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.

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 Diflstat for the Treatment of Secondary Dyslipidemia in Chronic Kidney Disease

1104 patients with Secondary Dyslipidemia and CKD （Chronic Kidney Disease） （females： 387; males： 717; aged： 70 4- 11 years） were given Diflstat with diet to evaluate efficacy and safety. The study lasted two years. Patients were assigned to three groups （A, B, C） based upon basal renal function. Group A consisted of 180 patients with GFR （glomerular filtration rate） of 67 4- 16 mL/min/m2. TC （Total-Cholesterol） （-31%）, LDLC （LDL-Cholesterol） （-42%）, TG （triglycerides） （-36.8%） levels, and nonHDLC （non HDLC holesterol） （-41%） and TC/HDLC ratio （-40%） were significantly reduced （P 〈 0.001）. GFR （＋2.5%） increased significantly. No significant changes were observed in HDLC （＋13%）. Group B was of 744 patients, 69% （males： 514）, 31% （females： 230） （median age： 70 ± 13 years）, and moderate stage Ill CKD （GFR： 38 ± 12 mL/min/l.73m2）. After 24 months the change of HDLC （＋3.5%） was not significant, while TC （-27%）, TG （-32%）, LDLC （-33%）, non-HDLC （33.4%）, TC/HDLC （-30%）, and GFR （＋2.1%） were statistically significant （P 〈 0.001）. Group C consisted of 180 patients, 51.6% （males： 93）, 48.3% （females： 87） （median age： 72±11 years）, with severe stage IV CKD （GFR： 19 mL/min/l.73m2）. HDLC （＋13%） was not significant, while TC （-32%）, TG （-38%）, LDLC （-35%）, non-HDLC （-38.5%）, TC/HDLC （-40%）, and GFR （＋2.1%） were statistically significant （P 〈 0.001）. An effective but safe lipid-lowering therapy in patients with CKD, may be crucial to prevent cardiovascular events. The treatment with Dill stat~ combined with diet is to be started as soon as possible in patients with CKD in order of improving lipid and lipoprotein profile, and reducing the progression of renal damage.

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.

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.

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.

Secondary Hyperparathyroidism in Dialysis Patients: Short- and Long-Term Outcomes of Conservative Parathyroidectomy

Secondary hyperparathyroidism (HPT) is frequent in dialysis patients. Parathyroidectomy (PTX) is indicated for patients who failed medical therapy. We reviewed the data from 184 dialysis patients who underwent PTX between January 2015 and January 2023. We aimed to evaluate the short and long term outcomes of PTX in dialysis patients, comparing the conservative 3/4 versus 7/8 techniques in this population.166 dialysis patients with secondary HPT were included. A conservative subtotal PTX (sPTX) 7/8 was performed in 72% of patients and sPTX 3/4 in 28% of them. Severe postoperative hypocalcaemiaocurred in 45 patients (27%). Hypocalcaemia was significantly more frequent in the sPTX 7/8 group (p = 0.012). One case of persistent HPT (0.6%) and 20 cases of recurrence (12%) were diagnosed. Recurrence was more frequent in the sPTX 3/4 group (15%). No deaths were reported during the perioperative period.

Parathyroid Hormone as a Marker for the Red Cell Fragility in Different Stages of Chronic Kidney Disease

Objective: The aim of the work is to study the relationship between Red blood cell osmotic fragility and level of parathyroid hormone in patients with different stages of Chronic Kidney Disease including End Stage Renal Disease. Background: Anaemia is one of the common complications associated with Chronic Kidney Disease (CKD) responsible for the increase in the morbidity and mortality in such patients. Several factors have been attributed to causing renal anaemia, amongst which hyperparathyroidism is one of the less recognised reasons. The level of PTH in early stages of chronic kidney disease has not been much studied. The excess amount of Parathyroid Hormone (PTH) secondary to CKD has been suggested to be a causative factor for anaemia. Method: A number of chronic kidney disease patients were studied for the relationship between Red cell osmotic fragility and level of parathyroid hormone. Results: This study was conducted on a number of 111 patients with chronic kidney disease classified into three groups. The study revealed a significant fall in Hb%, along with a rise in Median Osmotic Fragility (MOF) and PTH in the CKD patients. iPTH and MOF were significantly lower in group 3 as compared with cases in group 1. Also, iPTH and MOF were significantly lower in cases in group 2 as compared with cases in group 1. Conclusions: Based on our findings, secondary hyperparathyroidism has considerable effects on erythrocyte survival, contributing to increased fragility and anemia.

