Assessment of matrix Gla protein, Klotho gene polymorphisms, and oxidative stress in chronic kidney disease

Increased vascular calcification and oxidative stress are considered as extra renal risk factors at the pathogenesis cardiovascular events in chronic kidney disease (CKD). We investigated matrix Gla protein (MGP) (T-138C, Glu60X, Thr83Ala) and Klotho (Cys370Ser) gene polymorphisms, serum MGP levels, and oxidative stress status of 84 CKD patients and 37 healthy controls. The MGP gene Glu60X and Thr83Ala polymorphisms were significantly associated with CKD. The correlation between T-138C genotype of MGP gene, Cys370Ser genotype of Klotho gene, and CKD was not significant (p > 0.05). At the haplotype analysis, the combination of the X allele of Glu60X and the Thr allele of Thr83Ala showed a significantly increased risk of CKD (p < 0.05). X allele, Thr allele, and C allele of T-138C were associated with diabetes mellitus and CKD phenotypes occurring concurrently (p < 0.01). Serum zinc levels were significantly low in end-stage renal disease (ESRD) patients (p = 0.0001). The total comet score frequency of ESRD patients was higher than that of control group (p < 0.05). The urinary 8-hydroxy-2'-deoxyguanosine levels were significantly high in CKD patients (p < 0.05). According to this study, analyzing the distribution of MGP gene and oxidative stress status would be very informative in order to detect their role at CKD.     

Association of matrix Gla protein gene functional polymorphisms with loss of bone mineral density and progression of aortic calcification

Summary

Two matrix Gla protein (MGP) polymorphisms were associated with progression of aortic calcification and femoral neck bone loss in men. All these findings were also functionally corroborated in two vascular and bone in vitro systems indicating that MGP genetic variations can be partly responsible of higher risk of bone loss and vascular calcification.

Introduction

MGP plays an important role in bone and vascular mineralization as confirmed by MGP-deficient murine model. We therefore aimed to find a genetic association among -138T>C, -7G>A, and Thr83Ala MGP single-nucleotide polymorphisms (SNPs), bone loss, and progression of aortic calcification in a randomly selected general population of 296 individuals who participated in the European Vertebral Osteoporosis Study.

Methods

To evaluate the rate of change in bone mineral density (BMD) and the progression of aortic calcification, dual X-ray absorptiometry and lateral spine X-rays were performed at baseline and after 4 years of follow-up. Genotyping for the three polymorphisms was carried out using polymerase chain reaction and restriction fragment length analysis. In addition, functional studies of MGP-7G>A and Thr83Ala SNPs were performed on transiently transfected osteoblast-like UMR-106 and vascular smooth muscle A7r5 cells.

Results

The proportion of men who had lost BMD in the femoral neck was higher among homozygous -7AA and 83Ala-Ala (p?=?0.039 and p?=?0.009, respectively), and also featured a higher risk of progression of aortic calcifications (OR?=?5.6, 95 % CI?=?1.2–27.8 and OR?=?6.8, 95 % CI?=?1.4–32.3, respectively). No effect was observed in women. The MGP-7A allele produced a reduction in luciferase activity compared to MGP-7G: 47 % less in vascular cells and 34 % less in bone cells (p?=?0.001 and 0.012, respectively). In vascular cells under calcifying conditions, the MGP 83Thr allele showed a slightly higher, although not significant, inhibition than the MGP 83 Ala allele in calcium content suggesting functional differences between both variants.

Conclusion

These results suggest that MGP genetic variations could predict a higher risk of bone loss and progression of vascular calcification in men.     

Matrix GLA protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients

BACKGROUND: Increased vascular calcification plays an important role in the pathogenesis of cardiovascular events in chronic kidney disease (CKD) patients. It is the result of an active ossification process counteracted by 'protective' proteins, such as matrix GLA protein (MGP). Polymorphisms of MGP have been identified. METHODS: The aim of this study was to define the distribution of two MGP polymorphisms (-7, -138) in 99 hemodialysis (HD) patients, in 26 patients with CKD stage 3 and in 135 age- and sex-matched healthy controls. Patients were followed up for 12 months to record any cardiovascular deaths. The cause of death was determined by medical doctors, considering the medical history of each patient. The primers were designed with Primer Express software. RESULTS: MGP -138TT homozygotes were more frequent in the HD group versus controls (p = 0.0004). Additionally, the frequency of the T allele was significantly higher in the HD group (p = 0.0006). The frequency of the A allele of MGP-7 was significantly higher both in the HD group (p = 0.033) and in the CKD group (p = 0.0017) versus controls. MGP-7 GG homozygotes were significantly less common in the CKD group than in controls (p = 0.037). Combination -138TT -7AA was significantly more frequent in both CKD patients (p = 0.001) and in HD patients (p = 0.029) than in controls. Seventeen out of 99 HD patients experienced fatal cardiovascular events. Sixteen (94.1%) were -138TT homozygotes and either -7AA homozygotes or -7GA heterozygotes. CONCLUSION: This study suggests that CKD and HD patients have a different distribution of MGP gene polymorphism as compared with the normal population. Altered MGP gene polymorphism may be a negative prognostic factor for the progression to end-stage renal disease and for cardiovascular events in CKD patients.     

Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy

Left ventricular hypertrophy (LVH) is a common complication in patients with CKD and an independent risk factor for death. Changes in the levels of uremic solutes or Klotho have been reported to be related to CKD, whereas the relationships between these factors and CKD-associated LVH remain unclear. Here, we investigated the interaction between Klotho and indoxyl sulfate (IS), a typical uremic solute, in CKD-associated LVH. In a survey of 86 patients with CKD, a negative relationship was found between serum levels of IS and Klotho (r=−0.59, P<0.001). Furthermore, serum levels of IS and Klotho were independently associated with LVH (for IS: r=0.69, P<0.001; for Klotho: r=−0.49, P<0.001). In normal mice, intraperitoneal injection of IS for 8 weeks induced LVH accompanied by substantial downregulation of renal Klotho. Notably, IS-induced LVH was more severe in heterozygous Klotho-deficient (kl/+) mice. In vitro, treatment with Klotho strongly inhibited IS-induced cardiomyocyte hypertrophy by blocking oxidative stress and inhibiting p38 and extracellular signal–regulated protein kinase 1/2 signaling pathways. In a mouse model of CKD-associated LVH, the renal expression of Klotho was lower and the level of serum IS was higher than in healthy controls. Moreover, treatment of CKD mice with Klotho protein significantly restrained the development of LVH. Taken together, these results suggest that Klotho is an endogenous protector against IS-induced LVH, and the imbalance between Klotho and IS may contribute to the development of LVH in CKD.     

Synergistic effect of follicle‐stimulating hormone receptor and androgen receptor gene variants on semen quality

Follicle‐stimulating hormone (FSH), interacting with its receptor (FSHR), participates in the production of spermatozoa and androgens. Androgens exert their effects on male sex determination, development and sperm production by binding to androgen receptor (AR). In the present study, we sought to explore the potential synergistic effects of FSHR and AR gene variants on sperm quality. 200 oligozoospermic and 250 normozoospermic men were examined. DNA was extracted from spermatozoa, and the FSHR 307 (T/A), FSHR 680 (N/S) and AR (CAG)_n polymorphisms were genotyped. Their parallel analysis revealed six combined genotypes. A gradual reduction of sperm motility, from long AR allele‐Thr307Thr/Asn680Asn carriers to long AR allele‐Ala307Ala/Ser680Ser carriers and from short AR allele‐Thr307Thr/Asn680Asn carriers to short AR allele‐Ala307Ala/Ser680Ser carriers was revealed in normozoospermic men (P < 0.001). Similar associations were observed in oligozoospermic men (P < 0.001). In our series, the synergism of the long AR alleles with the FSHRThr307/Asn680 allelic variant was associated with increased sperm motility, while the synergism of the short AR alleles with the FSHRAla307/Ser680 allelic variant was associated with decreased motility, supporting the significance of these genes in semen quality.     

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

Abstract

The association of transforming growth factor-β1 (TGF-β1) polymorphisms with the risk of chronic kidney diseases (CKD) remains elusive. We aimed to perform a meta-analysis to evaluate the relationship between TGF-β1 polymorphisms and the susceptibility to CKD. Association studies were searched according to a defined criteria using electronic databases. The strength of association between TGF-β1 polymorphisms and CKD risk was evaluated by odds ratio (OR) with the corresponding 95% confidence interval (CI). Nine case–control studies were identified. T allele at the +869 T/C polymorphism was associated with a lower risk of CKD in Asians (p?=?0.003). TT genotype at the +869 T/C polymorphism was associated with a lower risk of CKD in overall populations and Asians (p?=?0.007 and <10^?4, respectively). CC genotype at the +869 T/C polymorphism was associated with the risk of CKD in Asians (p?=?0.002). T allele at the ?509 T/C polymorphism was associated with the risk of CKD in overall populations and Asians (p?=?0.044 and 0.050, respectively). TT genotype at the ?509 T/C polymorphism was associated with CKD risk in overall populations, Caucasians and Asians (p?<?10^?4, <10^?4, and <10^?4, respectively). No evidence of significant publication bias was noted. In conclusion, T allele at the +869 T/C polymorphism may be a protective factor against CKD risk in Asians. TT genotype at the +869 T/C polymorphism may be an indicator of lower risk of CKD in overall populations and Asians. CC genotype at the +869 T/C polymorphism may predict the susceptibility to CKD in Asians. T allele at the ?509 T/C polymorphism may be an indicator of CKD risk in overall populations and Asians. TT genotype at the ?509 T/C polymorphism was a risk factor for CKD onset in overall populations, Caucasians and Asians.     

