Longitudinal Analysis of Renal Function Changes in Elderly Populations: Health Status Evaluation and Risk Factor Assessment.

Background: This study aims to investigate GFR decline in elderly subjects with varying physical conditions and analyze key risk factors impacting renal function changes. Methods: We obtained data from patients between 2017 and 2019, and matched healthy elderly subjects based on gender and age. Data collected for all subjects included annual measurements of fast blood glucose (GLU), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c), blood albumin (ALB), blood uric acid (UA), urine protein (UP), and systolic blood pressure (SBP). Additionally, information on coexisting diseases was gathered. The Full Age Spectrum (FAS) equation was used to calculate eGFR. Results: A total of 162 patients with complete 3-year renal dynamic imaging were included, including 84 patients in the kidney disease group (K group) and 78 patients in the non-kidney disease group (NK group). Ninety individuals were selected as the healthy group (H group). The annual decline rate in the K group was the fastest, which exceeded 5mL/min/1.73m2 (P < 0.05). Group (K group: ß=-40.31, P<0.001; NK group: ß=-26.96, P<0.001), ALB (ß=-0.38, P=0.038) and HbA1c (ß=1.36, P=0.029) had a significant negative impact on the eGFR changes. For participants who had negative proteinuria: K group had the most significant annual eGFR decline. Conclusion: The presence of kidney disease, along with proteinuria nor not, can lead to a marked acceleration in kidney function decline in elderly. We categorize elderly individuals with an annual eGFR decline of more than 5 mL/min/1.73m2 as the "kidney accelerated aging" population.

A novel SPE-LC-MRM strategy for serum demethylzeylasteral quantitation developed with an 18O-labeled internal standard.

Natural bioactive compounds (NBCs) are widely used in clinical treatment. For example, Tripterygium wilfordii Hook f. is commonly known in China as Lei-Gong-Teng which means thunder god vine. This herb is widely distributed in Eastern and Southern China, Korea, and Japan. The natural bioactive compounds of this herb can be extracted and made into tripterygium glycoside tablets. It is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA), nephrotic syndrome (NS), autoimmune hepatis (AIH), and so on. However, many NBCs are difficult to reliably quantify in the serum due to the effects of matrix and RSD. In addition, the targeted compound's internal standard (IS) is rarely sold due to the complex isotope internal standard synthesis pathway. In this study, a new quantitation method for 18O labeling combined with off-line SPE was formulated. We contrasted the recoveries and matrix effects of various separation methods in order to choose the best method. Furthermore, we optimized the conditions for SPE loading and washing. An isotopic internal standard was prepared by the 16O/18O exchanging reaction in order to eliminate the matrix effects. The method's accuracy and precision met the requirements for method validation. The recovery of this method was close to 60%. The relative standard deviation (RSD) of the high-concentration sample was 2%, and the limit of detection (LOD) was 1 ng/mL. This method could be used to analyze the clinical serum concentration of demethylzeylasteral. Sixty samples were collected from 10 patients with diabetes nephropathy. The quantitation results of demethylzeylasteral in patients' serum obtained using this method exhibited a correlation between therapeutic drug monitoring (TDM) and decreased urinary protein. This work may have broad implications for the study of drug metabolism in vivo and the clinical application of low-abundance and difficult-to-quantify NBCs.

Diffusion-weighted, intravoxel incoherent motion, and diffusion kurtosis tensor MR imaging in chronic kidney diseases: Correlations with histology.

OBJECTIVES: To probe the correlations of parameters derived from standard DWI and its extending models including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) with the pathological and functional alterations in CKD. MATERIAL AND METHODS: Seventy-nine CKD patients with renal biopsy and 10 volunteers were performed with DWI, IVIM, diffusion kurtosis tensor imaging (DKTI) scanning. Correlations between imaging results and the pathological damage [glomerulosclerosis index (GSI) and tubulointerstitial fibrosis index (TBI)], as well as eGFR, 24 h urinary protein and Scr) were evaluated.CKD patients were divided into 2 groups: group 1: both GSI and TBI scores <2 points (61 cases); group 2: both GSI and TBI scores ≥2 points (18 cases). RESULTS: There were significant difference in cortical and medullary MD, and cortical D among 3 groups and between group 1 and 2. Cortical and medullary MD, cortical D, and medullary FA were negatively correlated with GSI score (r = -0.322 to -0.386, P < 0.05). Cortical and medullary MD and D, medullary FA were also negatively correlated with TBI score (r = -0.257 to -0.395, P < 0.05). These parameters were all correlated with eGFR and Scr. Cortical MD and D showed the highest AUC of 0.790 and 0.745 in discriminating mild and moderate-severe glomerulosclerosis and tubular interstitial fibrosis, respectively. CONCLUSIONS: The corrected diffusion-related indices, including cortical and medullary D and MD, as well as medullary FA were superior to ADC, perfusion-related and kurtosis indices for evaluating the severity of renal pathology and function in CKD patients.

