The presence of exudative thickening of Bowman's capsule predict poor prognosis in diabetic kidney disease.

BACKGROUND: The relationship between Bowman's capsule thickening and progression of diabetic kidney disease (DKD) remains uncertain. METHODS: Renal biopsy specimens from 145 DKD patients and 20 control subjects were evaluated for Bowman's capsule thickness. Immunohistochemical staining assessed col4α2, laminin ß1, and albumin expression. In a discovery cohort of 111 DKD patients with eGFR ≥ 30 ml/min/1.73 m2, thickening was classified as fibrotic or exudative. The composite endpoint included CKD stage 5, dialysis initiation, and renal disease-related death. Prognosis was analyzed using Kaplan-Meier and Cox regression analyses. Two validation cohorts were included. RESULTS: Three types of thickening were observed: fibrotic, exudative, and periglomerular fibrosis. Parietal epithelial cell matrix protein accumulation contributed to fibrotic thickening, while albumin was present in exudative thickening. Bowman's capsule was significantly thicker in DKD patients (5.74 ± 2.09 µm) compared to controls (3.38 ± 0.43 µm, P < 0.01). In discovery cohort, the group of exudative thickning had a poorer prognosis(median time 20 months vs 57 months, P = 0.000). Cox multivariate analysis revealed that exudative thickening of Bowman's capsule were associated with a poor prognosis. The validation cohorts confirmed the result. CONCLUSIONS: Various mechanisms contribute to Bowman's capsule thickening in DKD. The proportion of exudative thickening may serve as a valuable prognostic indicator for DKD patients.

Notoginsenoside Fc, a novel renoprotective agent, ameliorates glomerular endothelial cells pyroptosis and mitochondrial dysfunction in diabetic nephropathy through regulating HMGCS2 pathway.

BACKGROUND: Diabetic nephropathy (DN) is the primary cause of end-stage renal disease (ESRD), and the therapeutic strategies for DN are limited. Notoginsenoside Fc (Fc), a novel saponin isolated from Panax Notoginseng (PNG), has been reported to alleviate vascular injury in diabetic rats. However, the protective effects of Fc on DN remain unclear. PURPOSE: To investigate the beneficial effects and mechanisms of Fc on DN. METHODS: Db/db mice were treated with 2.5, 5 and 10 mg·kg-1·d-1 of Fc for 8 weeks. High glucose (HG) induced mouse glomerular endothelial cells (GECs) were treated with 2.5, 5 and 10 µM of Fc for 24 h. RESULTS: Our data found that Fc ameliorated urinary microalbumin level, kidney dysfunction and histopathological damage in diabetic mice. Moreover, Fc alleviated the accumulation of oxidative stress, the collapse of mitochondrial membrane potential and the expression of mitochondrial fission proteins, such as Drp-1 and Fis1, while increased the expression of mitochondrial fusion protein Mfn2. Fc also decreased pyroptosis-related proteins levels, such as TXNIP, NLRP3, cleaved caspase-1, and GSDMD-NT, indicating that Fc ameliorated GECs pyroptosis. In addition, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) expression was increased in diabetic group, which was partially abrogated by Fc. Our data further proved that knockdown of HMGCS2 could restrain HG-induced GECs mitochondrial dysfunction and pyroptosis. These results indicated that the inhibitory effects of Fc on mitochondrial damage and pyroptosis were associated with the suppression of HMGCS2. CONCLUSION: Taken together, this study clearly demonstrated that Fc ameliorated GECs pyroptosis and mitochondrial dysfunction partly through regulating HMGCS2 pathway, which might provide a novel drug candidate for DN.

Association between disability in activities of daily living and phase angle in hemodialysis patients.

