Serum sclerostin levels, arteriovenous fistula calcification and 2-years all-cause mortality in prevalent hemodialysis patients / Niveles de esclerostina sérica, calcificación de la fístula arteriovenosa y mortalidad por todas las causas a los 2 años en pacientes en hemodiálisis prevalente

Background: Bone and mineral abnormalities, and cardiovascular calcification are associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). Recent studies have implicated Wnt signaling pathway in the pathogenesis of bone metabolism and vascular calcification. Sclerostin is a soluble inhibitor of Wnt signaling pathway and has been shown to be associated with decreased bone turnover and vascular calcification in CKD patients. Objectives: The aim was to investigate whether the circulating levels of sclerostin are associated with all-cause mortality in prevalent hemodialysis patients. Methods: Data are prospectively collected for 24 months for survival analysis in 350 prevalent hemodialysis patients. At baseline, serum sclerostin levels were measured and arteriovenous fistula calcification was detected by using a 64-detector computerized tomographic scanner. Results: During the follow-up, 84 (24%) patients died. Patients who died had higher serum sclerostin levels. Kaplan-Meier curve revealed that patients with increasing tertiles of serum sclerostin levels at baseline, had a worse survival. In the multivariate Cox regression analysis age, albumin, and presence of arteriovenous fistula calcification, but not sclerostin levels, were found to be independent predictors of survival in maintenance hemodialysis patients. Conclusion: Further clinical studies with longer follow-up are needed to clarify the impact of serum sclerostin levels on morbidity and mortality of maintenance hemodialysis patients. Clinical trial registration number: The study was performed as a post hoc survival analysis of the patients involved in a single-center prospective trial investigating the association between serum sclerostin levels and arteriovenous fistula calcification and patency [Balcý M, et al. Herz 2015;40:289–97] with a Clinicaltrials.gov number: NCT01382966 (AU)

Antecedentes: Algunas anomalías minerales óseas y la calcificación cardiovascular están asociadas con un aumento en la mortalidad cardiovascular en pacientes con enfermedad renal crónica (ERC). Estudios recientes han implicado a la vía de señalización Wnt en la patogenia del metabolismo óseo y la calcificación vascular. La esclerostina es un inhibidor soluble de la vía de señalización Wnt y se ha demostrado que está relacionada con una reducción del recambio óseo y de la calcificación vascular en pacientes con ERC. Objetivo: El objetivo fue investigar si los niveles circulantes de esclerostina están asociados con la mortalidad por todas las causas en pacientes en hemodiálisis prevalente. Métodos: Se recogieron datos de manera prospectiva durante 24 meses para el análisis de supervivencia en 350 pacientes en hemodiálisis prevalente. Al inicio del estudio se midieron los niveles de esclerostina sérica y se detectó calcificación de la fístula arteriovenosa mediante el uso de un escáner tomográfico computarizado de 64 detectores. Resultados: Durante el período de seguimiento, murieron 84 pacientes (24%). Los pacientes que murieron presentaban elevados niveles de esclerostina sérica. La curva de Kaplan-Meier reveló que los pacientes con terciles en aumento de esclerostina sérica al inicio del estudio tenían peores tasas de supervivencia. En el análisis de regresión de Cox multivariado, la edad, los valores de albúmina y la existencia de calcificación de la fístula arteriovenosa, pero no los niveles de esclerostina, demostraron ser los indicadores independientes de supervivencia en pacientes en hemodiálisis de mantenimiento. Conclusión: Se necesitan más estudios clínicos con un seguimiento más extenso para aclarar el impacto de los niveles de esclerostina sérica en la morbimortalidad de los pacientes en hemodiálisis de mantenimiento. Número de registro del ensayo clínico: El estudio se llevó a cabo como un análisis post hoc de supervivencia de los pacientes involucrados en un ensayo prospectivo de un único centro, que investigaba la asociación entre niveles de esclerostina sérica y la calcificación y permeabilidad de la fístula arteriovenosa [Balcý M, et al. Herz 2015;40:289-97], con el númeroNCT01382966 en Clinicaltrials.gov (AU)

Serum sclerostin levels, arteriovenous fistula calcification and 2-years all-cause mortality in prevalent hemodialysis patients.