Anti-Xa level monitoring of low-molecular-weight heparin during intermittent venovenous hemofiltration.

Low-molecular-weight heparin (LMWH) is an anticoagulant used to prevent clotting during blood purification treatments. This study aimed to evaluate the clinical use of the anti-factor Xa level (anti-Xa) for monitoring LMWH anticoagulant levels during intermittent venovenous hemofiltration (IVVHF). This prospective observational study enrolled patients who required IVVHF for renal failure in Beijing Hospital between May 2019 and February 2021. The LMWH anticoagulation was assessed by the coagulation grade of the filter and line. One hundred and ten participants were included. There were 90 patients with a filter and line coagulation grade of ≤ 1 and 20 patients with grade > 1. The anti-Xa level of 0.2 IU/mL was a critical value. The multivariable logistic regression analysis showed that anti-Xa level > 0.2 IU/mL (odd ratio [OR] = 2.263; 95% CI: 1.290-4.871, P = 0.034) and cardiovascular disease (OR = 10.028; 95% CI: 1.204-83.488; P = 0.033) were independently associated with the coagulation grade of the filter and line. Anti-Xa level could monitor LMWH anticoagulation during IVVHF.

Randomized Phase 2 Trial of Telitacicept in Patients With IgA Nephropathy With Persistent Proteinuria.

Introduction: To date, no specific therapies have been approved for immunoglobulin A nephropathy (IgAN) treatment. Telitacicept is a fusion protein composed of transmembrane activator and calcium-modulating cyclophilin ligand interactor and fragment crystallizable portion of immunoglobulin G (IgG), which neutralizes the B lymphocyte stimulator and a proliferation-inducing ligand. Methods: This phase 2 randomized placebo-controlled trial aimed to evaluate the efficacy and safety of telitacicept in patients with IgAN. Participants with an estimated glomerular filtration rate (eGFR) >35 ml/min per 1.73 m2 and proteinuria ≥0.75 g/d despite optimal supportive therapy, were randomized 1:1:1 to receive subcutaneous telitacicept 160 mg, telitacicept 240 mg, or placebo weekly for 24 weeks. The primary end point was the change in 24-hour proteinuria at week 24 from baseline. Results: Forty-four participants were randomized into placebo (n = 14), telitacicept 160 mg (n = 16), and telitacicept 240 mg (n = 14) groups. Continuous reductions in serum IgA, IgG, and IgM levels were observed in the telitacicept group. Telitacicept 240 mg therapy reduced mean proteinuria by 49% from baseline (change in proteinuria vs. placebo, 0.88; 95% confidence interval, -1.57 to -0.20; P = 0.013), whereas telitacicept 160 mg reduced it by 25% (-0.29; 95% confidence interval, -0.95 to 0.37; P = 0.389). The eGFR remained stable over time. Adverse events (AEs) were similar in all groups. Treatment-emergent AEs were mild or moderate, and no severe AEs were reported. Conclusion: Telitacicept treatment led to a clinically meaningful reduction in proteinuria in patients with IgAN in the present phase 2 clinical trial. This effect is indicative of a reduced risk for future kidney disease progression.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Lupus nephritis: new progress in diagnosis and treatment.

Systemic lupus erythematosus (SLE) is a chronic multifactorial autoimmune disease that affects many organs, including the kidney. Lupus nephritis (LN) is a common manifestation characterized by heterogeneous clinical and histopathological findings, and often associates with poor prognosis. The diagnosis and treatment of LN is challenging, depending largely on renal biopsy, and there is no reliable non-invasive LN biomarker. Up to now, the complete remission rate of LN is only 20%∼30% after receiving six months of standard treatment, which is far from satisfactory. Moreover, adverse reactions to immunosuppressants, especially glucocorticoids, further compromise the prognosis of LN. Biological reagents targetting autoimmune responses and inflammatory pathways, bring hope to the treatment of intractable lupus. The European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) and KDIGO (Kidney Disease: Improving Global Outcomes) have been working on and launched the recommendations for the management of LN. In this review, we update our knowledge in the pathogenesis, diagnosis, and management of LN and prospect for the future potential targets in the management of LN.