Carotid intima media thickness is independently associated with urinary sodium excretion in patients with chronic kidney disease

Abstract

Atherosclerosis-induced premature vascular diseases are the leading cause of mortality among patients with chronic kidney disease (CKD). The pathogenetic mechanism of atherosclerosis in patients with CKD has not been fully explained. Experimental studies have demonstrated that high dietary sodium intake not only increases circulatory volume and blood pressure, but also facilitates development of atherosclerosis by reducing production-bioavailability of nitric oxide due to oxidative stress and accordingly by enhancing endothelial and arterial stiffness. In this study, we investigated the relationship between sodium consumption and carotid artery intima-media thickness, which is the indicator of atherosclerosis, by determining daily urinary sodium excretion, which is a reliable indicator of sodium consumption, in our patient group. Our patient group included 193 patients with stage 2–4 non-diabetic CKD and without a history of atherosclerotic disease. We determined that 77% of our patients have been consuming more than 2 g of sodium per day, which is the upper limit of sodium consumption recommended for patients with CKD. We determined a positive linear correlation between carotid artery intima-media thickness and patient age (p?<?0.001), C-reactive protein (p?<?0.001), urinary sodium excretion (p?<?0.001), body mass index (p?=?0.002), systolic blood pressure (p?=?0.002), hemoglobin (p?=?0.030), triglycerides (p?=?0.043), and diastolic blood pressure (p?=?0.049). We also found a negative linear correlation between carotid artery intima-media thickness and glomerular filtration rate (p?=?0.008). We found that urinary sodium excretion is the determinant of intima-media thickness even if all factors associated with intima-media thickness are adjusted, and that intima-media thickness increases by 0.031 (0.004–0.059) mm per 2 g increase in daily sodium excretion, independent from overall factors (p?=?0.025). Our results reveal a relation between urinary sodium excretion and carotid artery intima-media thickness and suggest that excessive sodium consumption predisposes development of atherosclerosis in patients with CKD.     

High serum chemerin level in CKD patients is related to kidney function,but not to its adipose tissue overproduction

Abstract

Chemerin is an adipokine modulating inflammatory response and affecting glucose and lipid metabolism. These disturbances are common in CKD. The aim of the study was: (a) to evaluate circulating chemerin level at different stages of CKD; (b) to measure subcutaneous adipose tissue chemerin gene expression; (c) to estimate the efficiency of renal replacement therapy in serum chemerin removal. 187 patients were included into the study: a) 58 patients with CKD; (b) 29 patients on hemodialysis; (c) 20 patients after kidney transplantation. 80 subjects constituted control group. Serum chemerin concentration was estimated by ELISA. The adipose tissue chemerin mRNA level was measured by RT-qPCR. The mean serum chemerin concentration in CKD patients was 70% higher than in the control group (122.9?±?33.7 vs. 72.6?±?20.7?ng/mL; p?<?0.001) and it negatively correlated with eGFR (r?=??0.71, p?<?0.001). The equally high plasma chemerin level was found in HD patients and a HD session decreased it markedly (115.7?±?17.6 vs. 101.5?±?16.4?ng/mL; p?<?0.001). Only successful kidney transplantation allowed it to get down to the values noted in controls (74.8?±?16.0 vs. 72.6?±?20.7?ng/mL; n.s.). The level of subcutaneous adipose tissue chemerin mRNA in CKD patients was not different than in patients of the control group. The study demonstrates that elevated serum chemerin concentration in CKD patients: (a) is related to kidney function, but not to increased chemerin production by subcutaneous adipose tissue, and (b) it can be efficiently corrected by hemodialysis treatment and normalized by kidney transplantation.     

