Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

BACKGROUND: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. METHODS: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. RESULTS: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). CONCLUSIONS: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

Positive effects of dietary supplementation with nutraceuticals on male subclinical hypogonadism: a pilot study.

BACKGROUND: Lifestyle modifications (i.e., physical activity [PA] and lower dietary intake) often are not sufficient to improve testosterone (TE) levels and promote weight loss in men with metabolic hypogonadism. The aim of the study was to investigate the effects of a nutraceutical formulation containing myoinositol, alpha lipoic acid, folic acid and SelectSIEVE® as add-on treatment to lifestyle modifications in improving obesity-related subclinical hypogonadism. METHODS: Body composition, insulin resistance, testicular and erectile function were investigated in 15 males (age=39.5±14.5 years; Body Mass Index [BMI]=30.2±3.8 kg/m2, with subclinical hypogonadism (TE levels <14 and normal luteinizing hormone [LH]). After a run-in three months unsupervised PA period (T1), the nutraceutical supplement was administered two-times per day for three additional months (T2). RESULTS: BMI, the percentage fat mass, insulinemia and Homeostasis Model Assessment Index (P<0.01) along with glycemia (P<0.05) were significantly reduced at T2 compared to T1, respectively; fat free mass (FFM) was significantly higher at T2 compared to T1 (P<0.01). Also, TE, LH and 5-item international index of erectile function score were significantly increased at T2 compared to T1 (P<0.01), respectively. CONCLUSIONS: The combination of unsupervised PA and nutraceutical supplement improves body composition, insulin sensitivity and TE production in overweight-obese men with metabolic hypogonadism. Further controlled studies in the long-term are warranted to elucidate potential changes in fertility.

The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

Clinical scoring systems for the risk of cardiovascular autonomic neuropathy in type 1 and type 2 diabetes: A simple tool.

This study was aimed at developing a clinical risk score for cardiovascular autonomic neuropathy (CAN) for type 1 and type 2 diabetes. In a retrospective cross-sectional one-centre study in an unselected population, 115 participants with type 1 diabetes (age 41.1 ± 12.2 years) and 161 with type 2 diabetes (age 63.1 ± 8.9 years), well-characterized for clinical variables, underwent standard cardiovascular reflex tests (CARTs). Strength of associations of confirmed CAN (based on 2 abnormal CARTs) with clinical variables was used to build a CAN risk score. CAN risk score was based on resting heart rate, HbA1c, retinopathy, nephropathy, cardiovascular disease in both type 1 and type 2 diabetes, and on HDL cholesterol, systolic blood pressure, and smoking in type 1 diabetes or insulin treatment and physical activity in type 2 diabetes (range 0-10). In type 1 diabetes, CAN risk score showed an area under the ROC curve (AUC) of 0.890 ± 0.034, and at cut-off of 4 sensitivity of 88%, specificity of 74.4%, and negative predictive value (NPV) of 95.7% for confirmed CAN. In type 2 diabetes, CAN risk score showed an AUC of 0.830 ± 0.051 and at the cut-off of 4 sensitivity and specificity of 78.6% and 73.5%, respectively, and NPV of 97.3% for confirmed CAN. These newly developed CAN risk scores are accessible in clinical practice and, if confirmed in a validation study, they might identify asymptomatic individuals with diabetes at greater risk of CAN to be referred to CARTs, thus limiting the burden of a universal screening.

[Urinary tract infections in nephrology: antibiotic therapy in the era of antibiotic resistance].

Urinary tract infections (UTIs) are an emerging health problem. Kidney patients with UTI are at increased risk of antimicrobials resistance (AMR) and bad prognosis. In the nephrological setting, optimizing the management of UTIs is certainly a challenge, but it is indispensable for a favorable clinical outcome and in fighting AMR. When UTIs caused by multidrug-resistant germs are suspected, it is necessary to initiate empirical antibiotic therapy timely, pending microbiological study and bacterial sensitivity. The empirical choice of antibiotic must be based on: guidelines, resistance rates recorded in the region, and knowledge of pharmacokinetic and pharmacodynamic characteristics of the drug, in order to maximize efficacy, reduce adverse effects and minimize AMR development. Recently, the clinical use of old drugs such as colistin has increased, due to the limited circulation of resistant bacterial strains. On the other hand, ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, imipenem/cilastatin/relebactam and meropenem-vaborbactam are very promising new antibiotics. Ongoing clinical studies will be able to determine the place for these interesting molecules in the treatment of infections and in fighting AMR.

