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To investigate whether cornea verticillata affects corneal topography, tomography, densitometry, or biomechanics of Fabry patients with ocular manifestations and to compare these results with those obtained from healthy subjects. This prospective, cross-sectional study included 23 Fabry patients (Fabry group) with cornea verticillata and the 37 age- and sex-matched healthy subjects (control group). After comprehensive ophthalmological examinations, corneal topography, tomography, and densitometry measurements were taken using Pentacam HR and corneal biomechanics were captured via Corvis ST for all participants. All the investigated topographic and tomographic values were similar in the eyes with Fabry disease (FD) and the controls (P > 0.05). The corneal densitometry values of patients with FD were statistically significantly higher in all the concentric zones and layers, except posterior 0–2 mm and posterior 2–6 mm zones, compared to the controls (P

Purpose: To evaluate retinal thicknesses and retinal microcirculation in healthy controls and in diabetic patients with or without microalbuminuria. Methods: Eighty-six diabetic patients without diabetic retinopathy (DR) (44 normoalbuminuric, 42 microalbuminuric) and 51 healthy controls were enrolled in this cross-sectional, prospective study. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed. Correlations between OCTA parameters with mean urinary albumin levels were evaluated. Results: The mean vessel densities of superficial capillary plexus (SCP), whole disc, and peripapillary area were significantly decreased in patients with microalbuminuria compared to patients with normoalbuminuria and controls (p < 0.05 for all). The mean vessel density of deep capillary plexus was significantly reduced in patients with microalbuminuria compared to controls (p < 0.05 for all). There were no significant differences in retinal thickness between groups (p > 0.05). Both duration of diabetes and urinary albumin levels were significantly and moderately correlated with mean vessel density of whole SCP in diabetic patients (r = 0.330, p = 0.021; r = 0.356, p = 0.017, respectively). Conclusion: Diabetic eyes without clinically detectable DR show impaired retinal microcirculation. Microalbuminuria is associated with alterations of retinal microcirculation in diabetic patients without DR. Evaluation of retinal microcirculation is likely useful for detecting early changes related to microvascular complications in type 2 diabetic patients.

Objective: The incidence of diabetes and its complications are greatly increasing world-wide. Diabeticnephropathy (DN) is the main cause of end-stage renal disease and is associated with high morbidity and mortality. It is important to predict patients with high risk for DN in the early stage. We selected the genes which have an important role on diabetic kidney disease. We aimed to investigate the association between DNA methylation levels of targeted genes and albuminuria in patients with early DN. Methods: We collected the clinical data of patients with type 2 diabetes mellitus. We measured spot urine albumin creatinine ratio to calculate albuminuria level. We divided patients into two groups based on albumin excretion as patients with (n = 69) and without DN (n = 27). We performed methylation profiling after bisulfite conversion by pyrosequencing method. The mean value of percent methylation level of each gene was calculated. Results: We compared targeted genes (TIMP-2, AKR1B1, MMP-2, MMP-9, MYL9, SCL2A4, SCL2A1, SCL4A3) methylation levels and albuminuria. We found significant negative correlation between TIMP-2 and AKR1B1 gene methylation levels and albuminuria levels. Conclusions: The present study provided evidence that hypomethylation of TIMP-2 and AKR1B1 genes can be associated with albuminuria in patients with early DN. We may speculate that the hypomethylation of TIMP-2 and AKR1B1 genes may be an early surrogate marker of DN.

Obesity has grown into an epidemic across the globe. Mirroring this growth in the number of obese individuals in the general population, the prevalence of obesity and extremely morbid obesity (body mass index >50 kg/m2) is similarly rising in patients with end-stage renal disease (ESRD). Obesity, and more so, extremely morbid obesity, creates additional challenges for clinicians aiming at providing the best treatment options to patients with ESRD. Although literature is available regarding renal replacement therapy (RRT) for obese patients, literature about challenges facing clinicians managing ESRD in the extremely obese patients is lacking. Furthermore, the optimal strategies and goals for managing these patients with ESRD are not well defined. To our knowledge, no study has been done evaluating RRT options available to extremely morbid obese patients and the challenges associated with these options. Here, we report a case series and discuss the potential challenges faced by extremely obese patients with ESRD requiring RRT.

Ultrasonography (US) is an inexpensive, noninvasive and easy imaging procedure to comment on the kidney disease. Data are limited about the relation between estimated glomerular filtration rate (e-GFR) and all 3 renal US parameters, including kidney length, parenchymal thickness and parenchymal echogenicity, in chronic kidney disease (CKD). In this study, we aimed to investigate the association between e-GFR and ultrasonographic CKD score calculated via these ultrasonographic parameters. One hundred and twenty patients with stage 1–5 CKD were enrolled in this study. The glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. US was performed by the same radiologist who was blinded to patients’ histories and laboratory results. US parameters including kidney length, parenchymal thickness and parenchymal echogenicity were obtained from both kidneys. All 3 parameters were scored for each kidney, separately. The sum of the average scores of these parameters was used to calculate ultrasonographic CKD score. The mean age of patients was 63.34 ± 14.19 years. Mean kidney length, parenchymal thickness, ultrasonographic CKD score and median parenchymal echogenicity were found as 96.2 ± 12.3, 10.97 ± 2.59 mm, 6.28 ± 2.52 and 1.0 (0–3.5), respectively. e-GFR was positively correlated with kidney length (r = 0.343, p

