Subendocardial viability ratio predicts cardiovascular mortality in chronic kidney disease patients.

BACKGROUND: The subendocardial viability ratio (SEVR), calculated by pulse wave analysis, is an index of myocardial oxygen supply and demand. Here we analyze the relation between SEVR and cardiovascular mortality in the chronic kidney disease (CKD) population of a post hoc analysis of a multicenter, prospective, randomized, nonblinded study. METHODS: We studied 212 consecutive asymptomatic outpatients receiving care at 12 nephrology clinics in south Italy. Inclusion criteria were age >18 years, 6 months of follow-up before the enrollment and stage 3-4 CKD. RESULTS: During follow-up, 34 subjects died, 29 of them for cardiovascular causes. SEVR correlated inversely with vascular calcifications (r = -0.37) and myocardial mass (r = -0.45); SEVR changed from 1.33 ± 0.24 to 1.36 ± 0.16 (p = NS; baseline and final values, respectively) in living patients, and from 1.16 ± 0.31 to 0.68 ± 0.26 in deceased patients (p < 0.001). Kaplan-Meier curves show that that a greater reduction of SEVR values during the study (third tertile) significantly predicts cardiovascular mortality (p < 0.0001). CONCLUSIONS: This post hoc analysis shows that a reduction of SEVR values impacts cardiovascular mortality in CKD patients.

Sleep disorders in kidney disease.

Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

[Acute and persistent antiproteinuric effect of a low-protein diet in chronic kidney disease]. / Acuto e persistente effetto antiproteinurico della dieta ipoproteica artificiale nella malattia renale cronica.

This study aimed to evaluate the anti-proteinuric effect of a very-low-protein diet supplemented with essential amino acids and keto analogs in patients with moderate to advanced chronic kidney disease and proteinuria already treated with both ACE inhibitors and angiotensin-receptor blockers. The study was a prospective randomized controlled cross-over trial comparing a very-low-protein diet (VLpD) and a low-protein diet (LpD). We enrolled 32 consecutive patients between June 2000 and June 2005. They were randomized to receive a VpLD (group A) or an LpD (group B) for 6 months; thereafter, patients of both groups were switched to the other diet (group A to LpD; group B to VpLD) for a further 6 months. Finally, all patients were randomized again within each group to receive either LpD or VLpD and were followed for another year. The VLpD group showed a significant reduction of urinary protein excretion during the diet period, with a nadir at the fourth month of treatment; the amount of urinary protein reduction was about 58%. Serum advanced glycation end products (AGE) significantly decreased in 10 patients (5 of group A, 5 of group B; -18% and -19%, respectively) during VLpD. Univariate analysis showed that proteinuria correlated indirectly with VpLD and directly with AGE. This study demonstrates that in patients with moderate to advanced chronic kidney disease and severe proteinuria, a VLpD reduces both proteinuria and serum AGE, even in the presence of complete inhibition of the renin-angiotensin system.

High-tone external muscle stimulation in end-stage renal disease: effects on symptomatic diabetic and uremic peripheral neuropathy.

