Incidence, risk factors and outcome of postoperative acute kidney injury in China.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

Longer serum phosphorus time in range associated with lower mortality risk among peritoneal dialysis patients: a multicenter retrospective cohort study.

BACKGROUND: Relationship between serum phosphorus time in range and mortality risk in peritoneal dialysis (PD) patients remains uncertain. We aimed to evaluate the association between serum phosphorus time in range and all-cause mortality in Chinese PD population. METHODS: This was a multicenter, retrospective, cohort study of 1,915 patients collected from January 2008 to October 2020 in 4 Chinese centers. Serum phosphorus time in range was estimated as the months during the first year that a patient's serum phosphorus level was within the target range (defined as 1.13-1.78 mmol/L). The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) mortality and PD withdrawal. Cox proportional hazards regression model with comprehensive adjustments was used to assess the association. RESULTS: The primary outcome occurred in 249 (13.0%) PD patients over a median follow-up of 28 months. Overall, the serum phosphorus time in range was negatively associated with all-cause mortality (per 3-month increments, adjusted HR [aHR], 0.83; 95%CI: 0.75-0.92), CV mortality (per 3-month increments, aHR, 0.87; 95%CI: 0.77-0.99), and PD withdrawal (per 3-month increments, aHR, 0.89; 95%CI: 0.83-0.95). Competing-risk model showed that the relationship of serum phosphorus time in range with all-cause mortality remained stable. None of the variables including demographics, history of diabetes and CV disease, as well as several PD-related and clinical indicators modified this association. CONCLUSIONS: PD patients with longer serum phosphorus time in range in the first year was negatively associated with all-cause mortality and CV mortality. Our findings highlight the importance of maintaining serum phosphorus levels within 1.13-1.78 mmol/L for PD patients.

Detecting Neonatal AKI by Serum Cystatin C.

SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.

Genome-Wide Association Analysis of Protein-Coding Variants in IgA Nephropathy.

SIGNIFICANCE STATEMENT: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility. BACKGROUND: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated. METHODS: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression. RESULTS: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03). CONCLUSIONS: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility.

Relationship of serum total cholesterol and triglyceride with risk of mortality in maintenance hemodialysis patients: a multicenter prospective cohort study.

OBJECTIVE: The relationship between serum total cholesterol (TC) and triglyceride (TG) levels and mortality in maintenance hemodialysis (MHD) patients remains inconsistent. We aimed to explore the individual and combined association of TC and TG levels with the risk of mortality in Chinese MHD patients. METHODS: 1036 MHD patients were enrolled in this multicenter, prospective cohort study. The serum levels of total cholesterol and triglycerides were measured at baseline. The primary outcome was all-cause mortality and secondary outcome was cardiovascular disease (CVD) mortality. RESULTS: During a median follow-up duration of 4.4 years (IQR= 2.0-7.9 years), 549 (53.0%) patients died, and 297 (28.7%) deaths were attributed to CVD. Compared with patients with TC levels in the first three quartiles (<182.5 mg/dL), a significantly higher risk of all-cause mortality was found in participants with TC in the fourth quartile (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.17-1.76). However, a significantly lower risk of all-cause mortality was observed in participants with TG in the fourth quartile (≥193.9 mg/dL) (HR, 0.78; 95%CI: 0.63-0.98), compared with participants with TG in the first three quartiles. Similar trends were observed in CVD mortality. When analyzed jointly, patients with lower TC (<182.5 mg/dL) and higher TG (≥193.9 mg/dL) levels had the lowest risk of all-cause mortality and CVD mortality.Conclusions: In MHD patients in southern China, higher TC levels were associated with higher risk of mortality, while higher TG levels were related to lower risk of mortality. Patients with lower TC and higher TG levels had the best survival prognosis.

Statin initiation and risk of incident kidney disease in patients with diabetes.

BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

Macrophage Migration Inhibitory Factor (MIF) as a Stress Molecule in Renal Inflammation.

