Single Nucleotide Polymorphisms (SNPs) of URAT1 (rs7932775) and ABCG2 (rs3825016) on Chronic Kidney Disease Patients with Hyperuricemia

Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.

Efficacy and Safety of Febuxost at in the Treatment of Chronic Kidney Disease with Hyperuricemia: A Meta- Analysis

Background Febuxostat and allopurinol have different pharmacological mechanisms,the efficacy of febuxostat in chronic kidney disease complicated with hyperuricemia remains controversial.A meta-analysis and systemic review was conducted to investigate the efficacy and safety of febuxostat in CKD populations complicated with hyperuricemia.Methods A comprehensive search was conducted in multiple electronic databases based on the inclusion and exclusion criteria,before December 2016,searching for the published studies,including Chinese and English,relating to the use of febuxostat in CKD populations complicated with hyperuricemia,and manual retrieval of the inclusion literature.Literature evaluation and data extraction were performed by two reviewers,Rev Man 5.3 was used to perform the meta-analysis.Results Seven studies with 482 CKD patients were included in the meta-analysis.We found that febuxostat can significantly slow the decreasing speed of e GFR[RR=4.90,95%CI(1.95,7.84),P=0.001],and reduce serum uric acid[RR=-99.30,95%CI(-172.24,-26.37),P=0.008]levels in CKD patients complicated with hyperuricemia when compairing with control group.There was no significant difference in the levels of systolic blood pressure[RR=-2.19,95%CI(-9.99,5.61),P=0.58],diastolic blood pressure[RR=-2.30,95%CI(-7.33,2.73),P=0.10],low density lipoprotein[RR=-0.47,95%CI(-7.64,6.69),P=0.90]between the two groups.Compared with the control group,the use of febuxostat increase the incidence of adverse reaction[RR=4.73,95%CI(1.04,21.43),P=0.04]in patients.Conclusions Febuxostat can significantly lower serum uric acid level and effectively delay the process of chronic renal failure in CKD patients complicated with hyperuricemic,increases the incidence of adverse reaction,no significant difference in SBP,DBP,LDL,when compared with control group.

Patient selection and preparation strategies for the use of contrast material in patients with chronic kidney disease

The prevalence of chronic kidney disease and peripheral arterial disease is increasing.Thus,it is increasingly problematic to image these patients as the number of patients needing a vascular examination is increasing accordingly.In high-risk patients with impaired kidney function,intravascular administration of iodinated contrast media can result in contrast-induced acute kidney injury and Gadolinium can induce nephrogenic systemic fibrosis(NSF).It is important to identify these highrisk patients by means of se-creatinine/e glomerular filtration rate.The indication for contrast examination should counterbalance the increased risk.One or more alternative examination methods without contrast media,such as CO 2 angiography,Ultrasound/Doppler examination or magnetic resonance angiography without contrast should be considered,but at the same time,allow for a meaningful outcome of the examination.If contrast is deemed essential,the patient should be well hydrated,the amount of contrast should be restricted,the examination should be focused,metformin and diuretics stopped,and renal function monitored.Sodium bicarbonate and N-acetylcysteine are popular but their efficiency is not evidence-based.There is no evidence that dialysis protects patients with impaired renal function from contrast-induced nephropathy or NSF.

Diabetic patients with chronic kidney disease: Non-invasive assessment of cardiovascular risk

The prevalence and burden of diabetes mellitus and chronic kidney disease on global health and socioeconomic development is already heavy and still rising.Diabetes mellitus by itself is linked to adverse cardiovascular events,and the presence of concomitant chronic kidney disease further amplifies cardiovascular risk.The culmination of traditional(male gender,smoking,advanced age,obesity,arterial hypertension and dyslipidemia)and non-traditional risk factors(anemia,inflammation,proteinuria,volume overload,mineral metabolism abnormalities,oxidative stress,etc.)contributes to advanced atherosclerosis and increased cardiovascular risk.To decrease the morbidity and mortality of these patients due to cardiovascular causes,timely and efficient cardiovascular risk assessment is of huge importance.Cardiovascular risk assessment can be based on laboratory parameters,imaging techniques,arterial stiffness parameters,ankle-brachial index and 24 h blood pressure measurements.Newer methods include epigenetic markers,soluble adhesion molecules,cytokines and markers of oxidative stress.In this review,the authors present several non-invasive methods of cardiovascular risk assessment in patients with diabetes mellitus and chronic kidney disease.

