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Chronic pain is a common concern and is considered to be one of the major problems in patients with chronic physical disorders. We studied the effect of pain in patients with hypertension with or without chronic kidney disease (CKD) and the association between pain and symptoms of depression. The study involved 158 hypertensive individuals (59.5% male, mean age 55 years), of whom 47 (29.8%) had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). Pain was assessed with the pain/discomfort domain of the EuroQol-5 D, while depressive symptoms were assessed with the depression module of the Patient health questionnaire (PHQ-9). The prevalence of chronic pain in our sample was 44.3%. Women exhibited chronic pain more often compared to men (57.1% vs. 42.9%, p < 0.001). The presence of CKD was not significantly associated with a higher prevalence of chronic pain among hypertensive patients. Depressive symptoms were significantly associated with the presence of chronic pain. These findings were confirmed in the logistic regression analysis. Chronic pain is common in hypertensive individuals and the association with depression warrants further investigation and may have practical implications in managing these patients.

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OBJECTIVE: Obesity and renal disease are both associated with low serum 25(OH)D. The aims of the present study were to (a) assess vitamin D status and compare serum vitamin D levels in overweight/obese versus normal-weight individuals according to eGFR and (b) assess the role of 25(OH)D in the development of secondary hyperparathyroidism (SHPT). DESIGN: Serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), calcium, and phosphate were measured in 104 subjects with BMI > 25 kg/m2. Participants were categorized according to eGFR (ml/min/1.73m2): G1 ≥ 60 (n = 53), G2 30-59 (n = 35), and G3 15-29 (n = 16). Fifty normal-weight individuals with comparable eGFR served as controls: G1-nw (n = 23), G2-nw (n = 18), and G3-nw (n = 9). RESULTS: 25(OH)D levels were lower in G1 compared to those in G1-nw (21.7 ± 6.5 vs 26.5 ± 7.0 ng/ml, p = 0.005), G2 versus G2-nw (19.0 ± 6.0 vs 25.0 ± 5.2 ng/ml, p = 0.001), and G3 vs G3-nw (15.8 ± 4.7 vs 20.3 ± 4.5 ng/ml, p = 0.030). 1,25(OH)2D and PTH levels were similar in obese/overweight versus normal-weight individuals in each of the eGFR categories. Factors independently associated with low 25(OH)D levels were BMI > 25 kg/m2, lower eGFR, and female gender. Mean 25(OH)D levels were < 30 ng/ml in both overweight and controls, in all eGFR groups. SHPT was universally observed when eGFR was < 30 ml/min/1.73m2. CONCLUSIONS: Lower serum 25(OH)D but similar 1,25(OH)2D and PTH levels were observed in overweight/obese compared to normal-weight individuals. Even though vitamin D insufficiency was common across all eGFR categories, secondary hyperparathyroidism was more prevalent as eGFR declined.

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Kidney transplantation is the treatment of choice for a significant number of patients with end-stage renal disease. Although immunosuppression therapy improves graft and patient's survival, it is a major risk factor for infection following kidney transplantation altering clinical manifestations of the infectious diseases and complicating both the diagnosis and management of renal transplant recipients (RTRs). Existing literature is very limited regarding osteomyelitis in RTRs. Sternoclavicular osteomyelitis is rare and has been mainly reported after contiguous spread of infection or direct traumatic seeding of the bacteria. We present an interesting case of acute, bacterial sternoclavicular osteomyelitis in a long-term RTR. Blood cultures were positive for Streptococcus mitis, while the portal entry site was not identified. Magnetic resonance imaging of the sternoclavicluar region and a three-phase bone scan were positive for sternoclavicular osteomyelitis. Eventually, the patient was successfully treated with Daptomycin as monotherapy. In the presence of immunosuppression, the transplant physician should always remain alert for opportunistic pathogens or unusual location of osteomyelitis.