Renal inflammation is an initial pathological process during progressive renal injury regardless of the initial cause. Macrophage migration inhibitory factor (MIF) is a truly proinflammatory stress mediator that is highly expressed in a variety of both inflammatory cells and intrinsic kidney cells. MIF is released from the diseased kidney immediately upon stimulation to trigger renal inflammation by activating macrophages and T cells, and promoting the production of proinflammatory cytokines, chemokines, and stress molecules via signaling pathways involving the CD74/CD44 and chemokine receptors CXCR2, CXCR4, and CXCR7 signaling. In addition, MIF can function as a stress molecule to counter-regulate the immunosuppressive effect of glucocorticoid in renal inflammation. Given the critical position of MIF in the upstream inflammatory cascade, this review focuses on the regulatory role and molecular mechanisms of MIF in kidney diseases. The therapeutic potential of targeting MIF signaling to treat kidney diseases is also discussed.

Dietary Plant Protein and Mortality Among Patients Receiving Maintenance Hemodialysis: A Cohort Study.

RATIONALE & OBJECTIVE: Although greater dietary intake of protein has been associated with beneficial health effects among patients receiving maintenance hemodialysis (MHD), the effects of plant protein intake are less certain. We studied the association of the proportion of protein intake derived from plant sources with the risk of mortality among patients receiving MHD and explored factors that may modify these associations. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,119 Chinese hemodialysis patients aged over 18 years receiving MHD in 2014-2015. PREDICTORS: The proportion of plant protein intake to total protein intake. OUTCOMES: All-cause mortality and cardiovascular disease (CVD) mortality. ANALYTICAL APPROACH: Segmented regression models were fit to examine the association of plant protein intake proportion with the risk of all-cause mortality and CVD mortality. Multivariable-adjusted Cox proportional and cause-specific hazards models were used to estimate the hazard ratios (HR) and 95% CI for these outcomes. RESULTS: The means of plant protein intake normalized to ideal body weight and plant protein intake proportion were 0.6±0.2 (SD) g/kg per day and 0.538±0.134, respectively. During a median follow-up period of 28.0 months, 249 deaths occurred, with 146 of these deaths resulting from CVD. Overall, there was a U-shaped association between plant protein intake proportion and the risk of all-cause mortality, with an inflection point at 45%. Among patients with a plant protein intake proportion<45%, there was a 17% lower rate of mortality with each 5% greater plant protein intake proportion (HR, 0.83 [95% CI, 0.73-0.96]). Among patients with plant protein intake proportion≥45%, there was a 9% greater rate of mortality with each 5% greater plant protein intake proportion. A similar U-shaped association was observed for CVD mortality, with an inflection point at 44%. LIMITATIONS: Observational study, potential unmeasured confounding. CONCLUSIONS: There was a U-shaped association between plant protein intake proportion and the risk of all-cause and cardiovascular mortality in MHD patients. If confirmed, these findings suggest a potential avenue to improve outcomes in this patient population.

Higher dietary fibre intake is associated with lower CVD mortality risk among maintenance haemodialysis patients: a multicentre prospective cohort study.

High fibre intake is associated with reduced mortality risk in both general and chronic kidney disease populations. However, in dialysis patients, such data are limited. Therefore, the association between dietary fibre intake (DFI) and the risk of all-cause and CVD mortality was examined in this study. A total of 1044 maintenance haemodialysis (MHD) patients from eight outpatient dialysis centres in China were included in this study. Data on DFI were collected using 24-h dietary recalls for 3 d in a week and were normalised to actual dry weight. The study outcomes included all-cause and CVD mortality. Over a median of 46 months of follow-up, 354 deaths were recorded, of which 210 (59 %) were due to CVD. On assessing DFI as tertiles, the CVD mortality risk was significantly lower in patients in tertiles 2-3 (≥0·13 g/kg per d; hazard ratio (HR) 0·71; 95 % CI 0·51, 0·97) compared with those in tertile 1 (<0·13 g/kg per d). A similar but non-significant trend was found for the association between DFI (tertiles 2-3 v. tertile 1; HR 0·83; 95 % CI 0·64, 1·07) and all-cause mortality. In summary, higher DFI was associated with lower CVD mortality risk among Chinese MHD patients. This study emphasises the significance of DFI in MHD patients and provides information that is critical for the improvement of dietary guidelines for dialysis patients.

Nomogram predicting the risk of three-year chronic kidney disease adverse outcomes among East Asian patients with CKD.