BACKGROUND: Disability in activities of daily living (ADL) significantly increases the risk of mortality among patients undergoing hemodialysis. Malnutrition and decreased exercise capacity are closely correlated with ADL disability. Phase angle (PhA) has been proposed as a measure of nutritional status and exercise capacity. This study aims to investigate the prevalence of ADL disability in hemodialysis patients and its association with PhA. METHODS: A prospective, observational study was conducted, involving hemodialysis patients treated between November 2019 and January 2020 in an affiliated hospital of Chinese university. ADL was measured using both basic ADL (BADL) scales and instrumental ADL (IADL) scales. PhA measurements were obtained using a BIA device while the patients were in the supine position after dialysis. RESULTS: A total of 237 hemodialysis patients with a mean age of 60.01 ± 13.55 years were included in this study. The prevalence of disability in ADL was 43.5%. Multivariable analysis results showed a robust association between low PhA and disability in both BADL and IADL (for each unit decrease in PhA: odds ratio 4.83 [95% CI: 2.56-9.0], and 3.57 [95% CI: 2.14-5.95], respectively). The optimal cut-off values of PhA for disability in BADL and IADL were 4.8 and 5.4, with the area under the ROC curve (AUC) were 0.783 (0.727, 0.835) and 0.799 (0.743, 0.848), respectively. CONCLUSIONS: Low PhA is strongly associated with disability in ADL in hemodialysis patients. These findings suggest that PhA may serve as a potentially objective measure of ADL disability in hemodialysis patients.

Risk Factors and Drug Efficacy for Severe Illness in Hemodialysis Patients Infected with the Omicron Variant of COVID-19.

INTRODUCTION: The Omicron variant of the novel coronavirus (COVID-19) has been spreading more rapidly and is more infectious, posing a higher risk of death and treatment difficulty for patients undergoing hemodialysis. This study aims to explore the severity rate and risk factors for hemodialysis patients infected with the Omicron variant and to conduct a preliminary analysis of the clinical efficacy of drugs. METHODS: Clinical and biochemical indicators of 219 hemodialysis patients infected with the Omicron variant were statistically analyzed. The patients were divided into two groups based on whether they were severely ill or not, and multiple regression analysis was conducted to determine the risk factors for severe illness. The severely ill patients were then grouped based on discharge or death, and the treatment drugs were included as influencing factors for multiple regression analysis to determine the risk factors and protective factors for death of severely ill patients, and drug efficacy analysis was conducted. RESULTS: Analysis showed that diabetes, low oxygen saturation, and high C-reactive protein (CRP) were independent risk factors for severe illness in hemodialysis patients infected with the Omicron variant. A history of diabetes and high C-reactive significantly increased the risk of severe illness in patients (aOR: 1.450; aOR: 1.011), while a high oxygen saturation level can reduce this risk (aOR: 0.871). In addition, respiratory distress was an independent risk factor for death in severely patients, significantly reducing the probability of discharge for patients (aOR: 0.152). The drugs thymalfasin and Tanreqing significantly increased the probability of discharge for patients (aOR: 1.472; aOR: 3.104), with the latter having a higher correlation, but with a relatively longer effective course. CONCLUSION: Hemodialysis patients infected with the Omicron variant of COVID-19 should pay special attention to their history of diabetes, CRP, and oxygen saturation levels, as well as respiratory distress symptoms, to reduce the risk of severe illness and death. In addition, thymalfasin and Tanreqing may be considered in treatment.

Deacetylation of FOXP1 by HDAC7 potentiates self-renewal of mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are widely used in a variety of tissue regeneration and clinical trials due to their multiple differentiation potency. However, it remains challenging to maintain their replicative capability during in vitro passaging while preventing their premature cellular senescence. Forkhead Box P1 (FOXP1), a FOX family transcription factor, has been revealed to regulate MSC cell fate commitment and self-renewal capacity in our previous study. METHODS: Mass spectra analysis was performed to identify acetylation sites in FOXP1 protein. Single and double knockout mice of FOXP1 and HDAC7 were generated and analyzed with bone marrow MSCs properties. Gene engineering in human embryonic stem cell (hESC)-derived MSCs was obtained to evaluate the impact of FOXP1 key modification on MSC self-renewal potency. RESULTS: FOXP1 is deacetylated and potentiated by histone deacetylase 7 (HDAC7) in MSCs. FOXP1 and HDAC7 cooperatively sustain bone marrow MSC self-renewal potency while attenuating their cellular senescence. A mutation within human FOXP1 at acetylation site (T176G) homologous to murine FOXP1 T172G profoundly augmented MSC expansion capacity during early passages. CONCLUSION: These findings reveal a heretofore unanticipated mechanism by which deacetylation of FOXP1 potentiates self-renewal of MSC and protects them from cellular senescence. Acetylation of FOXP1 residue T172 as a critical modification underlying MSC proliferative capacity. We suggest that in vivo gene editing of FOXP1 may provide a novel avenue for manipulating MSC capability during large-scale expansion in clinical trials.

