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Objectives: In the general population aortic stiffening assessed by carotid femoral pulse wave velocity (cf-PWV) is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. Our study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to brain microcirculation changes reflected by impaired cognitive function. Methods: Among 244 patients, finally 44 with CKD stage 1; 47 stage 2; 25 stage 3; 35 stage 4, with mean age 58.4 years (64.5% males), were enrolled in a cross-sectional study. Cognitive impairment measured by Mini Mental State Examination (MMSE), Clock – drawing test (Clock-test), and Instrumental Activity of Daily Living (IADL) was considered as primary outcome. We directly measured brachial, aortic, systolic blood pressure, pulse pressure, mean blood pressure and cf-PWV. Results: Our patients revealed a significant linear deterioration in all the domains of cognitive function according to CKD stages, assessed by MMSE, Clock-test and IADL. The risk of cognitive dysfunction increased significantly from CKD stage 3 to 4 (p

We present a case which emphasizes the importance of performing a kidney biopsy in each case of acute kidney injury (AKI) of unknown etiology. The unexpected histological diagnosis of granulomatous interstitial nephritis (GIN) is a rare cause of AKI. The main causes of GIN include drugs (NSAIDs, antibiotics), sarcoidosis, and infections (mycobacterial and fungal). In our case, a 68-year-old woman was admitted with AKI, absence of symptoms and unremarkable history, apart from coronary heart disease. Renal biopsy was performed, since history as well as clinical and laboratory data could not define a cause of AKI. A more meticulous clinical and laboratory investigation followed the histological diagnosis in order to rule out sarcoidosis, vasculitis or any other known causes of GIN. Finally the diagnosis was characterized as AKI due to idiopathic GIN. The patient responded well to corticosteroids.

Alcoholic patients commonly develop a variety of acid-base and electrolyte disturbances. The aim of this review is to describe the most commonly encountered abnormalities and their significant role in the patients’ morbidity and mortality. Physicians should be aware of these clinically important disturbances caused by alcohol abuse and their underlying pathophysiological mechanisms involved for their appropriate management. Alcoholic Keto Acidosis (AKA) is a medical emergency is more common than previously thought and is characterized by an increased anion gap metabolic acidosis. However, in AKA mixed acid-base disorders are commonly observed. Alcoholic patients also exhibit severe electrolyte derangements. Multifactorial origin hypomagnesaemia is the most common electrolyte abnormality observed. Hypocalcaemia is also a frequent electrolyte disturbance and is commonly associated with hypomagnesaemia. Hypokalemia is occasionally encountered in these patients, while multifactorial origin hypophosphatemia is the second common electrolyte abnormality found. Hyponatremia is also a common electrolyte derangement and may occur subsequent to several mechanisms mediated by alcohol toxicity. Of special interest is the so-called beer potomania syndrome in poor nourished patients who consume a large amount of water with beer leading to hyponatremia. Chronic alcoholism and its comorbidities are a predisposing factor for the development of Central Pontine Myelinolisis during rapid correction of hyponatremia. Occasionally, alcoholic patients could be presented with alcohol-related intoxication mainly due to simultaneous methanol or ethylene glycol intoxication. In these cases the determination of the serum osmolal gap is used as a screening tool to identify potential toxins.

Background/Aim: We investigated the potential role of the membrane type on phosphate kinetics. Methods: Six patients on dialysis (HD) were studied using modified cellulose (Hemophan), ethylene-vinyl alcohol (EVAL) and polyacrylonitrile (PAN). Total (TPR), extracellular (EPR) and intracellular (IPR) phosphate removal and effective dialyzer phosphate clearance (Kd) were determined by the DDQ method. The intercompartment transfer coefficient (KC) was calculated using a mathematical model. Erythrocyte phosphate (PERY) and 2,3-biphosphoglycerate (2,3-BPG) concentrations were determined before and after HD. Results: TPR was 1.2 ± 0.4, 1.10 ± 0.4 and 1.09 ± 0.4 g with Hemophan, EVAL and PAN, respectively (p = n.s.). EPR and IPR were independent of membrane type. There was no difference in KC between membranes (321 ± 70, 338 ± 92 and 341 ± 83 ml/min, respectively). The PERY and 2,3-BPG remained statistically insignificant for all membranes. Conclusion: Our results show that the type of membrane does not influence the kinetics of phosphate during dialysis, neither in the transfer from plasma to dialysate nor from the intra- to the extracellular compartment.

