Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease.

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.

Diagnostic Usefulness of the Protein Energy Wasting Score in Prevalent Hemodialysis Patients.

OBJECTIVE: To study whether the score proposed by the International Society of Renal Nutrition and Metabolism to define the protein energy wasting (PEW) syndrome has diagnostic validity in patients undergoing dialysis. DESIGN AND METHODS: Cross-sectional study including 468 prevalent hemodialysis patients from Canary Islands, Spain. Individual PEW syndrome criteria and the number of PEW syndrome categories were related to other objective markers of PEW using linear and logistic regression analyses: subjective global assessment, handgrip strength, bioimpedance-assessed body composition, and levels of high-sensitivity C-reactive protein. RESULTS: Study participants (34% women) had a median age of 66 years, 37 months of maintenance dialysis, and 50% were diabetics. About 23% of patients had PEW (≥3 PEW categories), and 68% were at risk of PEW (1-2 PEW categories). Low prealbumin was the most frequently found derangement (52% of cases), followed by low albumin (46%), and low protein intake (35%). Across higher number of PEW syndrome categories, patients showed a longer dialysis vintage and had lower creatinine, triglycerides, and transferrin (P for trend <.001 for all). All nutritional assessments not included in the PEW definition worsened across higher number of PEW categories. In multivariable regression analyses, there was a linear inverse relationship between muscle and fat mass as well as handgrip strength with the number of PEW syndrome categories. Likewise, the proportion of subjective global assessment-defined malnutrition and serum concentration of C-reactive protein gradually increased despite adjustment for confounders (P for trend <.05 for all). CONCLUSION: The PEW score reflects systemic inflammation, malnutrition and wasting among dialysis patients and may thus be used for diagnostic purposes.

Determination of orientations of aromatic groups in self-assembled peptide fibrils by polarised Raman spectroscopy.

In this paper we describe a novel combination of Raman spectroscopy, isotope editing and X-ray scattering as a powerful approach to give detailed structural information on aromatic side chains in peptide fibrils. The orientation of the tyrosine residues in fibrils of the peptide YTIAALLSPYS with respect to the fibril axis has been determined from a combination of polarised Raman spectroscopy and X-ray diffraction measurements. The Raman intensity of selected tyrosine bands collected at different polarisation geometries is related to the values and orientation of the Raman tensor for those specific vibrations. Using published Raman tensor values we solved the relevant expressions for both of the two tyrosine residues present in this peptide. Ring deuteration in one of the two tyrosine side chains allowed for the calculation to be performed individually for both, by virtue of the isotopic shift that eliminates band overlapping. Sample disorder was taken into account by obtaining the distribution of orientations of the samples from X-ray diffraction experiments. The results provide previously unavailable details about the molecular conformation of this peptide, and demonstrate the value of this approach for the study of amyloid fibrils.

Homocysteinylated protein levels in internal mammary artery (IMA) fragments and its genotype-dependence. S-homocysteine-induced methylation modifications in IMA and aortic fragments.

The resistance of internal mammary artery (IMA) toward atherosclerosis is not well understood. In plasma, homocysteine (Hcy) occurs in reduced, oxidized, homocysteine thiolactone and a component of proteins as a result of N- or S-homocysteinylation. We evaluated S/N-homocysteinylated protein levels in IMA fragments of patients undergoing coronary artery bypass grafting, and whether they were affected by genetic common variants. We tested whether tHcy, Hcy-S-protein levels, genotypes or Hcy-induced methylation modifications were related to differences in iNOS, Ddah2, and eNOS gene expression between territories. A small percentage of Hcy-S-proteins were found in IMA fragments. The Mthfr C677T (rs1801133) and Pon-1 Leu55Met (rs854560) variants were associated with Hcy-S-proteins. We observed a gradual difference according to Hcy-S-protein levels in the methylation degree of the Ddah2 gene promoter in aortic, but not in IMA, fragments. No correlation between the degree of methylation and the Ddah2 gene expression levels was found in both types of analyzed fragments. Total Hcy but not Hcy-S-proteins correlated with iNOS promoter methylation. Analyzed variants seem to contribute to the in vivo Hcy binding properties to IMA. The contribution of the Hcy-derived methylation modifications to Ddah2 and eNOS gene expression seems to be tissue-specific and independent of the Ddah2/ADMA/eNOS pathway. Hcy-derived methylation modifications to the iNOS gene promoter contribute to a lesser extent to iNOS gene expression.