[Atheroembolic renal disease: risk factors, diagnostics, histology, and therapeutic approaches].

The increase in patients' average age, the enhancement of anticoagulation therapy and the growth of vascular interventions represent the perfect conditions for the onset of atheroembolic renal disease. AERD is observed in patients with diffuse atherosclerosis, generally after a triggering event such as surgery on the aorta, invasive procedures (angiography, catheterization of the left ventricle, coronary angioplasty) and anticoagulant or fibrinolytic therapy. The clinical signs are heterogeneous, a consequence of the occlusion of downstream small arterial vessels by cholesterol emboli coming from atheromatous plaques of the aorta, or one of its main branches. The proximity of the kidneys to the abdominal aorta, and the high flow of blood they receive, make them a major target organ. For this reason, AERD represents a pathological condition that always needs to be taken into account in the nephropathic patient, although its systemic nature makes the diagnosis difficult. This manuscript presents a review of the existing literature on this pathology, to provide an updated summary of the state of the art: risk factors, diagnostics, histology and therapeutic approaches.

[SGLT2 inhibitors, beyond glucose-lowering effect: impact on nephrology clinical practice].

Epidemiological data show an increasing diffusion of diabetes mellitus worldwide. In the diabetic subject, the risk of onset of chronic kidney disease (CKD) and its progression to the terminal stage remain high, despite current prevention and treatment measures. Although SGLT2 inhibitors have been approved as blood glucose lowering drugs, they have shown unexpected and surprising cardioprotective and nephroprotective efficacy. The multiple underlying mechanisms of action are independent and go beyond glycemic lowering. Hence, it has been speculated to extend the use of these drugs also to subjects with advanced stages of CKD, who were initially excluded because of the expected limited glucose-lowering effect. Non-diabetic patients could also benefit from the favorable effects of SGLT2 inhibitors: subjects with renal diseases with different etiologies, heart failure, high risk or full-blown cardiovascular disease. In addition, these drugs have a good safety profile, but several post-marketing adverse event have been reported. The ongoing clinical trials will provide clearer information on efficacy, strength and safety of these molecules. The purpose of this review is to analyze the available evidence and future prospects of SGLT2 inhibitors, which could be widely used in nephrology clinical practice.

Treatment of juxta-anastomotic stenoses for failing distal radiocephalic arteriovenous fistulas: Drug-coated balloons versus angioplasty.

The aim of our study is to report the results of two types (type A, type B) paclitaxel drug-coated balloon compared with standard percutaneous transluminal angioplasty in the treatment of juxta-anastomotic stenoses of mature but failing distal radiocephalic hemodialysis arteriovenous fistulas. Two groups of 26 and 44 patients treated with two different drug-coated balloon are compared with a control group of 86 treated with standard percutaneous transluminal angioplasty. A color Doppler ultrasound was performed to evaluate stenosis and for treatment planning. We assess primary patency, defined as the absence of dysfunction of the arteriovenous fistulas, patent lesion or residual stenosis < 30% and no need for further reintervention of target lesion. Primary patency and secondary patency are evaluated after 12 months with color Doppler ultrasound for the whole arteriovenous fistulas, defined as absolute (absolute primary patency, absolute secondary patency) and target lesion. Postprocedural technical and clinical success was 100%. After 12 months, absolute primary patency is 81.8% for type A, 84.1% type B, and 54.7% for standard percutaneous transluminal angioplasty; target lesion primary patency is 92% type A, 86.4% type B, and 62.8% standard percutaneous transluminal angioplasty; absolute secondary patency is 95.4% type A, 95.5% type B, and 80.7% standard percutaneous transluminal angioplasty; target lesion secondary patency is 100% type A, 97.7% type B, and 80.7% standard percutaneous transluminal angioplasty. All the patients treated with drug-coated balloon (type A + type B) have an absolute primary patency of 83.3%, a target lesion primary patency of 87.9%, an absolute secondary patency of 95.5%, and a target lesion secondary patency of 98.4%. Our study confirms that the use of drug-coated balloon, indiscriminately among different brands, improves primary patency with statistically significant difference in comparison with standard percutaneous transluminal angioplasty and decreases reintervention of target lesion in juxta-anastomotic stenoses of failing distal arteriovenous fistulas maintaining the radiocephalic fistula as long as possible.

