hepassocin (also known as hepatocyte-derived fibrinogen related protein or fibrinogen-like 1) is a novel hepatokine that causes hepatic steatosis and induces insulin resistance. However, the role of hepassocin in renal function status remains unclear. Our objective was to investigate the association of plasma hepassocin level with fatty liver and renal function status in patients with stable angina. Methods: Plasma hepassocin levels were determined by enzyme-linked immunosorbent assays in 395 consecutive patients with stable angina. Renal function was defined as an estimated glomerular filtration rate (eGFR). Fatty liver was defined by ultrasonography and fibrosis-4 (FIB-4) index. Results: With increasing hepassocin tertiles, patients had higher prevalence of fatty live, an increased waist-to-hip ratio, and neutrophil count, monocyte count, and FIB-4 index, higher levels of uric acid, blood urine nitrogen and higher sensitivity C-reactive protein. They also had incrementally lower eGFR, serum hemoglobin and albumin levels. In multiple linear stepwise regression analysis, only eGFR was significantly independent negatively associated with plasma hepassocin levels. Conclusion: Our results indicate that circulating hepassocin in patients with stable angina is associated with fatty liver and renal function, which suggests that increased plasma hepassocin may be involved in the pathogenesis of fatty liver and CKD.

Patients with progressing chronic kidney disease (CKD) are more likely to experience cardio‐ and cerebrovascular events than progressing to end‐stage renal disease. The authors explored whether retinal microvascular calibers differed with the degree of renal impairment and between the standard and extended optic disk and may serve as a simple additional tool for risk stratification in this highly vulnerable patient cohort. The authors analyzed central retinal arteriolar and venular equivalent calibers (CRAE, CRVE) at different retinal zones (zone B&C) using digital retinal imaging in hypertensive patients with stage 2 (n = 66) or stage 3 CKD (n = 30). Results were adjusted for age, sex, HbA1c, and 24‐hour diastolic blood pressure. Mean eGFR was 77.7 ± 8.9 and 48.8 ± 7.9 ml/min/1.73 m2 for stage 2 and 3 CKD, respectively. CRAE and CRVE in zones B and C were significantly lower in patients with stage 3 CKD compared to patients with stage 2 CKD (CRAE‐B:141.1 ± 21.4 vs. 130.5 ± 18.9 µm, p = .030; CRAE‐C:137.4 ± 19.4 vs 129.2 ± 18.2 µm, p = .049; CRVE‐B:220.8 ± 33.0 vs. 206.0 ± 28.4 µm, p = .004; and CRVE‐C:215.9 ± 33.0 vs. 201.2 ± 25.1µm, p = .003). In patients with stage 2 CKD, CRAE‐B was higher than CRAE‐C (141.1 ± 21.4 vs. 137.4 ± 19.4µm, p

Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt‐sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first‐in‐class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin‐sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)‐mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single‐molecule property that may be considered as first‐line antihypertensive therapy. Further investigations are needed to validate its safety for long‐term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.

It is unclear whether aspirin is beneficial for prevention of CVD in patients with CKD. We performed a secondary analysis of the ALLHAT trial to assess the effect of baseline aspirin use on nonfatal myocardial infarction (MI) or fatal coronary heart disease (CHD), all‐cause mortality, and stroke. Baseline characteristics of aspirin users and nonusers were used to generate propensity‐matched cohorts. Using conditional Cox proportional hazard regression models, we examined the effect of aspirin on the outcomes in the cohort at large and across 3 levels of kidney function (eGFR ≥90, 60–89, and

Despite improvements in pharmacotherapy, morbidity and mortality rates in community-based populations with chronic heart failure still remain high. The increase in medical complexity among patients with heart failure may be reflected by an increase in concomitant non-cardiovascular comorbidities, which are recognized as independent prognostic factors in this population. Heart failure and chronic kidney disease share many risk factors, and often coexist. The presence of kidney failure is associated with incremented risk of cardiovascular and non-cardiovascular mortality in heart failure patients. Chronic kidney disease is also linked with underutilization of evidence-based heart failure therapy that may reduce morbidity and mortality. More targeted therapies would be important to improve the prognosis of patients with these diseases. In recent years, serum uric acid as a determinant of cardiovascular risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia are at increased risk of cardiac, renal and vascular damage and cardiovascular events. Moreover, elevated serum uric acid predicts worse outcome in both acute and chronic heart failure. While studies have raised the possibility of preventing heart failure through the use of uric acid lowering agents, the literature is still inconclusive on whether the reduction in uric acid will result in a measurable clinical benefit. Available evidences suggest that chronic kidney disease and elevated uric acid could worsen heart failure patients’ prognosis. The aim of this review is to analyse a possible utilization of these comorbidities in risk stratification and as a therapeutic target to get a prognostic improvement in heart failure patients.

The prevalence of chronic pain in patients with chronic kidney disease (CKD) and diabetes mellitus is high and correlates with higher frailty risk, but satisfactory pain control frequently fails, necessitating opioid initiation. We aimed to examine whether opioid use affected their outcomes and whether such a relationship was modified by frailty. From the longitudinal cohort of diabetes patients (n = 840,000), we identified opioid users with CKD (n = 26,029) and propensity score-matched them to opioid-naïve patients in a 1:1 ratio. We analyzed the associations between opioid use and long-term mortality according to baseline frailty status, defined by the modified FRAIL scale. Among all, 20.3% did not have any FRAIL items, while 57.2%, 20.6%, and 1.9% had 1, 2, and at least 3 positive FRAIL items, respectively. After 4.2 years, 16.4% died. Cox proportional hazard regression showed that opioid users exhibited an 18% higher mortality risk (HR 1.183, 95% CI 1.13-1.24) with a dose- and duration-responsive relationship, compared to opioid-naive ones. Furthermore, the mortality risk posed by opioids was observed only in CKD patients without frailty but not in those with frailty. In conclusion, opioid use increased mortality among patients with CKD, while this negative outcome influence was not observed among frail ones.