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were established showing the poor prognosis in some diseases, such as cardiovascular diseases and malignancies. The risk of mortality in patients with end-stage renal disease (ESRD) was higher than normal population. In this study, we aimed to investigate the relationship between NLR, PLR, and all-cause mortality in prevalent hemodialysis (HD) patients.Eighty patients were enrolled in study. NLR and PLR obtained by dividing absolute neutrophil to absolute lymphocyte count and absolute platelet count to absolute lymphocyte count, respectively. The patients were followed prospectively for 24 months. The primary end point was all-cause mortality.Mean levels of neutrophil, lymphocyte, and platelet were 3904 ± 1543/mm(3), 1442 ± 494/mm(3), 174 ± 56 × 10(3)/mm(3), respectively. Twenty-one patients died before the follow-up at 24 months. Median NLR and PLR were 2.52 and 130.4, respectively. All-cause mortality was higher in patients with high NLR group compared to the patients with low NLR group (18.8 vs. 7.5 %, p = 0.031) and in patients with higher PLR group compared to patients with lower PLR group (18.8 vs. 7.5 %, p = 0.022). Following adjusted Cox regression analysis, the association of mortality and high NLR was lost (p = 0.54), but the significance of the association of high PLR and mortality increased (p = 0.013).Although both NLR and PLR were associated with all-cause mortality in prevalent HD patients, only PLR could independently predict all-cause mortality in these populations.

WOS: 000392937800028 PubMed ID: 28006774 Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of a-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed a-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fa bry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin. (C) 2016 The Author(s) Published by S. Karger AG, Basel Sanofi Genzyme Corporation; Intensificacion ISCIII and REDINREN [RD012/0021] We are indebted to our patients and their families for volunteering to contribute their medical information to the physicians who are dedicated to their care. This work was supported by grants from Sanofi Genzyme Corporation. The lead investigator had full access to all data in the study. All investigators take responsibility for the accuracy of the individual data that they entered in the system provided by FMF Arthritis Vasculitis and Orphan disease Research (FAVOR). AO was supported by Intensificacion ISCIII and REDINREN RD012/0021.

Background: Chronic kidney disease (CKD) patients who experience superimposed acute kidney injury (AKI) have been shown to be at higher risk of long-term sequelae of AKI when compared to those who do not experience AKI. It remains unclear whether the need for temporary dialysis intervention following superimposed AKI in patients with CKD has any effect on the long-term major adverse cardiovascular events (MACE). This study examines the relationship between temporary dialysis therapy following AKI and long-term major cardiovascular events in patients with background CKD. Methods: The study population consists of adults who developed AKI while on admission at the University of Virginia Medical Center between January 1, 2002 and December 31, 2012, and who had preadmission estimated glomerular filtration rate (eGFR) between 20 and 60 mL/min/1.73 m2 and survived beyond 30 days of AKI. Demographic and baseline clinical variables were used to generate propensity score. Survivors who had temporary dialysis were matched to those managed conservatively according to the propensity score in a ratio of 1:3. Results: Overall, 6,634 (n = 381 and 6,253 in the temporary dialysis-requiring AKI and non-dialysis AKI groups respectively) met entry criteria for the full cohort. Of these, 381 (5.7%) received temporary dialysis. There were 3,147 (47.4% of all patients) MACE events during the study period. The crude incidence for MACE after 30 days of AKI was similar in both dialyzed and non-dialyzed patients. After the propensity score matching, the adjusted hazard ratio for MACE in dialyzed versus non dialyzed patients was 1.162 (95% CI 0.978-1.381). Conclusions: Treatment of AKI with temporary dialysis in hospitalized patients with baseline eGFR between 20 and 60 mL/min/1.73 m2 was not associated with an increased risk for subsequent admission for MACE. If confirmed by prospective studies, clinicians may not need to worry that the dialysis procedure may contribute to additional risk for long-term MACE in CKD patients with superimposed AKI.