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The Klotho gene displays an extremely shortened life span with loss of function missense mutations leading to premature multiple organ failure, thus resembling human premature aging syndromes. The transmembrane form of Klotho protein functions as an obligatory co-receptor for FGF23. Klotho and FGF23 are crucial components for the regulation of vitamin D metabolism and subsequently blood phosphate levels. The secreted Klotho protein has multiple regulatory functions, including effects on electrolyte homeostasis, on growth factor pathways as well as on oxidative stress, which are currently the object of extensive research. Klotho protein deficiency is observed in many experimental and clinical disease models. Genetic polymorphisms such as the G-395A polymorphism in the promoter region of the Klotho gene have been associated with the development of essential hypertension. The kidneys are the primary site of Klotho production, and renal Klotho is decreased in CKD, followed by a reduction in plasma Klotho. Klotho deficiency has been both associated with progression of CKD as well as with its cardinal systemic manifestations, including cardiovascular disease. Thus, Klotho has been suggested both as a risk biomarker for early detection of CKD and additionally as a potential therapeutic tool in the future.

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INTRODUCTION: Within this longitudinal study we investigated the association of inflammation markers C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) and endothelial dysfunction markers intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with left ventricular mass indexed for height(2.71) (LVMI) in hypertensive predialysis CKD patients. MATERIAL AND METHODS: From 2004 to 2005, 182 incident consecutive adult patients from the outpatient CKD clinics of two hospitals in Greece with CKD and hypertension or using antihypertensive medication, were included. Of these, 107 patients underwent CRP (mg/l) and LVMI (g/height(2.71)) measurements annually for three years. RESULTS: In the longitudinal analyses, using linear mixed modeling, a higher IL-6 (ß = 1.9 (95%ci:0.38;3.5), inflammation score based on CRP, IL-6 and TNF-α (ß = 5.0 (95%ci:0.72; 9.4) and VCAM-1 (ß = 0.01 (95%ci:0.005;0.02) were associated with higher LVMI. These models were adjusted for age, gender and primary renal disease, and for confounders that on top changed the beta with ≥ 10%, i.e. diuretic use (for IL-6 and inflammation score). CONCLUSION: The results suggest that in predialysis CKD patients, inflammation as well as endothelial dysfunction may play an important role towards the increase in LVMI.

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BACKGROUND: Quality of Life (QoL) is often poor in people undergoing dialysis and this sometimes contributes to the high rate of morbidity and mortality. The aim of our study is to assess the QoL of patients on haemodialysis in Greece and discuss the socio-demographic factors that affect QoL in this period of financial crisis. DESIGN/PATIENTS: Patients with CKD not on dialysis, plus those undergoing Haemodialysis (HD) and Peritoneal Dialysis (PD) were invited to complete the SF-36 questionnaire electronically, supervised by a trained nurse. Patients were asked about their marital status, education level and monthly household income. Additionally, patients were requested to comment on their subjective financial difficulties. RESULTS: A total of 172 patients were enrolled in the study, 39 of them were undergoing PD, 90 on HD and 43 had CKD. Among those with CKD, on HD and PD, 9.3%, 17.8% and 23.1%, respectively, had 'some/a lot' difficulties in copying with financial problems. The physical component summary score was significant lower in HD, while the summary score of the mental component showed no differences between the groups. In multiple linear regression analysis, age and dialysis had significantly negative correlations with physical functioning scores. Those who were divorced or widowed tended to perform worse in physical scores compared with those who were married. Mental scores were affected only by coping with financial difficulties. CONCLUSIONS: In general terms, people with CKD patients present with a poor QoL. Apart from the burden of the renal disease per se, social and economic factors (divorce, financial difficulties) seem to aggravate their status, especially in this period of financial crisis.

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OBJECTIVE: It has been suggested that aliskiren has a long half-life and maintains a blood pressure (BP)-lowering effect following a missed dose. We tested the hypothesis that every other day (eod) administration of aliskiren has the same effects as the once daily (od) dosing in albuminuric hypertensive patients. METHODS: Fifteen hypertensive patients, after a 4-week wash-out period on clonidine, received 300 mg aliskiren od as the sole treatment. In patients who remained out of target, other nonrenin-angiotensin system blockers were added. Patients who completed a 24-week (w24) treatment period were switched to eod administration of aliskiren for an additional period of 24 weeks (w48). RESULTS: Thirteen patients completed the full study protocol. The mean office BP was reduced at the end of w24 (-9/3 mmHg), a reduction that continued to be observed at w48 (-11/1 mmHg). At the end of the study, the 48 h ambulatory BP monitoring was divided into two 24 h periods. The mean 24 h systolic BP, and the mean daytime systolic and diastolic BP were significantly lower (P<0.05) in the first 24 h (when aliskiren was taken) compared with the second period. Central hemodynamics showed no significant differences at any time during monitoring. Administration of aliskiren resulted in a median reduction of urine albumin/creatinine ratio of 103 mg/g (od) and 102 mg/g (eod). Differences in plasma renin activity, plasma renin concentration, and aldosterone-level measurements were not significant. CONCLUSION: The BP-lowering effect of eod aliskiren administration, although adequate, is less efficient compared with od administration, despite the fact that in terms of reducing albuminuria, it appears to be effective.