BACKGROUND: Bone and mineral abnormalities, and cardiovascular calcification are associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). Recent studies have implicated Wnt signaling pathway in the pathogenesis of bone metabolism and vascular calcification. Sclerostin is a soluble inhibitor of Wnt signaling pathway and has been shown to be associated with decreased bone turnover and vascular calcification in CKD patients. OBJECTIVES: The aim was to investigate whether the circulating levels of sclerostin are associated with all-cause mortality in prevalent hemodialysis patients. METHODS: Data are prospectively collected for 24 months for survival analysis in 350 prevalent hemodialysis patients. At baseline, serum sclerostin levels were measured and arteriovenous fistula calcification was detected by using a 64-detector computerized tomographic scanner. RESULTS: During the follow-up, 84 (24%) patients died. Patients who died had higher serum sclerostin levels. Kaplan-Meier curve revealed that patients with increasing tertiles of serum sclerostin levels at baseline, had a worse survival. In the multivariate Cox regression analysis age, albumin, and presence of arteriovenous fistula calcification, but not sclerostin levels, were found to be independent predictors of survival in maintenance hemodialysis patients. CONCLUSION: Further clinical studies with longer follow-up are needed to clarify the impact of serum sclerostin levels on morbidity and mortality of maintenance hemodialysis patients. CLINICAL TRIAL REGISTRATION NUMBER: The study was performed as a post hoc survival analysis of the patients involved in a single-center prospective trial investigating the association between serum sclerostin levels and arteriovenous fistula calcification and patency [Balci M, et al. Herz 2015;40:289-97] with a Clinicaltrials.gov number: NCT01382966.

Independent association between serum sclerostin levels and carotid artery atherosclerosis in prevalent haemodialysis patients.

BACKGROUND: Sclerostin is a soluble inhibitor of the Wnt signalling pathway and has been shown to be associated with decreased bone turnover and vascular and/or valvular calcification in patients with chronic kidney disease. Common carotid artery intima-media thickness (CIMT) assessment and common carotid artery (CCA) plaque identification with ultrasound imaging are well-recognized tools for the identification and monitoring of atherosclerosis. The aim of the present study was to investigate whether the circulating levels of sclerostin might be associated with carotid artery atherosclerosis in prevalent haemodialysis patients. METHODS: In this cross-sectional study, serum sclerostin concentrations were measured using a commercially available enzyme-linked immunosorbent assay kit. CIMT was measured and carotid plaques were identified by B-mode and Doppler ultrasound imaging. RESULTS: One hundred and twenty-two prevalent haemodialysis patients were involved in the study. Serum sclerostin levels were higher in patients with plaques in CCA than patients free of plaques (227 ± 166 versus 117 ± 91 pmol/L, P = 0.016). A significant correlation was recorded between serum sclerostin levels and CIMT (r = 0.459, P < 0.0001). In the multiple regression analysis, sclerostin concentrations were one of the independent factors that remained significantly associated with CIMT. CONCLUSION: Sclerostin is independently associated with CIMT although further studies are needed.

Urinary sodium excretion and ambulatory blood pressure findings in patients with hypertension.

Use of ambulatory blood pressure (BP) monitoring (ABPM) allows for identification of dipping, nondipping, extreme dipping, and reverse dipping of BP. Using office BP and ABPM, hypertension subtypes can be identified: sustained normotension (SNT), white-coat hypertension, masked hypertension, and sustained hypertension. The comparison of hemodynamic parameters and salt intake has not been investigated among these patient groups. Office BP, ABPM, augmentation index (AIx), pulse wave velocity (PWV), cardiac output (CO), and total peripheral resistance (TPR) were automatically measured. Estimation of salt intake was assessed by 24-hour urinary sodium excretion. Urinary sodium excretion was not different among groups. AIx, PWV, CO, and TPR were lowest in patients with SNT. CO was lowest while AIx adjusted for a heart rate of 75 beats per minute, PWV, and TPR were highest in the extreme dipper group. No relationship was detected between hypertension subtypes and urinary sodium excretion.

