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.

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.

[Acute and chronic effects of standard hemodialysis and soft hemodiafiltration on interdialytic serum phosphate levels]. / Effetti acuti e cronici della emodialisi standard e dell'emodiafiltrazione-soft sui livelli interdialitici della fosforemia.

INTRODUCTION: The dialytic management of hyper-phosphoremia, which is inadequate because of insufficient intra-dialytic removal of phosphate (P), is further limited by PDR-P, i.e. the significant increase in serum P levels during the early postdialytic period. Patients and methods. To investigate the effects of enhanced P removal by haemodiafiltration on the inter-dialytic phosphoremia, we studied 12 uremic patients that were switched, with cross-over randomised modality, to a single session of standard hemodialysis (HD) and hemodiafiltration (HDF) (Acute Study). Blood samples were obtained before the treatment, at the end (T0), after 30, 60, 90 and 120 minutes, and at 24, 48 and 68 hours. During both dialytic treatments the whole effluent dialysate was collected to evaluate the intradialytic removal of P. Thereafter, patients were randomised to receive either HD or HDF for three months, in the presence of constantly similar Kt/V, food intake and dose of phosphate binder (Chronic Study). RESULTS: Acute Study. Compared to HD, P removal in HDF was about 44% greater in the presence of identical predialytic P levels (6.0+/-0.2 and 5.9+/-0.4 mg/dl) and Kt/V (1.35+/-0.06 and 1.34+/-0.05); however, the inter-dialytic decline of serum P levels did not differ (-50+/-3% versus -42+/-3%, p=0.098). In HDF, PDR-P was faster (30 min versus 90 min) and better (at T120: +69+/-6% versus +31+/-4%, p<0.001). The higher P levels were maintained throughout the inter-dialytic period whereas Ca x P changed in parallel. Chronic Study. During the three months, pre-dialytic serum P diminished in HDF (from 5.8+/-0.2 to 4.4+/-0.3 mg/dl, p<0.05), while it remained unchanged in HD. A similar pattern of changes was detected in Ca x P. CONCLUSIONS: Enhancement of P removal, acutely amplifies the extent of PDR-P, but allows better control of Ca-P homeostasis in the medium term. This effect is likely to be dependent on the enhanced mobilisation of phosphate from a deep compartment.

Cis-platin-Mecy as salvage chemotherapy in recurrent advanced ovarian carcinoma.

Cis-platin (DDP) has proved to be highly active in the treatment of ovarian adenocarcinoma. The Authors have treated 12 patients with istologically proven advanced ovarian carcinoma with a type of alternating regimen consisting of four weekly DDP courses (1 mg/kg b.w./week) followed by monthly courses high-dose methotrexate (750 mg/mq i.v.) plus cyclophosphamide (250 mg/mq for 5 days) (Mecy). The alternating regimen DDP + Mecy proved to have significant activity as a salvace chemiotherapy regimen for patients with advanced ovarian carcinoma.