Effects of Etelcalcetide on Bone Microstructure in the Adenine-Induced Chronic Kidney Disease Rat Model

Objective: Chronic kidney disease (CKD) with secondary hyperparathyroidism (SHPT) increases the risk of fragility fractures with deterioration of cortical and trabecular bone microstructure. Etelcalcetide (EC), which is used to treat SHPT, reduces parathyroid hormone (PTH) levels in the blood. However, the details of the effects of EC on the microstructure of cortical and trabecular bone remain unclear. This study investigated whether EC improved the cortical and trabecular bone microstructure in CKD model rats. Methods: Eight-week-old, male Wistar rats were fed with a 0.75% adenine diet for 4 weeks to establish the CDK model rats. At 20 weeks of age, the rats were divided into two groups (n = 9 - 11 in each group): CKD group (vehicle administration) and EC group (0.6 mg/kg, daily). EC was injected for 4 weeks starting at 20 weeks of age. After treatment, the biochemical tests, measurement of bone mineral density and bone strength, and evaluation of cortical and trabecular bone microstructure were performed. Results: Compared with the CKD group, the EC group showed significantly lower serum blood urea nitrogen, calcium, and inorganic phosphorus levels (p p p p p Conclusions: EC significantly improved cortical microstructure and cortical porosity, suppressing deterioration of cortical bone strength and loss of trabecular bone in the adenine-induced CKD model rats.

Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism

AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics(etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory(calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ~2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables.RESULTS Fifty-three patients(66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product(P = 0.03 and P = 0.006, respectively). They also had lower mortality(32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events(27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg^2/dL^2 [RR 1.48(1.06, 2.08), P = 0.03], presence of vascular calcification [1.33(1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25(1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality.CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.

焦剑老师治疗慢性肾脏病继发高尿酸血症的经验

本文旨在介绍焦剑老师治疗慢性肾脏病继发高尿酸血症的经验。焦剑老师认为本病的基本病因病机为肾虚血瘀,湿浊内蕴。临床上老师主张在疾病早期进行积极干预,以补肾活血,祛湿降浊为治疗大法,拟生黄芪、川芎、丹参、大黄、蒲黄炭、醋五灵脂、土茯苓、萆薢为基础方,结合患者不同的临床表现,辨证施治,同时制定合理的饮食方案,在临床应用中取得了良好的疗效。

Before the Jury Is out on Cinacalcet’s Cardiovascular Effects in Hemodialysis Patients: Is Troponin a Missing Link?

Raised levels of the cardiac biomarker, Troponin I, are frequently encountered in hemodialysis patients and appear to be prognostic indicators for cardiovascular risk. Though evidence suggests that control of secondary hyperparathyroidism may reduce cardiac endpoints, the effect of the calcimimetic agent, cinacalcet, remains controversial. This retrospective study aimed at evaluating troponin levels in hemodialysis patients with severe secondary hyper parathyroidism (SHPT) who are on cinacalcet vs controls on conventional treatment. In addition, clinical outcomes including all-cause, cardiovascular morbidity and mortality were compared among both groups. A decline in Troponin I levels was observed in the cinacalcet group, this however was not translated clinically into improved survival. In fact, all-cause and cardiac mortality was similar in the two groups. Conversely, comparison of the incidence of cardiovascular events revealed lower rates in the cinacalcet group including cardiac, cerebral and peripheral vascular complications. Given some of our study limitations, further long-term, placebo-controlled trials are necessary to definitively establish the effect of cinacalet on cardiac biomarkers and ultimately its impact on clinical outcomes.

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.