Combination therapy with an angiotensin II receptor blocker and an HMG-CoA reductase inhibitor in experimental subtotal nephrectomy.

BACKGROUND: Angiotensin receptor 1 blockers (ARB) are standard nephroprotective drugs in chronic kidney disease. There is less evidence for a nephroprotective effect of HMG-CoA reductase inhibitors (statins) and much less is known about potential benefits of combination therapy. We evaluated the therapeutic potential of a statin alone or in combination with an ARB in experimental chronic kidney disease. METHODS: Subtotally nephrectomized (5/6 Nx) rats were treated early with vehicle, losartan, cerivastatin or losartan/cerivastatin. Expression of messenger RNA (mRNA) was assessed by real-time reverse transcription-polymerase chain reaction. Tissue proteins were localized by immunohistochemistry. Nuclear factor-κB (NF-κB) activation was measured in whole kidneys. RESULTS: In contrast to the sham group, at 6 weeks, vehicle-treated 5/6 Nx rats displayed renal lesions, albuminuria and increased blood pressure, serum creatinine and total kidney NF-κB p65 DNA-binding activity and preproendothelin-1, fibronectin and type I and III collagen mRNA. NF-κB activation correlated with albuminuria and histological renal injury. Losartan or combination therapy preserved renal function, abrogated albuminuria and improved glomerular and interstitial histology. Cerivastatin alone preserved renal function and improved interstitial injury but did not influence albuminuria, glomerular histology or NF-κB activation. Losartan/cerivastatin normalized kidney NF-κB activation and extracellular matrix mRNA expression pattern. The effect of losartan alone on these parameters was less intense. All treatments decreased preproendothelin-1 mRNA and preserved interstitial capillaries. CONCLUSIONS: In a chronic kidney disease model, early treatment with either an ARB or a statin preserved renal function although the mechanisms differed. Combination therapy with an ARB and a statin did not confer clear-cut advantages on biochemical and histological parameters over ARB alone, although it further improved the kidney NF-κB and gene expression profile.

Telmisartan-induced eNOS gene expression is partially independent of its PPAR-gamma agonist property.

PURPOSE: Telmisartan, an angiotensin II receptor blocker (ARB), also acts as an activator of peroxisome proliferator-activated receptor-gamma (PPAR-gamma; PPAR-γ). Several studies have explored the PPAR-γ-endothelial nitric oxide synthase (eNOS) pathway associated with improvement of endothelial function by telmisartan. The ability of telmisartan to induce gene expression and protein level of eNOS and PPARγ in adipocytes was investigated. METHODS: Expression of aP2, PPARγ, eNOS and iNOS genes were measured using the quantitative real-time polymerase chain reaction. The changes, at the protein level, were explored by Western blot, which evaluated the native and phosphorylated eNOS forms, eNOS-Ser(1177) and eNOS-Thr(495). RESULTS: Adipocytes, exposed to telmisartan, exhibited an increase in PPARγ gene expression but a decrease in protein level. Nonetheless, after the exposure to telmisartan, eNOS-Ser(1177) phosphorylation, associated with eNOS activity increment, reached its highest value while eNOS-Thr(495) phosphorylation, involved in the inhibition of eNOS activity, showed its lowest value. CONCLUSION: The results suggest that telmisartan preserves eNOS activity via a mechanism that is partially independent of the PPARγ-eNOS pathway in adipocytes.

Infrared linear dichroism spectroscopy on amyloid fibrils aligned by molecular combing.

We report the use of molecular combing as an alignment method to obtain macroscopically oriented amyloid fibrils on planar surfaces. The aligned fibrils are studied by polarized infrared spectroscopy. This gives structural information that cannot be definitively obtained from standard infrared experiments on isotropic samples, for example, confirmation of the characteristic cross-ß amyloid core structure, the side-chain orientation from specific amino acids, and the arrangement of the strands within the fibrils, as we demonstrate here. We employed amyloid fibrils from hen egg white lysozyme (HEWL) and from a model octapeptide. Our results demonstrate molecular combing as a straightforward method to align amyloid fibrils, producing highly anisotropic infrared linear dichroism (IRLD) spectra.