Demethylzeylasteral reduces the level of proteinuria in diabetic nephropathy: Screening of network pharmacology and verification by animal experiment.

This study aimed to use network pharmacology to detail the natural components isolated from Triptergium wilfordii Hook F (TwHF) and examine the effect of the main component (demethylzeylasteral, DEM) on rat models of diabetic nephropathy (DN). In this study, we used network pharmacology to detail the natural components isolated from TwHF, referenced a gene library when screening for components effective in the management of DN, and DEM was confirmed in DN rats. All data were analyzed using the Discovery Studio 4.5 System and the systems Dock online docking method platform. All 24 rats were divided into 4 groups: control, DN, TwHF, and DEM. Blood and urine samples were tested at 0, 8, and 12 weeks. Renal histopathological changes were scored. Network pharmacology indicated that 370 compounds and 46 small molecules (including DEM) were biologically active constituents of TwHF, mainly affecting the inflammatory response through PI3K-Akt and Jak-STAT pathways. Proteinuria in the TwHF and DEM groups was significantly lower than in the DN group (p ≤ .001), and the decrease in proteinuria in the DEM group was more obvious than in the TwHF group (p = .004). The tubular interstitial scores were better in the DEM group than in the TwHF and DN groups. These results indicate that DEM effectively reduced proteinuria and alleviated the tubular interstitial changes in rat models of DN, which may be provide a scientific foundation for the development of novel drugs for treatment of DN.

Using Two Detection Methods to Observe the Changes and Significance of Free Light Chain in Serum and Urine in Patients with Renal Insufficiency.

Background: Free light chains κ and λ (FLC κ, FLC λ) are of great significance in diagnostic and monitoring monoclonal gammopathy. Freelite and N-Latex methods are two common monitoring methods at present. But the two meanings are not completely equivalent, especially for patients with renal insufficiency. We analyzed the changes of serum and urine FLC in renal insufficiency patients without monoclonal gammopathy and the clinical significance of these changes. Methods: This study is an observational study. Patients ≥ 18 years old, who met the diagnostic criteria of chronic kidney disease (CKD), excluding monoclonal gammopathy, were selected. Fasting serum and 24-hour urine were taken to detect serum FLC κ, serum FLC λ, SCr, serum ß 2-microglobulin, urinary FLC κ, urinary FLC λ, urinary α 1-microglobulin, and urinary ß 2-microglobulin. Results: There was a good correlation between the two methods for determining serum/urinary FLC. No matter serum or urine, FLC showed a good correlation with renal function by the N-Latex method, but not by the Freelite method. Under the N-Latex method, FLC κ/λ remained stable, which was basically within the reference range of healthy people and was not affected by renal function. There was a good correlation between FLC detected by N-Latex and microglobulin in serum and urine. Conclusion: When the concentration of FLC is low, the N-Latex method is more recommended to monitor FLC. The FLC measured by the N-Latex method is more closely related to renal function. The ratio of FLC κ/λ determined by the N-Latex method remained stable within the recommended range.

Value of contrast-enhanced ultrasound for diagnosis and follow-up of renal artery stenosis in patients with chronic kidney disease.

OBJECTIVE: To evaluate whether contrast-enhanced ultrasound (CEUS) is an accurate, non-nephrotoxic diagnostic method and follow-up tool for use in patients with chronic kidney disease (CKD) and renal artery stenosis (RAS). METHODS: In this prospective and monocentric study, we compared the sensitivity and specificity of CEUS for the diagnosis of RAS in CKD patients, using digital subtraction angiography (DSA) or computed tomographic angiography (CTA) as the gold standard methods. Further, the value of CEUS for distinguishing restenosis from other diseases was assessed. The ultrasound physicians conducted the examinations and served as the CEUS report readers who were blinded to the DSA or CTA results. RESULTS: Patients with RAS (n = 60) were enrolled. Average patient age was 64.4 ± 18.0 years and median estimated glomerular filtration rate was 66.1 mL/min/1.73 m2. CEUS was used to image 94 stenotic renal arteries and DSA- or CTA-verified stenosis was present in 96 renal arteries. The kappa value for CEUS was 0.776 (P < 0.001), with an accuracy of 92.5%, a sensitivity of 94.7%, and a specificity of 84.0%. The accuracy of CEUS was the same for the diagnosis of the CKD3b-5 group as for the CKD1-3a group (100% vs. 87.5%, P = 0.148). There was no difference in CEUS accuracy for the diagnosis of Takayasu RAS compared with atherosclerotic RAS (95.8% vs. 91.7%, P = 0.795). Twenty-nine CEUS examinations were performed to follow in-stent restenosis or progression of RAS, with a median follow-up time of 5.0 months (range 1.0-20.0). Two cases of in-stent restenosis in patients suffering from deteriorating kidney function and recurrent hypertension were examined by CEUS. CONCLUSION: CEUS examination is a credible alternative for diagnosing moderate and severe RAS in patients with CKD, and is a reliable tool for follow-up surveillance after renal artery revascularization treatment. It shouldn't be thought as a color-coded duplex ultrasonography rescue in these patients.