BACKGROUND: Chronic kidney disease (CKD) is a common health challenge. There are some risk models predicting CKD adverse outcomes, but seldom focus on the Mongoloid population in East Asian. So, we developed a simple but intuitive nomogram model to predict 3-year CKD adverse outcomes for East Asian patients with CKD. METHODS: The development and internal validation of prediction models used data from the CKD-ROUTE study in Japan, while the external validation set used data collected at the First People's Hospital of Foshan in southern China from January 2013 to December 2018. Models were developed using the cox proportional hazards model and nomogram with SPSS and R software. Finally, the model discrimination, calibration and clinical value were tested by R software. RESULTS: The development and internal validation data-sets included 797 patients (191 with progression [23.96%]) and 341 patients (89 with progression [26.10%]), respectively, while 297 patients (108 with progression [36.36%]) were included in the external validation data set. The nomogram model was developed with age, eGFR, haemoglobin, blood albumin and dipstick proteinuria to predict three-year adverse-outcome-free probability. The C-statistics of this nomogram were 0.90(95% CI, 0.89-0.92) for the development data set, 0.91(95% CI, 0.89-0.94) for the internal validation data set and 0.83(95% CI, 0.78-0.88) for the external validation data-set. The calibration and decision curve analyses were good in this model. CONCLUSION: This visualized predictive nomogram model could accurately predict CKD three-year adverse outcomes for East Asian patients with CKD, providing an easy-to-use and widely applicable tool for clinical practitioners.

Rituximab for the treatment of idiopathic membranous nephropathy with nephrotic syndrome: a systematic review and meta-analysis

Background/aim: This meta-analysis comprehensively investigated the efficacy and safety of rituximab (RTX) in patients with idiopathic membranous nephropathy (IMN). Materials and methods: We searched the MEDLINE, EMBASE and Cochrane Registry of Controlled Trials databases from January 2000 to January 2020. Studies evaluating the efficacy and safety of RTX in the treatment of IMN with nephrotic syndrome (NS) were included. Results: Nine studies (total of 357 patients) were included in the meta-analysis. The pooled complete response and overall response (OR) rates at 12 months were 13.2% [95% con fidence interval (CI), 0.09­0.18] and 60% (95% CI, 0.48­0.72), and those at 24 months were 27.8% (95% CI, 0.22­0.34) and 66% (95% CI, 0.6­0.72), respectively. The pooled OR rates for the low-, standard-, and high-dose groups were 39.3%, 64%, and 60%, respectively, and those for the first-line and second-line groups were 58% and 54%, respectively. Conclusion: Treatment of IMN with RTX has comparable efficacy to other immunosuppressive treatments (ISTs). RTX has the advantages of no requirement for steroids and lower rates adverse event and relapse rates. Patients who relapse or are resistant to other IST agents also respond to RTX. RTX-based regimens and other B-cell-targeted therapies may represent the future of IMN therapy.

Relationship between Serum Uric Acid and Mortality Risk in Hemodialysis Patients: A Multicenter Prospective Cohort Study.

BACKGROUND: Several studies have reported that low serum uric acid (SUA) levels are related to increased risk of mortality in maintenance hemodialysis (MHD) patients. However, the possible detrimental effects of high SUA on the mortality risk have not been well examined. Moreover, the possible effect modifiers for the SUA-mortality association have not been fully investigated. To address the aforementioned gap, we aimed to explore the nonlinear relationship between SUA levels and all-cause and cardiovascular disease (CVD) mortality risk, and to examine any possible effect modifiers in MHD patients. METHODS: We conducted a multicenter, prospective cohort study among 1,018 MHD patients from 8 hemodialysis centers. The primary outcome was all-cause mortality, and the secondary outcomes were CVD mortality and non-CVD mortality. RESULTS: The mean value for SUA in the total population was 8.5 ± 1.9 mg/dL. The lowest and highest quintiles of SUA were <7.0 and >10.1 mg/dL, respectively. Over a median follow-up of 45.6 months, 343 deaths were recorded, of which 202 (58.9%) were due to CVD. When SUA was assessed as quintiles, a significantly higher risk of all-cause mortality was found in patients in quintile 1 (<7.0 mg/dL; hazard ratio [HR], 1.33; 95% confidence interval [CI]: 1.02-1.73) or quintile 5 (≥10.1 mg/dL; HR, 1.47; 95% CI: 1.09-2.00), compared to those in quintiles 2-4 (7-10.1 mg/dL). Moreover, the U-shaped SUA-mortality association was mainly found in those with lower C-reactive protein levels (<3 compared with ≥3 mg/L; p for interaction = 0.018). Similar trends were found for CVD mortality and non-CVD mortality. CONCLUSION: There was a U-shaped relationship between SUA levels and the risk of all-cause mortality, CVD mortality, and non-CVD mortality in MHD patients.