Background: Regional citrate anticoagulatio∂n (RCA) is being used increasingly in critically ill patients who require continuous renal replacement therapy (CRRT). RCA may be avoided in patients with liver disease be- cause of perceived increased risk of metabolic com- plications. The study compares the circuit lifespan and metabolic complications using RCA for CRRT at vary- ing levels of liver dysfunction. Methods: Data was collected retrospectively including the number of days on CRRT, number of circuit (re)ini- tiations within that time and serum ionized and total calcium, bicarbonate, and sodium, repeatedly during treatment. Model for end-stage liver disease (MELD) scores were calculated and patients were divided into 4 groups according to MELD score quartiles. Results: A total of 697 patients were included in the present study. The median circuit survival time was not different between groups. The median minimum serum ionized calcium levels during treatment were significantly lower in groups 3 and 4 (p

Background: An elevated serum uric acid level is strongly associated with endothelial dysfunction and inflammation, both of which are common in chronic kidney disease (CKD). We hypothesized that endothelial dysfunction in subjects with CKD would correlate with uric acid levels. Materials and Methods: We evaluated the association between serum uric acid level and ultrasonographic flow-mediated dilatation (FMD) in 263 of 486 patients with recently diagnosed CKD (stage 3–5) (48% male, age 52 ± 12 years). To minimize confounding, 233 patients were excluded because they were diabetic, had established cardiovascular complications or were taking drugs (renin-angiotensin system blockers, statins) interfering with vascular function. Results: Serum uric acid level was significantly increased in all stages of CKD and strongly correlated with estimated glomerular filtration rate (eGFR-MDRD); FMD was inversely associated with serum uric acid (r = –0.49, p < 0.001). The association of serum uric acid with FMD remained after adjustment for age, gender, smoking, LDL cholesterol, eGFR, high-sensitivity C-reactive protein, systolic blood pressure, proteinuria, and homeostatic model assessment index (β = –0.27, p < 0.001). Conclusion: Increased serum uric acid is an independent predictor of endothelial dysfunction in subjects with CKD.

Respiratory functions are affected during hemodialysis. The strength of respiratory muscles, ultrafiltration rate, and acid-base balance have been suggested as important factors. L-carnitine is crucial for energy producing, utilization of fatty acid, and possible amino acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. This study was performed to investigate the chronic effects of L-carnitine treatment on respiratory functions in adults receiving chronic hemodialysis therapy.A total of 20 hemodialysis patients were scheduled to take L-carnitine supplementation (20 mg/kg three times/week) (group 1), and the rest of 20 hemodialysis patients served as the control group and were observed without supplementation with L-carnitine (group 2). Pre- and post-dialytic L-carnitine levels and post-dialytic respiratory functions tests were performed in both groups at baseline and after six months.The average concentration of free and total carnitine levels increased significantly after six months of supplementation (p0.01). While a statistically significant increase between postdialytic forced expiratory volume in one second/forced vital capacity values after treatment period (77.10 +/- 12.15 and 83.00 +/- 14.49, before and after treatment, respectively, p0.05) was observed, the increase of vital capacity, forced expiratory volume in one second, and forced expiratory flow between 25-75% of expired vital capacity were not significant in the treatment group (p0.05).Intravenous L-carnitine supplementation could contribute to the management of respiratory dysfunction in chronic hemodialysis patients by improving FEV1/FVC. The mechanism by which LC causes these effects merits further investigation.

Renal ischemia/reperfusion (I/R) injury is a major cause of acute renal failure. Silymarin is extracted from Silybum marianum and Cynara cardunculus seeds and fruits. The aim of this study is to investigate whether silymarin administration prevents the damage induced by I/R in rat kidneys. Thirty male Wistar rats were randomly divided into five experimental groups (n = 6, each) as follows; control group, sham-operated group, I/R group, silymarin group, and I/R + silymarin group. In the I/R and I/R + silymarin groups, both renal arteries were occluded using nontraumatic microvascular clamps for 45 min. Then, at the end of 24 h of reperfusion, the animals were killed. Kidney function tests, the serum and tissue antioxidant enzymes and oxidant products were determined. Animals that were subjected to I/R exhibited significant increase in serum urea, creatinine, and cystatin C levels compared with the rats treated with silymarin prior to the I/R process (P

Although dyspepsia is very common in uremic patients, there is not much data on the prevalence of dyspepsia undergoing continuous ambulatory peritoneal dialysis (CAPD). The aims of this study are to assess the prevalence of dyspepsia, Helicobacter pylori, and the association between dyspeptic symptoms and diabetes. One hundred and thirty CAPD patients were included in the study. The presence or absence of dyspepsia was assessed by using the Hong Kong Index of Dyspepsia (HKID) Questionnaire. A score of ≥16 indicates the presence of dyspepsia. The patients who were diagnosed with dyspepsia had endoscopic examination and were judged to be infected with H. pylori if the organism was demonstrated in the biopsy. Sixty-four of 130 CAPD patients (49.2%) had a HKID score of 16 or more. H. pylori was identified in 17 of 64 CAPD patients with dyspepsia (26.6%). Thirty-four patients (25.8%) were diabetic, and there was no association between diabetes and dyspepsia (P = 0.68). The most frequent finding in patients with dyspepsia was gastritis or gastric ulcer in endoscopic evaluation. The mean serum albumin level was also not statistically significantly different between the two groups. Dyspepsia is common and the prevalence of H. pylori infection is 26.6% in our CAPD patients with dyspepsia. Dyspepsia is not associated with the presence of H. pylori and diabetes in CAPD patients. Large-scale studies are needed to elucidate dyspepsia related risk factors and physiopathological mechanisms.