Nomogram to predict the progression of patients with primary membranous nephropathy and nephrotic syndrome.

BACKGROUND: The outcome of patients with primary membranous nephropathy (pMN) who present with nephrotic syndrome (NS) is variable and difficult to predict. The goal of this study was to develop a nomogram to predict the risk of progression for specific individuals. METHODS: This retrospective study involved biopsy-proven patients with pMN and NS treated between January 2012 and June 2018. The primary outcome of our investigation was progression, defined as a reduction of estimated glomerular filtration rate (eGFR) that was equal to or over 20% compared with baseline at the end of follow-up or the onset of end-stage renal disease (ESRD). We used backwards stepwise logistic regression analysis to create a nomogram to predict prognosis. The model was validated internally using bootstrap resampling. RESULTS: A total of 111 patients were enrolled. After a median follow-up of 40.0 months (range 12-92 months), 18.9% (21/111) patients showed progression. Backwards stepwise selection using the Akaike information criterion (AIC) identified the following four variables as independent risk factors for progression, which were all used in the nomogram: age ≥ 65 years [odds ratio (OR) 7.004; 95% confidence interval (CI) 1.783-27.505; p = 0.005], Ln (sPLA2R-Ab) (OR 2.150; 95% CI 1.293-3.577; p = 0.003), Ln (proteinuria) (OR 5.939; 95% CI 1.055-33.436; p = 0.043) and Ln (Uα1m/Cr) (OR 2.808; 95% CI 1.035-7.619; p = 0.043). The discriminative ability and calibration of the nomogram revealed good predictive ability, as indicated by a C-index of 0.888 (95% CI 0.814-0.940) and a bootstrap-corrected C-index of 0.869; calibration curves were also well fitted. A receiver operating characteristic (ROC) curve for the nomogram score revealed significantly better discrimination than each of the three risk factors alone, including Ln (sPLA2R-Ab) [area under the curve (AUC) 0.769], Ln (proteinuria) (AUC 0.653) and Ln (Uα1m) (AUC 0.781) in the prediction of progression (p < 0.05). The optimal cutoff value of the nomogram score was 117.8 with a positive predictive value of 44.4% and a negative predictive value of 98.5%. CONCLUSION: The nomogram successfully achieved good predictive ability of progression for patients with pMN who present with NS. It can therefore help clinicians to individualize treatment plans and improve the outcome of pMN.

von Willebrand factor variants in C3 glomerulopathy: A Chinese cohort study.

C3 glomerulopathy (C3G) is a rare renal disease characterized by predominant glomerular C3 staining. Complement alternative pathway dysregulation due to inherited complement defects is associated with C3G. To identify novel C3G-related genes, we screened 86 genes in the complement, coagulation and endothelial systems in 35 C3G patients by targeted genomic enrichment and massively parallel sequencing. Surprisingly, the most frequently mutated gene was VWF. Patients with VWF variants had significantly higher proteinuria levels, higher crescent formation and lower factor H (FH) levels. We further selected two VWF variants to transiently express the von Willebrand factor (vWF) protein, we found that vWF expression from the c.1519A > G variant was significantly reduced. In vitro results further indicated that vWF could regulate complement activation, as it could bind to FH and C3b, act as a cofactor for factor I-mediated cleavage of C3b. Thus, we speculated that vWF might be involved in the pathogenesis of C3G.

The relationship between sclerostin and carotid artery atherosclerosis in patients with stage 3-5 chronic kidney disease.