Drug-eluting balloon for the treatment of failing hemodialytic radiocephalic arteriovenous fistulas: our experience in the treatment of juxta-anastomotic stenoses.

PURPOSE: The purpose of this article is to report our experience with drug-eluting balloons for the treatment of juxta-anastomotic stenoses of failing radiocephalic hemodialytic arteriovenous shunt and to evaluate the primary and secondary patency (PP and SP). METHODS: After approval by the local hospital's Ethical and Scientific Review Board, 26 consecutive patients with juxta-anastomotic stenosis of radiocephalic hemodialytic shunt were treated with angioplasty with drug-eluting balloon. The main objective was to evaluate PP defined, in accordance with the Kidney Disease Outcomes Quality Initiative recommendation, as the absence of dysfunction of the vascular access, patent lesion or residual stenosis <30% and no need for further reintervention of the target lesion (TL). PP and SP at 6, 12 and 24 months were evaluated, with echo color doppler and phlebography, for both arteriovenous fistulae, defined as absolute, and TL. RESULTS: Immediate postprocedural technical and clinical success was 100% for all the patients; we had only one technical failure in repeated treatments. At 6 months the absolute and TL PP was 96.1%; at 12 months the absolute PP was 81.8%, TL PP 90.9%, absolute SP 95.4%, TL SP 100%; at 24 months the absolute and TL PP was 57.8%; absolute and TL SP 94.7%; only one arteriovenous fistula was lost during the period. CONCLUSIONS: The use of drug-eluting balloons, after standard angioplasty, improves primary patency and decreases reinterventions of TL in juxta-anastomotic stenoses of failing native dialytic arteriovenous shunts.

Venae comitantes as a potential vascular resource to create native arteriovenous fistulae.

PURPOSE: The arteriovenous fistula (AVF) represents the gold standard for hemodialysis (HD) vascular access. In some critical cases, use of the deep venous circle may represent an alternative approach and venae comitantes could be employed for this purpose. METHODS: Sixty patients with chronic renal failure in which the deep venous circle was used to create an AVF were identified; of the 48 who had a direct anastomosis between the brachial artery and vena comitans, 42 had a long-term follow-up (mean follow-up 59 weeks), while six were lost to follow-up. RESULTS: Immediate success (patency and palpable thrill) was achieved in 88% of cases (primary and early failure 12%). Primary accessibility rate was 62%, while 11 patients required a second surgical approach to make the vein accessible to needling. Secondary accessibility rate of 71% was due to surgical revisions. In the 80-week observation period, the complication rate was 10% with irreversible loss of the AVF in all these cases. Cumulative patency was 71% at the 80th week. Including all 42 patients, technical and functional success rate, defined as vein accessibility to needling and chance of an adequate HD treatment, was 62%. CONCLUSIONS: AVF employing venae comitantes may represent a suitable alternative in the absence of other vascular accesses for HD.

[Multislice computed tomographic angiography in the assessment of central veins for endovascular treatment planning: comparison with phlebography]. / Angio-TC MS nello studio dei vasi venosi centrali per la pianificazione del trattamento endovascolare: studio comparativo con la flebografia.

