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Introduction Platelets interact with circulating CD34+ progenitor cells inducing their differentiation into endothelial progenitor cells (EPCs) and further promoting EPC maturation into endothelial cells, an important step for endothelial regeneration and angiogenesis. PSCK9 is a serine protease that may not only play a crucial role in binding to the low density lipoprotein receptor (LDL-R) increasing its endosomal and lysosomal degradation thus inhibiting its recycling to the cell surface, leading to increasing LDL-cholesterol levels in plasma, but may also exhibit several, independent on LDL-R, activities on a plethora of cell types, including platelets. Purpose We investigated whether monoclonal antibodies (mabs) against PCSK9 could affect platelet interaction with CD34+ cells as well as their differentiation into EPCs, in patients with Familial Hypercholestorelemia (FH). Patients and methods Patients with FH (n=11, 8 men and 3 women, mean age 53±10 years) being under statin/ezetimibe therapy (40mg statin/ 10mg ezetimibe) participated in the study. Patients exhibited resisting high LDL-cholesterol levels, therefore following the existing guidelines, they received mab against PCSK9 (7 evolocumab, 140mg/ml and 4 alirocumab, 150mg/ml) every two weeks. Blood samples were drawn before and after 4 doses of the antibody i.e. after two months (Follow-up). In addition to the patients' serum lipid profile, the endothelial phenotype of CD34+ (membrane expression levels of KDR which is a receptor for VEGF and an endothelial phenotype marker) on CD34+ cells (CD34+-KDR+ cells) and the formation of platelet-CD34+ (CD61+-CD34+) and platelet-KDR+ (CD61+-KDR+) conjugates were also determined by flow cytometry on whole blood after dual labelling with anti-VEGFR-R2/KDR-PE, anti-CD61-PerCP and anti-CD34-FITC. The results were expressed as the %gated of CD34+-KDR+ cells, as well as CD61+-CD34+ and CD61+-KDR+ conjugates. Results The baseline LDL-cholesterol levels were significantly reduced from 172±43 mg/dl to 51±17 at follow-up, p=0.0001. Importantly, the formation of CD61+-CD34+ and CD61+-KDR+ conjugates were increased from baseline to follow-up (from 1.39±1.3 to 2.23±2.8, p=0.037) and (from 2.91±4.2 to 5.92±6.01, p=0.014), respectively. The membrane expression of KDR on CD34+ cells was also increased from 0.79±0.9 to 1.36±0.90, p=0.042, which reflects the increase in the CD34+ endothelial phenotype. Conclusion We show for the first time that the mabs against PCSK9, significantly increase the CD34+ endothelial phenotype in FH patients, which may at least partially attributed to the increase in the platelet interaction with CD34+ cells (platelet-CD34+ conjugates). The underlying mechanisms as well as the consequences of this effect at the clinical level for these patients are under investigation.

Introduction There is limited data on cardiometabolic characteristics and treatment of underage patients with familial hypercholesterolemia (FH). Accurate estimation of low-density lipoprotein cholesterol is essential to tailor hypolipidemic treatment. Purpose To report lipid profile and current treatment of underage patients with FH in Greece as recorded in the HELLAS-FH registry. Also, to compare the Friedewald with the Martin/Hopkins equation, (which provides a customized estimation of VLDL-C) and the Dahlen's formula [(which adjusts the LDL-C measurements for the amount of cholesterol in Lp(a)]. Methods Underage patients with FH were evaluated. Lipid profile, current treatment regimen as well as LDL-C levels as assessed with different formulas were evaluated. Results A total of 191 children were included (51.0% boys, 11.0±3.5 years old). Children at baseline had mean LDL-C as calculated by the Friedewald equation (LDL-CF) 233±65 mg/dL and median Lp(a) 15.3 (IQR 8–51) mg/dL. A total of 59.2% of subjects were receiving hypolipidemic treatment, mainly statins (29.4%) and sterols/stanols (25.5%). Children on hypolipidemic therapy had mean LDL-CF 183±98 mg/dL with 22.1% achieving an LDL-C≤130 mg/dL. When LDL-C was calculated based on the Martin-Hopkins equation (LDL-CM/H) respective values were 180±58 mg/dL and 24.8%. When LDL-C was corrected for Lp(a) [= LDL-CM/H − (Lp(a) * 0.30)], LDL-C was 174±105 mg/dL with 33.3% of patients within the LDL-C target. Conclusions Nearly two-thirds of children were receiving some kind of hypolipidemic treatment at the time of registration. For those on treatment, LDL-C goal is achieved by one in five, which rises to 1 in 3 when LDL-C is corrected for Lp(a) levels.