Background Vestibular neuronitis (VN) is a relatively common condition characterized by the acute onset of vertigo, nausea and vomiting, in the absence of auditory or central nervous system involvement. The exact aetiology (inflammatory, viral or vascular?) remains obscure. Lipoprotein (a) [Lp(a)] is an atherogenic particle. Its serum levels are mainly genetically determined and vary widely between individuals. Whether Lp(a) is consistently a positive acute-phase reactant is controversial. Purpose We evaluated the alterations in lipidaemic parameters and serum biological markers (including acute-phase reactants) in adult patients presenting acutely with VN. Subjects and methods A total of 34 consecutive VN patients (24 men and 11 women) and 37 apparently healthy controls (25 men and 12 women) were studied. Laboratory evaluation was performed during the acute episode and 6 months later (stable state). Results Serum Lp(a) concentrations were significantly lower at the time of presentation (median value 6·4 vs. 16·4 mg dL−1 in the stable state, P

The platelet-activating factor acetylhydrolase activity associated with high density lipoprotein (HDL-PAF-AH) may substantially contribute to the antioxidant, anti-inflammatory, and overall antiatherogenic effects of HDL. Two enzymes associated with HDL express PAF-AH catalytic activity, PAF-AH itself and paraoxonase-1 (PON1). The relative contribution of these enzymes in the expression of PAF-AH activity on HDL remains to be established. We investigated whether the PON1 polymorphisms (M55L and Q192R) or the PAF-AH polymorphism V379A could affect the PAF-AH activity associated with HDL in both normolipidemic and dyslipidemic (type IIA and IIB) populations. We show for the first time that the PON1 M55L polymorphism significantly affects the HDL-PAF-AH activity in all studied groups, the PON1 L55L individuals having lower enzyme activity compared to those having 1 M and 2 M alleles. No differences in the HDL content concerning the major apolipoprotein and lipid constituents were observed between individuals carrying the PON1 L55L and those with the M55M polymorphism. Our results provide evidence that PON1 significantly contributes to the pool of HDL-PAF-AH activity in human plasma, and suggest that the low PAF-AH activity in HDL carrying the PON1 L alloenzyme may be an important factor contributing to the low efficiency of this HDL in protecting LDL against lipid peroxidation.

Objective It has been suggested that aliskiren has a longhalf-life and maintains a blood pressure (BP)-loweringeffect following a missed dose. We tested the hypothesisthat every otherday (eod) administration of aliskiren has thesame effects as the once daily (od) dosing in albuminurichypertensive patients.Methods Fifteen hypertensive patients, after a 4-weekwash-out period on clonidine, received 300mg aliskiren odas the sole treatment. In patients who remained out oftarget, other nonrenin–angiotensin system blockers wereadded. Patients who completed a 24-week (w24) treatmentperiod were switched to eod administration of aliskiren foran additional period of 24 weeks (w48).Results Thirteenpatients completed the full study protocol.The mean office BP was reduced at the end of w24(−9/3mmHg), a reduction that continued to be observedat w48 (−11/1mmHg). At the end of the study, the 48hambulatory BP monitoring was divided into two 24hperiods. The mean 24h systolic BP, and the mean daytimesystolic and diastolic BP were significantly lower (P

The first renal disease described from Hippocrates is nephrolithiasis with renal colic, which is the pain of stone passage and is also a common renal problem with easily recognizable characteristics. There has been much written about dietary factors, which have unequivocally been proved to play an important role in the formation of kidney stones. In this regard, it is of interest that the contribution of factors such as stressful events, life style, or occupation in the formation of kidney stones has not been well studied. This review examines the clinical evidence of the stressful events and other environmental factors affecting the occurrence of kidney stones.

Purpose: This study was undertaken to determine individual renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and Methods: The authors initially examined (study t1) 25 patients with ADPKD (12 female, 13 male; ages 18 to 68 years). The serum creatinine concentration and glomerular filtration rate, measured by Tc-99m DTPA, were 1.5 ± 0.56 mg/dl and 65.7 ± 31 ml.minute -1 .1.73 m 2 , respectively. Thirteen patients had a follow-up study (t2) 2 years after their initial evaluations. Individual renal function was assessed on Tc-99m DMSA renal scans. Results: The mean (± SD) difference between left kidney DMSA (DMSA-L) and right kidney DMSA (DMSA-R) was 7.04 % ± 16.48%. In 20 patients (80%), the left kidney had a lower percentage contribution to the total renal function compared with the right kidney. When the results of the two studies were compared, deterioration in renal function was noted. In the t1 study, the mean serum creatinine concentration and glomerular filtration rate were 1.7 mg/dl and 67.02 ml.minute -1 .1.73 m 2 respectively, and in the t2 study these values were 2.01 mg/dl and 57.15 ml.minute -1 .1.73 m 2 , respectively. No difference, however, was found in individual renal function in the two studies. Conclusions: In patients with ADPKD, the percentage contribution of each kidney to total renal function is not equal and remains stable during the progression of renal failure.

Normotensive patients with microvascular angina exhibit increased diastolic blood pressure and blood pressure loads during daily activities and decreased diurnal variation of systolic blood pressure, compared with age- and sex-matched normotensive controls. The abnormal blood pressure profile could play a role in the pathogenesis of microvascular angina.