Nocturia, a common and bothersome symptom of benign prostatic hyperplasia (BPH), may cause sleep disturbances. Patients with nocturia may have difficulty returning to their normal sleep after repeated episodes of waking and voiding. Therefore, nocturia may have an impact on the circadian rhythm of blood pressure (BP). The association between nocturia and the circadian rhythm of BP was investigated in this study.A total of 100 male patients who had been diagnosed with BPH and 53 healthy male subjects were included in the study. Nocturnal urinary frequency was assessed by means of a questionnaire and recorded in both groups. Ambulatory BP monitoring was performed in all patients over a 24-h period.Patient characteristics and laboratory parameters were similar in both groups. Seventy-five patients (75%) in the BPH group and 20 subjects (37.7%) in the control group were non-dippers, i.e. they did not have a normal nocturnal fall in BP, and this difference was statistically significant (p=0.001). Eighty-nine patients in the BPH group and 13 in the control group had nocturia. Seventy-one patients (79.8%) with nocturia were non-dippers and the difference compared to the patients without nocturia in the BPH group was significant (p=0.003), whereas four patients with nocturia (30.8%) were non-dippers in the control group.Our findings indicate that non-dipping was more prevalent in elderly men with BPH and nocturia. BPH and nocturia may be etiological factors in the pathogenesis of non-dipping, which is an indicator of early cardiovascular disease. Further studies must focus on this relationship and, especially, on whether treatment of nocturia and BPH helps to treat non-dipping or not.

Objective To compare ultrafiltration under continuous ambulatory peritoneal dialysis (CAPD) and automated PD (APD), disclosing potential effects on serum B-type natriuretic peptide (BNP) levels and echocardiographic findings. Patients and Methods This cross-sectional clinical study included 32 patients on CAPD and 30 patients on APD without clinical evidence of heart failure or hemodynamically significant valvular heart disease. Peritoneal equilibration tests, BNP levels, and echocardiographic measurements were performed in each subject. BNP measurements were also performed in 24 healthy control subjects. Results Patients on APD had lower ultrafiltration and higher values of BNP and left ventricular mass index (LVMI) compared with patients on CAPD (respectively: 775 ± 160 vs 850 ± 265 mL, p = 0.01; 253.23 ± 81.64 vs 109.42 ± 25.63 pg/mL, p = 0.001; 185.12 ± 63.50 vs 129.30 ± 40.95 g/m2, p = 0.001). This occurred despite higher mean dialysate glucose concentrations and far more extensive use of icodextrin in the APD group. Conclusion Treatment with APD is associated with higher plasma BNP levels and LVMI compared to CAPD. This may be the result of chronic fluid retention caused by lower ultra-filtration in APD patients.

Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in patients with glomerular filtration rate (GFR)60 ml/min. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function.Forty-eight hyperuricemic and 21 normouricemic patients were included in the study. Hyperuricemic patients received 300 mg/day allopurinol for three months. All patients' serum creatinine level, 24-h urine protein level, glomerular filtration rate, and blood pressure levels were measured at baseline and after three months of treatment.A total of 59 patients completed the three-month follow-up period of observation. In the allopurinol group, serum uric acid levels, GFR, systolic and diastolic blood pressure, and C-reactive protein (CRP) levels significantly improved (P0.05). However, urine protein excretion remained unchanged (P0.05). No correlation was observed between changes in GFR and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P0.05).We bring indirect evidence that hyperuricemia increases blood pressure, and decreases GFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease (CKD) patients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension.

Background: Peritonitis is an important cause of morbidity and mortality in patients receiving peritoneal dialysis (PD). However, there are no data about the comparison of the incidence of peritonitis among PD solution types. The aim of the present study was to compare the incidence of peritonitis among PD solutions in PD patients treated either with Nutrineal or with Extraneal or with conventional glucose solutions. Materials and Methods: A total of 147 patients (60 female and 87 male) who underwent PD were included in the study. Of these patients, 47 used only glucose solutions (group I), 79 used glucose solutions combined with Extraneal (group II) and 21 used glucose solutions combined with Nutrineal (group III). The laboratory values and demographics of the patients were noted. Results: There was no significant difference in the frequency of peritonitis among the three groups. Peritonitis occurred in 14 of 47 patients (29.8%) in group I, in 28 of 79 patients (35.4%) in group II and in 6 of 21 patients (28.6%) in group III. Patients with serum albumin levels below 3 g/dl had a significantly higher peritonitis rate than patients with serum albumin levels above 3 g/dl (p < 0.05). Conclusion: We have shown that a low serum albumin level is an important risk factor for the development of peritonitis in CAPD patients. The PD solution does not appear to be a risk factor for the development of peritonitis in CAPD patients, although this question should be studied further with larger numbers.