The association between dietary energy intake and the risk of mortality in maintenance haemodialysis patients: a multi-centre prospective cohort study.

Maintenance haemodialysis (MHD) is the use of a machine to filter wastes, salts and fluid from blood for at least 3 months to prolong the life of patients with advanced kidney failure. Although low dietary energy intake (DEI) has been observed in MHD patients, few studies have related DEI to the risk of mortality. To explore this relationship, a study included 1039 MHD patients from eight centres was conducted. DEI was assessed by three 24-h diet recalls and was normalised to ideal body weight (IBW). All-cause mortality and CVD mortality were the primary and secondary outcomes, respectively. During a median follow-up of 28 months, a U-shaped relationship was observed between DEI and all-cause or CVD mortality. The risk of all-cause mortality decreased significantly with the increase of DEI in participants with DEI <167·4 kJ/kg IBW per d (hazard ratio (HR) 0·98; 95 % CI 0·96, 1·00) and increased significantly with the increase of DEI in those with DEI ≥167·4 kJ/kg IBW per d (HR 1·12; 95 % CI 1·04, 1·20). Similarly, the risk of CVD mortality decreased with the increase of DEI in participants with DEI <152·7 kJ/kg IBW per d (HR 0·96; 95 % CI 0·93, 0·99) and increased with the increase of DEI in participants with DEI ≥152·7 kJ/kg IBW per d (HR 1·11; 95 % CI 1·04, 1·18). In summary, there was a U-shaped association between DEI and all-cause or CVD mortality, with a turning point at about 167·4 and 152·7 kJ/kg IBW per d, respectively, in MHD patients.

Suspension precipitation: A simple sediment-collecting method for microbiological culturing in diagnosis of peritonitis
.

BACKGROUND: Rapid and accurate microbiological detection is crucial for effective treatment of peritonitis patients with peritoneal dialysis (PD). Although centrifugation of dialysis effluents can increase the pathogen culture-positive rate, a lack of both centrifugation facilities and experienced staff has prevented its widespread implementation, particularly in basic-level hospitals in developing countries. Thus, we developed a simple peritoneal sediment-collecting method, suspension precipitation method, for microbiological diagnosis of peritonitis. MATERIALS AND METHODS: In the suspension precipitation method, drained effluent bags from individual patients were hung for 1 hour to allow the suspension to drip to the bottom layer of the bag for sediment collection. Sediments obtained by centrifugation from the same batch of dialysis effluent were used as positive controls. Both sediment sample types were then cultured in blood-culture bottles. Subsequent analysis of the pathogen-positive detection rate and species comparison between the two methods were undertaken. RESULTS: Among 90 PD patients, the pathogen positive-detection rate between methods was comparable, as demonstrated by 75 (83.33%) with the suspension precipitation method and 77 (85.56%) by the centrifugation method. Their positive pathogen species were also similar, and the concordance rate was 97.78%. CONCLUSION: The suspension precipitation method is a simple, convenient, and reliable peritoneal sediment-collecting method that is suitable for a wide array of uses, particularly in basic-level hospitals without centrifugation technology.

Effect of the Combination of Hemodialysis and Hemoperfusion on Clearing Advanced Glycation End Products: A Prospective, Randomized, Two-Stage Crossover Trial in Patients Under Maintenance Hemodialysis.