In this study, we studied the effect and possible mechanism of TGF-β1 on vascular calcification. We found that the serum levels of TGF-β1 and cycloxygenase-2 (COX-2) were significantly increased in patients with chronic kidney disease. Phosphate up regulated TGF-β1 in vascular smooth muscle cells (VSMCs). TGF-β1 decreased the markers of VSMCs, but increased osteogenic markers and calcification in aortic segments. The phosphate-induced osteogenic markers were reduced by the TGFβR I inhibitor (LY364947), which also attenuated the potential of phosphate to reduce VSMC markers in VSMCs. Both phosphate and TGF-β1 increased the protein level of β-catenin, which was partially mitigated by LY364947. TGF-β1 decreased sclerostin, and exogenous sclerostin decreased the mineralization induced by TGF-β1. LY364947 reduced the phosphate and TGF-β1 induced COX-2. Meanwhile, the effects of TGF-β1 on osteogenic markers, β-catenin, and sclerostin, were partially reversed by the COX-2 inhibitor. Mechanistically, we found that p-Smad2/3 and p-CREB were both enriched at the promoter regions of sclerostin and β-catenin. TGF-β1 and COX-2 were significantly elevated in serum and aorta of rats undergoing renal failure. Therapeutic administration of meloxicam effectively ameliorated the renal lesion. Our results suggested that COX-2 may mediate the effect of TGF-β1 on vascular calcification through down-regulating sclerostin in VMSCs.

Increased arterial stiffness is independently associated with renal function decline in patients with diabetes mellitus (DM). Whether DM has additional deleterious effects on central hemodynamics and arterial stiffness in chronic kidney disease (CKD) patients is yet unknown. This study aimed to compare ambulatory central BP, arterial stiffness parameters, and trajectories between patients with diabetic and non‐diabetic CKD. This study examined 48 diabetic and 48 non‐diabetic adult patients (>18 years) with CKD (eGFR

Hyperuricemia, i.e. increased serum uric acid (UA) concentration, is a common problem in clinical practice. While there are clear guidelines concerning management of symptomatic hyperuricemia in acute conditions such as gout, urolithiasis or acute urate nephropathy, less is known about their secondary prevention. Moreover, despite the ongoing debate on the role of UA in the pathogenesis of chronic kidney disease, hypertension, cardiovascular disease and heart failure, the management of asymptomatic hyperuricemia in patients with these chronic conditions is still mainly up to physicians’ judgement. Individual considerations should always be taken into account when prescribing urate-lowering therapy. In this narrative review study, we attempt to present current trends concerning treatment of patients with either symptomatic or asymptomatic hyperuricemia in the light of the available knowledge on the role of hyperuricemia in the development of gout, renal, cardiovascular and other diseases.

The vascular adhesion protein-1 (VAP-1) inhibitor ASP8232 reduces albuminuria in patients with type 2 diabetes and chronic kidney disease. A mechanism-based model was developed to quantify the effects of ASP8232 on renal markers from a placebo-controlled Phase 2 study in diabetic kidney disease with 12 weeks of ASP8232 treatment. The model incorporated the available pharmacokinetic, pharmacodynamic (plasma VAP-1 concentration and activity), serum and urine creatinine, serum cystatin C, albumin excretion rate, urinary albumin-to-creatinine ratio, and urine volume information in an integrated manner. Drug-independent time-varying changes and different drug effects could be quantified for these markers using the model. Through simulations, this model provided the opportunity to dissect the relationship and longitudinal association between the estimated glomerular filtration rate and albuminuria and to quantify the pharmacological effects of ASP8232. The developed drug-independent model may be useful as a starting point for other compounds affecting the same biomarkers in a similar time scale. Electronic supplementary material The online version of this article (10.1007/s10928-020-09716-x) contains supplementary material, which is available to authorized users.

Background: SARS-CoV-2 has raged around the world since March, 2020. We aim to describe the clinical characteristics and risk factors of severe patients with COVID-19 in Guangzhou. Results: The severity and mortality of COVID-19 was 10.4% and 0.3% respectively. And each 1-year increase in age (OR, 1.057; 95% CI, 1.018-1.098; P=0.004), Wuhan exposure history greater than 2 weeks (OR, 2.765; 95% CI, 1.040-7.355; P=0.042), diarrhea (OR, 24.349; 95% CI, 3.580-165.609; P=0.001), chronic kidney disease (OR, 6.966; 95% CI, 1.310-37.058; P = 0.023), myoglobin higher than 106 μg/L (OR, 8.910; 95% CI, 1.225-64.816; P=0.031), white blood cell higher than 10×109/L (OR, 5.776; 95% CI, 1.052-31.722; P=0.044), and C-reactive protein higher than 10 mg/L (OR, 5.362; 95% CI, 1.631-17.626; P=0.006) were risk factors for severe cases. Conclusion: Older age, Wuhan exposure history, diarrhea, chronic kidney disease, elevated myoglobin, elevated white blood cell and C-reactive protein were independent risk factors for severe patients with COVID-19 in Guangzhou. Methods: We included 288 adult patients with COVID-19 and compared the data between severe and non-severe group. We used univariate and multivariate logistic regression methods to explore risk factors of severe cases.