Introduction Familial hypercholesterolemia (FH) as well as elevated Lp(a) levels are both associated with increased cardiovascular disease (CVD) risk. There are limited data on the association of Lp(a) levels with CVD in FH Patients. Purpose To evaluate the association between Lp(a) levels and CVD in adult FH patients included in the HELLAS-FH registry in Greece. Methods Adult patients with FH and measured Lp(a) levels were included in this analysis. Demographics, CVD prevalence and lipid profile were evaluated. Results A total of 337 patients were evaluated (46% male, 48.3±15.4 years old). The median [IQR] of Lp(a) at baseline was 22.6 (9.7–56.2) mg/dL. Patients were categorized into 4 different groups according to the Lp(a) levels quartiles. There was no gender or age difference between the 4 groups. Moreover, all groups had similar smoking status, hypertension, body mass index and type 2 diabetes prevalence. There was no significant difference between groups regarding baseline and on treatment lipid profile. We observed a significant positive association between Lp(a) quartile and coronary artery disease (CAD) prevalence (p=0.004). Patients in the highest vs lowest quartile had greater CAD prevalence (21.7% vs 7%, p=0.006). No association was observed between Lp(a) quartile and the prevalence of cerebrovascular disease or peripheral artery disease. Conclusions Elevated Lp(a) levels have a positive correlation with CAD in patients with FH.

Introduction The majority of patients with homozygous familial hypercholesterolemia (HoFH) phenotype are treated additionally to lipid lowering (LL) drugs (statin + ezetimibe ± colesevelam) with lipoprotein apheresis (LA) sessions. The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in HoFH patients. Patients and methods In 12 HoFH patients treated with LL drugs ± biweekly LA sessions (9 patients) the 5–40 mg daily of lomitapide was added. Lipid profile [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high density lipoprotein cholesterol (HDL-C)] before (LL drugs ± LA) and after lomitapide treatment were evaluated. Results The follow-up period of lomitapide treatment for 12 patients was 3–24 months (13.8±7.9). The median baseline LDL-C levels was 1000 mg/dL (339–1150). During LL drug therapy, patients showed a median LDL-C level of 383.5 mg/dL (Range: 214–866 mg/dL) and with LL drugs + Time-averaged levels (CAVG) the median was 288.1 mg/dL (Range: 183.69–716.65 mg/dL). The addition of lomitapide at the average dosage of 21.4 mg/day lowered LDL-C levels by 56.8% comparing to LL drugs alone therapy [mean reduction 262.12, 95% CI (105.53, 418.71), p=0.005] and by 54% [mean reduction −182.89, 95% CI (−342.35, −23.43), p=0.031] comparing to LL drugs + LA (CAVG). The CAVG of LDL-C in LL drugs + LA patients compared with LL drugs + lomitapide was 54% in favour of lomitapide (p=0.031). After lomitapide administration to LL drugs + LA treatment, 78% patients discontinued LA and 2 patients reduced their LA frequency by 50%. During follow-up, 2 patients (16.6%) reported side effects (transient diarrhea, 1 patient had liver transaminase >5× ULN and had to decrease dose of lomitapide). Two patients stopped lomitapide due to diet and alcohol restrictions. Median and ranges of lipid and lipoprotein values before any intervention, after LL drugs, LL drugs plus LA, LL drugs plus LA (CAVG) and LL drugs plus lomitapide Total Cholesterol LDL-C HDL-C Triglycerides Before any intervention 1000 (339–1150) 900 (245–1070) 34.5 (25–50) 125 (87–314) After LL drugs 434 (278–915) 383.5 (214–866) 36 (27–51) 113 (62–198) LL drugs + LA (CAVG) 336.13 (248.57–784.16) 288.07 (183.69–716.65) 42.81 (25.84–46.68) 105.09 (55.79–166.68) LL drugs + Lomitapide 228.5 (118–554) 173.5 (74–515) 37.5 (29–50) 83.5 (23–316) LDL graph Conclusions Treatment with lomitapide in HoFH patients has beneficial effect with constant decrease of LDL-C by 57% compared with classical LL therapy and by 54% compared with classical LL therapy and CAVG and seems to be with good safety profile. Although, in some cases the hybrid (all availably drug treatment and LA) therapy may be needed.

