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BACKGROUND: Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation. METHODS: Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µg thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression. RESULTS: Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm. CONCLUSIONS: Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs. Copyright © 2020 by the American Society of Nephrology.

Individualized weighing of the risk benefit of anticoagulation is recommended in patients with atrial fibrillation (AF) who have low established risk scores or, conversely, are at increased risk for bleeding. Parameters of arterial stiffness and wave reflection could improve risk stratification, but their use has not been evaluated in arrhythmia. We measured carotid-femoral pulse wave velocity (PWV), central augmentation index (AI), and central pulse pressure (CPP) using the SphygmoCor system in 34 patients (53 to 85 years; 25 males) with AF before and after elective electrical cardioversion. Agreement was assessed using the intraclass correlation coefficient (ICC) and the coefficient of variation, completed with Bland–Altman plots. After cardioversion, mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly by 8 mmHg and 18 bpm, respectively. PWV decreased from 11.8 m/s to 10.7 m/s, AI increased from 24% to 29%, and CPP rose from 38 mmHg to 43 mmHg. The decrease in PWV was related to the decrease in MAP (beta = 0.57; R2 = 0.33; P

BACKGROUND Hypomagnesemia is associated with a disturbed glucose metabolism. Insulin hypo-secretion predicts diabetes in the general population and in transplant recipients. We aimed to assess whether magnesium improves insulin secretion and glycemic control after transplantation in prevalent hypomagnesemic kidney transplant recipients. MATERIAL AND METHODS We conducted an open-label, randomized, parallel-group study. Eligible participants were adults more than 4 months after kidney transplantation on tacrolimus with persisting serum magnesium concentrations

Background: Individualized weighing of the risk-benefit of anticoagulation is recommended in patients with atrial fibrillation (AF) that have low established risk scores or, conversely, are at increased risk for bleeding1. Parameters of arterial stiffness and wave reflection could improve risk stratification, but their use has not been validated in arrhythmia2–3. Methods: We measured carotid-femoral pulse wave velocity (PWV), central augmentation index (AI) and central pulse pressure (CPP) using the SphygmoCor (AtCor Medical, Sydney, Australia) system in 34 patients (53 to 85 years; 25 males) with AF before and after elective electrical cardioversion. Agreement was assessed using the intraclass correlation coefficient (ICC) and the coefficient of variation, completed with Bland-Altman plots. Results: Following cardioversion, mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly by 7 mmHg and 18 bpm respectively. PWV decreased from 11.8 m/s to 10.7 m/s, AI increased from 24% to 29%, and CPP rose from 45 mmHg to 50 mmHg. The decrease in PWV was related to the decrease in MAP (beta = 0.57; R2 = 0.33; P < 0.001) whereas changes in AI and CPP were related to the decrease in HR (AI: beta = −0.59; R2 = 0.35; P < 0.001, CPP: beta = −0.52; R2 = 0.26; P = 0.001). After adjustment for changes in MAP and HR, reliability analysis showed an excellent agreement for PWV (ICC = 0.89; 95%CI: 0.79–0.95) but moderate agreement for AI (ICC = 0.59; 95%CI: 0.17–0.80). Excellent agreement was also found for CPP (ICC = 0.89; 95%CI: 0.78–0.94). Figure 1.A. Scatter plot showing PWV before (PWVt0) and after (PWVt1) cardioversion. The solid line Is the Ihie of identity, the broken line the regression line for PWVt1 vs PWt0 (Passini & Bablok regression). B. Bland-Altman plot showing the proportional difference (%) between P∖) between PWV after (PVWt1) and PWV before (PWVt0) cardioversion. The solid line represents the mean value ot PWV and the dotted lines mean ± 2 SD. Figure 2.A. Scatter plot showing Al before (Alt0) and after (Alt1) cardioversion. The solid line is the line of identity, the broken line the regression line for Alt1 vs Alt0 (Passing & Bablok regression). B. Bland-Altman plot showing the proportional difference (%) between Al after (Alt1) and Al before (Alt0) cardioversion. The solid line represents the mean value of Al and the dotted lines mean±2 SD. Conclusions: Measurement of PWV and CPP is reliable in patients with AF, as they appear unaffected by the presence of arrhythmia.

Background— In previous studies on the effect of renal stenting on arterial hypertension, patients were selected mainly on the basis of angiographic parameters of the renal artery stenosis. The aim of the present study was to evaluate whether translesional pressure gradients could identify the patients with renal artery stenosis who might benefit from stenting. Methods and Results— A total of 53 consecutive hypertensive patients with unilateral RAS scheduled for renal artery intervention were recruited. Transstenotic pressure gradients were measured at baseline and during maximal hyperemia, before renal artery stenting. Twenty-four-hour ambulatory blood pressure measurements were performed in all patients before and 3 months after the intervention. Average reductions in systolic blood pressure and diastolic blood pressure at follow-up were −20±30 mm Hg and −2±12 mm Hg, respectively. At multivariate analysis, dopamine-induced mean gradient was the only independent predictor of the variations of both systolic blood pressure (regression coefficient=−4.03, standard error=1.11; P P =0.009). Patients who showed a decline in systolic blood pressure from the baseline value >20 mm Hg were considered as “responders.” The optimal cutoff for identification of “responders” was a dopamine-induced mean gradient ≥20 mm Hg (area under the curve, 0.77; 95% confidence interval, 0.64 to 0.90; P =0.001). Conclusions— A dopamine-induced mean pressure gradient of ≥20 mm Hg is highly predictive of arterial hypertension improvement after renal stenting, and therefore this measurement is useful for appropriate selection of patients with arterial hypertension.