Background: Chronic kidney diseases (CKD) are usually associated with dyslipidemia. Statin therapy has been primarily recommended for the prevention of cardiovascular risk in patients with CKD; however, the effects of statins on kidney disease progression remain controversial. This study aims to investigate the effects of statin treatment on renal handling of water in patients and in animals on a high-fat diet. Methods: Retrospective cohort patient data were reviewed and the protein expression levels of aquaporin-2 (AQP2) and NLRP3 inflammasome adaptor ASC were examined in kidney biopsy specimens. The effects of statins on AQP2 and NLRP3 inflammasome components were examined in nlrp3-/- mice, 5/6 nephroectomized (5/6Nx) rats with a high-fat diet (HFD), and in vitro. Results: In the retrospective cohort study, serum cholesterol was negatively correlated to eGFR and AQP2 protein expression in the kidney biopsy specimens. Statins exhibited no effect on eGFR but abolished the negative correlation between cholesterol and AQP2 expression. Whilst nlrp3+/+ mice showed an increased urine output and a decreased expression of AQP2 protein after a HFD, which was moderately attenuated in nlrp3 deletion mice with HFD. In 5/6Nx rats on a HFD, atorvastatin markedly decreased the urine output and upregulated the protein expression of AQP2. Cholesterol stimulated the protein expression of NLRP3 inflammasome components ASC, caspase-1 and IL-1β, and decreased AQP2 protein abundance in vitro, which was markedly prevented by statins, likely through the enhancement of ASC speck degradation via autophagy. Conclusion: Serum cholesterol level has a negative correlation with AQP2 protein expression in the kidney biopsy specimens of patients. Statins can ameliorate cholesterol-induced inflammation by promoting the degradation of ASC speck, and improve the expression of aquaporin in the kidneys of animals on a HFD.

A systematic review and meta-analysis was conducted in an attempt to systematically collect and evaluate the associations of epidemiological, comorbidity factors with the severity and prognosis of coronavirus disease 2019 (COVID-19). The systematic review and meta-analysis was conducted according to the guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Sixty nine publications met our study criteria, and 61 studies with more than 10,000 COVID-19 cases were eligible for the quantitative synthesis. We found that the males had significantly higher disease severity (RR: 1.20, 95% CI: 1.13-1.27, P

Introduction Valvular heart diseases (VHD) are becoming a significant problem in the Polish population. Coexistence of chronic kidney disease (CKD) in patients with VHD increases the risk of death and affects further therapeutic strategy. Aim Analysis impact of CKD on long-term prognosis in patients with VHD. Material and methods The inclusion criteria were met by 1025 patients with moderate and severe VHD. Mean observation time was 2528 ± 1454 days. Results The average age of the studied population was 66.75 (SD = 10.34), male gender was dominant 56% (N = 579). Severe aortic valve stenosis (AVS) occurred in 28.2%, severe mitral valve insufficiency (MVI) in 20%. CKD occurred in 37.1% (N = 380) patients mostly with mitral stenosis (50%, N = 16) and those with severe MVI (44.8%, N = 94). During the observational period, 52.7% (N = 540) deaths were noted. Increased risk of mortality was associated mostly with age (OR: 1.02, 95% CI: 1.00–1.03, p p p p = 0.01) and coexisting of AVS (OR: 1.19, 95% CI: 1.04–1.35, p = 0.01). Conclusions Mitral valve defects more often than aortic valve defects coexist with chronic kidney disease. Regardless of the stage, chronic kidney disease is an additional factor affecting the prognosis in patients with heart defects. Factors increasing the risk of death were age, creatinine concentration and reduced EF. The monitoring of renal function in patients with VHD should be crucial as well as the implementation of treatment at an early stage.

The mortality rate of elderly patients with Coronavirus Disease 2019 (COVID-19) was significantly higher than the overall mortality rate. However, besides age, leading death risk factors for the high mortality in elderly patients remain unidentified. This retrospective study included 210 elderly COVID-19 patients (aged ≥ 65 years), of whom 175 patients were discharged and 35 died. All deceased patients had at least one comorbidity. A significantly higher proportion of patients in the deceased group had cardiovascular diseases (49% vs. 20%), respiratory diseases (51% vs. 11%), chronic kidney disease (29% vs. 5%) and cerebrovascular disease (20% vs. 3%) than that in the discharged group. The median levels of C-reactive protein (125.8mg/L vs. 9.3mg/L) and blood urea nitrogen (7.2mmol/L vs. 4.4mmol/L) were significantly higher and median lymphocyte counts (0.7×109/L vs. 1.1×109/L) significantly lower in the deceased group than those in the discharged group. The survival curve analysis showed that higher C-reactive protein (≥5mg/L) plus any other abnormalities of lymphocyte, blood urea nitrogen or lactate dehydrogenase significantly predicted poor prognosis of COVID-19 infected elderly patients. This study revealed that the risk factors for the death in these elderly patients included comorbidities, increased levels of C-reactive protein and blood urea nitrogen, and lymphopenia during hospitalization.

Prenatal malnutrition could promote renal dysfunction in adulthood, but it is unclear whether the detrimental effect could be transmitted to the next generation. We investigated whether famine exposure was associated with variation of estimated glomerular filtration rate(eGFR) in two generations and explored the mediation role of methylation alterations. The longitudinal analysis included 2909 participants from Suihua rural area. F1 and F2 generations were divided into non-famine and famine group based on their birth year and exposure status of their parents, respectively. The eGFR was calculated by using the chronic kidney disease epidemiology collaboration equation. We applied mixed-effect models to investigate the association between famine and ΔeGFR and tested blood DNA methylomes in 46 families across two generations. The mediation-analysis models were utilized to examine the mediation effect of methylation alterations on the famine-ΔeGFR association. In mixed-effect models, famine exposure was associated with declined ΔeGFR level in F1(β:-8.32;95%CI:-11.51,-5.12) and in F2(β:-6.11;95%CI:-11.88, -0.43). Methylation850K BeadChip data showed only 19 of 961 F1 differentially methylated sites showed concordant alterations in F2. The mediation-analysis results showed methylation alterations on AGTR1 and PRKCA might mediate the famine-ΔeGFR association. Overall, prenatal famine exposure may have long-term effects on eGFR decline across consecutive generations which might be partly mediated by methylation alterations on AGTR1 and PRKCA.