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BACKGROUND: Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD. METHODS: Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement. RESULTS: A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR<40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers. CONCLUSIONS: In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.

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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.

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BACKGROUND: Toll-like receptors (TLRs) are key players in the innate immune system whose activation leads to an inflammatory response. Inflammation plays an important role in the pathogenesis of chronic kidney disease (CKD) and diabetes mellitus. The aim of our study was to assess the proinflammatory state of nondialysis CKD patients by evaluating the membrane expression of TLR2 and TLR4 and the intracellular IL-1ß and IL-6 production in response to the ligand Pam3Cys-Ser-(Lys)4 (Pam3CSK4). METHODS: 85 nondialysis CKD patients [mean estimated glomerular filtration rate: 34 (17-90) ml/min/1.73 m(2)] were divided in 2 groups: 55 nondiabetic CKD patients (CKD group) and 30 patients with diabetic nephropathy (DN group). The two groups were compared with 36 healthy subjects (control group). TLR2 and TLR4 membrane expression in monocytes and Pam3CSK4-induced intracellular production of IL-1ß and IL-6 were assessed by flow cytometry. RESULTS: Both patient groups showed increased TLR2 membrane expression compared with the control group, both at baseline (p < 0.05 for both) and after Pam3CSK4 stimulation (p < 0.05 for both). The DN group exhibited significantly higher TLR4 expression at baseline compared to the CKD and control groups (p < 0.04 and p < 0.02, respectively). Intracellular IL-1ß and IL-6 levels at baseline were significantly lower in CKD patients compared to the DN and control groups. After Pam3CSK4 stimulation, intracellular IL-1ß and IL-6 increased in all groups, but were lower in the CKD group versus the control group or DN group, which exhibited higher levels than the controls. CONCLUSIONS: Nondialysis CKD patients showed significant alterations in TLR2 and TLR4 membrane expression, and impaired Pam3CSK4-induced cytokine production in monocytes, a phenomenon that is markedly influenced by the presence of diabetes.

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Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD), characterized by extensive intraperitoneal fibrosis and encasement of bowel loops. It typically associates with long-term PD and progressive loss of ultrafiltration. The management of EPS has evolved substantially from the original report of this entity and now includes immunosuppressive agents, antifibrotic agents, nutritional support, and surgical intervention. Although the exact cause of this condition remains obscure and despite the possible positive effect of immunosuppression on EPS, it has been described in the post-transplant setting upon the discontinuation of PD. We report such a case of a former PD patient who presented with EPS a month after renal transplantation. This article will highlight the current views regarding the management of post-transplant EPS and introduce the problem of long-term PD patients on the deceased-donor transplant waiting list.

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BACKGROUND: This study aimed to investigate the association of both body mass index (BMI) and waist circumference (WC) with left ventricular mass (LVM) in hypertensive predialysis chronic kidney disease (CKD) patients. METHODS: From 2004 to 2005, 206 consecutive incident adult patients from the outpatient CKD clinics of two hospitals in Greece were included. Inclusion criteria were the presence of CKD and hypertension. BMI (kg/m(2)), WC (cm) and LVM (g) were assessed annually for 3 years. RESULTS: The mean age was 68.1 years, mean BMI 29.1 kg/m(2) and mean WC was 103.7 cm. The median LVM was 245.7 g (n = 179). In the cross-sectional data, linear regression models showed that WC {ß = 1.2 [95% confidence interval (CI) 0.15; 2.3]}, and not BMI [ß = 2.1 (95% CI: -0.70; 4.8)], was significantly associated with LVM. After adjustment for age, sex, primary renal disease, smoking and history of cardiovascular disease, both BMI [ß = 4.7 (95% CI: 2.0; 7.4] and WC [ß = 1.2 (95% CI: 0.14; 2.3)] were significantly associated with LVM. These associations were pronounced in CKD stage 1-3, but not in CKD stage 4-5. In the longitudinal analysis, linear mixed models adjusting for confounders showed that both an increase in BMI [ß = 2.9 (95% CI: 0.74; 5.1)] and an increase in WC [ß = 1.1 (95% CI: 0.28; 1.8)] were significantly associated with an increase in LVM. CONCLUSIONS: In hypertensive predialysis CKD patients, both BMI and WC were associated with LVM in CKD stage 1-3, but not in CKD stage 4-5. In the longitudinal analysis, both an increase in BMI and WC were associated with an increase in LVM. Future studies should focus on mechanisms responsible for the associations between anthropometric variables and LVM.