IL-17C neutralization protects the kidney against acute injury and chronic injury.

BACKGROUND: Interleukin-17C (IL-17C), a member of the IL-17 cytokine family, plays a pathogenic role in kidney diseases. Our previous studies have shown that pre-administration of IL-17C neutralizing antibody attenuated acute kidney injury (AKI, a common acute inflammation associated renal disease). In this study, we explored whether post-ischemia reperfusion (IR) of IL-17C blockade has therapeutic effects on AKI and whether IL-17C is involved in the pathogenesis of diabetic nephropathy (DN), a major type of chronic inflammation-associated kidney disease. METHODS: 12-week-old male C57BL/6JGpt mice were treated with IL-17C neutralizing antibody or normal IgG control antibody at 3 h after reperfusion. Renal injury, inflammation, and oxidative stress were assessed. Additionally, we examined renal IL-17C expression in patients with DN and db/db mice and evaluated albuminuria, mesangial matrix accumulation and podocyte loss in db/db mice with IL-17C neutralization. Knockdown of NF-κB p65 using siRNA, and blocking Hypoxia-inducible factor-1α (HIF-1α) using YC-1 in mice and HIF-1α Decoy in HK2 cells were investigated to explore the possible signaling pathway involved in IL-17C regulation. FINDINGS: We found that delayed IL-17C neutralization had similar reno-protective effects on renal ischemia-reperfusion injury (IRI). Additionally, renal IL-17C expression was increased in patients with DN and db/db mice, while IL-17C blockade significantly attenuated DN, accompanied with blunted albuminuria, mesangial matrix accumulation, and podocyte loss. Moreover, IL-17C neutralization significantly repressed the expression of downstream pro-inflammatory cytokines, inflammatory cell infiltration, and Th17/IL-17A activation both in mice with renal IRI and DN. Mechanistical studies demonstrated that hypoxia or high glucose-induced IL-17C up-regulation was predominantly mediated by NF-κB pathway. INTERPRETATION: IL-17C participates in the pathogenesis of AKI and DN and inhibition of IL-17C shows potential as a therapeutic strategy for AKI and DN. FUNDING: The National Natural Science Foundation of China (81770741, 81700601 and 81870504).

Total cholesterol and mortality in peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Total cholesterol is inversely associated with mortality in dialysis patients, which seems implausible in real-world clinical practice. May there be an optimal range of total cholesterol associated with a lower mortality risk? We aimed to evaluate the optimal range for peritoneal dialysis (PD) patients. METHODS: We conducted a retrospective real-world cohort study of 3565 incident PD patients from five PD centers between January 1, 2005, and May 31, 2020. Baseline variables were collected within one week before the start of PD. The associations between total cholesterol and mortality were examined using cause-specific hazard models. RESULTS: 820 (23.0%) patients died, including 415 cardiovascular deaths, during the follow-up period. Restricted spline plots showed a U-curved association of total cholesterol with mortality. Compared with the reference range (4.10-4.50 mmol/L), high levels of total cholesterol (> 4.50 mmol/L) were associated with increased risks of all-cause (hazard ratio [HR] 1.35, 95% confidence index [CI] 1.08-1.67) and cardiovascular mortality (HR 1.38, 95% CI 1.09-1.87). Similarly, compared with the reference range, low levels of total cholesterol (< 4.10mmol/L) were also associated with high risks of all-cause (HR 1.62, 95% CI 1.31-1.95) and cardiovascular mortality (HR 1.72, 95% CI 1.27-2.34). CONCLUSION: Total cholesterol levels at the start of PD between 4.10 and 4.50 mmol/L (158.5 to 174.0 mg/dL), an optimal range, were associated with lower risks of death than higher or lower levels, resulting in a U-shaped association.