Disturbed renal lipid metabolism, especially cholesterol dysregulation plays a crucial role in the pathogenesis of chronic kidney disease (CKD). We recently reported that angiotensin (Ang) II could induce cholesterol accumulation and injury in podocytes. However, the underlying mechanisms for these alterations remain unknown. Methods: Bioinformatics analysis of renal biopsy specimens from patients with hypertensive nephropathy (HN) suggests the involvement of Sirtuin 6 (Sirt6) in Ang II-induced dysregulation of glomerular cholesterol. Using a podocyte-specific Sirt6 knockout mouse model, the effects of Sirt6 on Ang II-induced cholesterol accumulation in podocytes and the therapeutic efficacies of cholesterol-lowering agents were evaluated. Results: Cholesterol accumulation was detected in the podocytes of Ang II-infused mice, whereas selective deletion of Sirt6 in podocytes not only increased cholesterol accumulation in these cells but also exacerbated Ang II-induced kidney injury. Deletion of Sirt6 also attenuated the protective effect of cyclodextrin (CD) on Ang II-induced urinary albumin excretion, glomerulosclerosis and podocyte injury. In addition, we demonstrated that Sirt6 affected cholesterol efflux in podocytes by regulating the expression of ATP-binding cassette transporter G1 (ABCG1). Conclusions: These findings provide evidence that Sirt6 is a potential target for renin-angiotensin system (RAS)-associated podocyte injury and provide a rationale for the application of cholesterol-lowering agents in patients with CKD.

The aim of this study was to determine whether serum symmetric dimethylarginine (SDMA) and cystatin C (CysC) levels can be utilized as more accurate markers of early kidney dysfunction in dogs. Forty-one client-owned dogs with chronic kidney disease (CKD), which were clinically stable, and ten beagles as healthy controls were included. All dogs underwent physical examination, systemic blood pressure measurement, complete blood cell count, and plasma biochemistry analyses. Frozen serum was used for SDMA and CysC analyses. Data analysis was performed using Kruskal Wallis, Pearson's correlation, Bland-Altman plots, and receiver operating characteristic curve. SDMA and CysC levels were significantly higher in patients with CKD at various International Renal Interest Society (IRIS) stages than in the healthy controls. In particular, CysC level was the only biomarker that could indicate the earliest stage of CKD (IRIS stage I). Similar to these results, CysC level showed better sensitivity and specificity compared to the other biomarkers in early CKD dogs.

Background and purpose Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk factors. Experimental approach Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomized rat model and in CKD patients. Key results Six aryl-containing metabolites (ACMs) were significantly increased from Week 1 to Week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2 and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy and IgA nephropathy. Most importantly, 1-aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly up-regulated the mRNA expressions of AhR and its three target genes in both mice and NRK-52E cells, while this effect was partially weakened in AhR small hairpin RNA-treated mice and NRK-52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups. Conclusion and implications We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment.

PurposeThis study aims to evaluate the prevalence of depression and associated risk factors among patients on hemodialysis in Jazan area, Saudi Arabia.Design/methodology/approachThe study was conducted on 211 randomly selected hemodialysis patients in Jazan area, Saudi Arabia, using an observational cross-sectional design. Patients were screened for depressive symptoms using the depression, anxiety and stress scale 42 (DASS-42). Descriptive statistics were used to present sociodemographic data. Multiple logistic regression was implemented to identify the predictors of depression. Data were entered and analyzed using SPSS 22.0 software.FindingsThe study found the overall prevalence of depression among patients on hemodialysis to be 43.6 per cent. Of them, 12.8 per cent were mildly depressed, 15.6 per cent were moderately depressed and 15.1 per cent fell in the severe or extremely severe category. Depression was significantly associated with marital status, education level and the presence of sleep disturbances. The study indicates a high prevalence of depressive symptoms among patients on hemodialysis in Jazan. A higher rate of depressive symptoms was observed in currently unmarried, lower-educated patients and those with sleep disturbance.Originality/valuePeriodic evaluation of patients on hemodialysis for depression is needed to allow for early intervention.

Objective Older adults with co‐morbidities have been reported to be at higher risk for adverse outcomes of coronavirus disease 2019 (COVID‐19). The characteristics of COVID‐19 in older patients and its clinical outcomes in different kidney disease groups are not well known. Methods Data were retrieved from a national multicentric database supported by Turkish Society of Nephrology, which consists of retrospectively collected data between 17 April 2020 and 31 December 2020. Hospitalised patients aged 18 years or older with confirmed COVID‐19 diagnosis suffering from stage 3‐5 chronic kidney disease (CKD) or on maintenance haemodialysis (HD) treatment were included in the database. Non‐uraemic hospitalised patients with COVID‐19 were also included as the control group. Results We included 879 patients [388 (44.1%) female, median age: 63 (IQR: 50‐73) years]. The percentage of older patients in the CKD group was 68.8% (n = 188/273), in the HD group was 49.0% (n = 150/306) and in the control group was 30.4% (n = 70/300). Co‐morbidities were higher in the CKD and HD groups. The rate of presentation with severe‐critical disease was higher in the older CKD and HD groups (43.6%, 55.3% and 16.1%, respectively). Among older patients, the intensive care unit (ICU) admission rate was significantly higher in the CKD and HD groups than in the control group (38.8%, 37.3% and 15.7%, respectively). In‐hospital mortality or death and/or ICU admission rates in the older group were significantly higher in the CKD (29.3% and 39.4%) and HD groups (26.7% and 30.1%) compared with the control group (8.6% and 17.1%). In the multivariate analysis, in‐hospital mortality rates in CKD and HD groups were higher than control group [hazard ratio (HR): 4.33 (95% confidence interval [CI]: 1.53‐12.26) and HR: 3.09 (95% CI: 1.04‐9.17), respectively]. Conclusion Among older COVID‐19 patients, in‐hospital mortality is significantly higher in those with stage 3‐5 CKD and on maintenance HD than older patients without CKD regardless of demographic characteristics, co‐morbidities, clinical and laboratory data on admission.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4-5D. Guidance is provided for clinicians caring for CKD stages 4-5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.