Anti-albuminuric effects of the angiotensin AT1 receptor blocker telmisartan in hypertensive patients.

We evaluated the anti-hypertensive and anti-albuminuric effect of the angiotensin receptor blocker telmisartan alone and in combination with torasemide and amlodipine. Patients were hypertensive, both diabetics and non-diabetics with persistent microalbuminuria. Our primary endpoint was a change in microalbuminuria levels, while the secondary endpoints were changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine levels, and glomerular filtration rate.After the 16-week treatment period, the patients significantly reduced microalbuminuria levels (76.4 ± 52.4 µg/min; p < 0.001), SBP (16.4 ± 8.7 mmHg; p < 0.001) and DBP (17.7 ± 5.9 mmHg; p < 0.001). Both diabetics and non-diabetics showed an identical pattern of significance with respect to the whole population. Systolic blood pressure, DBP, and microalbuminuria were significantly reduced as a consequence of therapy, both in diabetics and non-diabetics.

Kidney transplants in HIV-positive recipients under HAART. A comprehensive review and meta-analysis of 12 series.

BACKGROUND: Kidney transplantation is being introduced gradually for the treatment of end-stage renal disease in patients who are human immunodeficiency virus (HIV) positive. Our aim was to review the outcomes of kidney transplantation in HIV-positive recipients who were being treated with highly active antiretroviral therapy (HAART). METHODS: Eligible papers were English language manuscripts, published between July 2003 and April 2009 and available through Medline, that described three or more recipients of kidney transplants who were HIV positive and undergoing HAART. The regimens for induction and maintenance therapy, organ rejection, patient survival, CD4 counts, HIV progression, infectious complications and deaths were recorded. The survival at 1 year, organ rejection and infectious complications were evaluated using a random effects model with 95% confidence intervals (CI). RESULTS: Twelve case series met the defined criteria. Induction therapy consisted most commonly of the administration of anti-CD25 monoclonal antibodies, and triple immunosuppressive therapy was used most commonly for maintenance. Among the 254 patients, 1-year survival was 0.93 (95% CI, 0.90-0.96), organ rejection was diagnosed in 0.36 (95% CI, 0.25-0.49) and infectious complications occurred in 0.29 (95% CI, 0.17-0.43). The CD4 counts decreased after transplantation but recovered later. Acquired immune deficiency syndrome (AIDS)-defining infections occurred in three patients. CONCLUSIONS: Kidney transplantation appears to be safe in patients undergoing HAART. However, larger series of patients are needed to determine the best protocols for the induction and maintenance of immunosuppression.

A synergistic association of ACE I/D and eNOS G894T gene variants with the progression of immunoglobulin A nephropathy - a pilot study.

BACKGROUND: Individual variability in the natural history and response to therapy of immunoglobulin A nephropathy (IgAN) suggests a complex multifactorial pathogenesis. We investigated whether single nucleotide polymorphisms (SNPs) involved in the non-immunologic progression of renal disease are related with disease progression. METHODS: This is a pilot historic cohort study of 64 Caucasian patients with biopsy-proven IgAN and a median follow-up of 70 months. Three SNPs of the renin-angiotensin system genes (angiotensin I converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT(1)R) 1166A/C), 2 of the endothelial nitric oxide synthase (eNOS), 4a/b and G894T, and 1 of the bradykinin 1 receptor, G-699C, were genotyped. The primary outcome was 'kidney survival' defined as a 30% decrease of baseline creatinine clearance; annualized decrease of glomerular filtration rate was also calculated. RESULTS: Proteinuria, histological lesions, and mean arterial pressure were related to an unfavorable outcome. The simultaneous presence of the DD and GG variants of the ACE and eNOS genes was related to an unfavorable outcome as compared with other combinations [hazard ratio ranging from 4.7 (95% CI 1.52-14.33) to 8.4 (95% CI 2.45-29.10)] after controlling for proteinuria, mean arterial pressure and baseline histological lesions. CONCLUSION: This study suggests that in our population with IgAN, an interaction between ACE and eNOS polymorphisms may be a prognostic factor for renal function deterioration.

Sensorimotor recovery after partial facial (mystacial pad) transplantation in rats.