Musculoskeletal Ultrasound Evaluates Renal Injury and Predicts Renal Outcome in Patients with Gout.

Introduction: Kidney injury diagnosis is often delayed in patients with gout. We aimed to determine the characteristics of gout patients with CKD using musculoskeletal ultrasound (MSUS) and whether MSUS could be used as an auxiliary assessment to evaluate kidney injury and predict renal outcome in patients with gout. Methods: Clinical information, laboratory indicators, and MSUS findings were collected and compared between gout-only patients (gout - CKD) and gout patients with CKD (gout + CKD). Multivariate logistic regression was applied to identify risk factors for clinical and MSUS characteristics in both groups. Correlation analysis between MSUS signs and kidney-related indicators was performed, and the effects of MSUS characteristics on renal prognosis were evaluated. Results: In total, 176 patients with gout were included, namely, 89 gout - CKD and 87 gout + CKD cases. After adjusting for confounders, the gout patients with CKD showed more frequent episodes in the previous year, higher ultrasound semiquantitative scores, and more tophi than gout patients without CKD. Additionally, the number of tophi, bone erosion, and synovial hypertrophy measured by MSUS was found to be negatively correlated with the eGFR. The existence of tophi was independently associated with an increased risk of a ≥10% decline in eGFR in the first-year follow-up (OR, 3.56; 95% CI, 1.382-9.176). Conclusions: Ultrasound-detected tophi, bone erosion, and synovial hypertrophy were associated with kidney injury in gout patients. The existence of tophi was associated with faster renal function deterioration. MSUS could be a potential auxiliary diagnostic method to evaluate kidney injury and predict renal outcome in gout patients.

Evaluation of safety, effectiveness and treatment patterns of sodium zirconium cyclosilicate in management of hyperkalaemia in China: a real-world study protocol.

INTRODUCTION: Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China's drug review and approval process. METHODS AND ANALYSIS: This is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05271266.

The Qi-Bang-Yi-Shen formula ameliorates renal dysfunction and fibrosis in rats with diabetic kidney disease via regulating PI3K/AKT, ERK and PPARγ signaling pathways.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and a growing public health problem worldwide. Losartan potassium (Los), an angiotensin II receptor blocker, has been used to treat DKD clinically. Recently, multi-herbal formula has been shown to exhibit therapeutic activities in DKD in China. Thus, we aimed to explore the protective effects of combination of Los and Qi-Bang-Yi-Shen formula (QBF) on DKD rats. Streptozotocin (STZ) injection was used to establish a rat model of DKD. Next, the bloodurea nitrogen (BUN), creatinine (CRE) and uric acid (UA) levels were detected in serum samples from DKD rats. Hematoxylin and eosin (H&E), periodic Acid Schiff (PAS) and Masson staining were performed to observe glomerular injury and glomerular fibrosis in DKD rats. In this study, we found that QBF or Los treatment could decrease serum BUN, CRE, UA levels and reduce urine albumin-to-creatinine ratio (ACR) in DKD rats. Additionally, QBF or Los treatment obviously inhibited glomerular mesangial expansion and glomerular fibrosis, attenuated glomerular injury in kidney tissues of DKD rats. Moreover, QBF or Los treatment significantly reduced PI3K, AKT and ERK1/2 protein expressions, but increased PPARγ level in kidney tissues of DKD rats. As expected, combined treatment of QBF and Los could exert enhanced reno-protective effects compared with the single treatment. Collectively, combination of QBF and Los could ameliorate renal injury and fibrosis in DKD rats via regulating PI3K/AKT, ERK and PPARγ signaling pathways. These findings highlight the therapeutic potential of QBF to prevent DKD progression.