OBJECTIVE AND DESIGN: Pain and peripheral neuropathy are frequent complications of end-stage renal disease (ESRD). Because drug treatment is associated with numerous side effects and is largely ineffective in many maintenance hemodialysis (MHD) patients, nonpharmacologic strategies such as electrotherapy are a potential recourse. Among various forms of electrostimulation, high-tone external muscle stimulation (HTEMS) is a promising alternative treatment for symptomatic diabetic peripheral polyneuropathy (PPN), as demonstrated in a short-term study. Based on these novel findings, we performed a prospective, nonrandomized, pilot trial in MHD patients to determine (1) whether HTEMS is also effective in treating diabetic PPN in the uremic state, and (2) whether uremic PPN is similarly modulated. PATIENTS AND INTERVENTIONS: In total, 40 MHD patients diagnosed with symptomatic PPN (25 with diabetic and 15 with uremic PPN) were enrolled. Both lower extremities were treated intradialytically with HTEMS for 1 hour, three times a week. Initially, a subgroup of 12 patients was followed for 4 weeks, and a further 28 patients for 12 weeks. The patients' degree of neuropathy was graded at baseline before HTEMS and after 1 and 3 months, respectively. Five neuropathic symptoms (tingling, burning, pain, numbness, and numbness in painful areas) as well as sleep disturbances were measured, using the 10-point Neuropathic Pain Scale of Galer and Jensen (Neurology 48:332-338, 1997). A positive response was defined as the improvement of one symptom or more, by at least 3 points. Other parameters included blood pressure, heart rate, dry body weight, and a routine laboratory investigation. RESULTS: The HTEMS led to a significant improvement in all five neuropathic symptoms, and to a significant reduction in sleep disturbances for both diabetic and uremic PPN. The response was independent of the patient's age, with a responder rate of 73%. The improvement of neuropathy was time-dependent, with the best results achieved after 3 months of treatment. The HTEMS was well-tolerated by nearly all patients. CONCLUSIONS: This pilot study shows for the first time that HTEMS can ameliorate the discomfort and pain associated with both diabetic and uremic PPN in MHD patients, and could be a valuable supplement in the treatment of pain and neuropathic discomfort in patients who do not respond to, or are unable to participate in, exercise programs during hemodialysis treatment.

Prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients--the Campania Dialysis Registry.

BACKGROUND: This study investigated prevalence and correlates of anemia and uncontrolled anemia in chronic hemodialysis patients. METHODS: A cross-sectional analysis was performed on registry data for 2,746 chronic (>6 months) hemodialysis patients aged 25-84. Data collection included years of dialysis, hours of dialysis/wk, disease causing hemodialysis, body mass index (BMI), erythropoietin (EPO) treatment, hemoglobin, markers of viral hepatitis, serum albumin, calcium, and phosphorus. RESULTS: Prevalence was 88.7% for anemia (hemoglobin <11 g/100 mL and EPO treatment at any Hb level), 39.4% for uncontrolled anemia (hemoglobin<11 g/100 mL). Gender, years of dialysis, hereditary cystic kidney disease (HCKD), and low BMI (<24 kg/m2) were independent correlates of anemia (P<0.001). Gender, HCKD, low BMI, serum albumin and calcium were independent correlates of uncontrolled anemia (P<0.05). An interaction was found between age (not correlated with anemia and uncontrolled anemia) and the association of gender with uncontrolled anemia (P<0.05). EPO doses were higher in patients with high prevalence of uncontrolled anemia than in patients with low prevalence (i.e., women vs men, other diseases vs HCKD, low vs not-low BMI, P<0.01). Gender, years of dialysis, HCKD, BMI, serum albumin, and calcium were independent correlates of the hemoglobin/EPO dose ratio in patients on EPO treatment (P<0.05). CONCLUSION: Anemia and uncontrolled anemia are more frequent in hemodialysis patients with shortterm dialysis, diseases other than HCKD, low BMI, and female gender. Gender effect was lower in elderly patients. Uncontrolled anemia was also associated with low serum albumin and calcium, suggesting that these parameters are indices of EPO resistance.

Overexpression of chromatin assembly factor-1/p60 predicts biological behaviour of laryngeal carcinomas.

This study analysed the immunohistochemical expression of the CAF-1/p60 protein in laryngeal cancers. CAF-1/p60 assumes an independent discriminative and prognostic value in laryngeal neoplasms; the presence of this protein in carcinoma in situ compared with laryngeal precancerous and larynx infiltrating tumours. We assessed the immunohistochemical expression of CAF-1/p60 in 30 cases of moderate and/or severe dysplasia, 30 cases of carcinoma in situ and 30 cases of laryngeal squamous cell carcinoma (LSCCs). CAF-1/p60 expression increased significantly according to the high index of neoplastic cellular replication; therefore, CAF-1/p60 was overexpressed in neoplastic cells and its moderate-severe expression is correlated with poorer prognosis compared to less expression. In conclusion, overexpression of the CAF-1/p60 protein is related to a risk of higher morbidity and mortality and is a reliable independent prognostic index of laryngeal carcinoma. CAF1-p60 protein overexpression can be used in cancer management as an indicator of malignant evolution, especially in carcinoma in situ.