The dysfunction of a vascular access for hemodialysis and its loss may depend on drainage difficulties of the superficial or deep venation due to hemodynamically significant stenosis or obstruction of a central vein, which generally involve the innominate-subclavian veins or superior vena cava. These alterations are often neglected due to their central and deep location; when there is hemodynamic compensation, they may remain asymptomatic. For these reasons every suspect clinical sign for central vein stenosis (gross arm syndrome or venous hypertension in an arteriovenous fistula) must not be ignored, as timely intervention is essential for functional recovery of the vessel and for the protection of the arteriovenous fistula. The modern imaging techniques ensure thorough diagnostic assessment, while the possibilities of endovascular treatment with interventional radiology allow, in a large proportion of cases, optimal minimally invasive treatment, but above all the recovery of venation in a hemodialyzed patient. We report our experience with multislice computed tomographic angiography (MS-CTA) and reconstruction software for treatment planning of central vein stenosis or obstruction. Forty-nine patients were studied with MS-CTA (GE 16). Images were acquired in the venous phase (120-180 seconds after contrast medium injection) followed by digital vascular reconstruction (AutoBone for bone removal, vessel analysis for caliber and length measurements, thin and curved MIP, MPR). Within a week control phlebography was performed. The venous tree was divided into seven segments and analyzed in a double-blind fashion with a distinction between patent segments, 50-70% stenosis, >70% stenosis, occlusion, and collateral vascular beds. There was excellent correspondence in all the examined segments for patency, >70% stenosis, and occlusion, with high sensitivity (98%), specificity (99.3%), and diagnostic accuracy (99.1%). The binomial test demonstrated a highly significant concordance (alpha=0.99) for all patients and in all vascular segments with the exception of 70% stenoses, in which MS-CTA gave a slight overestimate. In the central venous district, color Doppler ultrasonography may not be as effective as for the peripheral study of arteriovenous fistulae, and second-level imaging techniques such as MS-CTA are more useful. We suggest that endovascular treatment must be preceded by MS-CTA. This examination shows the lesions that may benefit from endovascular treatment and recognizes ''uncrossable'' lesions, ie, the ones that will not benefit from treatment. Moreover, it allows accurate planning of endovascular treatment by showing the lesion type (stenosis or obstruction), the position and extension of the involved vessels, the vessel caliber above and below the lesion, and the possible presence of a collateral vascular bed. MS-CTA with dedicated reconstruction software, if correctly performed and accurately reconstructed, is a precious tool for diagnosis and treatment planning.

Vascular endothelial growth factor, left ventricular dysfunction and mortality in hemodialysis patients.

OBJECTIVES: Vascular endothelial growth factor induces nitric oxide-dependent angiogenic effects and participates in the inflammatory response. This cytokine is over-expressed in the myocardium in experimental models of pressure overload and renal mass ablation, and vascular endothelial growth factor is increased in end-stage renal disease. We investigated the relationship between vascular endothelial growth factor, left ventricular function (by midwall fractional shortening) and mortality in a prospective cohort study in 228 hemodialysis patients. RESULTS: Serum vascular endothelial growth factor concentration was associated directly with interleukin-6 and tumor necrosis factor-alpha (P < 0.01) and inversely with albumin (P = 0.007) but was independent of the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine. Vascular endothelial growth factor was inversely related with midwall fractional shortening (P = 0.002) and predicted mortality (P = 0.02). In multivariate analyses testing the involvement of this angiogenic cytokine in left ventricular dysfunction and death, these links remained substantially unmodified after adjustment for Framingham risk factors, risk factors peculiar to end-stage renal disease (Hb, Ca, P) and previous cardiovascular complications. However, these links became weaker and not significant when biomarkers of inflammation and asymmetric dimethylarginine were sequentially introduced into the multivariate models. In crude and adjusted analyses, left ventricular function was lowest in patients who displayed both high vascular endothelial growth factor and high asymmetric dimethylarginine, intermediate in patients with either high vascular endothelial growth factor or high asymmetric dimethylarginine and highest in those with low asymmetric dimethylarginine and low vascular endothelial growth factor (P = 0.001). CONCLUSION: Vascular endothelial growth factor is associated with left ventricular systolic dysfunction and mortality in hemodialysis patients. Vascular endothelial growth factor appears to be in the pathway whereby inflammation and nitric oxide inhibition lead to cardiomyopathy and death in hemodialysis patients.