Introduction: Blockade of the renin-angiotensin system (RAS) is a critical approach to the management of hypertension, especially in proteinuric patients. It is well proven that the direct renin inhibitor aliskiren shows comparable clinical efficacy to the angiotensin II receptor blocker valsartan on blood pressure control and albuminuria. However, there is only limited data on the hand-to-hand effectiveness of these two RAS blockers in improving arterial stiffness. We tested whether aliskiren or valsartan would improve arterial stiffness in hypertensive patients with albuminuria who are already on antihypertensive therapy. Material and methods: Thirty-four patients with hypertension and albuminuria < 1 g, after a wash-out period of three weeks, were randomized to aliskiren or valsartan in a 24-week randomized parallel-group study. Results: A nonsignificant difference in blood pressure was seen between the two treatment groups. Albuminuria was significantly reduced in both groups (56% for the aliskiren group, p < 0.05, and 38% for the valsartan group, p < 0.05). Only valsartan but not aliskiren significantly reduced carotid-femoral pulse wave velocity (–1.1 ± 0.8 m/s ( p = 0.02) for valsartan and +0.1 ± 0.7 m/s (ns) for aliskiren). Conclusion: The results of our study showed that valsartan improves arterial stiffness to a significantly greater extent than aliskiren, despite a similar antihypertensive and antiproteinuric effect.

In patients with kidney dysfunction hyperphosphatemia is more evident as renal failure progresses. It is related to increased FGF-23 levels, secondary hyperparathyroidism, and accelerated progressive vascular calcification. In CKD patients advanced coronary artery calcification is strongly associated with future cardiovascular events, cardiovascular death, and all-cause mortality. Apart from the above, phosphate per se is suspected as a causal risk factor for CKD progression. Keeping serum phosphorus within the target values are linked to improvement in life expectancy. A low phosphate diet, an efficient dialysis removal of phosphate load, and the administration of phosphate binders are the main recommended steps to control hyperphosphatemia. Calcium-based phosphate binders can lead to a positive calcium balance, hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and coronary artery and aortic calcification. On the other hand Sevelamer hydrochloride and Lanthanum carbonate has been shown to be effective, safe and useful therapeutic tools for hyperphosphatemia. When prescribe pharmacological agents, one must take into account the large increase in health-care expenditure and the choice of phosphate binder should be individualized.

The sympathetic nervous system has a profound effect on the kidney's ability to regulate blood pressure and, vice versa, the kidney has an important effect on the overall sympathetic tone. As a result, renal sympathetic nerves are crucial for initiation and the maintenance of systemic hypertension. It is fairly well established that efferent renal sympathetic nerve activity contributes significantly to homeostatic regulation of renal blood flow, glomerular filtration rate, renal tubular epithelial cell solute and water transport, and hormonal release. The afferent nerves from the kidney activate central sympathetic nervous system activity, participate in a reflex control system via reno-renal reflexes and are involved in cardiovascular regulation and pathogenesis of hypertension in CKD patients whose kidney ischemia also seems to play a key role. Sympathetic nerve modulation in hypertension had been considered as a therapeutic strategy long before the advent of modern pharmacological therapies. Renal sympathetic denervation with a percutaneous, catheter-based approach results in significant and sustained blood pressure reduction in patients with resistant hypertension. This procedure has also beneficial effects in multiple organs function. However, renal physiology and the long term observed benefits with the use of renal sympathetic denervation have not completely elucidated.

Cognitive dysfunction (CO/DY) in chronic kidney disease (CKD) patients has long been recognized. Hypertension is also associated with CO/DY. The study describes associated factors with CO/DY in CKD patients compared to hypertensive subjects.Ninety-six hypertensive subjects without CKD, 19 patients with CKD stages I-II, 33 with CKD III, 42 with CKD stage IV, 33 on hemodialysis (HD) and 33 on peritoneal dialysis (PD) were included in our study. Cognitive impairment measured by MMSE, clock-drawing test and IADL was considered as primary outcome.In all groups tested, age was significantly associated with CO/DY by almost all cognitive function tests. Among CKD patients, CKD stage and DM were significantly associated with CO/DY by all three cognitive function tests. PTH levels were also associated with CO/DY by MMSE and clock-drawing tests. In hypertensives, pulse pressure (PP) was associated with CO/DY by clock-drawing and IADL tests, while those receiving CCBs as monotherapy were less likely to have CO/DY by IADL test. For dialysis patients, DM was significantly related to CO/DY by MMSE and clock-drawing tests. In the same group of patients Hb11 g/dl was significantly correlated with CO/DY by MMSE, dialysis modality and Kt/V1.2 by IADL test. PD patients were less likely to present with CO/DY by clock-drawing test.In every CKD stage, the risk of CO/DY increased significantly. Low Hb levels (Hb11 g/dl) and increased serum PTH levels were associated with CO/DY while DM plays also a significant role in cognitive function deterioration. Among hypertensive subjects, those with PP ≤60 mmHg or receiving CCBs showed a better executive function.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality not only amongst the general population, but also in patients with chronic kidney disease (CKD). Persons with CKD are much more likely to die of CVD than to experience kidney failure. Clinical trials have demonstrated that statins are gaining widespread acceptance as a principal therapy for the primary and secondary prevention of atherosclerosis and CVD. In CKD patients the role of statins in primary prevention of CVD remains to be clarified. The absolute benefit of treatment with a statin seems to be greater among nondialysis-dependent-CKD patients. Studies in end-stage renal disease patients on dialysis did not confirm these results. Recently, however, the Study of Heart and Renal Protection (SHARP) has suggested that statins with ezetimibe may be beneficial even in dialysis patients. Clinical studies with statins on proteinuria reduction and renal disease progression have yielded conflicting results. Some studies have shown a prominent reduction in proteinuria, while other studies have shown that statins had no effect or may cause proteinuria at high doses. This review examines the clinical evidence of the observed benefits of kidney function with the use of this drug category in CKD patients.