Pathophysiology of the cardio-renal syndromes types 1-5: An uptodate.

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome (CRS) has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS (acute cardio- renal syndrome) is characterized by acute worsening of cardiac function leading to AKI (5, 6) in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury (AKI), while type 4 represent cardiovascular involvement in chronic kidney disese (CKD) patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases.

Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation.

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15-49ml/min) and those on dialysis.

Long-term results of kidney transplantation with cyclosporine- and everolimus-based immunosuppression.

The aim of the study was to evaluate safety and efficacy of everolimus with cyclosporine (CsA) in de novo renal transplant recipients. The immunosuppressive regimen, including basiliximab, everolimus (3 mg), and low-dose CsA, was administered to 17 patients, of whom 15 were part of a multicenter randomized study that stipulated cessation of steroids at 7 days posttransplantation in 5 recipients. Five patients underwent dialysis after transplantation for delayed graft function (DGF; 29%), all of whom showed a good recovery within 3 weeks. The mean follow-up was 45.7 months (SD +/- 13). The 1-year graft survival was 100%. We observed one acute rejection episode. No patient experienced a cytomegalovirus infection. Increased cholesterol and triglyceride levels were reported in almost all patients. Severe arthralgia (n = 3) was treated by everolimus dose reduction to maintain trough levels at 3 ng/mL. We noted a high rate of switch to mycophenolate mofetil (MMF) throughout follow-up (n = 7), due to everolimus-induced side effects. However, we did not observe normalization of lipids after the switch: patients always required stain treatment, resulting in slightly lower serum cholesterol and triglycerides. Everolimus plus CsA was effective to prevent acute rejection after kidney transplantation. To manage the induced side effects of the drugs C(2) monitoring is mandatory, targeting 350 ng/mL during 1 year and 200 to 250 ng/mL thereafter. Careful reduction of everolimus trough levels to 3 ng/mL is recommended for patients with arthralgia.

Graft failure due to hemolytic uremic syndrome recurrence.

The hemolytic uremic syndrome (HUS) is a severe disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. We herein report our experience with a 43-year-old female patient who underwent a second cadaveric kidney transplantation in February 2005, for adult-onset HUS. The first renal transplantation, which was performed in 1996, required removal after 3 weeks for probable recurrence of HUS. The immunosuppressive regimen for the second transplant included basiliximab, tacrolimus, mycophenolate mofetil, and steroids. On postoperative day (POD) 7, she received steroid treatment for an acute rejection episode with improved renal function. On POD 19 due to worsening renal function, a graft biopsy showed HUS recurrence, thus we instituted hemodialysis and then plasmapheresis treatments. At two months after transplantation, the patient continued under plasmapheresis treatment due to clinical evidence of HUS. On POD 80, cytomegalovirus infection was diagnosed and intravenous gancyclovir treatment started for 3 weeks. After 110 days from transplant, a deterioration in renal function was evident: the graft was swollen and painful with Doppler ultrasound showing patency of both the renal artery and vein but, low blood flow. After 2 weeks of hemodialysis, the patient underwent transplantectomy. In adult-onset HUS the recurrence rate reduces graft survival, particularly among patients undergoing second transplantation.

Fourteen years of hemodialysis with a central venous catheter: mechanical long-term complications.