Hyperuricemia in Hypertension and Chronic Kidney Disease: Risk Factors, Prevalence and Clinical Correlates: A Descriptive Comparative Study

Introduction: Uric acid is a product of purine metabolism and elevated serum concentration are very common in, and linked with hypertension and chronic kidney disease, conditions associated with heavy health burden and cardiovascular complications particularly in sub Sahara Africa. An assessment of factors relating hyperuricemia to hypertension and chronic kidney disease would therefore be necessary as way of mitigating the poor quality of life, morbidity and mortality associated with these diseases in low income nations. Methods: A single centre, descriptive comparative study in which the demographic, clinical and laboratory data of hypertensive and non-dialyzed chronic kidney disease (CKD) patients were analyzed. Serum biochemical parameters with uric acid, hematocrit and urine dip strip protein were assessed. Predictors of hyperuricemia were determined using multivariate analysis. Results: One hundred and thirty nine hypertensives and 69 CKD were studied. The mean age of the participants was 54.3 ± 11.7 years, hypertensives (52.9 ± 15.7 years) and CKD (57.3 ± 16.1 years). Both groups had more males, P = 0.8. Majority (78.3%) of the CKD cohorts had stage 4 or 5 (non-dialyzed) disease. The systolic and diastolic blood pressure, creatinine and uric acid were lower in hypertension than in CKD, P = 0.07, P = 0.05, P < 0.001 and P = 0.004 respectively. The hematocrit, albumin and GFR were higher in HTN than CKD, P < 0.001, P < 0.001 and P < 0.001 respectively. The prevalence of hyperuricemia was 56.2%. The mean uric acid was 505.9 ± 23.6 mmol/L, 382 7 ± 10.5 mmol/L for hypertensive and 755.9 ± 14.8 mmol/L for CKD, P < 0.001. The prevalence of systolic HTN, proteinuria, hypoalbuminemia and anemia were 51%, 75%, 46% and 59%, and were higher in males. Hyperuricemia was related to advancing age, proteinuria, elevated creatinine, hypoalbuminemia, anemia and hypertriglyceridemia. Proteinuria (OR—4.66, 95% CI—2.42 - 9.65), elevated creatinine (OR—3.12, 95% CI—2.40 - 6.92), hypoalbuminemia (OR—2.92, 95% CI—1.83 - 5.78) and anemia (OR—4.01, 95% CI—3.78 - 7.99) independently predicted hyperuricemia. Conclusion: Hyperuricemia is commoner in CKD than hypertension and was higher in males and positively correlated with the blood pressure, proteinuria and creatinine, but negatively related to hematocrit, albumin and glomerular filtration rate. Independent predictors of hyperuricemia were proteinuria, elevated creatinine, hypoalbuminemia and anemia. Measures are needed to prevent and treat hyperuricemia to reduce the health burden associated with hypertension and CKD.

Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Effect of Uric-acid-lowering Therapy on Progression of Chronic Kidney Disease: A Meta-analysis

The efficacy and safety of uric-acid-lowering therapy （UALT） on slowing the progression of chronic kidney disease （CKD） accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials （RCTs） which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine （MD=-62.55 μol/L, 95% CI： -98.10 to -26.99） and blood urea nitrogen （MD= -6.15 mmol/L, 95% CI -8.17 to -4.13） as well as the decrease of glomerular filtration rate [MD=5.65 mL/（min.l.73 m2）, 95% CI： 1.88 to 9.41], decreased systolic blood pressure （SBP） （MD= -6.08 mmHg, 95% CI： -11.67 to -0.49）, and reduced the risk of the renal disease progression （RR=0.30, 95% CI： 0.19 to 0.46）. However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure （P〉0.05）. We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease:Findings from the Salford Kidney Study

BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive agents was associated with all-cause mortality,independent of blood pressure control(hazard ratio:1.15;95%confidence interval:1.04-1.27,P=0.006).Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed(log-rank,P<0.001).CONCLUSION Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm.Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents.Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Neutrophil Lymphocyte Ratio as an Inflammatory Marker in Chronic Kidney Disease: Determinants and Correlates

Introduction: Inflammation has been implicated as a major reason for the higher morbidity and mortality in chronic kidney disease (CKD) compared to the diseases that commonly precedes it. The neutrophil lymphocyte ratio (NLR) has increasingly been reported to be a marker of systemic inflammation. We studied the neutrophil lymphocyte ratio and its relationship with kidney function and other markers of inflammation in health and in CKD. Methods: Two hundred and forty four participants in three cohorts: healthy, CKD stage 1 - 2 and, stage 3 - 4, were studied. Data of clinical, NLR, uric acid, urine albumin creatinine ratio (UACR), electrolytes were documented and independent associates of NLR were determined. Results: The NLR was higher in the CKD cohorts, P Conclusion: The NLR as an inflammatory marker is elevated in chronic kidney disease, and increases with disease severity hence it can be a useful tool in determining the presence and severity of inflammation in CKD.

Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives

Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.

基于数据挖掘分析孙伟治疗慢性肾脏病合并高尿酸血症用药规律

目的运用数据挖掘方法探讨孙伟教授治疗慢性肾脏病合并高尿酸血症处方的用药规律。方法收集江苏省中医院孙伟教授2016年至2022年期间门诊就诊的慢性肾脏病合并高尿酸血症患者首诊医案,建立数据库,运用数据挖掘软件进行用药频数及性味归经统计、频繁模式、聚类和复杂网络分析。结果共纳入349例处方,涉及中药143味,药物频数总计8438次,高频药物有黄芪、紫苏梗、白术、石韦、郁金、虎杖、党参、杜仲、当归、续断、川芎等,以补虚药、利水渗湿药、活血化瘀药为主,性味以温、甘居多,多归属肝、脾、肺、肾、胃经。常用药物组合有黄芪-白术-党参-紫苏梗,杜仲-续断,石韦-土茯苓,当归-川芎-郁金等。结论孙伟教授认为本病病机为“肾虚湿瘀”,遣方用药应以“益肾清利和络泄浊”为主要治则治法。

White blood cell count and the incidence of hyperuricemia:insights from a community-based study

Hyperuricemia(HUA)is a risk factor for chronic kidney disease(CKD).The relationship between HUA and white blood cell(WBC)count remains unknown.A sampling survey for CKD was conducted in Sanlin community in 2012 and 2014.CKD was defined as proteinuria in at least the microalbuminuric stage or an estimated GFR of 60 mL/(min·1.73 m2).HUA was defined as serum uric acid>420µmol/L in men and>360µmol/L in women.This study included 1024 participants.The prevalence of HUA was 17.77%.Patients with HUA were more likely to have higher levels of WBC count,which was positively associated with HUA prevalence.This association was also observed in participants without CKD,diabetes mellitus,hyperlipidemia,or obesity.Multivariate logistic regression analysis showed that WBC count was independently associated with the risk for HUA in male and female participants.Compared with participants without HUA,inflammatory factors such as high-sensitivity C-reactive protein,tumor necrosis factor-α,and interleukin 6 increased in participants with HUA.Hence,WBC count is positively associated with HUA,and this association is independent of conventional risk factors for CKD.

Effect of Laparoscopic Peritoneal Dialysis Catheterization on Patients with Stress Response

Objective:To observe the effect of laparoscopic peritoneal dialysis(PD)catheterization on stress response.Methods:The clinical data of 60 patients with stage 5 chronic kidney disease treated in our hospital from March 2016 to October 2019 were analyzed retrospectively.According to the different operation methods,they were divided into two groups.34 patients who received open PD catheterization were included in the control group,and 26 patients who received laparoscopic PD catheterization were used as the observation group.The intraoperative indexes,C-reactive protein(CRP),procalcitonin(PCT)levels and complications were compared between the two groups.Results:In the observation group,the bleeding volume was(16.27±4.13)mL,less than that in the control group,the operation time was(48.93±10.16)min,shorter than that in the control group,the incidence of catheter displacement was lower than that in the con-trol group,the difference was statistically significant(P<0.05).There was no significant difference in the levels of CRP and PCT between the two groups(P>0.05);the levels of CRP(47.25±16.91)mg/L and PCT(0.07±0.01)μg/L in the observation group were lower than those in the control group(P<0.05).Conclusion:Laparoscopic PD catheteri-zation in the treatment of end-stage renal disease has the advantages of small trauma,mild stress response and quick postoperative recovery,and it can reduce the occurrence of catheter displacement and the risk of PD catheterization.

高尿酸血症对慢性肾脏病及合并症影响的研究进展

正常情况下,血尿酸水平在人体内保持动态平衡,尿酸排泄主要通过肾脏,其次在肠道,当人体血尿酸的动态平衡被破坏时会导致高尿酸血症。目前临床研究表明,高尿酸血症在慢性肾脏病的发生发展中具有重要的影响,并且共患病加速了慢性肾脏病合并症的发生发展和死亡风险。本文就尿酸代谢及高尿酸血症概述、高尿酸血症对慢性肾脏病和合并症的影响及对慢性肾脏病患者的降尿酸治疗影响及进展等方面作一综述。