Background Coping with the stresses of chronic disease is considered as a key factor in the perceived impairment of health related quality of life (HRQL). Little is known though about these associations in chronic kidney disease (CKD). The present study aimed to investigate the relationship of defensive coping and HRQL among patients in different CKD stages, after adjusting for psychological distress, sociodemographic and disease-related variables. Methods The sample consisted of 98 CKD patients, attending a university nephrology department. Seventy-nine (79) pre-dialysis patients of disease stages 3 to 4 and 19 dialysis patients were included. HRQL was assessed by the 36-item Short-Form health survey (SF-36), defensive coping by the Rationality/Emotional Defensiveness (R/ED) scale of the Lifestyle Defense Mechanism Inventory (LDMI) and psychological distress by the depression and anxiety scales of the revised Hopkins Symptom CheckList (SCL-90-R). Regression analyses were carried out to examine the association between SF-36 dimensions and defensive coping style. Results Patients on dialysis had worse scores on SF-36 scales measuring physical aspects of HRQL. In the fully adjusted analysis, a higher defensive coping score was significantly associated with a lower score on the mental component summary (MCS) scale of the SF-36 (worse mental health). In contrast, a higher defensive score showed a small positive association with the physical component summary (PCS) scale of the SF-36 (better health), but this was marginally significant. Conclusions The results provided evidence that emotional defensiveness as a coping style tends to differentially affect the mental and the physical component of HRQL in CKD. Clinicians should be aware of the effects of long-term denial and could examine the possibility of screening for defensive coping and depression in recently diagnosed CKD patients with the aim to improve both physical and mental health.

In the early 1960s, microalbuminuria was noted as a predictor of nephropathy and higher cardiovascular risk in patients with type 1 diabetes mellitus. Over the past four decades, however, the epidemiological evidence has become far stronger, implicating it as a cardiovascular risk marker than a risk factor associated with nephropathy. Microalbuminuria is also a marker of endothelial dysfunction, increased vascular leakage of albumin, and a marker of inflammation. In this context, it is also a marker for risk of developing hypertension and making it more difficult to control blood pressure if hypertension is already present. This chapter reviews the role of microalbuminuria as a marker of cardiovascular risk and nephropathy identifier. It also reviews the association of microalbuminuria with other cardiovascular risk factors and the pathophysiological association between microalbuminuria and vascular damage. In addition, the chapter reviews trial data that evaluated microalbuminuria for its prognostic significance on cardiovascular outcomes, as well as existing therapeutic interventions for reducing urinary albumin excretion in patients with high cardiovascular risk.

Blood pressure (BP) in the prehypertensive range is associated with an increased risk for cardiovascular (CV) disease. Patients with co-morbidities are at greater risk for chronic kidney disease (CKD) development in the presence of prehypertension. Lifestyle changes can alter the natural history of prehypertension; however, long-term adherence is rare and thus, their impact on outcomes is limited. Pharmacological therapy in patients with prehypertension and demonstrable target organ damage with blockers of the renin-angiotensin system has demonstrated benefits on markers of CKD outcomes such as microalbuminuria. There are no data, however, on 'hard end points' such as doubling of creatinine or need for renal replacement therapy. In patients with diabetes, monitoring changes in albuminuria, along with assessment of BP in the prehypertensive range, is important to optimize early management and impact the attenuation of CKD progression. Data from natural history studies in patients with type 1 diabetes indicate that increases within the microalbuminuria range antedate increases in BP within the prehypertensive range. Even within the microalbuminuria range, however, systolic BP increases above 125 mm Hg are predictive of nephropathy. Thus, nephrologists need to ensure that their colleagues appreciate the importance of not only early BP intervention but also of monitoring albuminuria changes in order to have maximal impact on CKD prevention.