Semen quality in men with chronic kidney disease and its correlation with chronic kidney disease stages

The aim of this study was to assess whether chronic kidney disease (CKD) has any impact on semen quality parameters in men with CKD stage 1–5. Results were collected from 66 men with different CKD stages (age 18–50 years). Age and BMI (body mass index) were recorded for each male. Higher CKD stage had a significant negative linear trend on semen volume (P < 0.05), progressive motility (P < 0.01), nonprogressive motility (P < 0.001), sperm concentration (P < 0.01), total sperm number (P < 0.01), cytoplasmic droplets (P < 0.01), teratozoospermia index (P < 0.05) and accessory gland markers, α‐glucosidase activity (P < 0.05), zinc (P < 0.01) and fructose (P < 0.01). BMI per se had no significant effect on semen volume, sperm number, sperm concentration, morphology, α‐glucosidase activity, fructose concentration or zinc level. A significant negative correlation between BMI and sexual‐hormone‐binding globulin (SHBG) (P < 0.01) was observed but not with other sex hormones. Age per se was related to a significant decrease of sperm concentration (P < 0.05), normal forms (P < 0.01) and testosterone level (P < 0.05). Our results indicate that CKD stage per se is a factor determining the number of spermatozoa available in the epididymis for ejaculation, in part independent of age‐related decrease of testosterone level and BMI.     

Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis

Summary

The P2X₇ receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X₇ receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three of these polymorphisms were associated with BMD and fracture risk.

Introduction

The P2X₇ receptor is an ATP-gated cation channel. P2X₇ receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X₇ receptor gene, we wanted to investigate the effect of these polymorphisms on BMD and risk of vertebral fractures in a case–control study including 798 individuals.

Methods

Genotyping was carried out using TaqMan assays. BMD was measured using dual energy X-ray absorptiometry, and vertebral fractures were assessed by lateral spinal X-rays.

Results

The rare allele of a splice site polymorphism, 151?+?1: G-T, was associated with increased fracture risk and reduced BMD in women. Two other loss-of-function polymorphisms, Glu496Ala and Gly150Arg, were also associated with BMD. The Glu496Ala variant allele was associated with decreased lumbar spine BMD in women and decreased total hip BMD in men. The 150Arg allele was associated with decreased total hip BMD in women and men combined. The minor allele of the gain-of-function polymorphism, Ala348Thr, was associated with reduced fracture risk and increased BMD at all sites in men. The Gln460Arg variant allele, which has been associated with increased receptor function in monocytes, was associated with increased total hip BMD in women. With the exception of His155Tyr for which we found conflicting results in men and women, our results are consistent with the phenotype of the knockout mouse. Analysis of a haplotype containing Ala348Thr, Gln460Arg, and Glu496Ala showed that the effects of the haplotypes on BMD and fracture were driven by Ala348Thr in men and by Gln460Arg and Glu496Ala in women.

Conclusion

In conclusion, we found that functional polymorphisms in the P2X₇ receptor gene and haplotypes containing three of these polymorphisms are associated with osteoporosis.     

Prevalence of Chronic Kidney Disease in the Black Sea Region,Turkey, and Investigation of the Related Factors with Chronic Kidney Disease

We aimed to assess the prevalence of CKD in the Black Sea Region, Turkey, and to evaluate any relationship between age, gender, diabetes, obesity, hypertension, and CKD. This study was conducted in 70 different areas in Tokat Province in the Black Sea Region, in the northern part of Turkey. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine using MDRD formulas. CKD-defined estimated GFR was lower than 60 mL/min/1.73m². A total of 1,079 persons were included in this study (mean age 41.4±17 years [range: 18–95 years], 49.4% males, 50.6% living in an urban area). Of the 1,079 individuals, 5.28% were diabetic, 22.9% were obese, and 37.8% were hypertensive. CKD was found in 62 of them (5.75%). The prevalence of CKD was 5.58% in non-diabetics and 8.77% in diabetics. No significant differences were found between two groups. The prevalence of CKD was 3.77% in non-hypertensive individuals and 8.82% in hypertensive patients, and 4.46% in non-obese and 9.31% in obese. The evident significant differences were found between groups (p < 0.0001 and p = 0.004, respectively). The prevalence of CKD increased with age within our population. A salient observation was the markedly higher prevalence of CKD in females than males (p = 0.046). There was an inverse correlation between eGFR and age (r = 0.529, p < 0.0001). The overall prevalence of CKD was 5.75% in general population. The prevalence of CKD increased with age within our population. Age, gender, obesity and hypertension were found to be significant risk factors for development of CKD in our population.     