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BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiologic entity characterized by headache, visual disturbances, seizures, and the presence of edema on MRI scan, predominantly in the posterior white matter. Regarding end-stage renal disease (ESRD) and PRES, only a few cases of children on peritoneal dialysis (PD) and adults on hemodialysis have been described in the literature. CASES: We report 4 cases of adult patients on PD who presented with PRES, all of which were due to hypertension and inadequate management of fluid balance. The patients expressed typical PRES symptoms such as headache, visual disorders, and tonic/clonic seizures. The patients recovered completely and the MRI lesions disappeared after strict control of volume status. CONCLUSION: Nephrologists should be aware of the syndrome, especially when they manage hypertensive ESRD patients not compliant with the fluid and diet restrictions. MRI scan is the only diagnostic tool for defining the syndrome. Early diagnosis is important, since complete remission is achieved after appropriate treatment.

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PURPOSE: 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. METHODS: 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. RESULTS: 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 Hb <11 g/dl was significantly correlated with CO/DY by MMSE, dialysis modality and Kt/V >1.2 by IADL test. PD patients were less likely to present with CO/DY by clock-drawing test. CONCLUSIONS: In every CKD stage, the risk of CO/DY increased significantly. Low Hb levels (Hb <11 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.

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Renovascular hypertension refers to the rise of arterial pressure due to reduced perfusion of the kidney caused by the stenotic renal artery/ies. The most common cause of stenotic renal artery is atherosclerosis. Atherosclerotic renal stenosis is usually part of a systemic syndrome that involves hypertension, intrinsic renal damage, and cardiovascular morbidity. So far, large trials have not proven the superiority of interventional therapies to medical management. As a result, renal artery stenosis should be treated mainly as a coronary artery disease equivalent focusing on rigorous management of hypertension, hyperglycemia, and hyperlipidemia. Antihypertensive treatment should include renin-angiotensin system blockade medication in most cases, while HMG-CoA reductase inhibitors (statins) can be used even in chronic kidney disease with safety. Lifestyle modifications, such as cessation of smoking, and antiplatelet therapy have reduced the risk of cardiovascular events in high-risk patients.

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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.

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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.

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BACKGROUND/AIM: Increased apoptosis along with enhanced inflammation has been reported in hemodialysis and pre-dialysis patients. However, there is limited information at which stage during the progression of chronic kidney disease (CKD) the balance between pro- and anti-apoptotic mechanisms is disturbed and inflammatory response is activated. The aim of this study was to investigate possible alterations in apoptotic and inflammatory markers during CKD (stages 1-4) progression and the probable interactions between them. METHODS: In a cross-sectional study, 152 steady-state CKD outpatients (83 males, 55%) with mean estimated glomerular filtration rate 46 (29-76) ml/min/1.73 m(2) were studied. Apoptosis was assessed in peripheral blood mononuclear cells by estimating Bcl-2 expression, annexin V-propidium iodine staining and serum soluble Fas (sFas) and Fas-ligand. Serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6 and plasma levels of fibrinogen were measured as markers of inflammation. RESULTS: Bcl-2 expression was found to decrease significantly in both lymphocytes and monocytes from CKD stage 1 to 4. In contrast, the activity of sFas increased significantly and so did the levels of TNF-α and fibrinogen. The majority of these alterations occurred as soon as patients entered stage 3 of CKD. A multivariate regression analysis demonstrated that CKD remained a significant predictor of the aggregate of the assessed markers. CONCLUSIONS: Apoptosis appeared to increase across CKD stages 1-4, and this was associated with increased proinflammatory activity.

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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.

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