Hypertension and hyperlipidemia, two powerful risk factors of cardiovascular disease (CVD), often coexist. Therefore, treatment should consider the beneficial properties of drugs used to treat either condition. Statins, the mainstay of lipid-lowering therapy, result in a significant clinical benefit both in primary and secondary CVD prevention. In addition to their hypolipidemic capacity, other properties may contribute to statin-induced benefits. Clinical and experimental evidence indicates that statins may modulate blood pressure (BP). The mechanisms by which statins reduce BP seem to be largely independent of their lipid effects. Although small, reductions in BP are possibly clinically relevant. Large landmark studies confirm that statins can reduce CVD risk in hypertensive patients. These findings suggest that statins could be prescribed as an adjunct in treating hypertension with dyslipidemia or even in patients with "normal" cholesterol levels. Whether the effect of statins on BP is accompanied by an additional decrease in clinical outcomes needs to be investigated in long-term, large-scale trials.

The metabolic syndrome is a clustering of risk factors including central obesity, insulin resistance, dyslipidaemia and hypertension. This syndrome is associated with increased risk of cardiovascular disease and is a common early abnormality in the development of type 2 diabetes. The pathogenesis of the syndrome has multiple origins. Obesity and sedentary lifestyle coupled with genetic factors interact to produce the syndrome. Here, we consider two components of the metabolic syndrome, dyslipidaemia and hypercoagulability.

Several studies have shown that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are useful in the treatment of hypertension, cardiovascular disease, chronic heart failure, and some types of nephropathy. In this context, dual renin-angiotensin system blockade with both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may be more effective than treatment with each agent alone. Many clinical trials have demonstrated the beneficial effect of this combined treatment on proteinuria, hypertension, heart failure, and cardiovascular events. Moreover, these studies demonstrated that dual renin-angiotensin system blockade is generally safe and well tolerated. Long-term studies are under way to confirm these effects and also investigate the effectiveness of dual reninangiotensin system blockade on cerebrovascular disease and prevention of type 2 diabetes mellitus. These studies are expected to define the optimal use of combination treatment in everyday clinical practice. This review considers the most important clinical trials that evaluated the effect of dual renin-angiotensin system blockade on blood pressure, heart failure, and renal function.

Background and Aim: HDL-cholesterot (HDL-C) is inversely related to the risk of ischemic heart disease. Many genes are reported to affect HDL-C serum levels in both hyperlipidemic and normolipidemic populations, though the data are controversial. We examined the effect of common gene polymorphisms known to interfere with HDL-C metabolism (apolipoprotein E, cholesterol ester transfer protein and apolipoprotein A-IV gene polymorphisms) on HDL-C plasma levels in normolipidemic subjects. Methods and results: The study population consisted of 200 normolipidernic individuals visiting our clinic for a routine check-up. None of the above gene polymorphisms affected HDL-C levels in our population. However, participants carrying the atlete E4 of the apolipoprotein (apo) E gene, the allele B1 of the TaqIB polymorphisms in the cholesterol ester transfer protein (CETP) gene and the allele T of the apoA-IV gene (A to T polymorphism at site 347) (n=28) had statistically significantly tower HDL-C levels compared to those not carrying the above allele combination (0.99+0.33 vs 1.28 0.35 mmol/L, p=0.04). Conclusion: In this study, we describe a subgroup of normolipidemic individuals with low HDL-C levels due to genetic variability, and we discuss the underlying possible mechanisms involved. (c) 2005 Elsevier Ltd. All. rights reserved. Nutrition Metabolism and Cardiovascular Diseases

Background We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels. Methods Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants. Results The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3 ± 101.1 μmol/L [5.4 ± 1.7 mg/dL]) compared with the apo E-3 allele (261.8 ± 89.2 μmol/L [4.4 ± 1.5 mg/dL]; p = .012) and the apo E-4 allele (243.9 ± 65.4 μmol/L [4.1 ± 1.1 mg/dL]; p = .010), whereas the apo E-2 allele was associated with a nonsignificant decrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9 ± 2.2% vs 8.7 ± 4.2% vs 8.9 ± 5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA. Conclusions Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.