Prevalence of severe carotid artery stenosis and its association with echocardiographic parameters in maintenance hemodialysis patients.

OBJECTIVES: We aimed to determine the prevalence of significant carotid stenosis in maintenance hemodialysis patients and to identify biochemical and echocardiographic predictors of significant carotid stenosis in those patients. STUDY DESIGN: One hundred and seventeen maintenance hemodialysis patients were included in this study. Echocardiography biochemical tests and carotid artery Doppler ultrasonography were performed in all patients. Data obtained from patients without severe carotid stenosis were compared with those obtained from patients with severe carotid stenosis. RESULTS: The mean age of the patients was 56.9±12.2 years. Eleven patients had carotid artery stenosis (9.4%). While there was a trend of higher left ventricle end diastolic diameter in severe carotid artery stenosis (p=0.06), no statistically significant biochemical or echocardiographic differences were noted between the patients. CONCLUSION: This study demonstrated that the prevalence of carotid artery stenosis is 5-10- fold higher than in the general population. All patients in a chronic hemodialysis program should be screened for carotid artery stenosis for prevention of cerebrovascular diseases.

Body shape index and mortality in hemodialysis patients.

OBJECTIVE: The relationship between various anthropometric parameters and mortality in hemodialysis (HD) patients is conflicting. Recently a new anthropometric parameter emerged, namely, body shape index (BSI). BSI is based on waist circumference (WC) but is independent of height, weight, and body mass index in predicting mortality in the general population. The aim of this study was to determine the relationship between BSI and mortality in HD patients. METHODS: This retrospective study evaluated the demographic characteristics and anthropometric measures including BSI, laboratory parameters, and mortality data in HD patients in a single center. RESULTS: There were 142 HD patients enrolled in the study. The median BSI was 0.0816. Because no normal value was defined for BSI, the patients were divided into two groups based on the median BSI: group 1 BSI < 0.0816 and group 2 BSI > 0.0816. During an average follow-up period of 40.1 ± 19.2 mo (range 12-88 mo), 36 (25.4%) patients had died. The Cox regression analysis of independence showed that increased age (hazard ratio [HR], 1.077, 95% confidence interval [CI],1.031-1.125; P = 0.001), presence of diabetes (HR, 2.855, 95% CI, 1.258-6.481; P = 0.012), hemoglobin (HR, 0.629, 95% CI, 0.452-0.875; P = 0.006), and albumin (HR, 0.442, 95% CI, 0.204-0.955; P = 0.038) were independently related with mortality. None of the anthropometric parameters including BSI were related with mortality. Kaplan-Meier analysis showed that there were no differences with respect to mortality among patients in group 1 and group 2 based on median BSI (P = 0.332, log-rank test). CONCLUSION: In conclusion, BSI is not independently associated with mortality in HD patients.

Are there any seasonal changes of cognitive impairment, depression, sleep disorders and quality of life in hemodialysis patients?

OBJECTIVE: Cognitive impairment, depression, sleep disorders and impaired quality of life are very common in hemodialysis (HD) patients. However, whether there are any seasonal changes of cognitive impairment, depression, sleep disorders and quality of life in HD patients is not known. METHODS: The laboratory parameters, depressive symptoms, health-related quality of life, sleep quality (SQ) and cognitive function, were measured twice. RESULTS: A total of 66 HD patients were enrolled. Pre-dialysis systolic blood pressure (BP) and pre-dialysis diastolic BP were higher, whereas predialysis creatinine and sodium were lower in January compared to July. Among domains of Short Form 36 (SF-36), physical functioning, role-physical limitation, general health perception, vitality, role emotional, Physical Component Summary Score (PCS) were higher, whereas Beck Depression Inventory (BDI) score was lower in July compared to January. Stepwise linear regression analysis revealed that only change in albumin and smoking status were related with seasonal change of BDI scores. Additionally only change in Mental Component Summary score of SF-36 were related with change in PCS score of SF-36 scores. CONCLUSIONS: Depressive symptoms and quality of life but not SQ and cognitive function showed seasonal variability in HD patients.