Cardiovascular (CV) disease is the leading cause of morbidity and mortality among people with chronic kidney disease (CKD). CKD has increased over the past decade to become a worldwide public health problem. The definition of a biomarker is a characteristic objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic response to a therapeutic intervention. Thus, biomarkers of kidney function would include serum creatinine and more recently estimated glomerular filtration rate (eGFR). These biomarkers and microalbuminuria, potential biomarker, predict CV events and mortality. Recent analyses of cross-sectional data indicate that eGFR is a much stronger predictor of CV events than is microalbuminuria. While microalbuminuria indicates endothelial dysfunction and is associated with increased risk for CV events, its level is related more to the level of blood pressure and glycemic control than directly to the pathophysiology of atherosclerosis. Hence, microalbuminuria could be viewed as a biomarker but not a risk factor for CV risk since, risk factors must be an integral part of the disease pathophysiology. Conversely, while microalbuminuria is not of prognostic value to predict CKD outcomes, increases over time into the albuminuria range, >200 mg/day, clearly indicate presence of kidney disease and are associated with a more rapid decline in kidney function. Thus, concomitant evaluation of both biomarkers eGFR and albuminuria is recommended to assess kidney function and CV risk thoroughly.

Impaired kidney function increases the risk of cardiovascular morbidity and mortality. Coexistence of hypertension and type 2 diabetes increases the risk of kidney damage, hypertension being an independent risk factor for kidney disease progression. Angiotensin II, through its inflammatory, proliferative, and thrombotic effects, adversely affects renal perfusion and increases oxidative stress, thus playing a pivotal role in kidney disease progression. Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors improve markers of kidney disease and slow kidney disease progression in diabetic and nondiabetic patients; this kidney protection may be in addition to their antihypertensive activity in those with advanced proteinuric nephropathy. Key beneficial effects of ARBs and ACE inhibitors throughout the kidney disease continuum are primarily explained by blood pressure lowering effects and partially by their direct blockade of angiotensin II. Recent studies have shown that telmisartan, an ARB with high lipophilicity and the longest half-life compared with other ARBs, provides benefits on markers of cardiovascular risk, that is, microalbuminuria and slowing of early-stage nephropathy.

Most guidelines in the Western world uniformly recommend two blood pressure (BP) goals

Hypertension is an important cardiovascular (CV) risk factor in patients with diabetes mellitus. In this setting, tight control of blood pressure (BP) significantly reduces CV morbidity and mortality. In the UK Prospective Diabetes Study, a 10 mmHg reduction in systolic blood pressure (SBP) was superior to a 0.7% decrease in glycosylated haemoglobin A1c (HbA1c) as far as reducing morbidity and mortality was concerned. In the Hypertension Optimal Treatment study, the risk of CV events decreased by 51% among patients with type 2 diabetes randomized to the lower BP level. Based on these findings, contemporary treatment guidelines recommend a target SBP/diastolic blood pressure of

Purpose of review Current therapies proven to slow the progression of diabetic nephropathy include blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Given our better understanding of the pathophysiology of diabetic nephropathy, newer therapies to treat this condition are slowly emerging. Recent findings Animal studies and a single clinical trial demonstrate efficacy of the renin inhibitor, aliskiren, to decrease a marker of nephropathy progression, that is albuminuria. On the basis of animal study results, pyridoxamine, an inhibitor of advanced glycation and ruboxistaurin, a protein kinase C inhibitor showed promise as new agent to treat nephropathy. The clinical trial results were less than gratifying, however. Sulodexide, a glycosaminoglycan, works to reduce proteinuria presumably by restoring the already reduced glycoproteins present in the glomerular basement membrane. Like other agents, sulodexide also looked promising in animal studies, but failed to demonstrate albuminuria reduction in a large multicentre clinical trial (SUN-Micro-Trial). Summary This review summarizes newer therapies for slowing the progression of diabetic nephropathy. Aliskiren shows promise from small clinical studies, but we await the results of the multicentre, international ALTITUDE trial in about 2012. On the basis of the results of trials only, pyridoxamine may have a chance at further evaluation, but that is also unclear.

The incidence of type 2 diabetes continues to increase in the western world over the past decade. Consequently, complications of this disease have reached crisis proportions. In addition to the classical oral hypoglycaemic agents, i.e. sulfonylureas, newer classes have emerged that work by different mechanisms such as insulin sensitizers. One such class are the thiazolidinediones (rosiglitazone and pioglitazone). These agents act as ligands for the gamma peroxisome proliferator-activated receptors (PPARs) and result in a lower glucose. Data from animal and human studies supports the concept that thiazolidinediones exert several other beneficial metabolic and vascular effects, in addition to glycaemic control, including improvement in lipid profile, blood pressure lowering, redistribution of body fat away from the central compartment, anti-inflammatory effects such as reduction in hs-CRP and microalbuminuria as well as subclinical vascular inflammation, improvement in endothelial function. Conversely, thiazolidinediones have well-established side effects, most important of which are fluid retention leading to weight gain and development of heart failure as well as an increased incidence of bone fractures. Moreover, evidence from clinical trials suggests that these agents do not reduce cardiovascular risk. This article discusses the pleiotropic effects of thiazolidinediones focusing on clinical cardiovascular outcomes as well as other potential therapeutic uses in the context of their side-effect profile.