Association between Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism and Diabetic Nephropathy Susceptibility

The association between endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphism and diabetic nephropathy (DN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS Glu298Asp gene polymorphism and DN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Eight articles were identified for the analysis of association between eNOS Glu298Asp gene polymorphism and DN risk. T allele was associated with DN susceptibility in overall populations, in Asians, and for Caucasians (overall populations, p = 0.005; Asians, p = 0.004; Caucasians, p = 0.002). Furthermore, GG genotype might play a protective role against DN onset for overall populations, Asians, Caucasians, and Africans. However, a link between eNOS Glu298Asp gene polymorphism and DN risk was not found in overall populations, Asians, Caucasians, and Brazil population. In conclusion, T allele might become a significant genetic molecular marker for the onset of DN in overall populations, in Asians, and for Caucasians. However, more studies should be performed in the future.     

Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency—genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor–23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1–, angiotensin II–, or high phosphate–induced fibrosis and abolished TGF-β1– or angiotensin II–induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor–23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.     

Renin-angiotensin system polymorphisms in Taiwanese primary vesicoureteral reflux

We studied the angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) gene polymorphisms for association with susceptibility to primary vesicoureteral reflux (VUR) and disease progression in 74 Taiwanese children, including 16 with end-stage renal disease (ESRD), and 117 normal controls. Polymerase chain reaction-amplified products containing the ACE gene T-5491C, A-5466C, T-3892C, A-3692C, A-240T, Alu I/D, the AGT gene C-532T, G-217A, G-152A, A-20C, A-6G, T174M, T235M, and the AT1R gene A-1138T, T-810A, T-713G, C-521T, AG-214CC, A-153G, A1166C polymorphisms were analyzed by restriction enzyme digestion, gel electrophoresis, or single-strand conformation polymorphism analysis. All the polymorphisms examined were in Hardy-Weinberg equilibrium. The strong non-random association within the ACE, AGT, and AT1R genes suggests low levels of intragenic recombination. None of these polymorphisms showed association with VUR susceptibility. However, the allele frequency distribution of the six ACE polymorphisms among primary VUR patients with or without ESRD was statistically different. The linked ACE T-A-T-A-A-I allele was observed significantly more frequently in VUR children with ESRD (P<0.001). A significant increase of left ventricular mass index was also found in the linked ACE T-A-T-A-A-I allele group compared with the non-ACE T-A-T-A-A-I allele group of patients aged 18 years with renal progression. The AGT A-6G genotype frequencies were significantly different when the analysis was stratified by genotype of the ACE polymorphisms. The data showed that ACE gene polymorphisms were associated with progressive renal deterioration in Taiwanese children with VUR and might act synergistically with the –6 G allele of the AGT gene.Kuo-Pao Liu and Ching-Yuang Lin contributed equally to this work     

Single‐nucleotide polymorphism in Turkish patients with adolescent idiopathic scoliosis: Curve progression is not related with MATN‐1, LCT C/T‐13910, and VDR BsmI

The role of genetics in the etiopathogenesis of adolescent idiopathic scoliosis (AIS) is unclear. In this study, we investigated the relationship between AIS and polymorphisms in MATN‐1, LCT C/T‐13910, and VDR BsmI genes. 53 Turkish adolescents with diagnosed AIS and 54 healthy adult individuals were included in the study. MATN‐1, LCT C/T‐13910, and VDR BsmI gene mutations were analyzed with real‐time PCR. We did not detect a statistically significant difference between AIS and control groups in respect to those three different gene polymorphisms (p < 0.05). We next evaluated the associations of all three SNPs with scoliosis curve severity. There was no significant difference between curve severity and gene polymorphisms (p < 0.05). In terms of gene polymorphisms, AIS patients with a family history of AIS did not significantly differ from AIS patients who did not have history (p < 0.05). AIS might be caused by many different gene mutations, biomechanical mechanisms that have been modified by environmental factors, different biological interactions, modulation of growth, or a synergy of different factors causing abnormal control of growth. However, the existing knowledge is still not enough to explain the etiopathogenesis of AIS. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1459–1463, 2012     

MCP-1 and soluble TWEAK levels are independently associated with coronary artery disease severity in patients with chronic kidney disease