The Effects of Fluid Hydration Status on Ultrasound Muscle Measurement in Hemodialysis Patients.

OBJECTIVE: This study aimed to explore the effects of fluid hydration status on ultrasound muscle measurement in hemodialysis (HD) patients. METHODS: Ultrasound muscle examination of the right rectus femoris and bioelectrical impedance analysis measurement of the right lower limb were performed in HD patients at the periods of predialysis and postdialysis. The correlations between the changes in the corresponding ultrasound and bioelectrical impedance analysis variables were analyzed. RESULTS: A total of 50 patients on maintenance HD were included, with mean age of 52.6 ± 13.5 years. Patients were 40% female (n = 20), and average dialysis duration was 2.62 ± 2.42 years. Compared to predialysis, the measurements of cross-sectional area, muscle thickness, echo intensity (EI), and their percentage changes all decreased significantly after the HD procedure (P < .05). The change in EI and its percentage change were significantly correlated with changes in total body water, intracellular water, and extracellular water (P < .05). CONCLUSIONS: The HD session may have significant effects on ultrasound muscle measurement. Both the indicators of muscle quantity (cross-sectional area and muscle thickness) and quality (EI) significantly decreased after HD, which may contribute to the change in fluid hydration status and the change in fluid composition.

Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development.

Chronic kidney disease (CKD) is a common cause of morbidity in human immunodeficiency virus (HIV)-positive individuals. HIV infection leads to a wide spectrum of kidney cell damage, including tubular epithelial cell (TEC) injury. Among the HIV-1 proteins, the pathologic effects of viral protein R (Vpr) are well established and include DNA damage response, cell cycle arrest, and cell death. Several in vitro studies have unraveled the molecular pathways driving the cytopathic effects of Vpr in tubular epithelial cells. However, the in vivo effects of Vpr on tubular injury and CKD pathogenesis have not been thoroughly investigated. Here, we use a novel inducible tubular epithelial cell-specific Vpr transgenic mouse model to show that Vpr expression leads to progressive tubulointerstitial damage, interstitial inflammation and fibrosis, and tubular cyst development. Importantly, Vpr-expressing tubular epithelial cells displayed significant hypertrophy, aberrant cell division, and atrophy; all reminiscent of tubular injuries observed in human HIV-associated nephropathy (HIVAN). Single-cell RNA sequencing analysis revealed the Vpr-mediated transcriptomic responses in specific tubular subsets and highlighted the potential multifaceted role of p53 in the regulation of cell metabolism, proliferation, and death pathways in Vpr-expressing tubular epithelial cells. Thus, our study demonstrates that HIV Vpr expression in tubular cells is sufficient to induce HIVAN-like tubulointerstitial damage and fibrosis, independent of glomerulosclerosis and proteinuria. Additionally, as this new mouse model develops progressive CKD with diffuse fibrosis and kidney failure, it can serve as a useful tool to examine the mechanisms of kidney disease progression and fibrosis in vivo.

[Discussions Concerning the Generalist-Specialist Combination Management Model of Chronic Kidney Disease]. / æ ¢æ€§è‚¾è„ç— "å ¨-专"结合管理模式探讨.