Most research in facial transplantation has been conducted in rats. This skill demanding model has a steep learning curve and is accompanied by high mortality rates. Investigations were carried out to minimize these disadvantages and a whiskers flap properly named mystacial pad flap, was developed. The mystacial pad contains the whiskers follicles of the rat, and our aim was to investigate the effect of repairing the nerves on the whiskers function after mystacial pad allotransplantation in rats. A total of 56 animals were studied in 6 groups. In the main study group (VI), 16 semi-allogenic vascularized mystacial flaps were transplanted from Lewis-Brown-Norway (RT1(l+n)) to Wistar-Lewis (RT1(l)) rats. This group was divided in 2 subgroups; in subgroup VIa (nonneurotized alloflap transplant group, n = 8), alloflaps were transplanted without nerve repairs, whereas in subgroup VIb (neurotized alloflap transplant group, n = 8) the facial and trigeminal nerves were repaired. Animals were kept under tapered doses of tacrolimus immunosuppression monotherapy. Clinical and neurophysiological explorations were performed to evaluate sensitivity and motor voluntary activity of the mystacial region after 6 weeks. Animals were euthanized after 8 weeks and histologic studies were performed. In group VI, each procedure required an average of 3.5 hours, and 87.5% of the recipients survived for 8 weeks. Sensitivity, motor activity, and histologic signs of recovery were found in the mystacial pad allotransplants after 6 weeks. Mystacial pad allotransplants in which nerves were repaired showed clinical, neurophysiological, and histologic signs of recovery. A functional facial subunit was successfully transplanted and sensorimotor function recovery could be demonstrated in rats.

Improved nephrology referral of chronic kidney disease patients: potential role of smartphone apps.

In chronic kidney disease (CKD), referral to nephrology is based on Kidney Disease: Improving Global Outcomes 2012 guidelines and is generally indicated when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2 or when there is a rapid decline of eGFR, elevated urinary albumin:creatinine ratio (>300 mg/g) or other 'alert' signs such as the presence of urinary red blood cell casts. Since eGFR declines with ageing in otherwise healthy individuals, we propose that the eGFR threshold for nephrology referral should be adjusted according to age. According to current recommendations, young patients without rapidly progressing CKD are referred more often to nephrology when CKD is more severe, compared with age-matched controls with normal eGFRs, than elderly CKD patients. In this commentary, we discuss the age factor and other specific situations not considered in current guidelines for nephrology referral of CKD patients.

Rosiglitazone but not losartan prevents Nrf-2 dependent CD36 gene expression up-regulation in an in vivo atherosclerosis model.

BACKGROUND: Thiazolidinediones exert anti-inflammatory and anti-oxidative roles and attenuate atherosclerosis by mechanisms partially independent of their metabolizing actions. High doses of angiotensin type 1 receptor (AT1R) blocker losartan (LST) seem to promote fat cell formation by preserving PPARgamma activity. METHODS: C57BL/6J diet-induced atherosclerotic susceptible mice randomly received a normal or a high-fat high-cholesterol (HFHC) diet and were treated with rosiglitazone (RG), LST or a vehicle for 12 weeks. RESULTS: HFHC was associated with increased PPARgamma gene expression without an over regulation of PPARgamma responsive genes, whereas RG and LST treatments were found to maintain PPARgamma activity without resulting in increased PPARgamma gene expression. A better anti-inflammatory and antioxidant profile in mice treated with RG regarding LST was observed in spite of a similar PPARgamma preserved activity. Chromatin immunoprecipitation (ChIP) assays revealed that animals under HFHC diet treated with RG showed a significant nuclear factor erythroid 2-like 2 (Nrf2)-dependent down-regulation of the expression of the CD36 gene. CONCLUSION: The PPARgamma agonist RG exerts antioxidant properties that significantly reduced Nrf-2-dependent CD-36 up-regulation in mice under HFHC diet. Because LST treatment was also associated with a preserved PPARgamma activity, our data suggests that these RG antioxidant effects are partially independent of its PPARgamma metabolizing properties.

Allelic variants of the human scavenger receptor class B type 1 and paraoxonase 1 on coronary heart disease: genotype-phenotype correlations.