The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate’s age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors.

eritoneal dialysis (PD) is a successful dialysis modal-ity that enables patients with end-stage kidneydisease to have a home-based treatment with many ad-vantages for their quality of life. In general, outcomes ofPD are equal to those of hemodialysis (HD). The reportedtechnique success of PD is, however, shorter than that ofHD. Whereas there are “positive” reasons for droppingout, such as transplantation or recovery of renal function,some patients transfer to HD because of peritonitis, in-adequate small solute clearance and/or ultrafiltration,and social factors (1). The impact of adequacy and prob-lems with maintaining euvolemia as reasons for dropoutincrease over time, especially as residual renal functiondeclines. Nevertheless, even anuric patients can be main-tained successfully on PD (2,3). Many patients are reluc-tant to transfer to HD, even when clinically indicated,because they perceive that such a transfer would ad-versely affect their quality of life. A proper presentationof different renal replacement therapies from the startof treatment onward (integrated care) could potentiallyavoid disappointment when a transfer is needed.One of the potential, although infrequent, complica-tions of long-term PD is encapsulating peritoneal scle-rosis (EPS); it is associated with high morbidity relatedto bowel obstruction and malnutrition. Reported mor-tality is around 50%, usually within 12 months of thediagnosis (4,5), although not all deaths are due to EPSitself (6). The first reports of EPS were from Japan andAustralia (4,7,8); more recently, there has been an in-creasing number of reports of EPS in Europe (9–11). Somenephrologists have suggested that there should be a timelimit to PD to prevent patients from developing this po-tentially devastating complication.The principal aims of this paper are1. To review existing information about epidemiologyof EPS and its risk factors;2. To determine whether there are any predictors forthe development of EPS that would guide the deci-sion to stop PD and transfer to HD; and3. To reach a consensus that should be given tonephrologists and their patients about the lengthof time it is advisable to remain on PD.GUIDELINES FOR EPSSo far, guidelines on the topic of EPS have been is-sued only by the Japanese Society for Peritoneal Dialy-sis (12). The UK guidelines are in the final process of

Mesenchymal stem cells (MSCs) are promising source of cell‐based regenerative therapy. In consideration of the risk of allosensitization, autologous MSC‐based therapy is preferred over allogenic transplantation in patients with chronic kidney disease (CKD). However, it remains uncertain whether adequate cell functionality is maintained under uremic conditions. As chronic inflammation and oxidative stress in CKD may lead to the accumulation of senescent cells, we investigated cellular senescence of CKD MSCs and determined the effects of metformin on CKD‐associated cellular senescence in bone marrow MSCs from sham‐operated and subtotal nephrectomized mice and further explored in adipose tissue‐derived MSCs from healthy kidney donors and patients with CKD. CKD MSCs showed reduced proliferation, accelerated senescence, and increased DNA damage as compared to control MSCs. These changes were significantly attenuated following metformin treatment. Lipopolysaccharide and transforming growth factor β1‐treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co‐culture with metformin‐treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin. In unilateral ureteral obstruction kidneys, metformin‐treated CKD MSCs more effectively attenuated inflammation and fibrosis as compared to untreated CKD MSCs. Thus, metformin preconditioning may exhibit a therapeutic benefit by targeting accelerated senescence of CKD MSCs., Increased senescence of CKD MSCs may contribute to poor regenerative potential. Metformin decreased CKD‐induced prelamin A accumulation and DNA damage signaling, which may lead to cellular senescence. We suggest metformin preconditioning as an effective strategy to overcome the senescence‐associated barrier to autologous patient‐derived MSC therapy in CKD.

Background Attempts to utilize eHealth in diabetes mellitus (DM) management have shown promising outcomes, mostly targeted at patients; however, few solutions have been designed for health care providers. Objective The purpose of this study was to conduct a feasibility project developing and evaluating a mobile clinical decision support system (CDSS) tool exclusively for health care providers to manage chronic kidney disease (CKD) in patients with DM. Methods The design process was based on the 3 key stages of the user-centered design framework. First, an exploratory qualitative study collected the experiences and views of DM specialist nurses regarding the use of mobile apps in clinical practice. Second, a CDSS tool was developed for the management of patients with DM and CKD. Finally, a randomized controlled trial examined the acceptability and impact of the tool. Results We interviewed 15 DM specialist nurses. DM specialist nurses were not currently using eHealth solutions in their clinical practice, while most nurses were not even aware of existing medical apps. However, they appreciated the potential benefits that apps may bring to their clinical practice. Taking into consideration the needs and preferences of end users, a new mobile CDSS app, “Diabetes & CKD,” was developed based on guidelines. We recruited 39 junior foundation year 1 doctors (44% male) to evaluate the app. Of them, 44% (17/39) were allocated to the intervention group, and 56% (22/39) were allocated to the control group. There was no significant difference in scores (maximum score=13) assessing the management decisions between the app and paper-based version of the app’s algorithm (intervention group: mean 7.24 points, SD 2.46 points; control group: mean 7.39, SD 2.56; t37=–0.19, P=.85). However, 82% (14/17) of the participants were satisfied with using the app. Conclusions The findings will guide the design of future CDSS apps for the management of DM, aiming to help health care providers with a personalized approach depending on patients’ comorbidities, specifically CKD, in accordance with guidelines.