Objective The more atherogenic lipid profile seen in peritoneal dialysis (PD) patients cannot fully explain the increased incidence of atherosclerosis in this population. Oxidative modification of low-density lipoproteins (LDL) is considered to play a central role in the atherogenic process, whereas high-density lipoprotein (HDL) protects LDL from oxidation. On the other hand, it has been suggested that the LDL and HDL of PD patients are more resistant to oxidation than those of control subjects, while PD-HDL equally protects LDL from oxidation compared to control-HDL. Two HDL-associated enzymes have been shown to protect both LDL and HDL from oxidation: paraoxonase (PON1) and HDL-associated platelet-activating factor acetylhydrolase (HDL-PAF-AH). Furthermore, low PON1 activity and high total plasma PAF-AH concentration, which represents mainly the LDL-associated enzyme, have been shown to be independent risk factors for coronary artery events in the general population. However, there are limited data regarding possible alterations of these enzymes in PD patients. The aim of our study was to examine the possible alterations of PON1 and PAF-AH activities in patients undergoing PD. Design A cross-sectional study. Setting A university medical center. Participants 56 PD patients of Caucasian origin and 86 matched controls were studied. Measurements In all subjects, serum PON1 activity toward paraoxon (paraoxonase) and phenylacetate (arylesterase), as well as total serum and HDL-PAF-AH activities were measured; PON1 genetic polymorphisms known to influence PON1 activity (Q192R and M55L) were determined. Results The PD patients exhibited significantly increased serum PON1 (paraoxonase) and PON1 (arylesterase) activities compared to controls, regardless of the PON1 polymorphisms or the levels of HDL cholesterol. Additionally, PD patients had significantly elevated activities of total serum PAF-AH and HDL-PAF-AH, independently of the levels of LDL or HDL cholesterol. The ratio of HDL-PAF-AH / total PAF-AH, which has recently been suggested to be a potential marker of atherogenicity, was decreased in these patients compared to controls. Moreover, no difference in the prevalence of PON1 polymorphisms between PD patients and controls was found. Conclusion The elevated activities of PON1 and HDL-PAF-AH could explain the increased resistance of PD-HDL to oxidation; the higher activity of total PAF-AH and the decreased HDL-PAF-AH / total PAF-AH ratio could contribute to the increased incidence of atherosclerosis in these patients.

● Background: Apolipoprotein E (ApoE) polymorphism has been shown to influence serum lipid parameters and ApoE levels in both healthy subjects and hemodialysis (HD) patients. Conversely, ApoE concentration significantly affects serum lipid levels in the general population, independently of ApoE polymorphism, by modulating lipoprotein production, lipolytic conversion, and receptor-mediated clearance. Therefore, studying the effect of ApoE polymorphism on serum lipid levels without taking into account ApoE levels could lead to confounding results. However, such a combined study has not been performed in HD patients to date. Methods: Three hundred one patients without diabetes on long-term maintenance HD therapy and 200 matched healthy subjects were studied. Determination of levels of fasting serum ApoE and other lipid parameters, as well as common ApoE genotypes, was performed in all subjects. Results: HD patients had a significantly lower prevalence of the 4 allele and greater levels of ApoE compared with the control population. ApoE2 allele carriers had significantly lower levels of ApoB and serum total, low-density lipoprotein, and non‐ high-density lipoprotein cholesterol, as well as increased ApoE levels. When ApoE levels were included in analysis, ApoE levels themselves were proven to be important determinants of serum lipid levels, whereas the effect of ApoE polymorphism became more pronounced. The combination of these 2 factors explains a much greater percentage of the variation in the studied parameters than each factor alone. Conclusion: For the first time, our study provides data to support that ApoE concentration in combination with the ApoE polymorphism significantly influences serum lipid parameters in HD patients. Am J Kidney Dis 44:300-308. © 2004 by the National Kidney Foundation, Inc.

Thyroid disorders are known to influence lipid metabolism and are common in dyslipidemic patients. Overt and subclinical hypothyroidism have an adverse effect on the serum lipid profile that may predispose to the development of atherosclerotic disease. Although thyroid substitution therapy is beneficial for patients with overt hypothyroidism, the question of whether subclinical hypothyroidism must be treated remains unanswered. The association between thyroid autoimmunity and lipoprotein (a) levels is controversial. Hyperthyroidism may be the underlying cause for acquired hypocholesterolemia or unexpected improvement of the lipid profile of a previously hyperlipidemic patient.