The relationship between serum total testosterone and 24-hour urinary sodium excretion in never-treated stage 1 essential hypertensive patients.

OBJECTIVES: To study the relationship between serum total testosterone (TT) and 24-hour urinary sodium excretion in newly diagnosed stage 1 essential hypertensive patients with normal renal function. STUDY DESIGN: In total, 80 never-treated stage 1 hypertensive patients were included. All patients provided medical history and underwent physical examination, blood pressure measurement, 12-lead electrocardiography, routine urine analysis, biochemical analysis, 24-hour urine collection to measure urinary sodium and protein excretion, and creatinine clearance calculation. RESULTS: Pearson correlation analysis revealed that logarithmically converted 24-hour urinary sodium excretion was correlated with age (r=-0.399, p<0.0001), body mass index, (r=0.304, p=0.006), systolic blood pressure (r=0.394, p<0.0001), serum potassium (r=0.233, p=0.037), creatinine clearance (r=0.600, p<0.0001), and logarithmically converted serum TT (r=-0.272, p=0.015). Stepwise linear regression analysis revealed that age (p<0.0001), creatinine clearance (p=0.015), systolic blood pressure (p<0.0001), potassium (p=0.021), and serum TT (p=0.002) were independently related to logarithmically converted 24-hour sodium excretion. CONCLUSION: We demonstrated that serum TT levels were independently related to 24-hour urinary sodium amount.

Which anthropometric parameter is best related with urinary albumin excretion and creatinine clearance in type 2 diabetes: body mass index, waist circumference, waist-to-hip ratio, or conicity index?

OBJECTIVE: We analyzed the relationships between body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and conicity index and 24-hour urinary albumin excretion rate (UAER) and creatinine clearance. DESIGN: Cross-sectional study. SETTING: Patients presenting to a state hospital. PATIENTS: Study involved patients with type 2 diabetes. METHODS: Study participants underwent medical history examination, measurement of office blood pressure (BP), measurement of anthropometric factors and calculations (including BMI, WC, waist-to-hip ratio, and conicity index), physical examination, biochemical analysis, and 24-hour urine specimen collection to determine creatinine clearance and UAER. RESULTS: In all, 202 patients with type 2 diabetes (male/female: 91/111, aged: 58.4 ± 10.1 years) were included. It was found that 24-hour UAER correlated with WC (rho: +0.176, P = .012), serum albumin (rho: -0.324, P < .0001), and systolic BP (rho: +0.153, P = .029), whereas creatinine clearance correlated with age (rho: -0.152, P = .031), BMI (rho: +0.191, P = .007), albumin level (rho: +0.365, P < .0001), and uric acid level (rho: -0.369, P < .0001). The stepwise linear regression analysis revealed that WC (P = .012), glycosylated hemoglobin (P = .018), and systolic BP (P = .043) were found to be independently related to logarithmically converted 24-hour UAER, whereas creatinine clearance was found to be related to duration of diabetes (P = .001), BMI (P = .008), presence of peripheral arterial disease (P = .021), fasting serum glucose level (P = .003), and uric acid level (P < .0001). However, after correction for body surface area, BMI was no longer associated with creatinine clearance. CONCLUSION: Among the anthropometric parameters, only an increase in WC was found to be independently related to 24-hour UAER. Although BMI was associated with creatinine clearance, this association was lost after creatinine clearance was corrected for body surface area.