Oral alendronate, risedronate, and raloxifene are effective treatment options in the management of postmenopausal osteoporosis. There is little previously reported about the renal safety profiles of these three agents in osteoporosis. We aimed to assess the risk of renal toxicity associated with oral alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively.One hundred and twenty-seven patients with osteoporosis and osteopenia according to lumbar or femoral-neck bone mineral density t score were enrolled in the study. The patients were randomized to alendronate 70 mg once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg per day (n = 36) for one year. Preliminary screening included medical history, physical examination, lumbar and femoral bone mineral densitometry measurement, and blood biochemical tests, including renal function tests. The biochemical markers were then assessed at the end of 12 months.There was no significant difference between basal and final renal function parameters of each group. Also these parameters did not differ between the three groups after 12 months of treatment period.These results demonstrate that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.

Currently, the pathogenesis of nondipper hypertension remains largely unclear in patients without any renal or endocrine pathology. It is well known that overt hypothyroidism is strongly associated with diastolic hypertension. However, no study has addressed the pathogenic role of TSH, free T3 (FT3), and free T4 (FT4) in nondipper hypertension. The aim of the present investigation is to evaluate if higher TSH, low FT3 and FT4 would be associated with a nondipper hypertension profile, in patients with normal renal function and without any overt thyroid hormone disorder. 131 subjects were screened and those who met the following inclusion criteria were enrolled: (1) glomerular filtration rate (GFR) >60 ml/min; (2) no history of thyroid disorders; (3) no history of thyroid hormone medication. All subjects underwent 24-hour ambulatory blood pressure monitoring on a usual working day. Of the total population, 59 patients (45%) were classified as dippers and 72 (55%) were classified as nondippers. The only significant differences between dipper and nondipper patients appear to be related to FT3 levels and GFR. Nondipper patients had lower FT3 levels (4.5 ± 0.6 vs. 4.0 ± 0.9 pmol/l, p = 0.02) and low GFR (80.5 ± 12.2 vs. 86.9 ± 16.9 ml/min, p = 0.03), compared to dipper patients. The final regression model included serum TSH, FT3 levels, and GFR; the only independent predictor of nondipper hypertension was FT3 (p = 0.04). In conclusion, even if the mechanisms of our findings remain incompletely understood, we demonstrate a graded independent relation between lower level of FT3 and the risk of nondipping. Further studies are warranted to confirm this relationship and to elucidate the pathogenetic mechanisms of this relationship.

Background and Aims: In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium×phosphate (Ca×P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. Methods: 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. Results: Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 ± 0.61 vs. 3.35 ± 0.44 mg/dl, p = 0.001), Ca×P product (35.4 ± 6.5 vs. 31.5 ± 5.0, p = 0.001) and PTH (75.7 ± 28.8 vs. 46.6 ± 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (β = 0.43, p = 0.001) and phosphate (β = 0.9, p = 0.03). Conclusion: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca×P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. However, the association between ambulatory blood pressure and ED has not been investigated in these patients. Forty-one patients with ADPKD having well-preserved renal function were included in the study. Ambulatory blood pressure monitoring was performed in all patients. Patients were divided into dipper and non-dipper groups. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. The mean 24-hour systolic blood pressure was similar in both groups (125.5 +/- 10.7 mmHg in dippers and 121.2 +/- 14.3 in non-dippers, p0.05). There was also no significant difference between the mean 24-hour diastolic blood pressures in both groups (82.3 +/- 9.6 mmHg in dippers and 77.1 +/- 8.6 mmHg in non-dippers, p0.05). The nocturnal fall rate in systolic blood pressure was 11.1 +/- 1.2% in dippers and 0.98 +/- 0.9% in non-dippers (p = 0.001). The nocturnal fall rate in diastolic blood pressure was 14.0 +/- 0.9% in dippers and 3.8 +/- 0.8% in non-dippers (p = 0.001). Endothelial-dependent dilatation was significantly higher in dippers compared to non-dippers (6.22 +/- 4.14% versus 3.57 +/- 2.52%, p = 0.025). Non-dipper patients with ADPKD show significant ED, which has an important impact on cardiovascular morbidity and mortality.

Biventricular diastolic dysfunction in patients with autosomal-dominant polycystic kidney disease. Background Left ventricular diastolic dysfunction has been shown in patients with autosomal-dominant polycystic kidney disease (ADPKD). However, there is no study evaluating right ventricular functions in these patients. Methods In the present study, diastolic functions of both ventricles in normotensive and hypertensive ADPKD patients with well-preserved renal function were investigated. Fifteen hypertensive and 16 normotensive patients with ADPKD with well-preserved renal function, 16 patients with essential hypertension, and 24 healthy subjects were included in the study. Conventional left and right ventricular echocardiographic measurements were performed in all subjects. Left and right ventricular functions were investigated both by myocardial performance index (MPI) [calculated by dividing the sum of isovolumic contraction time and isovolumic relaxation time (IVRT) by ejection time] and by tissue Doppler imaging (TDI). Results Left ventricular deceleration time and IVRT were significantly prolonged in hypertensive patients with ADPKD compared with patients with essential hypertension and even in normotensive patients with ADPKD compared with healthy subjects. Left and right MPIs were significantly higher in patients with ADPKD compared with healthy subjects, showing systolic and diastolic dysfunction. Moreover, by using TDI, the peak early diastolic mitral annular velocity (Em) to peak late diastolic mitral annular velocity (Am) ratio and the peak early diastolic tricuspid annular velocity (Et) to peak late diastolic tricuspid annular velocity (At) ratio were decreased in patients with ADPKD, suggesting biventricular diastolic dysfunction. Conclusion Both hypertensive and normotensive patients with ADPKD show significant biventricular diastolic dysfunction, suggesting cardiac involvement very early in the course of ADPKD.