Given the high prevalence of cardiovascular disease in people with chronic kidney disease (CKD) and the clear benefits of mortality reduction observed for most β−blockers in clinical trials, they are relatively underused in CKD patients [1,2]. The rationale for use of β-blockers in patients with CKD is reviewed in detail elsewhere [2,3] but is summarized in this editorial. Alterations in β- and α-receptor responsiveness are associated with sympathetic over-activity in CKD. This increased sympathetic activity is involved in the genesis of hypertension, and contributes to cardiac complications seen in CKD [2,3]. The contribution of the sympathetic nervous system to nephropathy progression is documented in sub-totally nephrectomized rats where non-hypotensive doses of β-blockers ameliorate development of glomerulosclerosis and cardiac injury [4]. In men, sympathetic over-activity, as assessed by sural nerve microneurography, was present in patients on haemodialysis [5], stage 4 nephropathy [6] and in early stage 2 nephropathy among patients with polycystic kidney disease [7]. The role of the damaged kidney in causing sympathetic over-activity is illustrated by normalization of sympathetic over-activity in haemodialysis patients following bilateral nephrectomy [5] and in renal allograft recipients when their shrunken native kidneys are removed [8]. The most common cause of death in stage 3 and higher CKD results from complications of cardiovascular disease. This may be due, in part, to inadequate treatment of blood pressure, where blood pressure goals were not attained and agents known to reduce mortality secondary to cardiovascular causes, i.e. aspirin, ACE inhibitors and β-blockers were not used [9]. In a separate study, β-blockers were used in fewer than 30% of haemodialysis patients [10]. This is surprising, since β-blockers are well-established, evidence-based therapy for reducing cardiovascular risk in hypertension associated with diabetes and after myocardial infarction [11,12]. Observational studies support definite survival benefits derived from β-blocker use in patients with advanced CKD [13,14]. Furthermore, a prospective

Background: Chronic kidney disease (CKD) is a worldwide public health problem. Systolic blood pressure as an associated feature of CKD has not been fully explored in community volunteer and nationally representative samples of the US population. Methods: This cross-sectional analysis evaluated hypertension and early-stage CKD in participants in the Kidney Early Evaluation Program (KEEP), a voluntary community-based health screening program administered by the National Kidney Foundation, and the National Health and Nutrition Examination Survey (NHANES) data to assess similarities and differences between these populations. Participants in both databases were 18 years or older. Results: The KEEP database included 88,559 participants and the NHANES included 20,095. Hypertension prevalence was greater in KEEP (69.6%) than NHANES (38.1%; P 0.001). Compared with NHANES participants, KEEP participants had greater rates of obesity (79.5% versus 51.5%; P 0.001) and diabetes (28.0% versus 8.9%; P 0.001). In participants with diabetes, KEEP had slightly greater rates of prevalent hypertension (88.5% versus 85.7%; P 0.03). In participants with hypertension, CKD stages 3 and 4 were more prevalent in KEEP than NHANES (79.1% versus 69.3%; P 0.001). Rates of CKD stages 3 and 4 were greater in KEEP than NHANES for the following subgroups: African Americans (72.4% versus 57.4%; P 0.001), smokers (69.1% versus 55.6%; P 0.002), and participants with hypercholesterolemia (80.2% versus 71.9%; P 0.001). Conclusions: In the volunteer KEEP population, rates of hypertension and CKD were greater than in NHANES, most prominently in African Americans and participants with increased cardiovascular risk. Am J Kidney Dis 53(S4):S22-S31. © 2009 by the National Kidney Foundation, Inc.