Serum fibroblast growth factor-23 (FGF-23) levels are independently associated with left ventricular mass and myocardial performance index in maintenance haemodialysis patients.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a phosphorus-regulating substance. Circulating FGF-23 levels increase markedly in dialysis patients and are independently associated with increased risk of mortality. Given the fact that cardiovascular disease is the leading cause of death in dialysis patients, the aim of this study was to test if elevated FGF-23 levels might be associated with left ventricular mass index (LVMI) and left ventricular index of myocardial performance (MPI) in maintenance haemodialysis patients. METHODS: In this cross-sectional study, plasma FGF-23 concentrations were measured using a C-terminal human enzyme-linked immunosorbent assay kit, and echocardiography was performed in 128 maintenance haemodialysis patients (65 women and 63 men, mean age: 55.5 ± 13 years, mean haemodialysis vintage: 52 ± 10 months, all patients are on haemodialysis thrice a week) and 40 control subjects (21 women and 19 men; mean age: 54 ± 11 years) with normal kidney function (eGFR > 90 mL/min/1.73 m(2)). RESULTS: Serum FGF-23 levels were elevated when compared with age- and gender-matched controls with preserved kidney function [(median 958 RU/mL; interquartile range 106-1894 RU/mL) vs (median 27 RU/mL; interquartile range 11-35), P < 0.0001]. Patients with a history of coronary artery disease and aortic valve calcifications had higher levels of log FGF-23 than those without (3.00 ± 0.22 vs 2.82 ± 0.26, P = 0.002; and 3.06 ± 0.19 vs 2.83 ± 0.26, P = 0.0001, respectively). Patients with MPI > 0.47 had higher serum FGF-23 levels than those with MPI < 0.47 [(median 1156 RU/mL; interquartile range 396-1894 RU/mL) vs (median 657 RU/mL; interquartile range 106-1102 RU/mL), P = 0.0001]. Significant correlations were recorded between log FGF-23 levels and LVMI (r = 0.281, P = 0,007) and MPI (r = 0.555, P = 0.0001). Multivariable-adjusted regression analyses revealed that increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (30% increase per 1-SD increase in log FGF-23 concentration, P = 0.002) and increased MPI (28.5% increase per 1-SD increase in log FGF-23 concentration, P = 0.001). CONCLUSIONS: Plasma FGF-23 concentration is independently associated with LVMI and MPI in maintenance haemodialysis patients. Further prospective studies are needed to clarify whether increased serum FGF-23 level is a marker or a potential mechanism for left ventricular involvement in patients with end-stage renal disease.

Simple renal cysts and circadian blood pressure: are they related to each other in patients with hypertension?

Previous studies have shown that the presence of simple renal cysts was related to hypertension. However, the relationship between simple renal cysts and circadian blood pressure was not studied before. Our study population comprised of newly diagnosed patients with essential hypertension. Medical history, physical examination and office blood pressure measurements, laboratory analysis, ambulatory blood pressure measurements, renal ultrasonography, and 24-h urine specimens were collected. In total, the study included 190 patients (male/female ratio 77/113; mean age 50.3 ± 11.3). Overall, 127 (66.8%) patients were dippers and 92 (48.4%) had at least one simple renal cyst. Thirty-five patients had solitary cysts and 57 patients had multiple cysts. Cysts were bilateral in 47 of patients. Most of ambulatory blood pressure recordings were higher in patients with at least one simple cyst when compared to patients without cysts. In multivariate logistic regression analysis, serum uric acid (P: 0.047, OR: 1.287, CI: 1.011-1.658), lower creatinine clearance (P: 0.001, OR: 1.030, CI: 1.012-1.049), presence of diabetes (P: 0.029, OR: 2.451, CI: 1.094-5.491), and presence of at least one cyst in each kidney (P: 0.002, OR: 3.087, CI: 1.533-6.212) were found to be independently related to nocturnal non-dipping. In conclusion, the presence of simple renal cysts is related to higher ambulatory BP and is associated with non-dipping phenomenon in patients with essential hypertension.

Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients.