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED) and intima-media thickness (IMT) are predictors for the development and progression of atherosclerosis. In the present study, ED and IMT were investigated in patients with ADPKD.Fifteen hypertensive and 16 normotensive patients with ADPKD with preserved renal function, 16 patients with essential hypertension, and 24 healthy subjects were included in the study. Endothelial function of the brachial artery was evaluated by means of high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was assessed by establishing reactive hyperemia, and endothelial-independent dilatation was determined by using sublingual isosorbide dinitrate. Carotid IMT was measured by means of high-resolution vascular ultrasound.EDD was significantly worse in hypertensive patients with ADPKD compared with patients with essential hypertension (9.1% +/- 4.1% versus 12.4% +/- 4.6%; P0.05) and even in normotensive patients with ADPKD compared with healthy subjects (13.1% +/- 5.2% versus 18.1% +/- 8.1%; P0.01). Moreover, carotid IMT was significantly greater in both hypertensive (0.71 +/- 0.10 mm; P0.01) and normotensive (0.57 +/- 0.14 mm; P0.001) patients with ADPKD compared with healthy subjects (0.45 +/- 0.10 mm).Both hypertensive and normotensive patients with ADPKD show significant ED and increased IMT, which are predictors of atherosclerosis.

Background Oral isotretinoin is currently the most effective therapy for acne, but is associated with numerous adverse effects. To investigate the cardiac effects of isotretinoin, acne patients receiving isotretinoin for 6 months were studied. Methods Twenty-six patients with acne vulgaris were enrolled in the study. The patients were treated with a dose of 0.8 mg/kg/day of isotretinoin (Roaccutane, Hoffman-La Roche, Basle, Switzerland) for 6 months. All participants were assessed pretreatment and at the third month of therapy with 24-h Holter monitoring of electrocardiography. Results Twenty-two patients completed the study (19 females and three males). Initial 24-h Holter monitoring showed normal sinus rhythm in all patients, with a mean heart rate of 79 beats/min (lowest, 63 beats/min; highest, 97 beats/min). At the third month of therapy, 24-h Holter monitoring showed normal sinus rhythm in all patients, with a mean heart rate of 81 beats/min (lowest, 67 beats/min; highest, 91 beats/min). All patients were in sinus rhythm throughout the recording period. None of the patients had supraventricular tachycardia or atrial arrhythmia. Conclusion In this study, 6 months of isotretinoin therapy significantly improved acne and did not cause any cardiac adverse effects at a dose of 0.8 mg/kg/day.

Gamma-glutamyltransferase (GGT) is an enzyme responsible for the extracellular catabolism of the antioxidant glutathione and recently implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is a prodromal feature of atherogenesis. Since oxidative stress is highly present in uremia and causally linked to endothelial dysfunction, we hypothesized that GGT may be a factor implicated in this process. Serum GGT and C-reactive protein (CRP) levels, estimated glomerular filtration rate (eGFR), and 24-h proteinuria were measured in 214 nondiabetic stages 3–5 CKD patients. The endothelium-dependent vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasound. We investigated the relationship between FMD and circulating serum GGT. Serum GGT levels were negatively associated with FMD (r = −0.41, p

Background: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are prone to falls. In this pilot study, we aimed to determine the incidence of falls in a cohort of HD patients during a 1-year period, to identify any specific risk factors that may predict falls in this cohort, and to assess whether falls can independently predict hospitalization, nursing home admissions and/or mortality over an additional 2 years. Materials and Methods: Baseline assessments followed by documentation of falls prospectively during a 1-year period were done on 76 HD patients. Patients were followed for an additional 2 years and four outcomes were recorded: all-cause death, nursing home admission, the number and duration of all hospitalizations. Results: 20 patients (26.3%) fell over a 12-month period. Elderly and females had a higher risk of falls than the younger and male population (p = 0.034 and 0.006 respectively). During the 2-year follow-up, compared to non-fallers, fallers had a 2.13-fold increase in risk of death, a 3.5-fold increase in risk of nursing home admission, and nearly a 2-fold increase in the number and duration of hospitalizations. Conclusions: Falls are common in HD patients, with a higher incidence in females and elderly, and are associated with worse outcomes, more so in recurrent fallers.