In recent years, the effective management of patients with chronic kidney disease (CKD) is gaining growing attention. In 2014, our hospital established the CKD generalist-specialist combination management model, which incorporates a set of CKD management processes. The generalist component incorporates the following, general practitioners from 6 community health centers in the surrounding areas (with about 650 000 permanent residents in the region) joining hands, setting up a management team composed of doctors and nurses, and formulating management protocols for patient follow-up, patient record management, screening, risk assessment, examination and treatment, nutrition and exercise, and two-way referrals. The specialist component of the model incorporates the following, providing trainings for general practitioners in the in the community in the form of lectures on special topics and case discussion sessions, and organizing 7 national-level workshops for continuing medical education in the past decade, covering about 1 400 participants. In addition, regular meetings of the support groups of patients with renal diseases were organized to carry out information and education activities for patients. We have set up 4 community-based training centers and 6 specialized disease management centers, including one for diabetic nephropathy. We have retrospectively analyzed the risk factors of elderly CKD patients by establishing the elderly physical examination database (which has a current enrollment of 26 000 people), the elderly community CKD cross-sectional survey database, and the elderly CKD information management system. After 10 years of management practice, the level of institutionalization and standardization of CKD specialty management in our hospital has been improved. Moreover, we have expanded the management team and extended the management base from the hospital to community. We have improved the level of CKD management in community health centers and improved the specialty competence of the general practitioners in the communities. The generalist-specialist combination management model makes it possible for CKD patients to receive early screening and treatment, obtain effective and convenient follow-up and referral services, and improve their quality of life. Patients with complications such as diabetes, hypertension, and sarcopenia could access treatments with better precision. It is necessary to carry out the generalist-specialist integrated management of CKD, which is worthy of further development and improvement.

Hyperlipidemia and mortality in patients on peritoneal dialysis.

BACKGROUND: New lipid-lowering therapy at the start of dialysis and measurement of lipid parameters over the follow-up period is not recommended in dialysis patients, which seems unappropriated in clinical practice. We aimed to examine the effect of hyperlipidemia on mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: A retrospective cohort study was performed, including 2939 incident CAPD patients from five dialysis facilities between January 1, 2005, and December 31, 2018. The primary outcome was all-cause mortality. The association between hyperlipidemia at the start of CAPD and all-cause mortality was evaluated using Cox proportional hazards regression. RESULTS: Of 2939 with a median age of 50.0 (interquartile range, 39.0-61.0), 1697 (57.7%) were men, 533 (18.1%) had hyperlipidemia, 549 (18.7%) had diabetes mellitus, 1915 (65.2%) had hypertension, and 410 (14.0%) had a history of CVD. During the median follow-up period of 35.1 months, 519 (17.7%) died, including 402 (16.7%, 47.4/1000 patient-years) in the non-hyperlipidemia group and 117 (22.0%, 71.1/1000 patient-years) in the hyperlipidemia group. Over the overall follow-up period, patients with hyperlipidemia had an equally high risk of all-cause mortality throughout follow-up as those without hyperlipidemia ([HR] 1.04, 95% confidence interval [CI] 0.83 to 1.31). However, from the 48-month follow-up onwards, hyperlipidemia was associated with a 2.26 (95% CI 1.49 to 3.43)-time higher risk of all-cause mortality than non-hyperlipidemia. Hypertension modified the association between hyperlipidemia and all-cause mortality (P for interaction < 0.001). A significantly increased risk of all-cause mortality was observed among patients with hypertension (HR 2.27, 95%CI 1.44-3.58). CONCLUSION: Among CAPD patients, hyperlipidemia at the beginning of CAPD was associated with a high risk of long-term mortality. Hypertension may mediate the association. Our findings suggested that long-term lipid-lowering treatment should be used in those patients with hyperlipidemia.

Low-Density Lipoprotein Cholesterol and Mortality in Peritoneal Dialysis.

Background: In dialysis patients, lowering low-density lipoprotein cholesterol (LDL-C) did not provide benefits, which seemed implausible in clinical practice. We hypothesized a U-shaped association between LDL-C and mortality in dialysis patients. Methods: In this multi-center retrospective real-world cohort study, 3,565 incident Chinese peritoneal dialysis (PD) patients between January 1, 2005, and May 31, 2020, were included. The associations between baseline LDL-C and mortality were examined using cause-specific hazard models. Results: Of 3,565 patients, 820 died, including 415 cardiovascular deaths. As compared with the reference range (2.26-2.60 mmol/L), both higher levels of LDL-C (> 2.60 mmol/L) and lower levels of LDL-C (< 2.26 mmol/L) were associated with increased risks of all-cause mortality (hazard ratio [HR],1.35, 95% confidence index [CI], 1.09-1.66; HR 1.36, 95%CI, 1.13-1.64) and cardiovascular mortality (HR, 1.31, 95% CI, 1.10-1.72; HR, 1.64; 95% CI, 1.22-2.19). Malnutrition (albumin < 36.0 g/L) modified the association between LDL-C and cardiovascular mortality (P for interaction = 0.01). A significantly increased risk of cardiovascular mortality was observed among patients with malnutrition and lower levels of LDL-C (HR 2.96, 95%CI 1.43-6.12) or higher levels of LDL-C (HR 2.81, 95%CI 1.38-5.72). Conclusion: Low and high levels of LDL-C at the start of PD procedure were associated with increased all-cause and cardiovascular mortality risks. Malnutrition may modify the association of LDL-C with cardiovascular mortality.

Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

INTRODUCTION: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. METHODS: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (ß2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of ß2M and PTH, while the secondary outcome was the reduction of the pruritus score. RESULTS: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of ß2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. CONCLUSION: The long-term HP + HD can reduce ß2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Infection profile and risk factors for mortality in patients with end-stage renal disease attributable to systemic lupus erythematosus: a two-center integrated study.

OBJECTIVE: Renal impairment is a significant complication of systemic lupus erythematosus (SLE). Additionally, infection in patients with end-stage renal disease (ESRD) attributable to SLE is common, and it increases the risk of mortality. This study explored the infection profile and risk factors for mortality in patients with ESRD attributable to SLE. METHODS: In this retrospective, observational study of 125 hospitalized patients, demographic, clinical, laboratory, treatment, and prognosis data were retrieved and analyzed. RESULTS: The 125 cases included 98 pulmonary infections (78.4%), 14 urinary infections (11.2%), and 13 intestinal infections (10.4%). Twenty-six patients died within 1 month after enrollment. Univariate Cox regression and Kaplan-Meier analyses revealed several possible indicators potentially influencing patient survival. Furthermore, multivariate Cox regression analysis identified a higher SLE Disease Activity Index-2000 score, recent higher-dose glucocorticoid use, hypertension, and catheter indwelling as risk factors for higher mortality. CONCLUSIONS: Infections were common in patients with advanced SLE and ESRD, and several risk factors might increase the risk of mortality. Once infection is identified, empiric antibiotics should be initiated immediately, and subsequent antibiotics should be applied per the results of drug sensitivity testing to clear the infection.

Efficacy and Safety of Salvia miltiorrhiza for Treating Chronic Kidney Diseases: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis evaluated the effects and potential harms of Salvia miltiorrhiza or its extracts Salvianolate and Tanshinone for the treatment of population with a chronic kidney disease (CKD). Methods: We searched for the randomized clinical trials (RCTs) through databases including the Cochrane Library, PubMed, Embase, Web of Science, Current Controlled Trials, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (Wanfang Data), China Biology Medicine Disc (SinoMed), and Chinese Clinical Trial Registry (ChiCTR). Meta-analysis was performed with STATA 16 software after data extraction. The risk of bias was assessed with the Cochrane risk-of-bias tool (RoB 2.0), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was employed to evaluate the quality of evidence. Result: A total of 32 studies were included involving 2264 participants. Compared to the control group, the treatment group significantly decreased serum creatinine (SCr) (SMD -0.60, 95% CI -0.79 to -0.41, P < 0.0001), blood urea nitrogen (BUN) (SMD -0.66, 95% CI -0.81 to -0.50, P < 0.0001), Cystatin C (CysC) (SMD -5.16, 95% CI -14.84 to 4.53, P=0.297), 24 hour urine protein (24 h UPE) (SMD -0.70, 95% CI -1.21 to -0.19, P=0.008), time to initiation of dialysis (Log RR 0.43, 95% CI 0.23 to 0.81, P=0.0089), serum total cholesterol (TC) (SMD -0.53, 95% CI -0.88 to -0.17, P=0.0042, P=0.0035), plasma fibrinogen (FIB) (SMD -0.79, 95% CI -1.12 to -0.46, P < 0.0001), C-reactive protein (CRP) (SMD -0.56, 95% CI -0.93 to -0.19, P=0.0029); increased creatinine clearance (Ccr) (SMD 0.92, 95% CI 0.43 to 1.41, P=0.0002), glomerular filtration rate (GFR) (SMD 0.56, 95% CI 0.30 to 0.83, P < 0.001), effective rate (Log RR 0.30, 95% CI 0.23 to 0.37, P < 0.0001), and hemoglobin (Hb) (SMD 0.42, 95% CI 0.13 to 0.71, P=0.0042). Moreover, the incidences of adverse effects were similar between the two groups. Conclusions: Salvia miltiorrhiza or its extracts Salvianolate and Tanshinone, as a complementary therapy to conventional medicine, presents potential impacts to improve kidney functions and delay the progression of CKD without obvious adverse effects. However, the certainty of the evidence and the risk of bias are suboptimal and further clinical studies are still required to determine the underlying effects.