Fibroblast growth factor-23 (FGF-23) has been suggested to play a role in vascular calcification in chronic kidney disease. Common carotid artery intima-media thickness (CIMT) assessment and common carotid artery (CCA) plaque identification using ultrasound are well-recognized tools for identification and monitoring of atherosclerosis. The aim of this study was to test that elevated FGF-23 levels might be associated with carotid artery atherosclerosis in maintenance hemodialysis (HD) patients. In this cross-sectional study, plasma FGF-23 concentrations were measured using a C-terminal human enzyme-linked immunosorbent assay kit. Carotid artery intima-media thickness was measured and CCA plaques were identified by B-Mode Doppler ultrasound. One hundred twenty-eight maintenance HD patients (65 women and 63 men, mean age: 55.5 ± 13 years, mean HD vintage: 52 ± 10 months, all patients are on HD thrice a week) were involved. The mean CIMT were higher with increasing tertiles of plasma FGF-23 levels (0.66 ± 0.14 vs. 0.75 ± 0.05 vs. 0.86 ± 0.20 mm, P<0.0001). Log plasma FGF-23 were higher in patients with plaques in CCA than patients free of plaques (3.0 ± 0.17 vs. 2.7 ± 0.23, P<0.0001). Significant correlation was recorded between log plasma FGF-23 and CIMT (r=0,497, P=0.0001). In multiple regression analysis, a high log FGF-23 concentration was a significant independent risk factor of an increased CIMT. Further studies are needed to clarify whether an increased plasma FGF-23 level is a marker or a potential mechanism for atherosclerosis in patients with end-stage renal disease.

Association among serum fetuin-A level, coronary artery calcification, and bone mineral densitometry in maintenance hemodialysis patients.

Patients with end-stage renal disease have a very high prevalence and extent of arterial calcification. A number of studies suggest that similar pathophysiologic mechanisms are responsible for development and progression of calcification of atherosclerotic plaque and bone formation. Fetuin-A is a potent calcification inhibitor and is expressed in bone, with not-yet well-defined functions. The aim of this study was to investigate the relation between bone mineral densitometry parameters, coronary artery calcification, and serum fetuin-A levels. In a cross-sectional design, we included 72 maintenance hemodialysis (HD) patients and 30 age- and gender-matched healthy controls. Serum fetuin-A levels were studied both in maintenance HD patients and healthy controls. Maintenance HD patients had radius, hip, and lumbar spine bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry and coronary artery calcification score (CACS) measured by electron-beam computed tomography. The associations between site-specific BMD parameters, CACS, and serum fetuin-A levels were studied in maintenance HD patients. CACS, mass, and volume of plaques in coronary arteries were significantly higher in patients with a T-score below -2.5 than above in the proximal region of the radius, neck and trochanter of the femur, and the lumbar spine. Mean serum fetuin-A concentration was 0.636 +/- 0.118 g/L in maintenance HD patients and it was less than healthy controls (0.829 +/- 0.100 g/L, P < 0.0001). CACS, mass, and volume of plaques in coronary arteries correlated significantly with the serum fetuin-A levels. Moreover, significant positive correlations were shown between the serum fetuin-A levels, BMD values, and T-scores of proximal radius, neck, and trochanter of the femur, but not with the lumbar spine. The present study demonstrates an association between serum fetuin-A levels, coronary artery calcification, and bone mineral densities--except for the lumbar spine, in maintenance HD patients. However, the results should be interpreted with caution because of the cross-sectional design of the study.

Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment.