The ideal dialysis access ensures adequate blood flow for dialysis, has a long life, and is associated with a low complication rate. Although no current type of access fulfills all these criteria, the native arteriovenous fistula (AVF) is close to doing so. Unfortunately, various kinds of vascular access (VA) are becoming more and more necessary to enable hemodialysis (HD). The central venous catheter (CVC), which is associated with higher morbidity and mortality, could be the only viable option to maintain permanent VA. We report an unusual complication in a patient, a 74-year-old female, who had been undergoing HD via a CVC for 14 yrs. A polyurethane CVC with a double lumen was inserted into the right internal jugular vein because an AVF was not feasible, and a polytetrafluoroethylene (PTFE) prosthesis was obstructed. In 2003, the CVC was removed due to stenosis and occlusion of the superior vena cava. A new CVC, also made of polyurethane and with a double lumen, was inserted into the left femoral vein. In January 2005, the patient reported a small rupture of about 3-4 mm located under the cuff of the CVC. For this reason, the left femoral vein had to be used, replacing the Optiflow one with a 40-cm long Tesio CVC, and the second catheter was inserted into the right femoral artery by conventional surgery. After 10 months, the patient returned once more, after the CVC in the left femoral vein had been removed because of malfunction and that the at-tempts to cannulate the same vein again had failed. Currently, two 70-cm long Tesio catheters implanted in the right femoral vein (whose tips almost reach the diaphragm) are used for dialysis sessions. The number of CVC implants has progressively increased amongst HD patients who are elderly, diabetic or who have been on long-term HD. The patient described in this case report is currently using a 70-cm long double Tesio catheter (single Tesio CVC in SPI silicon) placed in the right femoral vein. She has resumed therapy with dicumarol anticoagulants, maintaining INR within the 2.5-3.5 range. In conclusion, both the increase in the use of venous catheters for HD and in the survival of dialysis patients contribute towards the observation of rare complications associated with CVC use.

Infectious complications in renal transplant recipients.

Renal transplantation has become a well-established therapeutic option for end-stage renal disease, but infectious diseases remain a significant cause of morbidity and mortality. Although a wide variety of pathogens may cause infection, viral ones must be regarded as the single most important class of infections. Progress has been made both in the prevention and the early recognition treatment of infections that are closely linked to rejection. Immunosuppressive therapy is central to the pathogenesis of both. Because of the particular characteristics of transplant recipients, it is desirable to establish a close collaboration between nephrologists, surgeons, and infectious disease specialists for the management of these patients. In this article, we describe the different kinds of infectious disease that may affect patients with kidney transplant and the fundamental principles of clinical management, particularly our experience in Polyoma virus (BK) infection.

Sleep disorders in hemodialyzed patients--the role of comorbidities.

BACKGROUND: Sleep disorders are very frequent in hemodialyzed patients, but the relationship between these disorders and water withdrawal, urea removal and comorbidities has not been sufficiently clarified. METHODS: The study comprised a group of 88 patients in good nutritional condition, with target hemoglobin concentration, good control of blood pressure and optimal dry weight. After answering a questionnaire (SDQ) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) patients were assigned to one of 3 groups: those with no disturbances (no.20), those with subclinical disorders (n.35) and insomniacs (n.33). Yearly fluid and urea withdrawal by dialysis and the Charlson Comorbity Index were measured. RESULTS: Sleep disorders were observed in 77.27% of the patients. There was no difference in body fluid and urea withdrawal between groups. In the group of patients with no sleeping disturbances, the Charlson Comorbidity Index was significantly lower (p<0.001) than in patients with subclinical disorders or insomnia and emerged as a strongly associated with sleep disturbances. The study also attributes a predictive role to age, dialytic age, dialysis shift, antihypertensive drugs. The data indicate that, in evaluating sleeping disorders in patients on maintenance hemodialysis, comorbidities should be assessed.

[Bioelectrical analysis in uremic patients]. / La bioimpedenza nella clinica del paziente uremico.

Bioelectrical analysis (BIA) is an easy, repeatable, low cost, operator-independent method. BIA obtains two different goals, i.e. body water content evaluation, by the RXc Graph or the BIVA Z score and morbidity and mortality predictions by the phase angle. Therefore, BIA can be considered as part of the clinical examination for the evaluation of both hydration and nutritional status.

Simultaneous PET/MR head-neck cancer imaging: Preliminary clinical experience and multiparametric evaluation.