Background: Depression is common and associated with increased morbidity and mortality in elderly (≧65 years) hemodialysis patients. Beck’s Depression Inventory (BDI) and the Geriatric Depression Scale (GDS) have been used in different cohorts to screen for depression. Objectives: We aimed to evaluate the 15-item GDS (GDS-15) as such a tool in elderly hemodialysis patients and compare it with BDI, a previously validated tool in younger hemodialysis patients. Design: Cross-sectional study. Setting: Four out-patient hemodialysis units; 1 based in a university hospital and 3 based in the community. Participants: Hemodialysis patients aged 65 years and older. Intervention: Both tools were administered to all participants, and a geriatric psychiatrist blinded to the results evaluated them for depression by the gold standard psychiatric interview. Measurements: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for both tools were assessed against the psychiatric interview (n = 62). Results: Patients who were depressed according to the psychiatric interview had significantly higher GDS-15 and BDI scores compared to those not depressed (p < 0.01 both). ROC curves showed high predictive accuracy of the GDS-15 and BDI (area under the curve: 0.808 and 0.729) versus the psychiatric interview. The GDS-15 cutoff with the best diagnostic accuracy was 5 with a sensitivity of 63%, specificity of 82%, PPV of 60% and NPV of 83%. The BDI cutoff with the best diagnostic accuracy was 10 with a sensitivity of 68%, specificity of 77%, PPV of 57% and NPV of 85%. Conclusion: These results provide evidence that the GDS-15 shows validity in comparison to a gold standard and can be used to screen for depression in the elderly hemodialysis population.

There are few studies concerning the development of chronic kidney disease (CKD) in obese patients independent of its relation with other risk factors. Also, the role of inflammation in this relationship is unclear. In this study we aimed to test the hypothesis that obesity is associated with risk for CKD and whether this risk is associated with serum C-reactive protein (CRP) levels in an apparently healthy obese population.Biochemical parameters and urinary protein excretion were determined in 110 patients with body mass index (BMI)30.0 (calculated as kg/m2) and 50 age-matched healthy controls. Glomerular filtration rate was estimated by calculation of creatinine clearance.Of the patients, 17.3% had CKD. They had higher CRP levels than controls (6.52 +/- 0.58 mg/L and 4.48 +/- 1.26 mg/L, respectively, p=0.001). Furthermore, CRP levels were positively correlated with BMI, waist circumference, waist to hip ratio and proteinuria, and negatively correlated with glomerular filtration rate (GFR). When GFR was considered as the dependent variable in a multiple regression analysis, CRP maintained its significant correlation with GFR.Our study of apparently healthy obese individuals, has shown a significant association between BMI and CKD independent of other potential mediators. Furthermore, our findings suggest that inflammation may be the pathogenic mechanism of obesity-related CKD.

The atherosclerotic process progresses more dynamically in hemodialysis (HD) patients than in the general population. In HD patients, lower magnesium levels were reported to be associated with increased atherosclerosis of the common carotid artery. We tested the hypotheses that magnesium supplementation helps to improve carotid intima media thickness (IMT) in HD patients.A total of 47 patients on HD were included in the study. Patients were randomly divided into two groups: group A (Mg group), in which patients were given magnesium citrate orally at a dosage of 610 mg every other day for 2 months and group B (control group), in which patients received only calcium acetate therapy as a phosphate binder. At baseline and 2 months later, all patients underwent a carotid artery ultrasound scan to measure carotid IMT.At the end of 2 months, mean serum calcium, phosphorus, and calcium x phosphorus product were not changed in both groups. As expected, mean serum Mg level significantly increased in the Mg group at the end of 2 months. In addition, serum parathyroid hormone (PTH) level significantly decreased in the Mg group at the end of 2 months (P = 0.003). Baseline carotid IMT was similar between the groups. Bilateral carotid IMT was significantly improved in patients treated with magnesium citrate compared to initial values (P = 0.001 for left, P = 0.002 for right).Based on the present data, magnesium may play an important protective role in the progression of atherosclerosis in patients on dialysis. Further studies are needed to assess more accurately the role of magnesium in atherosclerotic regression in dialysis patients.

N-terminal probrain natriuretic peptide (NT-proBNP) is elevated in patients with heart failure. Numerous clinical trials have evaluated the efficacy of spironolactone in heart failure; however, no studies have directly examined the effects of spironolactone treatment on NT-proBNP level. This study investigated whether NT-proBNP levels decrease with daily spironolactone treatment. The study consisted of 117 adult patients with heart failure. All participants were divided into 3 groups, class I, class II, and class III, according to the New York Heart Association classification system. Patients were randomly assigned to receive spironolactone or were treated with another drug, other than spironolactone, as placebo. NT-proBNP plasma samples were taken at baseline and after 6 mo of treatment. A total of 62 patients were treated with daily spironolactone; 55 patients were followed with available treatment without spironolactone. The baseline demographic and laboratory parameters were similar for patients in all groups. At the end of 6 mo, spironolactone-treated patients had significantly lower NT-proBNP levels and significantly better ejection fractions than did patients in all New York Heart Association classes who were not treated with spironolactone. Results suggest that spironolactone decreases plasma NT-proBNP concentrations, and that the measurement of plasma NT-proBNP levels may be helpful in assessing therapeutic efficacy in patients who are treated for heart failure.