BACKGROUND: Matrix metalloproteinases, a family of proteolytic enzymes are thought to be involved in extracellular matrix accumulation during development of hypertensive target organ disease. The present study was designed to compare hypertensive patients with normotensive individuals with respect to serum levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and to search for the effect of antihypertensive treatment on the serum enzyme levels. METHODS: Thirty-three patients with stage 1 primary hypertension and sixteen age- and sexmatched control subjects were enrolled into the study. Serum MMP-9 and TIMP-1 levels were assessed in the hypertensive group before and after a 3-month-antihypertensive treatment (candesartan 8 mg/day to 17 patients and lisinopril 10 mg/day to 16 patients). RESULTS: Pre-treatment serum MMP-9 levels were higher in the hypertensive group (p=0.309) while serum TIMP-1 levels were lower (p=0.296). Serum MMP-9 levels were decreased (p<0.001) and TIMP-1 levels were increased (p=0.022) after the antihypertensive treatment. CONCLUSIONS: In hypertensive patients, increased MMP-9 activity could result in increased degradation of elastin relative to collagen and non-elasticity, while decreased TIMP-1 activity could lead to accumulation of poorly cross-linked, immature and unstable fibril degradation products, which result in misdirected deposition of collagen. Our study is important for revealing the role of the MMP enzyme system in the pathogenesis of hypertensive target organ disease.

Concomitant amyloidosis, renal papillary carcinoma and ipsilateral pelvicalyceal urothelial carcinoma in a patient with familial Mediterranean fever.

We report a case of a 58-year-old man with a history of long standing familial Mediterranean fever (FMF) and AA amyloidosis, who developed renal papillary carcinoma and renal pelvic urothelial carcinoma simultaneously. Although the association between chronic inflammatory states like FMF and AA amyloidosis has been well established, the relationship between amyloidosis and solid tumors is not defined as clearly. Furthermore, to the best of our knowledge, co-existence of two different types of kidney malignancy with amyloidosis in a patient with FMF has not been reported. Our patient was admitted to hospital with gross hematuria and renal insufficiency. Imaging studies revealed mass lesions in the middle portion of the right kidney. Right radical nephrectomy showed extensive amyloid deposition, co-existing with renal papillary carcinoma and poorly differentiated invasive urothelial carcinoma.

Effect of renin angiotensin system blockade on pentraxin 3 levels in type-2 diabetic patients with proteinuria.

BACKGROUND AND OBJECTIVES: Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data of 49 persons with stage 1 diabetic CKD and 32 healthy subjects in a prospective controlled trial. Endothelial dysfunction was determined by flow-mediated dilation (FMD). Serum PTX3, high-sensitivity C-reactive protein (hs-CRP) levels, and FMD were studied in baseline and after 12 wk of ramipril therapy. Stepwise multivariate regression analysis evaluated the association of FMD with clinical and serologic parameters. RESULTS: Serum PTX3, hsCRP, and albumin levels and proteinuria were significantly decreased, and FMD levels were significantly increased, after ramipril treatment. FMD was negatively correlated with serum PTX3, 24-h proteinuria, and hsCRP levels and positively correlated to serum albumin both at baseline and after the 12-wk treatment period. Multivariate regression analysis revealed that PTX3 levels were independently related to FMD both before and after ramipril treatment. CONCLUSIONS: Our study shows that serum PTX3 levels are associated with endothelial dysfunction in patients with stage 1 diabetic CKD, independent of CRP. In addition, short-term ACE-inhibitor treatment significantly improves FMD and normalizes PTX3, hsCRP, and urinary protein excretion. (NCT: The study was registered in clinicaltrials.gov as NCT00674596.).

The interleukin-10 promoter genotype predicts diastolic dysfunction in maintenance hemodialysis patients.

Interleukin-10 (IL-10) predominantly acts as an anti-inflammatory factor. Polymorphisms in the IL-10 gene promoter determine quantitative cytokine production. Doppler echocardiography and tissue Doppler imaging (TDI) are superior to conventional echocardiography to evaluate diastolic dysfunction. The IL-10 gene promoter polymorphism at position (-1082) was studied for its association with conventional and Doppler echocardiographic and TDI parameters in 112 hemodialysis (HD) patients. Blood pressure, serum C-reactive protein (CRP), and albumin levels were also examined for the association study. The genetic association study showed that among the HD patients, there was no difference in the prevalence of systolic and diastolic dysfunction between genotypes on conventional echocardiography. However, using Doppler echocardiography and TDI, high producers for the IL-10 -1082 promoter (-1082/GG) have higher E velocities, E/A values, lateral, and septal E' velocities and a lower isovolumic ventricular relaxation time than low (-1082/AA) and intermediate producers (-1082/GA). Significantly higher levels of serum CRP levels and lower plasma albumin levels were found in low and intermediate producers for the IL-10 -1082 promoter than high producers. The IL-10 genotype may balance the effects of inflammatory cytokines on the myocardium and may be a determinant of LV function in HD patients.