Albumin to Total Cholesterol Ratio and Mortality in Peritoneal Dialysis.

Background: Serum albumin and total cholesterol are associated with mortality. In clinical practice, evaluating the association of combining album and total cholesterol with mortality may be more reasonable. Thus, we examined the association between serum albumin to total cholesterol ratio and mortality in peritoneal dialysis (PD) patients. Methods: We conducted a retrospective cohort study of 3447 incident continuous ambulatory peritoneal dialysis (CAPD) patients from five PD centers in China from 1 January 2005 and 31 May 2020. The association between albumin to total cholesterol ratio and mortality was evaluated. Results: With a median follow-up of 39.3 months, 762 (22.1%) all-cause deaths occurred, including 382 (11.1%) cardiovascular deaths. As compared with a serum albumin to total cholesterol ratio of 0.77-0.82 (reference range), a higher ratio (>0.82) was associated with increased risks of all-cause mortality[hazards ratio (HR), 1.54; 95% confidence interval (CI), 1.16-2.05, E-value = 2.45] and cardiovascular mortality (HR, 2.10; 95% CI, 1.35-3.29, E-value = 3.62). A lower ratio (<0.77) was also associated with increased risks of all-cause mortality (HR, 1.46; 95% CI, 1.10-1.94, E-value = 2.28) and cardiovascular mortality (HR, 1.78; 95% CI, 1.14-2.78, E-value = 2.96) compared with the reference. No interaction was observed in subgroup analyses of age, sex, diabetes mellitus, hypertension, prior cardiovascular disease, and hyperlipidemia, and malnutrition (serum albumin <3.6 g/dL). Conclusion: An albumin to total cholesterol ratio before the start of PD between 0.77 and 0.82 was associated with a lower risk of death than a higher or lower ratio, resulting in a U-curve association. Therefore, serum albumin to total cholesterol ratio, as an inexpensive and readily available biochemical biomarker, may further improve the stratification risk of mortality in PD patients.

Evaluation of renal microperfusion in hyperuricemic nephropathy by contrast-enhanced ultrasound imaging.

Diagnostic tools for the early detection of renal injury caused by hyperuricemia are still lacking. Here, we investigated whether contrast-enhanced ultrasound (CEUS) could be used as a diagnostic tool for hyperuricemic nephropathy (HN). In the HN rat model, CEUS detected a significant decline in renal cortical perfusion compared with that in control rats. Peak intensity (PI) values correlated significantly with serum KIM-1 levels and fibrosis scores in HN rats. An early decline in PI values was also observed in chronic kidney disease (CKD) stage 1 patients with HN compared with the controls (61.1±4.52 dB versus 65.80±7.10 dB) and correlated with renal function in the patients with HN. In contrast, an increase in time to reach PI values was detected in HN patients with stage 1 CKD (15.14±1.75 s versus 14.52±4.75 s) and was more pronounced in CKD stage 4 patients (67.32±3.29 s). CEUS was able to detect abnormal renal perfusion in early CKD with HN, which correlated with renal function decline, suggesting that CEUS could be used as a noninvasive tool for assessing renal function in patients with HN.