PURPOSE: Sclerostin is an antagonist of the Wnt/ß-catenin pathway. We previously reported that sclerostin is closely related to carotid artery atherosclerosis and long-term outcome in hemodialysis patients. The present study investigated the association between sclerostin, renal function, and carotid artery atherosclerosis in non-dialysis patients with stage 3-5 chronic kidney disease (CKD 3-5ND). METHODS: A total of 140 patients with CKD 3-5ND were enrolled in this cross-sectional study. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate (eGFR). Atherosclerotic plaques in the carotid artery were detected by B-mode Doppler ultrasound. Blood samples were collected to assess serum sclerostin levels. Unconditional logistic regression analysis was used to identify risk factors for carotid atherosclerotic plaques. RESULTS: The median eGFR was 24.9 ml/min/1.73 m2 (interquartile range [IQR] 10.0-40.3 ml/min/1.73 m2) and median serum sclerostin level was 46.76 pmol/l (IQR 30.18-67.56 pmol/l). Carotid atherosclerotic plaques were detected in 104 subjects (74.3%). There was a negative association between sclerostin level and eGFR (r = - 0.214, p = 0.011). Unconditional logistic regression analysis revealed that sclerostin level was an independent risk factor for the occurrence of carotid plaques, with an odds ratio (95% confidence interval) of 1.026 (1.003, 1.051). CONCLUSION: Serum sclerostin increases with declining renal function in patients with CKD 3-5ND. Sclerostin is an independent risk factor for carotid atherosclerosis.

Differential analysis of urinary albumin for membranous nephropathy patients by online capillary isoelectric focusing - Mass spectrometry.

Membranous nephropathy (MN) is one of the most common causes of primary glomerular diseases worldwide. The M-type phospholipase A2 receptor (PLA2R), an antigen expressed in more than 70% of cases of idiopathic membranous nephropathy (IMN), is a biomarker which is now used by physicians for clinical diagnosis. Despite the prevalence of PLA2R in the cases of MN, it is not always effective to use PLA2R for differentiating primary or secondary MNs. On the other hand, urinary albumin assay is one of the de facto tests for kidney function testing for several decades. In this work, urinary albumin species between primary and secondary MN patients are compared using a newly developed capillary isoelectric focusing - mass spectrometry (CIEF-MS) technology. The distinct patterns of cationic and acidic urinary albumin species, as revealed by this novel CIEF-MS technology, suggest potential applications of this differential analysis for subtyping of membranous nephropathy. Further investigation of these cationic human albumin species in urine may provide clues to the disease onset and development of MN, thus facilitating treatment. In addition, this novel workflow of using CIEF-MS for urinary protein analysis may be beneficial to the research, pathology, prognosis, and diagnosis of many other types of kidney diseases, such as chronic kidney disease, diabetic nephrology, etc.

The Application of T.SPOT-TB Assay for Early Diagnosis of Active Tuberculosis in Chronic Kidney Disease Patients Receiving Immunosuppressive Treatment.

Background: The current study investigated the clinical application of the T-SPOT.TB assay for detecting tuberculosis (TB) infection in chronic kidney disease patients treated with immunosuppressive therapy. Methods: Clinical data from 91 patients were retrospectively analyzed. The rate of positive T-SPOT.TB results and spot numbers were compared before and after treatment. Clinical characteristics that may affect the test results were also investigated. Results: Two active TB cases were observed after immunosuppressive treatment, and eight patients with negative T-SPOT.TB results at baseline had positive results after treatment. No significant changes in spot numbers were observed for patients who were positive at baseline. Compared with pretreatment baseline, patients who received medium/high doses of corticosteroids had a greater number of T-SPOT.TB positive results (p = 0.016) and CFP-10 spots (p = 0.041) after treatment. For patients who received combination therapy with medium/high doses of corticosteroids, the T-SPOT.TB positive rate (p = 0.046) and CFP-10 spot number (p = 0.041) were increased after treatment, with no significant changes in the total number of spots or ESAT-6 spots. For those who received combination therapy with low doses of corticosteroids and those who received single immunosuppressive medication, there were no significant differences in the T-SPOT.TB positive rate, total spot number, or numbers of ESAT-6 and CFP-10 spots. Conclusion: The increase in positive T-SPOT.TB results was mainly associated with medium/high doses of glucocorticoids. The active TB cases might represent new infections. Regular monitoring using the T-SPOT.TB assay will help in the early detection of active TB.

Protocol for a prospective, cluster randomized trial to evaluate routine and deferred dialysis initiation (RADDI) in Chinese population.

BACKGROUND: The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. METHODS: The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18-80 years old, in stable CKD stages 4-5 (eGFR > 7 ml/min /1.73 m2), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m2 (routine dialysis group) and 5 ml/min/1.73 m2 or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. DISCUSSION: This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m2. With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. TRIAL REGISTRATION: The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.