Association of serum lipid profile and arteriovenous fistula thrombosis in maintenance hemodialysis patients.

BACKGROUND: Vascular access thrombosis represents a major cause of morbidity in the hemodialysis population. The role of serum lipid profile in access thrombosis is not sufficiently established. The aim of this study was to investigate the association between serum lipid profile and native arteriovenous fistula (AVF) thrombosis. METHODS: Clinical files of 99 maintenance hemodialysis patients were reviewed retrospectively for 3 years. Serum lipid profile, albumin and C-reactive protein (CRP) were measured. Catheter angiography was performed in patients with AVF dysfunction and AVF thrombosis. RESULTS: Patients with AVF thrombosis and patent AVF had similar serum levels of total cholesterol and triglyceride levels. However, patients with AVF thrombosis had significantly lower low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and albumin and higher serum CRP levels than patients with patent AVFs. CONCLUSIONS: Serum levels of lipid subfractions are associated with AVF thrombosis in maintenance hemodialysis patients. Larger and prospective cohort studies are needed to confirm these observations.

Enterococcal endocarditis associated with crescentic glomerulonephritis.

Glomerulonephritis secondary to infective endocarditis (IE) is an uncommon diagnosis and is usually associated with cardiac valvular infection by blood-culture-positive bacteria. We report a case of necrotizing glomerulonephritis associated with culture-positive endocarditis caused by Enterococcus faecalis. The patient presented with renal abnormalities and was further investigated by renal biopsy. He had immune complex-mediated necrotizing and crescentic glomerulonephritis with mesengial and capillary deposition of immunoglobulin M (Ig M), Ig G, and complement 3 (C3). He was treated with antibiotics, including ampicillin and gentamicin. In addition, steroid and cyclophosphamide were administered. The patient died of renal failure 48 days after hospital admission. In conclusion, glomerulonephritis caused by Enterococcus faecalis endocarditis is an immune-complex-mediated disease characterized by necrotizing and crescentic glomerular lesions that can be fatal despite aggressive antimicrobial and immunosuppressive therapy.

Magnetic resonance imaging of the rotator interval in patients on long-term hemodialysis: correlation with the range of shoulder motions.

OBJECTIVE: To assess the rotator interval of patients on long-term hemodialysis with magnetic resonance imaging (MRI) for the presence of adhesive capsulitis and to correlate these findings with shoulder motions. METHODS: Seventeen shoulders in 16 patients (mean age, 53.8 years) on hemodialysis (range of duration, 4-28 years) who had pain and limited range of shoulder motion underwent MRI. Rotator interval was inspected in 3 regions (subcoracoid area, above the subscapularis muscle, and around the biceps tendon) on sagittal magnetic resonance images with regard to increased nonfatty soft tissue intensity as none, mild, moderate, and marked. Magnetic resonance images were evaluated by 2 musculoskeletal radiologists with consensus. Ranges of motion for external and internal rotation and abduction and forward flexion were assessed either normal or mildly, moderately, and severely limited. RESULTS: Increased nonfatty soft tissue intensity within the rotator interval fat was observed in 11 shoulders (65%). Very strong positive correlation was found between the limitation of external rotation and the presence of nonfatty soft tissue infiltrating all 3 areas of the rotator interval fat (rs, between 0.81 and 0.96; P < 0.001). Strong positive correlation was found between the hemodialysis duration and the presence of nonfatty soft tissue infiltrating all 3 areas of the rotator interval fat (rs, between 0.68 and 0.71; P