Venlafaxine-propafenone interaction resulting in hallucinations and psychomotor agitation.

OBJECTIVE: To report a case of visual hallucinations and psychomotor agitation probably induced by an interaction between venlafaxine and propafenone. CASE SUMMARY: An 85-year-old woman was admitted for evaluation of a mood disorder on March 20, 2006. Her general practitioner had prescribed sertraline for treatment, which had started about 6 months earlier. The patient's medical history included hypertension, supraventricular tachycardia, chronic bronchitis, and arthritis, for which she received ramipril, ticlopidine, torsemide, theophylline, acetaminophen, and triazolam. The patient had also received propafenone 150 mg every 12 hours for 3 years. Results of biochemical tests were normal; however, a computed tomography (CT) scan of the brain showed signs of cortical atrophy. Sertraline was discontinued after a few days because of its reduced effectiveness and was replaced with extended-release venlafaxine 75 mg/day. No other changes to the patient's drug therapy were made. Four weeks later, because of the persistence of psychiatric disturbance, the venlafaxine dosage was increased to 150 mg/day. Ten days later the patient returned to our observation due to the onset of visual hallucinations lasting about 2 hours, especially at night, and psychomotor agitation. Venlafaxine was discontinued, with a complete remission of hallucinations and psychomotor agitation in about 4 days. The Naranjo probability scale indicated a probable relationship between venlafaxine and the patient's symptoms. Citalopram was started one month later for the persistence of mood disorders, with no adverse effects. DISCUSSION: A CT scan documented signs of cortical atrophy in our patient's brain but excluded vascular brain injury, while clinical evaluation and anamnesis excluded a relationship between hallucinations and cortical atrophy. Genetic and pharmacologic factors may be involved in venlafaxine-induced adverse effects. Venlafaxine is metabolized primarily by CYP2D6 and is a substrate of P-glycoprotein. Propafenone, a known substrate and inhibitor of both CYP2D6 and P-glycoprotein, could therefore be involved in venlafaxine-induced hallucinations through the increase of venlafaxine plasma concentrations. CONCLUSIONS: To prevent the onset of clinical disturbances during venlafaxine treatment, we suggest careful evaluation of concomitant treatment with CYP2D6 or P-glycoprotein inhibitors (eg, propafenone) and, when possible, venlafaxine serum concentration monitoring.

Low triiodothyronine and cardiomyopathy in patients with end-stage renal disease.

OBJECTIVES AND METHODS: Low free plasma triiodothyronine (fT3) is associated with inflammation and cardiovascular damage in patients with end-stage renal disease (ESRD). We investigated the relationship between fT3, left ventricular systolic function and left ventricular mass in a group of 234 dialysis patients, and modelled the association between fT3 and cardiomyopathy in statistical analyses including both direct (interleukin-6 and C-reactive protein) and inverse (serum albumin) acute phase inflammation markers. RESULTS: Plasma fT3 concentration in dialysis patients was significantly (P < 0.001) reduced in comparison with healthy participants and clinically euthyroid patients with normal renal function. Left ventricular systolic function was depressed (P

Left ventricular systolic function monitoring in asymptomatic dialysis patients: a prospective cohort study.

Although it is well established that compromised systolic function predicts cardiovascular (CV) complications in symptomatic and asymptomatic patients with ESRD, it still is unknown whether repeated echocardiographic measurements of systolic function in asymptomatic patients with ESRD is useful for monitoring the evolution of cardiomyopathy in these patients. The prognostic value for CV events of changes in systolic function, as measured by midwall fractional shortening (mwFS) in a cohort of 191 dialysis patients, was tested. Echocardiography was performed twice, 17 +/- 2 mo apart. Changes in mwFS (ch-mwFS) that occurred between the second and the first echocardiographic studies then were used to predict CV events during the ensuing 27 +/- 13 mo. After the second echocardiographic study, 85 patients had incident CV events. In a Kaplan-Meier analysis, there was a graded increase in the risk for fatal and nonfatal CV events across ch-mwFS quartiles (P = 0.005). On multivariate Cox regression analysis, ch-mwFS maintained an independent association with CV outcomes. In this analysis, the risk for CV events was 51% lower in patients who manifested an increase in mwFS (hazard ratio 0.49; 95% confidence interval 0.27 to 0.88; P = 0.02) than in those who had a decrease in mwFS. Changes in mwFS have an independent prognostic value for CV events, and periodic echocardiographic studies of systolic function are useful for monitoring asymptomatic dialysis patients.