Renal ischemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allograft. We investigated the effect of curcumin on ischemia-reperfusion (I/R) injury and the antioxidant effects of curcumin in rats.Thirty rats were randomly divided into five experimental groups (control, sham, curcumin, I/R and I/R+curcumin, n=6 each). Curcumin was administered (200 mg kg(-1)) orally to curcumin and I/R+curcumin groups for 7 days. Then, the rats were subjected to bilateral renal ischemia for 45 min and followed by reperfusion for 24 h. All rats were killed and kidney function tests, serum and tissue nitric oxide (NO), protein carbonyl (PC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined. Histopathological examinations were also performed.Curcumin significantly improved the urea and cystatin C levels in I/R+curcumin group compared to I/R group (p0.05). Reduction of serum GSH-Px was significantly improved by curcumin (p0.001), but SOD enzyme activity did not alter (p0.05). Treatment with curcumin also resulted in significant reduction in serum and tissue MDA, NO and PC and for tissue that were increased by renal I/R injury (p0.001 for serum and p0.05 for tissue, respectively). In histological examination, the rats treated with curcumin had nearly normal morphology of the kidney.Based on our results, it can be concluded that curcumin protects the kidneys against I/R injury via its antioxidant effects.

Amyloid-associated protein (secondary, reactive) amyloidosis occurs most frequently as a complication of chronic inflammatory disease. Renal involvement with amyloidosis is common and proteinuria is often the first symptom. We submit a case with severe proteinuria and hypoalbuminemia, and end-stage renal disease secondary to bronchiectasis-related amyloidosis. Bilateral embolization of the renal arteries was performed to prevent loss of albumin.

Background: Ischemia-reperfusion (I/R) injury is one of the leading causes of acute renal failure. β-(1→3)-Glucans are glucose polymers with a variety of stimulatory effects on the immune system. We designed this study to determine the possible protective effect of the orally administered soluble β-glucan against I/R injury. Methods: 30 rats were randomly divided into 5 experimental groups (control, sham operated, β-glucan, I/R and I/R+β-glucan groups, n = 6 each). β-Glucan was administered orally to 6 rats of the β-glucan and I/R+β-glucan groups. The rats were subjected to bilateral renal ischemia followed by reperfusion in the I/R and I/R+β-glucan groups. All of the rats were then sacrificed and kidney function tests, serum and tissue oxidants and antioxidants were evaluated. Results: The serum urea and cystatin C levels were significantly higher in the I/R group compared to the I/R+β-glucan group (p < 0.01). The serum and tissue antioxidant markers (SOD, GSH-Px) were significantly lower in the I/R group than the I/R+β-glucan group (p < 0.01). The serum oxidant markers (NO and PC) were significantly higher in the I/R group than the I/R+β-glucan group (p < 0.01). Conclusion: Based on the present data, we conclude that increased antioxidants and decreased oxidants modulated by β-glucan attenuated the renal I/R injury.

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. Statins have a beneficial effect in the reversal of ED. The aim of this study was to investigate the effects of a statin, simvastatin, on ED in patients with ADPKD. Sixteen patients with ADPKD having well-preserved renal function were included in the study. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. After the baseline evaluations of EDDs, patients were started treatment with simvastatin at a dose of 40 mg/day and were treated for six months. EDDs were recalculated after one and six months of therapy. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were also measured as markers of inflammation. Baseline EDD was 11.3 +/- 6.9% in patients with ADPKD. After one month of simvastatin treatment, EDD increased significantly to 14.6 +/- 4.6 % (P = 0.016 versus baseline). Endothelial-dependent dilatation further increased significantly to 18.9 +/- 7.5 % (P = 0.011 versus baseline, P = 0.048 versus first month) after six months of therapy. There was also a significant decrease in the level of IL-6 from 21.6 +/- 21.7 pg/mL to 9.1 +/- 3.5 pg/mL (P= 0.002). Six months of simvastatin therapy resulted in a significant improvement of ED in patients with ADPKD. This finding may be in part related to the pleiotropic effects of simvastatin.

Summary Endothelial dysfunction is an early key event in the development of atherosclerotic cardiovascular disease observed in chronic renal failure patients. The role of renal transplantation (RTx) on endothelial dysfunction is still unclear. The aim of this study was to evaluate the endothelial function of chronic renal failure patients before RTx (while they were on hemodialysis, HD), and after RTx (at the 6th and 12th months) by a noninvasive method, brachial arterial ultrasound. A total of 22 (17 male, mean age: 33.9 ± 11.6 years) RTx recipients were enrolled in the study. Endothelium-dependent vasodilation (EDD) was assessed by establishing reactive hyperemia. EDD prior to transplantation was significantly lower when compared with EDD measured at the 6th and 12th months after RTx (EDD pretransplantation: 6 ± 3.7%, EDD at the 6th month of RTx: 8.3 ± 2.3% and EDD at the 12th month of RTx: 12.1 ± 3.6%, P