OBJECTIVE: Hyperuricaemia is associated with indapamide administration. In contrast, micronised fenofibrate can significantly decrease serum uric acid levels. However, there are no data on the effect of combination therapy of indapamide with micronised fenofibrate on uric acid metabolism. METHODS: We studied 20 non-diabetic hypertensive patients with mixed dyslipidaemia in whom serum metabolic parameters, including uric acid levels in serum and urine, were measured before and after eight weeks of indapamide administration (2.5 mg once daily). This study was continued for a further eight weeks, when the indapamide was combined with micronised fenofibrate (200 mg once daily). RESULTS: Indapamide significantly decreased mean systolic and diastolic blood pressure (BP) from 153 +/- 9/97 +/- 8 mmHg to 138 +/- 8/93 +/- 4 mmHg (p< 0.05 for both comparisons). A significant increase in serum uric acid levels occurred after indapamide administration (from a mean value of 5.6 +/- 1.3 mg/dl (0.33 +/- 0.07 mmol/l) to 6.4 +/- 1.1 mg/dl (0.38 +/- 0.06 mmol/l), p < 0.01]. This effect was associated with a decrease in the fractional excretion of uric acid (from a mean value of 9.5 +/- 5% to 7 +/- 5.5%, p < 0.05). The addition of micronised fenofibrate significantly decreased plasma fibrinogen levels as well as total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB) and triglycerides, and increased high-density lipoprotein cholesterol and ApoA, levels. Fenofibrate administration was followed by a significant decrease in serum uric acid levels to 4.7 +/- 1.2 mg/dl (0.28 +/- 0.07 mmol/l), p < 0.01, owing to a substantial increase in fractional urate excretion to 11 +/- 3%, p < 0.01. CONCLUSION: The addition of micronised fenofibrate can correct the hyperuricaemic effect of indapamide administration. Current Medical Research and Opinion

OBJECTIVE: To report a case of possible cefotaxime-induced Stevens–Johnson syndrome (SJS). CASE SUMMARY: A 72-year-old woman with an upper urinary tract infection developed erosions and blisters on the skin and the mucous membranes, as well as fever and prostration, soon after the administration of cefotaxime. This presentation is consistent with the features of SJS. Resolution of the clinical manifestations was observed after discontinuation of the drug; all other drugs, infections, or immunologic disorders that could have caused this syndrome were carefully excluded. An objective causality assessment revealed that SJS was possibly associated with the use of cefotaxime. DISCUSSION: Although cephalosporins have been associated with an increased risk for SJS and cefotaxime has been suspected of being associated with SJS in a previous case–control study, this is the first full report for cefotaxime-related SJS in the literature. An immunologically mediated reaction may be the underlying mechanism. CONCLUSIONS: Although cefotaxime administration seems to be the underlying cause of the SJS observed in our patient, establishment of a definite causal relationship requires additional cases and supportive data.

Migraine is a common and disabling neurological disorder. Studies have shown that patients with migraine (especially those with typical aura with migraine) have an unfavorable cardiovascular risk profile and an increased risk of early-onset (

Background: Statin therapy has been shown to significantly decrease vascular events and overall mortality in primary and secondary prevention trials. This review considers the pharmacology, non-lipid-lowering effects and clinical trial evidence of fluvastatin based on a survey of PubMed entries.Findings: Recent clinical data show that treatment with fluvastatin is associated with a variety of benefits in different high-risk populations along with a good safety profile. Fluvastatin exerts non-lipid lowering-associated pleiotropic effects in both clinical and experimental studies. Furthermore, an extended-release formulation of fluvastatin with a favourable pharmacokinetic profile is available.Conclusion: Treatment with fluvastatin offers a convenient, safe and evidence-based approach to managing dyslipidaemias and preventing vascular events.

The more atherogenic lipid profile seen in peritoneal dialysis (PD) patients cannot fully explain the increased incidence of atherosclerosis in this population. Oxidative modification of low-density lipoproteins (LDL) is considered to play a central role in the atherogenic process, whereas high-density lipoprotein (HDL) protects LDL from oxidation. On the other hand, it has been suggested that the LDL and HDL of PD patients are more resistant to oxidation than those of control subjects, while PD-HDL equally protects LDL from oxidation compared to control-HDL. Two HDL-associated enzymes have been shown to protect both LDL and HDL from oxidation: paraoxonase (PON1) and HDL-associated platelet-activating factor acetylhydrolase (HDL-PAF-AH). Furthermore, low PON1 activity and high total plasma PAF-AH concentration, which represents mainly the LDL-associated enzyme, have been shown to be independent risk factors for coronary artery events in the general population. However, there are limited data regarding possible alterations of these enzymes in PD patients. The aim of our study was to examine the possible alterations of PON1 and PAF-AH activities in patients undergoing PD.A cross-sectional study.A university medical center.56 PD patients of Caucasian origin and 86 matched controls were studied.In all subjects, serum PON1 activity toward paraoxon (paraoxonase) and phenylacetate (arylesterase), as well as total serum and HDL-PAF-AH activities were measured; PON1 genetic polymorphisms known to influence PON1 activity (Q192R and M55L) were determined.The PD patients exhibited significantly increased serum PON1 (paraoxonase) and PON1 (arylesterase) activities compared to controls, regardless of the PON1 polymorphisms or the levels of HDL cholesterol. Additionally, PD patients had significantly elevated activities of total serum PAF-AH and HDL-PAF-AH, independently of the levels of LDL or HDL cholesterol. The ratio of HDL-PAF-AH/ total PAF-AH, which has recently been suggested to be a potential marker of atherogenicity, was decreased in these patients compared to controls. Moreover, no difference in the prevalence of PON1 polymorphisms between PD patients and controls was found.The elevated activities of PON1 and HDL-PAF-AH could explain the increased resistance of PD-HDL to oxidation; the higher activity of total PAF-AH and the decreased HDL-PAF-AH/ total PAF-AH ratio could contribute to the increased incidence of atherosclerosis in these patients.