OBJECTIVE: The antioxidant properties of high-density lipoprotein (HDL) have been attributed to paraoxonase (PON) enzyme activity. Human scavenger receptor class B type 1 (SR-BI; CD36 and lysosomal integral membrane protein-II analogous-1 [CLA-1]) plays a central role in HDL-mediated native and oxidized cholesteryl ester uptake. We tested for a significant contribution of common variant of these genes to coronary heart disease (CHD) risk and hypothesized that genetic-mediated PON activity and CLA-1/SR-BI receptor functional properties jointly reduce plasma oxidation status. METHODS AND RESULTS: We studied 304 cases and 315 controls. Polymorphisms were analyzed by polymerase chain reaction-restriction fragment analysis. CLA-1/SR-BI-relative expression levels and mRNA stability were analyzed by the comparative threshold cycle method. There was a significant difference in the male genotype distribution of the CLA-1/SR-BI exon 8 (C8/T8) variant between groups with an odds ratio of 1.7 (95% CI, 1.16 to 2.51). This significant risk was restricted to those subject carriers of Arg (R) and Leu (L) allele of the PON1 192 and 55 variants and was confirmed in multiple logistic regression analysis. CLA-1/SR-BI mRNA expression levels differed according to CLA-1/SR-BI genotypes. CONCLUSIONS: These data suggest a plausible genetic interaction between the CLA-1 exon 8 gene polymorphism and the risk of CHD in males.

[Concerning the significance of paraoxonase-1 and SR-B1 genes in atherosclerosis]. / Sobre los genes paraoxonasa-1 y SR-B1, y su importancia en la aterosclerosis.

High-density lipoprotein (HDL) is an independent protective factor against cardiovascular disease. The enzyme paraoxonase-1 (PON-1) contributes to the anti-atherogenic effects of HDL. In vitro studies have demonstrated that paraoxonase's substrates are highly heterogeneous and that some contribute to the development of atherosclerotic lesions. The atheroprotective role of PON-1 was established in genetically engineered animal models. In humans, the PON-1 Gln192Arg and Met55Leu polymorphisms appear to be associated with increased susceptibility to cardiovascular disease and with different PON-1 activity levels and concentrations. The CLA-1 (CD36 and Lysosomal integral membrane protein-II Analogous-1) gene is the human homologue of the murine SR-B1 (Scavenger Receptor class B type 1) gene. SR-B1 was the first high-affinity HDL receptor to be identified at the molecular level. The CLA-1 receptor plays a pivotal role in HDL-mediated reverse cholesterol transport by mediating the selective uptake of free cholesterol as well as of native and oxidized cholesteryl esters. Its atheroprotective role has also been established in transgenic mice studies. Several polymorphic variants of the CLA-1 gene have been described, some of which are associated with phenotypic changes in plasma lipoproteins. Both genes participate in the complex HDL metabolic pathway and, presumably, also in defense mechanisms against oxidative stress.

Peroxisome proliferator-activated receptor-gamma2-Pro12Ala and endothelial nitric oxide synthase-4a/bgene polymorphisms are associated with essential hypertension.

OBJECTIVE: Peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) belongs to the family of the nuclear hormone receptors and has been recently implicated in vascular biology. PPARgamma2(Pro12Ala) gene polymorphism is associated with obesity, body mass index and diabetes mellitus. The endothelial nitric oxide synthase (eNOS) (4a/b) gene polymorphism contributes to coronary heart disease and hypertension risk. We tested whether both polymorphic variants were associated with hypertension risk, and their inter-relationship with plasma homocysteine. DESIGN: A case-control study was conducted selecting 235 subjects with arterial hypertension and 223 normotensive matched controls. METHODS: Genotyping for the PPARgamma2(Pro12Ala) and the eNOS(4a/b) were performed by mutagenically separated polymerase chain reaction and by polymerase chain reaction. Glucose, lipid profile, plasma creatinine, homocysteine and microalbuminuria were measured. RESULTS We found a significant contribution of the PPARgamma2(Pro12Ala) and eNOS(4a/b) gene polymorphisms to hypertensive risk in our population (odds ratio, 1.9 and 1.6, respectively), confirmed by multiple logistic regression analysis. Those subjects with normal plasma homocysteine values had an increased hypertensive risk with an odds ratio of 2.6 for the PP genotype of the PPARgamma2 gene and an odds ratio of 1.8 for the a allele of the eNOS gene. CONCLUSIONS: Both analyzed polymorphisms were associated in a synergistic manner with hypertension. This effect manifested only in those subjects with normal homocysteine plasma values. Our findings suggest complex genotype-environmental interactions on hypertensive risk.