Hyperhomocysteinemia and arteriovenous fistula thrombosis in hemodialysis patients.

BACKGROUND: To date, the relationship between vascular access (VA) failure and plasma total homocysteine level has been investigated only in mixed dialysis populations (ie, patients with a native arteriovenous [AV] fistula or arterial graft), whereas almost no data exist for hemodialysis patients with a native AV fistula. METHODS: In this prospective cohort study, we examined the relationship between plasma total homocysteine level and the methylenetetrahydrofolate reductase (MTHFR) gene and VA-related incident morbidity in a cohort of 205 hemodialysis patients, all with a native AV fistula. RESULTS: During follow-up, 78 patients experienced 1 or more VA thrombotic episodes. Patients with incident VA thrombosis had a significantly greater plasma total homocysteine level compared with patients without this event (P = 0.046). In Kaplan-Meier survival analysis, the hazard ratio for VA thrombosis increased in parallel with homocysteine level, such that patients in the third homocysteine level tertile had a relative risk for this outcome 1.72 times (95% CI, 1.21 to 2.24) greater than in those in the first tertile (log-rank test, 6.81; P = 0.009). In a multiple Cox regression model, plasma total homocysteine level was confirmed to be an independent predictor of AV fistula outcome. Plasma total homocysteine level was significantly greater (P < 0.001) in patients with the TT genotype of the MTHFR gene than in those with the CT or CC genotype. CONCLUSION: VA thrombosis in dialysis patients is associated with hyperhomocysteinemia. Intervention studies are needed to clarify whether decreasing plasma homocysteine concentrations may prevent VA failure in hemodialysis patients.

Prognostic value of echocardiographic indicators of left ventricular systolic function in asymptomatic dialysis patients.

Patients with end-stage renal disease (ESRD) are at high risk for heart failure, but the prevalence and the prognostic value of asymptomatic systolic dysfunction in these patients are unknown. In this prospective cohort study, the authors have therefore assessed by echocardiography the prevalence and the prognostic value of systolic function as estimated by ejection fraction (EF), fractional shortening at endocardial level (endoFS), and at midwall (mwFS), in a cohort of 254 asymptomatic dialysis patients. Systolic dysfunction had a prevalence rate of 26% by endoFS and of 48% by mwFS. During the follow-up period, 125 patients had one or more fatal and nonfatal CV events. On multivariate COX regression analysis, the three LV systolic function indicators were independently associated with incident fatal and nonfatal CV events, and there were no differences in the predictive power of these indicators (P > 0.30). The prediction power of LV function indicators was largely independent of traditional and novel risk factors in ESRD such as C-reactive protein and asymmetric dimethyl arginine (ADMA). ADMA was significantly related with LV function indicators as well as with mortality and incident CV events, but these links were much reduced (P = NS) in models including LV function indicators. Of note, the risk of CV events was minimal in patients with normal LV mass and function, intermediate in patients with either LVH or systolic dysfunction, and maximal in patients displaying both alterations. The study of myocardial contractility by echocardiography provides prognostic information independently of LV mass and other risk factors in ESRD. Risk stratification by simple systolic function parameters may prove useful in secondary prevention strategies in these patients.

Prospective study of neuropeptide y as an adverse cardiovascular risk factor in end-stage renal disease.