Gut microbiota make up the largest microecosystem in the human body and are closely related to chronic metabolic diseases. Herein, 520 fecal samples are collected from different regions of China, the gut microbiome in chronic kidney disease (CKD) is characterized, and CKD classifiers based on microbial markers are constructed. Compared with healthy controls (HC, n = 210), gut microbial diversity is significantly decreased in CKD (n = 110), and the microbial community is remarkably distinguished from HC. Genera Klebsiella and Enterobacteriaceae are enriched, while Blautia and Roseburia are reduced in CKD. Fifty predicted microbial functions including tryptophan and phenylalanine metabolisms increase, while 36 functions including arginine and proline metabolisms decrease in CKD. Notably, five optimal microbial markers are identified using the random forest model. The area under the curve (AUC) reaches 0.9887 in the discovery cohort and 0.9512 in the validation cohort (49 CKD vs 63 HC). Importantly, the AUC reaches 0.8986 in the extra diagnosis cohort from Hangzhou. Moreover, Thalassospira and Akkermansia are increased with CKD progression. Thirteen operational taxonomy units are correlated with six clinical indicators of CKD. In conclusion, this study comprehensively characterizes gut microbiome in non‐dialysis CKD and demonstrates the potential of microbial markers as non‐invasive diagnostic tools for CKD in different regions of China., Compared with healthy controls, gut microbial diversity in CKD is significantly reduced, Klebsiella and Akkermansia are significantly increased, Roseburia and Faecalibacterium are significantly reduced, and the predictive function of gut microbiota such as ascorbate metabolism and lipopolysaccharide biosynthesis is significantly enhanced. Akkermansia increases along with the progression of CKD, which is positively correlated with serum creatinine and blood urea nitrogen, and negatively correlated with estimated glomerular filtration rate, and could be used as a therapeutic target to improve the prognosis of CKD. Importantly, gut microbial markers have strong diagnostic potential for CKD and achieve cross‐regional validation, which can be used as a non‐invasive diagnostic tool for CKD.

Background End-stage kidney disease (ESKD) continues to fundamentally impact the lives of First Nations (FN) patients. Home peritoneal dialysis (PD) offers patients more mobility and flexibility, but few Manitoba FNs have availed themselves of this option. Objective This paper discusses Manitoba FNs' experience of PD, to highlight enablers and barriers to expanding the use of PD in rural and remote Manitoba communities. Methods We analyzed interviews of individuals living with ESKD (N = 14), family caregivers (N = 14) and healthcare providers and administrators (N = 27). Results Barriers to PD uptake include medical suitability, patients' distrust of home modalities and fear in their ability to manage. Other factors include limited family support and lack of appropriate housing. Conclusions Assisted peritoneal dialysis (APD) is an emerging model where PD supplies are centrally located, and where a cohort of PD patients can provide mutual support with added assistance from an APD worker. This model could mitigate existing treatment barriers.

Planar cell polarity (PCP) pathways control the orientation and alignment of epithelial cells within tissues. Van Gogh‐like 2 (Vangl2) is a key PCP protein that is required for the normal differentiation of kidney glomeruli and tubules. Vangl2 has also been implicated in modifying the course of acquired glomerular disease, and here, we further explored how Vangl2 impacts on glomerular pathobiology in this context. Targeted genetic deletion of Vangl2 in mouse glomerular epithelial podocytes enhanced the severity of not only irreversible accelerated nephrotoxic nephritis but also lipopolysaccharide‐induced reversible glomerular damage. In each proteinuric model, genetic deletion of Vangl2 in podocytes was associated with an increased ratio of active‐MMP9 to inactive MMP9, an enzyme involved in tissue remodelling. In addition, by interrogating microarray data from two cohorts of renal patients, we report increased VANGL2 transcript levels in the glomeruli of individuals with focal segmental glomerulosclerosis, suggesting that the molecule may also be involved in certain human glomerular diseases. These observations support the conclusion that Vangl2 modulates glomerular injury, at least in part by acting as a brake on MMP9, a potentially harmful endogenous enzyme. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Background The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified. Methods We performed a meta-analysis of published large (>500 participants/arm) placebo-controlled SGLT-2 inhibitor trials after systematically searching MEDLINE and Embase databases from inception to 28th August 2021 (PROSPERO 2021 CRD42021240468). Findings Four heart failure trials (n=15,684 participants), four trials in type 2 diabetes mellitus at high atherosclerotic cardiovascular risk (n=42,568), and three trials in chronic kidney disease (n=19,289) were included. Relative risks (RRs) for all cardiovascular, renal and safety outcomes were broadly similar across these three patient groups, and between people with or without diabetes. Overall, compared to placebo, allocation to SGLT-2 inhibition reduced risk of hospitalization for heart failure or cardiovascular death by 23% (RR=0.77, 95%CI 0.73-0.80; n=6658), cardiovascular death by 14% (0.86, 0.81-0.92; n=3962), major adverse cardiovascular events by 11% (0.89, 0.84-0.94; n=5703), kidney disease progression by 36% (0.64, 0.59-0.70; n=2275), acute kidney injury by 30% (0.70, 0.62-0.79; n=1013 events) and severe hypoglycaemia by 13% (0.87, 0.79-0.97; n=1484). There was no effect of SGLT-2 inhibition on risk of non-cardiovascular death (0.93, 0.86-1.01; n=2226), but a net 12% reduction in all-cause mortality remained evident (0.88, 0.84-0.93; n=6188). However, the risk of ketoacidosis was 2-times higher among those allocated SGLT-2 inhibitors compared to placebo (2.03, 1.41-2.93; n=159; absolute excess in people with diabetes ∼0.3/1000 patient years). A small increased risk of urinary tract infection was evident (1.07, 1.02-1.13; n=5384) alongside a known increased risk of mycotic genital infections. Overall, risk of lower limb amputations was increased by 16% (1.16, 1.02-1.31; n=1074), but this risk was largely driven by a single outlying trial (CANVAS). Interpretations The relative effects of SGLT-2 inhibition on key safety and efficacy outcomes are consistent across the different studied groups of patient. Consequently, absolute benefits and harms are determined by the absolute baseline risk of particular outcomes, with absolute benefits on mortality and on non-fatal serious cardiac/renal outcomes substantially exceeding the risks of amputation and ketoacidosis in the main patient groups studied to date. Funding MRC-UK & KRUK.