Renin expression in hematological malignancies and its role in the regulation of hematopoiesis.

It has been demonstrated that some myeloid blasts express renin, but normal bone marrow (BM) does not display this expression. The aim of the present work was to analyze the renin expression in different hematological malignancies and different myeloid cell lines. We investigated the expression of renin by RT-PCR in BM from patients with hematological malignancies (106 patients), in nine normal BM from healthy donors and in leukemic cell lines (K562, KU812, MEG-01, U-937 and HL60), as well in K562 cell line subjected to differentiation treatments. We have observed renin expression in cells from acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cases. The highest frequency was observed in AML-non acute promyelocytic leukemia(APL) cases (47.2% of the cases). The disappearance of this expression was associated with the status of complete remission of AML. Renin is expressed in some myeloid human leukemia cell lines such as K562, KU812 and MEG-01. However, when K562 cells were treated with inducers of growth inhibition and/or differentiation, the expression did not disappear, indicating that renin expression is associated with a blastic phenotype rather than with cell proliferation. The obtained findings suggest that the renin expression could have a role on the disease development and could be used as an aberrant marker of leukemia.

[The involvement of the renin-angiotensin system gene polymorphisms in coronary heart disease]. / Relevancia de los polimorfismos génicos del sistema renina-angiotensina en la enfermedad coronaria.

INTRODUCTION AND OBJECTIVES: Previous studies angiotensin-converting enzyme gene insertion/deletion polymorphism ACE (I/D), angiotensinogen gene polymorphism, and angiotensin II AT1 receptor polymorphism in relation to coronary heart disease controversial results. This study was designed to analyze the association between these gene polymorphisms and the first coronary event in individuals residing on Grand Canary Island, Spain. PATIENTS AND METHOD: Case-control study. Case subjects (n = 304) were recruited at the first coronary event; age-matched controls (n = 315) were randomly selected from the Grand Canary population. Participants were examined for the usual risk factors. Blood samples were obtained for biochemical analyses and DNA extraction. Genotyping was performed by PCR and restriction analysis. RESULTS: Neither ACE (I/D) nor AT1 receptor polymorphism was associated with coronary heart disease, whereas the frequency distribution of AGT M235T genotypes among patients and control subjects (TT: 29% and 19%; MT: 48% and 50%; MM: 22% and 31%, respectively) was statistically different (p = 0.003). Multiple logistic regression analysis identified the TT genotype of the angiotensinogen gene (OR = 1.9; 95% CI 1.1-3.4), diabetes (OR = 4.4; 95% CI 2.0-9.4) and hypertension (OR = 2.1; 95% CI 1.3-3.3) as risk factors predicting the coronary event. CONCLUSIONS: Our results provide no evidence of an association between ACE (I/D) or AT1 receptor polymorphism and coronary heart disease. However, homozygosity for the T allele of the angiotensinogen gene, diabetes and hypertension independently place individuals at higher risk of experiencing a coronary event on Grand Canary Island.

Spanish Society of Nephrology document on KDIGO guidelines for the assessment and treatment of chronic kidney disease.

The new Kidney Disease: Improving Global Outcomes (KDIGO) international guidelines on chronic kidney disease (CKD) and the management of blood pressure (BP) in CKD patients are an update of the corresponding 2002 and 2004 KDOQI (Kidney Disease Outcomes Quality Initiative) guidelines. The documents aim to provide updated guidelines on the assessment, management and treatment of patients with CKD. The first guidelines retain the 2002 definition of CKD but present an improved prognosis classification. Furthermore, concepts about prognosis of CKD, recommendations for management of patients, and criteria for referral to the nephrologist have been updated. The second guideline retains the <130/80 mm Hg-goal for management of BP in patients with CKD presenting increased albuminuria or proteinuria (albumin-to-creatinine ratio 30-300 mg/g, and >300 mg/g, respectively) but recommends a less-strict goal of <140/90 mm Hg in patients with normoalbuminuria. The development of the guidelines followed a predetermined process in which the evidence available was reviewed and assessed. Recommendations on management and treatment are based on the systematic review of relevant studies. The GRADE system (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the quality of evidence and issue the grade of recommendation. Areas of uncertainty are also discussed for the different aspects addressed.