Advanced glycation end products (AGEs) are protein-bound uremic toxins and are elevated in patients with the end-stage of renal disease. The present study sought to develop an effective method to remove the circulating AGEs from patients using the combination of hemodialysis (HD) and hemoperfusion (HP). Thirty-six patients undergoing maintenance HD for 3 months were randomly divided into two groups. Patients in Group 1 received HD, followed by the combined HP + HD treatment once, whereas patients in Group 2 were first treated with HP + HD and then they received the HD treatment alone. Patients treated with HD alone did not alter higher levels of serum AGEs. In contrast, patients treated with the combined HP + HD exhibited significantly lower levels of serum AGEs and TNF-α. Results from this study demonstrate that the combination of HD + HP treatment may be an effective and better approach to remove the protein-bound uremic toxins and inflammatory cytokines.

Efficacy and Safety of Hydroxychloroquine in Patients with IgA Nephropathy: A Meta-Analysis.

AIM: The purpose of this study was to determine efficacy and safety of hydroxychloroquine (HCQ) for patients with IgA nephropathy (IgAN). METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure and VIP database up to February 2023 were searched for associated studies comparing HCQ with any other nonHCQ for treating IgAN. The effects of proteinuria, a 50% decrease in proteinuria, estimated glomerular filtration rate (eGFR) and adverse events in patients with IgAN were examined in a meta-analysis. Data were extracted and pooled using RevMan 5.3. RESULTS: Three randomized controlled trials (RCTs), two retrospective and two prospective studies (675 patients) that matched our inclusion criteria were identified. Compared with a control group, HCQ significantly reduced proteinuria (mean difference (MD): -0.26, 95% confidence interval (CI): -0.44 to -0.08, p < 0.01). Patients receiving HCQ plus renin-angiotensin system inhibitors (RASSi) had a better efficacy in proteinuria alleviation and a 50% decrease in proteinuria compared with control groups (MD: -0.38, 95% CI: -0.50 to -0.25, p < 0.001 and relative risk (RR) = 3.31, 95% CI: 1.73 to 6.36, p < 0.001). No appreciable variations were observed in eGFR between HCQ groups and control groups in treating patients with IgAN (MD: -2.00, 95% CI: -4.36 to 0.36, p = 0.10). Moreover, no serious adverse events were observed during HCQ treatment. CONCLUSIONS: Our results indicate HCQ is an efficient, secure treatment for IgAN.

Clinical characteristics and antibiotic treatment of peritoneal dialysis-associated peritonitis caused by Pseudomonas species: a review of 15 years' experience from southern China.

Pseudomonas can lead to peritoneal dialysis-associated peritonitis, which is characterized by a poor prognosis, such as a substantial failure rate and a high death rate. This study aimed to provide an overview of Pseudomonas peritonitis's clinical features, the regimens of antibiotic, antibiotic resistance, and outcomes in peritoneal dialysis (PD) patients. This study observed patients with Pseudomonas peritonitis in two large PD centers in South China from January 2008 to December 2022. The demographics, symptomatology, antibiotics regimens, resistance to common antibiotics, and clinical outcomes of all included patients were reviewed. A total of 3,459 PD patients were included, among them 57 cases of peritonitis caused by Pseudomonas, including 48 cases (84.2%) of Pseudomonas aeruginosa. The incidence rate of Pseudomonas peritonitis was 0.0041 episode per patient-year. Of them, 28.1% (16 cases) of the patients were accompanied by exit site infection (ESI), and all had abdominal pain and turbid ascites at the time of onset. The most commonly used antibiotic combination was ceftazidime combined with amikacin. Approximately 89% of Pseudomonas species were sensitive to ceftazidime, and 88% were sensitive to amikacin. The overall primary response rate was 28.1% (16 patients), and the complete cure rate was 40.4% (23 patients). There was no significant difference in the complete cure rate of peritonitis using three and other antibiotic treatment regimens (44.8% vs 46.4%; P = 0.9). The successful treatment group had higher baseline albumin level (35.9 ± 6.2; P = 0.008) and residual urine volume (650.7 ± 375.5; P = 0.04). Although the incidence of peritonitis caused by Pseudomonas was low, the symptoms were serious, and prognosis was very poor. Pseudomonas was still highly susceptible to first-line antibiotics currently in use against Gram-negative bacteria. Patients with successful treatment had higher albumin levels and higher urine output. IMPORTANCE: Although the incidence of peritoneal dialysis-associated peritonitis caused by Pseudomonas is very low, it seriously affects the technique survival of peritoneal dialysis patients. However, there are few studies and reports on Pseudomonas peritonitis in the Chinese mainland area. Therefore, the purpose of this study is to describe the clinical characteristics, the regimens of antibiotic, drug resistance, and outcome of peritoneal dialysis patients in southern China in the past 15 years and summarize the clinical experience in the treatment of Pseudomonas peritonitis.