Emerging scientific evidence suggests that increases in body iron represent a risk factor for the development of metabolic syndrome and diabetes. The aim of our study was to determine the body iron stores in patients with metabolic syndrome, and to evaluate the potential relationship of iron overload with specific features of the metabolic syndrome, such as fatty liver. A total of 490 individuals were enrolled. The diagnosis of metabolic syndrome was based on National Cholesterol Education Program-Adult Treatment Panel III (ATPIII) criteria. The metabolic syndrome group was consisted of 185 patients having three or more criteria, whereas individuals with less than three criteria constituted the control group. Metabolic syndrome patients displayed higher ferritin concentration as compared to control individuals. Ferritin levels were positively correlated with insulin concentration, as well as with Homeostasis Model Assessment (HOMA) index values. Multiple regression analysis revealed that ferritin was the most important independent determinant of insulin resistance indices. Patients with metabolic syndrome also exhibited increased concentrations of alanine aminotransferase and gamma-glutamyltranspeptidase compared to controls. Multiple regression analysis revealed that ferritin concentration was the most important determinant of gamma-glutamyltranspeptidase levels. Patients with the metabolic syndrome exhibit an increase in body iron stores as well as elevated concentrations of liver enzymes compared to the individuals who do not fulfill the criteria for the diagnosis of this syndrome. Our data support a direct role of increased body iron in the pathogenesis of insulin resistance, whereas iron overload may also contribute to the development of specific features of the metabolic syndrome, such as fatty liver. Metab Syndr Relat Disord

Objective. To evaluate the influence of clinical, biochemical and genetic markers on the response to antihypertensive treatment in patients with essential hypertension and the metabolic syndrome (MetS). Methods. Measurements of anthropometric indices, blood pressure (BP), and metabolic parameters were obtained from the medical records of 132 (77 women) newly diagnosed, untreated hypertensive patients. Renin-angiotensin-aldosterone system (RAAS) genes polymorphisms (including ACE I/D, angiotensinogen M235T, angiotensin II type 1 receptor [AT1-receptor] A1166C) were determined. Response to treatment was defined as BP less than 140/90 mmHg. Results. Patients with MetS (n=60) had higher systolic BP and pulse pressure and a more atherogenic lipid profile than patients without MetS.The frequencies of the ACE and the AT1-receptor gene polymorphisms were similar between patients with and without MetS. Response to treatment was positively associated with pulse pressure, and the presence of the C allele as well as the AC genotype of the AT1-receptor gene and inversely with age after adjustment for confounding factors. Conclusions. RAAS genes distribution does not differ between hypertensive patients with and without the MetS. Higher baseline pulse pressure levels, the presence of the C allele and/or the AC genotype may be in favour of a better response to structured antihypertensive treatment in patients with MetS. However, these findings need to be evaluated in future studies.

AIM: To access the association between albuminuria levels and arterial stiffness in non-diabetic patients with hypertension and chronic kidney disease (CKD) stages 1-2, treated with renin angiotensin blockade agents plus other hypertensive drugs when needed. METHODS: One hundred fifteen patients [median age 52 years (68% males)] were consequently enrolled in the study. For each patient, we recorded gender, age, body mass index (BMI), peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure, peripheral pulse pressure, central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), central pulse pressure (cPP), hematocrit, hemoglobin, hsCRP, total cholesterol triglycerides, high-density lipoprotein-C, low-density lipoprotein-C, calcium, phosphorus, parathormone, and albumin, as well as 24 h urine albumin excretion. According to 24-h urine albumin collection, patients were then classified as those with moderately increased albuminuria (formerly called macroalbuminuria) (≤ 300 mg/d) and those with severely increased albuminuria (formerly called macroaluminuria (> 300 mg/d). We considered aortic stiffness (AS) indices [carotid femoral pulse wave velocity (PWVc-f) and augmentation index (AIx)] as primary outcomes of the study. We explored potential correlations between severely increased albuminuria and AS indices using a multiple linear regression model. RESULTS: Fifty-eight patients were included in the moderately increased albuminuria group and 57 in the severely increased albuminuria. Blood pressure measurements of the study population were 138 ± 14/82 ± 1.3 mmHg (systolic/diastolic). There were no significant differences in age, sex, and BP measurements between the two groups. Patients with severely increased albuminuria had higher PWV and AIx than patients with moderately increased albuminuria (P < 0.02, P < 0.004, respectively). In addition these patients exhibited higher BMI (P < 0.03), hsCRP (P < 0.001), and fibrinogen levels (P < 0.02) compared to patients with moderately increased albuminuria. In multivariate linear regression analysis, severely increased albuminuria (β = 1.038, P < 0.010) pSBP (β = 0.028, P < 0.034) and Ht (β = 0.171, P = 0.001) remained independent determinants of the increased PWVc-f. Similarly, severely increased albuminuria (β = 4.385, P < 0.012), cSBP (β = 0.242, P < 0.001), cPP (β = 0.147, P < 0.01) and Ht levels (β = 0.591, P < 0.013) remained independent determinants of increased AIx. CONCLUSION: These findings demonstrate an independent association between AS indices and severely increased albuminuria in non-diabetic, hypertensive patients with CKD stages 1-2 treated with renin angiotensin aldosterone system blockers.