PURPOSE: To evaluate the role of simultaneous hybrid PET/MR imaging and to correlate metabolic PET data with morpho-functional parameters derived by MRI in patients with head-neck cancer. METHODS: Forty-four patients, with histologically confirmed head and neck malignancy (22 primary tumors and 22 follow-up) were studied. Patients initially received a clinical exam and endoscopy with direct biopsy. Next patients underwent whole body PET/CT followed by PET/MR of the head/neck region. PET and MRI studies were separately evaluated by two blinded groups (both included one radiologist and one nuclear physician) in order to define the presence or absence of lesions/recurrences. Regions of interest (ROIs) analysis was conducted on the primary lesion at the level of maximum size on metabolic (SUV and MTV), diffusion (ADC) and perfusion (K(trans), Ve, kep and iAUC) parameters. RESULTS: PET/MR examinations were successfully performed on all 44 patients. Agreement between the two blinded groups was found in anatomic allocation of lesions by PET/MR (Primary tumors: Cohen's kappa 0.93; FOLLOW-UP: Cohen's kappa 0.89). There was a significant correlation between CT-SUV measures and MR (e.g., CT-SUV VOI vs. MR-SUV VOI: ρ=0.97, p<0.001 for the entire sample). There was also significant positive correlations between the ROI area, SUV measures, and the metabolic parameters (SUV and MTV) obtained during both PET/CT and PET/MR. A significant negative correlation was observed between ADC and K(trans) values in the primary tumors. In addition, a significant negative correlation existed between MR SUV and ADC in recurrent tumors. CONCLUSION: Our study demonstrates the feasibility of PET/MR imaging for primary tumors and recurrent tumors evaluations of head/neck malignant lesions. When assessing HNC, PET/MR allows simultaneous collection of multiparametric metabolic and functional data. This technique therefore allows for a more complete characterization of malignant lesions.

Bioelectrical impedance analysis in heart transplantation: early and late changes.

The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

Normal values of the bioelectrical impedance vector in childhood and puberty.

The purpose of this study was to determine the reference, bivariate, and tolerance intervals of the whole-body impedance vector in Italian children. This was a cross-sectional, multicenter study, and participants were chosen from the general school population. The impedance vector (standard, tetrapolar analysis at 50-kHz frequency) was measured in 3110 subjects, ages 2 to 15 y, and 2044 healthy children (1014 male and 1030 female) with weight and height within the 95th percentile were selected for the analysis (resistance-reactance graph method). The age-specific 95% confidence intervals of mean vectors and the 95%, 75%, and 50% tolerance intervals for individual vector measurements were plotted using resistance and reactance components standardized by the subject's height. Mean vectors from both sexes with separate 95% confidence ellipses were considered as representative of eight different age groups, from 2 to 13 y. There was a statistically significant sex effect on vector distribution from boys and girls in the age group of 14 to 15 y. The impedance vector distribution of children was also compared with healthy adult subjects (354 male and 372 female, age 15 to 85 y). There was a progressive, statistically significant vector shortening from age 2 to 15 y toward the adults' vector position. In conclusion, we established the trajectory followed by the mean impedance vector in children over ages 2 to 15 y and also obtained the reference, bivariate, and 95%, 75%, and 50% tolerance intervals of the impedance vector by age for healthy children, with which the vectors from children with altered body composition can be tested.

Amino acid losses during CAPD.

Amino acid losses in peritoneal dialyzate during CAPD were less than 2 g a day (15, 128 micrometers). CAPD does not correct the tyrosine/phenylalanine ratio in plasma and does not prevent accumulation of 3-methylhistidine.

The prediction of single-frequency BIA variables from individual characteristics.

To define whether reference values for bioimpedance analysis (BIA) can be predicted in healthy individuals, individual characteristics and BIA variables (resistance index=height(2)/parallel resistance and reactance index= height(2)/parallel reactance) were evaluated in non-obese healthy individuals: 863 men and 769 women with an age range 20-70 years and body mass index (BMI) 19.0-29.9 kg/m(2). The following predictive equations were obtained using multiple regression analysis:Resistance index (cm(2)/ohm)Males 21.06 + 0.087xage + 1.091xweight -1.801xBMI,Females 20.35 + 0.037xage + 0.878xweight - 1.343xBMIReactance index (cm(2)/ohm)Males 0.57 + 0.117xweight - 0.096xBMIFemales 1.42 + 0.078xweight - 0.075xBMIIn conclusion, reference BIA values seem to be reasonably predicted based on individual characteristics.

Sirolimus in kidney transplantation from marginal donors.

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.