Background Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure. Methods Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy. Findings At the global level, albuminuria decreased TH (β = −0.07 mm, 95% CI: −0.12 mm to −0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = −0.11 mm, 95% CI: −0.16 mm to −0.07 mm, P = 3.74×10−6). No pleiotropy was detected. Interpretation Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis. Funding This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).

The Gram negative rods as Escherichia coli and Klebsiella pneumoniae belong to the most common etiology agents of urinary tract infections. The aim of our study was to assess the diversity of biofilm formed in different urinary tract diseases and their impact on monocytes’ adherence and activation. The bacteria were obtained from patients with different kidney problems. Some of the patients were after renal transplantation, some of them were not. Changes in the size and granularity of monocytes, as well as their adherence to biofilm, were assessed using FACSVerse flow cytometer after 1 h co-incubation of monocytes and bacterial biofilm in 37 °C. The obtained results were validated against monocytes incubated without bacteria. The isolates from patients with chronic kidney disease formed the most adherent biofilm regardless the presence or absence of inflammatory reaction. Adherence of monocytes also increased during therapy with immunosuppressive agents, but monocytes’ response was different when cyclosporine or tacrolimus were used. Additionally the presence of inflammatory reaction in patients with kidney disease modified the monocytes response when the immunosuppressive drugs were used. Considering the obtained results, we conclude that the changes of monocytes’ morphology in response to biofilm formed by Gram negative rods could become a tool to detect urinary tract infection, especially in those groups of patients, where the knowledge of ongoing inflammation is important and the standard tools fail to detect it.

Highlights • We measured EEG spectral changes during hemodialysis. • We found slowing of the EEG background activity during hemodialysis. • These changes were correlated with risk factors of dialysis disequilibrium syndrome., Objective To investigate the EEG spectral changes induced during hemodialysis in patients with chronic kidney disease (CKD), and to identify the risk factors associated with changes in the Central Nervous System (CNS) during hemodialysis. Paradoxical neurological deterioration at the end of hemodialysis sessions, known as dialysis disequilibrium syndrome (DDS) has been described, but previous studies on EEG spectral changes during hemodialysis were controversial. Methods We performed quantitative EEG spectral analysis in 56 consecutive patients who underwent hemodialysis. We compared EEG at the start and at the end of the hemodialysis, and we correlated the spectral changes with the biochemical and clinical characteristics of the patients, using multivariate analysis. Results At the end of hemodialysis sessions, we found a significant increase in total EEG power, relative power in delta frequency band and the ratio of delta-theta/alpha–beta power. EEG spectral changes were associated with younger age, recent start of hemodialysis therapy, level of uremia and lower level of glycaemia. Conclusions Quantitative EEG spectral analysis showed that hemodialysis induced slowing of the EEG background activity. These changes were associated with risk factors of DDS. Significance EEG spectral changes are potential biomarkers for monitoring CNS function during hemodialysis.

PurposeKidney transplantation (KT) is the treatment of choice for end-stage chronic kidney disease (CKD) and is well known to improve the clinical outcome of patients. However, the impact of KT on comorbid psychological symptoms, particularly depression and anxiety, is less clear, and recipients of living-donor (LD) organs may have a different psychological outcome from recipients of dead-donor (DD) organs.Design/methodology/approachIn total, 152 patients were included and analyzed using a cross-sectional design. Of these patients, 25 were pre-KT, 13 were post-KT with a LD transplant and 114 were post-KT with a DD transplant. The patients were tested for a variety of psychometric outcomes using the Hospital Anxiety and Depression Scale, the 12-Item Short Form Health Survey (assessing physical and mental health-related quality of life), the Resilience Scale, the Coping Self-Questionnaire and the Social Support Questionnaire.FindingsThe mean age of the patients was 51.25 years and 40 per cent of the patients were female. As expected, the post-KT patients had significantly better scores on the physical component of the Short Form Health Survey than the pre-KT patients, and there were no significant differences between the two post-KT groups. There were no significant differences among the groups in any of the other psychometric outcome parameters tested, including anxiety, depression and the mental component of health-related quality of life.Research limitations/implicationsKT and the origin of the donor organ do not appear to have a significant impact on the psychological well-being of transplant patients with CKD. Although the diagnosis and early treatment of psychological symptoms, such as depression and anxiety, remain important for these patients, decisions regarding KT, including the mode of transplantation, should not be fundamentally influenced by concerns about psychological impairments at the population level.Originality/valueCKD is a serious condition involving profound impairment of the physical and psychological well-being of patients. KT is considered the treatment of choice for most of these patients. KT has notable advantages over dialysis with regard to the long-term physical functioning of the renal and cardiovascular system and increases the life expectancy of patients. However, the data on the improvement of psychological impairments after KT are less conclusive.

Whether the abnormal circadian rhythm of urinary sodium excretion is associated with hypertension in chronic kidney disease (CKD) is poorly understood. In this study, we assessed the relationship between the circadian rhythm of urinary sodium excretion and hypertension. Urinary samples were collected during both the day (07:00 to 22:00) and night (22:00 to 07:00) to estimate night/day urinary sodium excretion ratios. Blood pressure (BP) and clinical data were also measured. A total of 1,099 Chinese CKD patients were recruited, 308 patients were excluded, and 791 patients were final enrolled in this study. Among them, 291 patients were normotensive and 500 were hypertensive CKD patients. A 1:1 propensity score matching (PSM) analysis was performed with age and estimated glomerular filtration rate (eGFR) matched between 190 normotensive and hypertensive patients. In the full cohort and PSM cohort, multivariate regression analysis showed that the night/day urinary sodium excretion ratio was an independent risk factor for clinical hypertension, whereas 24 h urinary sodium excretion, diurnal and nocturnal urinary sodium excretion were not. When the night/day urinary sodium excretion ratios were further divided into tertiles (tertile 1 < 0.47, tertile 2, 0.47-0.84 and tertile 3 > 0.84), multivariate analysis showed that tertile 3 was independently associated with hypertension in the full and PSM cohorts. In addition, tertile 3 was also independently associated with eGFR ≤ 60 mL/min/1.73 m2 and left ventricular hypertrophy. These data suggested that an abnormal circadian rhythm of urinary sodium excretion was independently associated with hypertension and target-organ damage. Individualized salt intake and therapeutic strategies should be used to normalize the natriuretic dipping profile in CKD patients.