BACKGROUND: Despite important recent advances in the understanding of the consequences of metabolic syndrome, its pathophysiological characteristics remain unclear. It has been proposed that disturbances in phosphate metabolism may contribute to the development of this constellation of cardiovascular risk factors. However, there have been insufficient clinical data supporting this hypothesis to date. The aim of our study is to confirm the presence of hypophosphatemia in patients with metabolic syndrome, as well as investigate mechanisms that may underlie the disturbances in phosphate metabolism in this patient group. METHODS: Two hundred fifty-five individuals were enrolled. The diagnosis of metabolic syndrome was based on Adult Treatment Panel III guidelines. Subjects with fewer than 3 criteria served as controls. RESULTS: Patients with metabolic syndrome showed significantly lower phosphate and magnesium levels compared with controls. Because fractional excretion of phosphate was similar in both groups, we assume that hypophosphatemia in patients with metabolic syndrome can be attributed to decreased dietary intake, as well as internal redistribution of this element. Lower magnesium values in the patient group may result from the same mechanisms as lower phosphate levels. In addition, hyperinsulinemia-induced renal magnesium wasting also may be a contributory factor. CONCLUSION: Patients with metabolic syndrome show significantly lower phosphate and magnesium levels compared with healthy individuals. The clinical significance of these disturbances, as well as their importance as targets for preventive or therapeutic interventions, remains to be established. Am J Kidney Dis

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.

Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P

Purpose: Although there are few data on the underlying mechanisms of primary open-angle glaucoma (POAG), it has been suggested that metabolic diseases may play a role in the evolution of the disease. We carried out the present study to investigate the involvement of metabolic disturbances in POAG pathogenesis. Material/methods: Serum metabolic parameters were evaluated in 49 POAG patients without a known history of diabetes mellitus and 72 age and sex matched individuals without glaucoma (control group). Results: Among the metabolic parameters examined, only fasting serum glucose and uric acid levels were found significantly higher in patients with glaucoma compared to the control population (117±17 mg/dl vs 105±11 mg/dl, p=0.05 and 6.2±1.9 mg/dl vs 5±1.2 mg/dl, p=0.006, respectively). Additionally, a considerably greater proportion of patients had disturbances of the carbohydrate metabolism and hyperuricemia. Conclusion: We conclude that disturbances of carbohydrate and uric acid metabolism could play a role in glaucoma damage and pathogenesis.

OBJECTIVE: A number of adverse metabolic effects are associated with indapamide administration, including an increase in serum uric acid levels. It has been reported that losartan can significantly decrease serum uric acid levels. However, there are no data on the effects of combination therapy of losartan with indapamide on uric acid metabolism. METHODS: We studied 20 hypertensive patients in whom serum metabolic parameters, including uric acid levels in serum and urine, were studied before and after eight weeks of indapamide administration (2.5 mg once daily) as well as eight weeks after combination treatment with indapamide (2.5 mg once daily)and losartan (50 mg/day). RESULTS: Indapamide evoked a significant decrease in systolic and diastolic blood pressure from a mean value of 157 +/- 12 mmHg/96 +/- 10 mmHg to a mean value of 139 +/- 14 mmHg/92 +/- 5 mmHg (p

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The effectiveness as well as the metabolic effects of the combination of diuretics [hydrochlorothiazide (HCT) vs indapamide (IND)] and perindopril (P) in 14 patients (7 male, 7 female) aged 37-62 years with mild idiopathic hypertension were studied. Following a 4-week wash-out period and a 4-week period of monotherapy with P (4 mg/daily), IND (2.5 mg/daily) or HCT (25 mg/daily) was added for 4 weeks. Selection of the diuretic agent was random. Following a 4-week wash-out period from the diuretic, in which only P was given, the alternative diuretic was administered for another period of 4 weeks. P decreased blood pressure levels significantly. However, the drug was more efficacious in patients with higher plasma renin activity (PRA). Combination treatment induced an additional decrease in the blood pressure levels, mainly in patients with lower PRA. The combination of P + HCT was more effective than the combination P + IND. The addition of either HCT or IND evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge. However, insulin levels did not change significantly during the study. Small but not statistically significant changes in serum electrolytes and lipid parameters were observed during the various phases of the study, while a statistically significant increase in the serum uric acid was noticed when the combination P + HCT was given. We conclude: (1) P in small doses is an effective and safe antihypertensive agent, (2) PRA has a predictive value in determining the effectiveness of P treatment, (3) the combination of P with small doses of HCT or IND is more efficacious than P alone, (4) the combination treatment has adverse effects in the carbohydrate tolerance, while there are not significant changes in serum electrolyte and lipid parameters. J Hum Hypertens

Pamidronate constitutes a major advance in the treatment of tumor-associated hypercalcemia. However, transient electrolyte abnormalities have been reported after pamidronate administration. We describe here a patient with multiple myeloma and severe hypercalcemia who developed transient but significant electrolyte disturbances (mainly hypophosphatemia and hypomagnesemia) after a single dose of 90 mg of pamidronate, focusing on the underlying pathophysiological mechanisms.