Chronic renal insufficiency is a situation characterized by high plasma concentration of neuropeptide Y (NPY). Because this neuropeptide interferes with cardiovascular (CV) function, it is possible that it is involved in the high CV-related morbidity and mortality of these patients. To test this hypothesis, a follow-up study was performed (average duration, 34 mo; range 0.2 to 52.0 mo) in a cohort of 277 patients with end-stage renal disease receiving chronic dialysis. Univariate analysis revealed that plasma NPY was directly related to plasma norepinephrine (r = 0.37, P < 0.001) and epinephrine (r = 0.17, P = 0.005), exceeding the upper limit of the normal range in the majority of patients with end-stage renal disease (170 of 277, 61%). One hundred thirteen patients had one or more fatal and nonfatal CV events; 112 patients died, 66 of them (59%) of CV causes. Plasma NPY failed to predict all-cause mortality but was an independent predictor of adverse CV outcomes (hazard ratio [10 pmol/L increase in plasma NPY], 1.32; 95% confidence interval, 1.09 to 1.60; P = 0.004) in a Cox proportional-hazard model that included a series of traditional and nontraditional CV risk factors. Plasma NPY maintained its predictive power for CV events in statistical model including plasma norepinephrine. Plasma NPY predicts incident CV complications in end-stage renal disease. Controlled trials are needed to establish whether interference with the sympathetic system, NPY, or both may reduce the high CV morbidity and mortality of dialysis patients.

Chlamydia pneumoniae, overall and cardiovascular mortality in end-stage renal disease (ESRD).

BACKGROUND: Cross-sectional and retrospective studies suggest that Chlamydia pneumoniae infection may contribute importantly to the high cardiovascular risk of patients with end-stage renal disease (ESRD). METHODS: We investigated the relationship between C. pneumoniae serology and survival and incident fatal cardiovascular events in a cohort of 227 ESRD patients (follow-up of 39 +/- 20 months). RESULTS: On univariate Cox regression analysis patients with anti-C. pneumoniae immunogloblulin A (IgA) titer > or = 1:16 had a significantly higher risk of all-cause and cardiovascular mortality when compared to patients without IgA antibodies. However, after data adjustment for age and smoking, the hazard ratio (HR) decreased substantially and became largely nonsignificant. Adjustments for traditional and nontraditional risk factors further decreased the independent association of IgA anti-C. pneumoniae and these outcomes (all-cause mortality HR, 1.08; 95% CI, 0.68 to 1.72; P = 0.74; cardiovascular mortality HR, 1.07; 95% CI, 0.60 to 1.89; P = 0.83). A similar loss of prognostic power was observed for IgG anti-C. pneumoniae so that in fully adjusted models the HRs were very close to those observed for IgA anti-C. pneumoniae (all-cause mortality HR, 1.13; 95% CI, 0.68 to 1.86, P = 0.64; cardiovascular mortality HR, 1.10; 95% CI, 0.60 to 2.00; P = 0.77). CONCLUSION: C. pneumoniae seropositivity is associated to shorter survival and incident fatal cardiovascular events in patients with ESRD but these associations are in large part attributable to the link between C. pneumoniae and well-established, traditional risk factors. It is highly unlikely that C. pneumoniae infection is a major risk factor in patients with ESRD.

Neuropeptide Y, left ventricular mass and function in patients with end stage renal disease.

OBJECTIVE: Neuropeptide Y (NPY) is released during sympathetic stimulation and mediates the central effects of the adipostatic hormone leptin. The plasma concentration of NPY and leptin is increased in patients with end stage renal disease (ESRD), but it is unknown whether these substances are related to biochemical markers of sympathetic activity and to alterations in left ventricular (LV) mass and function in these patients. DESIGN: We investigated the relationship between NPY, norepinephrine (NE), leptin and echocardiographic measurements in a cross-sectional study in 198 patients with ESRD. RESULTS: NPY was directly related to plasma NE and heart rate but it was largely independent of arterial pressure and of retention of metabolic waste products. NPY was significantly higher in patients with LV hypertrophy and in those with LV systolic dysfunction than in those without these alterations. Of note, NPY emerged as an independent correlate of LV mass index and of LV ejection fraction (LVEF) (both P