Wnt1 inhibits vascular smooth muscle cell calcification by promoting ANKH expression.

AIMS: Wnt signaling plays a critical role in vascular calcification (VC). Wnt factors induce different physiological and pathological effects on cardiovascular functions. Wnt1, a ligand of Wnt/ß-catenin signaling, promotes pro-angiogenesis and reduces myocardial infarction. The role of Wnt1 on VC in chronic kidney disease (CKD) is not fully understood. METHODS AND RESULTS: We used human vascular smooth muscle cells (VSMCs) and a rat model of chronic renal failure (CRF), and observed a native protective mechanism by which VC is reduced via the activation of Wnt1 and its transcriptional target ANKH inorganic pyrophosphate transport regulator (ANKH) gene. ANKH is an essential calcification inhibitor that effluxes inorganic pyrophosphate (PPi) from VSMCs to play an inhibitory role in VC. Vascular ANKH and plasma PPi were significantly downregulated in the rat model of CRF. The knockdown or inhibition of ANKH reversed the effect of Wnt1 on VC in VSMCs. Clinical analysis revealed low plasma levels of Wnt1 and PPi were associated with CKD in patients. Applying a Wnt/ß-catenin signaling agonist can alleviate the progression of VC. CONCLUSION: This work reveals the ANKH regulation of Wnt1 in VSMCs is essential for blocking VC. Our findings may contribute to the development of medications that target Wnt signaling and/or ANKH to inhibit VC.

Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis.

BACKGROUND: Previous clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD. METHODS: This retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression. RESULTS: Baseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022-1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612-0.900, p = 0.002) levels were independent predictors of all-cause mortality. CONCLUSIONS: Sclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.

The Ratio of Plasma and Urinary 8-oxo-Gsn Could Be a Novel Evaluation Index for Patients with Chronic Kidney Disease.

Nucleic acid oxidation plays an important role in the pathophysiology progress of a variety of diseases. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), which originate from DNA and RNA oxidation, were the most widely used indicators for oxidative stress. The study investigated the relation between 8-oxo-dGsn, 8-oxo-Gsn, and CKD. 146 patients with CKD were divided into five disease stages, and their fasting blood and morning urine were collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were quantified by LC-MS/MS. The ratio of urinary 8-oxo-Gsn to creatinine increased from stages 1 to 4 corresponding to the increased severity of CKD, but it decreased in stage 5. And plasma 8-oxo-Gsn gradually increased with the decline of renal function. In particular, the increased ratio of plasma and urine 8-oxo-Gsn in stage 5 exceeded the concentration of creatinine. This trend was similar to the estimated glomerular filtration rate (eGFR), which indicates that 8-oxo-Gsn could be an appropriate indicator for renal function. Our finding indicates that as the disease progresses, RNA oxidation is increased. The significant increase in the ratio of plasma and urinary 8-oxo-Gsn is a novel evaluation index of end-stage renal disease.

Path Analysis on Medical Expenditures of 855 Patients with Chronic Kidney Disease in a Hospital in Beijing.

BACKGROUND: Investigate into the medical expenditures of chronic kidney disease (CKD) patients through path analysis method of three consecutive years within a Grade-A tertiary hospital in Beijing to conduct the main influencing factors in diagnosis-related groups (DRGs) grouping of the diagnosis, and reassess the present grouping process to provide information and reference on cost control for hospitals and medical management departments. METHODS: Eight hundred and fifty-five inpatient cases whose first diagnosis were defined as CKD in the year 2014-2016 within the hospital were selected as the sample of the study, multiple linear regression and path analysis method were adopted in DRGs grouping process to investigate the main influencing factors of total medical expenditures and DRGs grouping process. RESULTS: The maximum proportion of the medical costs within CKD patients was the costs on treatment, with the highest of 35.3% on the year 2014, the second was the costs on drug, which accounted for <30% during consecutive years, and the third was the costs on examination, which accounted for about 20% on average. The main influencing factors of medical expenditures included the type of dialysis, length of hospitalization, the admission of Intensive Care Unit (ICU), and so on. The coefficients toward the effect for total costs were 0.416, 0.376, and 0.094, respectively. CONCLUSIONS: It is suggested that the type of dialysis and the admission of ICU were the major influencing factors of inpatient medical expenditures on CKD patients, and should be taken into consideration into the reassessment of DRGs grouping process to realize the localization and generalization of prospective payment system based on DRGs within the regional area and promote the implementation of medical cost control measures to reduce the economic burdens among patients and the society.