Apparent Treatment-Resistant Hypertension in the First Year Associated With Cardiovascular Mortality in Peritoneal Dialysis Patients.

BACKGROUND: Few reports have focused on the association between apparent treatment-resistant hypertension (aTRH) and cardiovascular (CV) mortality in peritoneal dialysis (PD) population, thus we conducted this retrospective cohort to explore it. METHODS: This was a retrospective cohort study conducted from January 2011 to January 2020 with PD patients in 4 Chinese dialysis centers. aTRH was defined according to the American College of Cardiology and American Heart Association guidelines. aTRH duration was calculated as the total number of months when patients met the diagnostic criteria in the first PD year. The primary outcome was CV mortality, and the secondary outcomes were CV events, all-cause mortality, combined endpoint (all-cause mortality and transferred to hemodialysis [HD]), and PD withdrawal (all-cause mortality, transferred to HD, and kidney transplantation). Cox proportional hazards models were used to assess the association. RESULTS: A total of 1,422 patients were finally included in the analysis. During a median follow-up period of 26 months, 83 (5.8%) PD patients incurred CV mortality. The prevalence of aTRH was 24.1%, 19.9%, and 24.6% at 0, 3, and 12 months after PD initiation, respectively. Overall, aTRH duration in the first PD year positively associated with CV mortality (per 3 months increment, adjusted hazards ratio [HR], 1.29; 95% confidence interval 1.10, 1.53; P = 0.002). After categorized, those with aTRH duration more than 6 months presented the highest adjusted HR of 2.92. Similar results were found for secondary outcomes, except for the CV event. CONCLUSIONS: Longer aTRH duration in the first PD year is associated with higher CV mortality and worse long-term clinical outcomes. Larger studies are warranted to confirm these findings. CLINICAL TRIALS REGISTRATION: There is no clinical trial registration for this retrospective study.

MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity.

Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/ß-catenin signaling. ß-catenin knockout blocked 2-AG/CB2-induced fatty acid ß-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.

Dipeptidyl peptidase 4 inhibitors vs. metformin for new-onset dementia: a propensity score-matched cohort study.

BACKGROUND: Hypoglycemic pharmacotherapy interventions for alleviating the risk of dementia remains controversial, particularly about dipeptidyl peptidase 4 (DPP4) inhibitors versus metformin. Our objective was to investigate whether the initiation of DPP4 inhibitors, as opposed to metformin, was linked to a reduced risk of dementia. METHODS: We included individuals with type 2 diabetes over 40 years old who were new users of DPP4 inhibitors or metformin in the Chinese Renal Disease Data System (CRDS) database between 2009 and 2020. The study employed Kaplan-Meier and Cox regression for survival analysis and the Fine and Gray model for the competing risk of death. RESULTS: Following a 1:1 propensity score matching, the analysis included 3626 DPP4 inhibitor new users and an equal number of metformin new users. After adjusting for potential confounders, the utilization of DPP4 inhibitors was associated with a decreased risk of all-cause dementia compared to metformin (hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.45-0.89). Subgroup analysis revealed that the utilization of DPP4 inhibitors was associated with a reduced incidence of dementia in individuals who initiated drug therapy at the age of 60 years or older (HR 0.69, 95% CI 0.48-0.98), those without baseline macrovascular complications (HR 0.62, 95% CI 0.41-0.96), and those without baseline microvascular complications (HR 0.67, 95% CI 0.47-0.98). CONCLUSION: In this real-world study, we found that DPP4 inhibitors presented an association with a lower risk of dementia in individuals with type 2 diabetes than metformin, particularly in older people and those without diabetes-related comorbidities.