Leptin potentially exerts atherogenic effects.This study evaluated the relationship between serum leptin levels and aortic stiffness in patients with stage 3–5 chronic kidney disease (CKD). Totally 205 participants were enrolled. Fasting blood sample were checked and serum leptin were measured by enzyme immunoassay. Aortic stiffness was measured as the carotid–femoral pulse wave velocity (cfPWV). 73 (35.6%) of 205 patients showed cfPWV >10 m/s were defined as aortic stiffness group. Compared with the remaining patients, the aortic stiffness group had high prevalence of diabetes mellitus, older age, higher waist circumference, body fat mass, systolic blood pressure, fasting glucose, and higher serum leptin level. In multivariable logistic regression analysis the independent predictors of cfPWV >10 m/s included leptin levels (odds ratio [OR]: 1.061, 95% confidence interval [CI]: 1.027–1.095, P < 0.001), age (OR: 1.064, 95% CI: 1.033–1.096, P< 0.001), and systolic blood pressure (OR: 1.021, 95% CI: 1.006–1.037, P = 0.006). Multivariable forward stepwise linear regression analysisshowed a positive association between log-transformed leptin levels and log-cfPWV (β = 0.192, adjusted R2 change = 0.042, P = 0.001). Thus, aortic stiffness is positively correlated with serum leptin levels in patients with stage 3–5 CKD. Abbreviations: BUN, blood urea nitrogen; cfPWV, carotid–femoral pulse wave velocity; CI, confidence interval; CKD, chronic kidney disease; Cre, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; SBP, systolic blood pressure; TCH, total cholesterol; TG, triglycerides

Chronic kidney disease (CKD) is a common renal disease in dogs and cats. Renal fibrosis is a main pathologic process leading of CKD progression. Renal biopsy is the gold standard for renal fibrosis assessment. However, it is not routinely performed in clinic due to its invasiveness. Therefore, the aim of this study was to evaluate the use of ultrasonographic strain elastography (SE), which is a non-invasive method for renal tissue stiffness determination and its association with renal function. Renal strain ratios and renal function were evaluated in 13 CKD dogs (CKDD), 38 healthy dogs (HD), 17 CKD cats (CKDC) and 26 healthy cats (HC). There were significantly lower renal cortical strain ratios than medullary strain ratios in all groups (HD; P

Background: Patients with chronic kidney disease (CKD) are associated with high prevalence rates of proteinuria, vascular calcification and cardiomegaly. In this study, we investigated relationships among proteinuria, aortic arch calcification (AoAC) and cardio-thoracic ratio (CTR) in patients with CKD stage 3A-5. In addition, we investigated correlations among proteinuria and decline in renal function, overall and cardiovascular (CV) mortality. Methods: We enrolled 482 pre-dialysis patients with CKD stage 3A-5, and determined AoAC and CTR using chest radiography at enrollment. The patients were stratified into four groups according to quartiles of urine protein-to-creatinine ratio (UPCR). Results: The patients in quartile 4 had a lower estimated glomerular filtration rate (eGFR) slope, and higher prevalence rates of rapid renal progression, progression to commencement of dialysis, overall and CV mortality. Multivariable analysis showed that a high UPCR was associated with high AoAC (unstandardized coefficient β: 0.315; p = 0.002), high CTR (unstandardized coefficient β: 1.186; p = 0.028) and larger negative eGFR slope (unstandardized coefficient β: -2.398; p < 0.001). With regards to clinical outcomes, a high UPCR was significantly correlated with progression to dialysis (log per 1 mg/g; hazard ratio [HR], 2.538; p = 0.003), increased overall mortality (log per 1 mg/g; HR, 2.292; p = 0.003) and increased CV mortality (log per 1 mg/g; HR, 3.195; p = 0.006). Conclusions: Assessing proteinuria may allow for the early identification of high-risk patients and initiate interventions to prevent vascular calcification, cardiomegaly, and poor clinical outcomes.

Background: Diabetes mellitus is the leading cause of diabetic nephropathy and a major public health issue worldwide. Approximately 20-30% of patients with type 2 diabetes mellitus (T2DM) have renal impairment. Fatty acid-binding protein 1 (FABP1) is expressed in renal proximal tubule cells and released into urine in response to hypoxia caused by decreased peritubular capillary blood flow, and FABP2 is responsible for the transport of free fatty acids in the intestinal endothelium cells. There is increasing evidence that FABP1 and FABP 2 play a role in the development and progression of chronic kidney disease. The aim of this study was to investigate the relation of circulating FABP1 and FABP2 levels to nephropathy in patients with T2DM. Methods: For this study, 268 subjects with T2DM who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The plasma FABP1 and FABP2 concentrations were examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with logistic regression to calculate the effects of FABP1 and FABP2 levels on diabetic nephropathy. Results: The FABP1 and FABP2 levels increased in parallel with the advancement of diabetic nephropathy. Increasing concentrations of FABP1 and FABP2 were independently and significantly associated with diabetic nephropathy. Multiple logistic regression analysis revealed FABP1 and FABP2 as an independent association factor for diabetic nephropathy, even after full adjustment of known biomarkers. Furthermore, receiver operating characteristic curve analysis showed that a FABP1 level of >33.8 ng/mL and a FABP2 level of >2.8 ng/mL were associated with diabetic nephropathy. Conclusion: Our results suggest that FABP1 and FABP2 may be novel biomarkers of diabetic nephropathy.