Background. There are conflicting results regarding the effect of apolipoprotein (ApoE) polymorphisms on the progression of a variety of renal diseases. However, there are no data on the possible effect of the ApoE alleles on serum creatinine levels and predicted glomerular filtration rate (GFR) in healthy subjects. Methods. 290 apparently healthy individuals were studied. ApoE genotyping was performed by the polymerase chain reaction; the Modification of Diet in Renal Disease equation (MDRD) predicted the GFR. Results. ApoE2 was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, as well as with higher levels of triglycerides in our population. Furthermore, the ApoE2 allele was associated with increased serum creatinine levels compared with both the E3 and E4 alleles (1.04±0.13 vs 0.92±0.13 vs 0.88± 0.11 mg/dl, respectively, P ¼ 0.0077), while the MDRD-predicted GFR was decreased in ApoE2 carriers compared with both E3 and E4 carriers (80.3±10.2 vs 88.1±9.6 vs 89.3±9.7 ml/min/1.73 m 2 , respectively, P ¼ 0.031). These observations remained significant statistically even if the effect of ApoE polymorphisms on age- and body-mass index-adjusted serum creatinine and MDRD-predicted GFR was separately analysed in both men and women. Although, ApoE4 carriers tended to exhibit lower levels of serum creatinine and higher values of predicted GFR compared with the E3 carries, these differences did not reach statistical significance. Conclusions. ApoE2 allele seems to be associated with increased serum creatinine levels and decreased MDRD-predicted GFR in healthy subjects.

Nephrol Dial Transplant

Apolipoprotein E (ApoE) is a major constituent of plasma lipoproteins with many biological actions of great significance. Beyond the known influence of ApoE polymorphisms on serum lipid profile, the pathogenesis of atherosclerosis, and the development of neurodegenerative disorders, ApoE also has a major role in the pathogenesis and progression of a variety of renal diseases, as well as in the atherosclerotic complications associated with them. Briefly, the polymorphisms of ApoE are major determinants of plasma lipid levels in uremic patients. They may affect the risk for cardiovascular disease in this population, predispose to the development of diabetic nephropathy, influence the severity of certain glomerulopathies, and regulate mesangial and glomerular functions locally in the kidney microenvironment. Finally, certain mutations of the ApoE gene are associated with a recently described nephropathy, termed lipoprotein glomerulopathy. Am J Kidney Dis

Nonoliguric renal insufficiency is a well-known nephrotoxic consequence of aminoglycosides, although reversible tubular damage in the absence of any change in the renal function has been occasionally found. Reported herein are 2 representative cases of a reversible tubular damage due to prolonged aminoglycoside administration: a patient with a Fanconi-like syndrome of proximal tubular dysfunction and a patient with a syndrome of hypokalemic metabolic alkalosis associated with hypomagnesemia.

AIMS AND METHODS: Hypouricaemia is not frequently encountered in alcoholic patients. Described herein is the case of a 69-year-old alcoholic patient. RESULTS: The patient presented with severe hypouricaemia (serum uric acid 95.2 micro mol/l) due to renal urate wasting associated with a cluster of other metabolic abnormalities in the context of a reversible generalized dysfunction of the proximal tubules that mimicked Fanconi syndrome. CONCLUSIONS: The underlying mechanisms of this rare presentation are discussed. Alcohol Alcohol

Journal of Hypertension