Abstract

Purpose: Patients diagnosed with chronic kidney disease (CKD) have a greater rate of cardiovascular mortality when compared with the general population. The soluble form of TNF-like weak inducer of apoptosis (TWEAK) and monocyte chemoattractan protein 1 (MCP-1) play important roles in cellular proliferation, migration and apoptosis. The current study aimed to analyze whether soluble TWEAK (sTWEAK) and MCP-1 levels are associated with the severity of coronary arterial disease (CAD) in CKD patients. Methods: Ninety-seven patients diagnosed with CKD stages 2–3 according to their estimated glomerular filtration rate and the presence of kidney injury were included in the study. Plasma sTWEAK and MCP-1 concentrations were determined using commercially available ELISA kits. Coronary angiographies were performed through femoral artery access using the Judkins technique. Results: Correlation analysis of sTWEAK and Gensini scores showed significant association (p?<?0.01, r²?=?0.287). Also significant correlation has been found in MCP-1 levels and Gensini scores (p?<?0.01, r²?=?0.414). When patients were divided into two groups with a limit of 17 according to their Gensini score, sTWEAK levels indicated a statistically significant difference (p?<?0.01). Conclusions: Our findings support a relationship between sTWEAK and MCP-1 levels and CAD in CKD stages 2–3 patients.     

Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients?

Background: Hypertension is one of the important contributing factors linked with both causation and development of kidney disease. It is a multifactorial, polygenic, and complex disorder due to interaction of several risk genes with environmental factors. The present study was aimed to explore genetic polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients. Methods: Three hundred patients were enrolled in the study. Ninety were hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients without CKD were taken as controls. Demographic data including age, sex, Body mass index (BMI), and other risk factors were also recorded. DNA was extracted from blood by salting out method. Genotyping of ACE gene was done by PCR technique. All the statistical analysis was done by using Epi Info and SPSS version 16 software (SPSS Inc., Chicago, IL). Results: Mean age was higher in the control group (p?<?0.05). Variables among two groups were compared out of which age, BMI, hemoglobin (Hb) was found to be statistically significant whereas other variables like systolic blood pressure, triglyceride and low-density lipoprotein were not. Blood urea and serum creatinine levels were statistically significant in the two genotypes (p?<?0.05). Total and HDL cholesterol were statistically significant for DD genotype of ACE gene (OR?=?1.42, 95% CI?=?0.72–2.81). Similarly, the risk for CKD among hypertensive patients was also associated with D allele of ACE gene (OR?=?1.25, 95% CI?=?0.86–1.79). Conclusion: It is concluded that ACE-DD genotype may be a risk factor for the causation and development of chronic kidney failure among hypertensive patients.     

Ultrasonic Gallbladder Function in Chronic Kidney Disease: Does Predialysis,Hemodialysis, or CAPD Affect it?

Background. There are contradictory reports about the prevalence of cholelithiasis in chronic kidney disease (CKD). The pathogenesis of gallstones is associated with the lithogenic changes of bile composition, increased tendency to nucleation, and decreased gallbladder motility. The studies related to these factors can predict the development of cholelithiasis. The aim of this study was to evaluate the ultrasonic gallbladder function in CKD and to compare it in predialysis (PreD), hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD) patients. Methods. Age, gender, and body mass index matched 49 CKD patients (14 PreD, 19 HD, 16 CAPD), and 17 control individuals were included in the study. Diabetic and cirrhotic patients were not included. Ultrasonic gallbladder volume was evaluated in pre- and postprandial period, and ejection fraction was calculated. We also measured several biochemical parameters (cholesterol, triglyceride, blood urea nitrogen (BUN), creatinine, calcium, Phosphorus, parathormone, albumin, total protein) in blood. Results. Preprandial gallbladder volume in PreD, HD, CAPD, and control groups were 26.7 ± 13.6, 20.8 ± 10.4, 23.2 ± 14.7, and 26.4 ± 14.8 mL, respectively (p > 0.05). Ejection fractions were 54.1 ± 22.9%, 54.9 ± 23.9%, 48.6 ± 15.9%, and 51.8 ± 19.2% in PreD, HD, CAPD, and control groups, respectively (p > 0.05). Serum triglyceride was higher in PreD patients than control group (207 ± 144 vs. 110 ± 48 mg/dL) (p < 0.05). Serum BUN, Cre, P, and PTH levels were higher in CKD groups than the control group, whereas serum total protein and albumin levels were higher in the control group (p < 0.05). Serum Ca was lower in PreD and HD patients than in the controls (p < 0.05). Conclusions. In conclusion, CKD and renal replacement therapy (HD and CAPD) do not affect gallbladder functions, but more studies are needed to evaluate prevalence of gallstones, gallbladder motility, and the composition of bile in CKD.