BACKGROUND Increasing evidence indicates that lipophilic and/or protein-bound substances such as p-cresol are responsible for adverse physiological alterations in uraemic patients. To better understand the evolution of p-cresol disposition in renal failure and dialysis patients, it is necessary to determine its kinetic characteristics and biotransformation pathways. METHODS We studied the biotransformation of p-cresol after intravenous injection of the compound in eight rats with normal renal function. Urine was collected in four 1 h intervals. To evaluate the presence of p-cresol metabolites, beta-glucuronidase was added to urine samples and the isolated unidentified chromatographic peak observed in previous experiments was submitted to tandem mass spectrometry (MS/MS) analysis. RESULTS Administration of p-cresol produced a p-cresol peak and an unknown peak, suggesting biotransformation of the compound. Addition of beta-glucuronidase to urine samples and incubation at 37 degrees C resulted in a marked decrease in the unidentified peak height (P

The immunosuppressive drugs tacrolimus and sirolimus may have a stimulatory influence on gastric emptying, in view of their macrolide structure. The aim of this study was to investigate in vitro the possible interaction of tacrolimus and sirolimus with motilin receptors in the rabbit antrum and duodenum.Rabbit duodenum strips were mounted under a load of 1 g in 10 ml organ baths containing Krebs solution. Erythromycin, tacrolimus, cyclosporin, and sirolimus were added to the bathing solution in a cumulative way; in a second series, after incubation with cyclosporin (10(-7) mol/l), tacrolimus (10(-8) mol/l), or sirolimus (3 x 10(-8) mol/l), a cumulative concentration-response curve to erythromycin was obtained. The effect of cumulatively added tacrolimus and nle(13)-porcine motilin on the contractile response to electrical field stimulation was tested in strips from the rabbit gastric antrum. Displacement by tacrolimus of (125)I-nle(13)-porcine motilin bound to its receptor was tested with crude homogenates of the smooth-muscle layer of the rabbit antrum.In rabbit duodenum strips, carbachol (10(-5) mol/l) induced a stable and reproducible contraction. Erythromycin induced concentration-dependent contractions. Expressed as a percentage of the response to carbachol, the maximal attained effect was 78%; the EC(50) was 4.8 x 10(-7) mol/l. Tacrolimus (10(-8) to 10(-5) mol/l), cyclosporin (10(-8) to 10(-5) mol/l), and sirolimus (10(-8) to 3 x 10(-5) mol/l) had no influence. The response to erythromycin (10(-8) to 3 x 10(-5) mol/l) in the presence of cyclosporin (10(-7) mol/l), tacrolimus (10(-8) mol/l), or sirolimus (3 x 10(-8) mol/l) did not differ from that obtained with erythromycin alone, except for a decrease of the EC(50) in the presence of tacrolimus (2.2 x 10(-7) mol/l) (P0.05 vs erythromycin alone). Motilin enhanced the response to electrical field stimulation of rabbit antral strips, but tacrolimus had no stimulatory effect. Tacrolimus weakly displaced motilin bound to its receptor. The pIC(50) was 4.97.As opposed to erythromycin, neither tacrolimus nor sirolimus showed a contractile effect in the rabbit duodenum. Tacrolimus did not activate the neural motilin receptor of the rabbit gastric antrum and had low affinity for the smooth-muscle motilin receptor. It is thus unlikely that these macrolide immunosuppressive drugs possess gastroprokinetic effects via motilin agonism.

Hemodialysis patients frequently experience such dyspeptic symptoms as nausea, vomiting, abdominal distension, early satiety, and anorexia. Gastroparesis might be a cause of malnutrition, and parameters of gastric emptying are inversely correlated with serum albumin levels. The aim of the present study is to determine whether delayed gastric emptying is related to dyspeptic symptoms. In 54 hemodialysis patients, a standardized history for dyspeptic symptoms was taken. In addition, gastric emptying for solids was measured in 26 patients, using the (13)C-octanoic acid breath test. There was a high prevalence of dysmotility-like dyspepsia in the hemodialyzed population. A significant difference in gastric emptying between dyspeptic hemodialysis patients and healthy volunteers and between dyspeptic and nondyspeptic hemodialysis patients was shown. There was a significant correlation between gastric emptying and dysmotility-like dyspepsia. Serum albumin level inversely correlated with gastric emptying. In conclusion, there is a high prevalence of dysmotility-like dyspepsia in hemodialysis patients. Dyspeptic patients have significantly delayed gastric emptying compared with both healthy volunteers and nondyspeptic patients.

European as well as US guidelines recommend the Modification of Diet in Renal Disease (MDRD) formula to determine the glomerular filtration rate (GFR) and, based on this, the staging of chronic kidney disease (CKD). The diagnosis of CKD is only established when a reduced eGFR has been observed for 3 months or longer. Because the MDRD equation is very complex, the calculation of eGFR is not possible without help from calculators or computers. Therefore, we converted this equation into simple, easy to use colour nomograms. These were drawn separately for men and women, on one hand, and for whites and blacks, on the other. These nomograms allow the determination of a patient’s eGFR in a quick and easy way and at any location.

Although there is overwhelming evidence that natriuretic peptides might be helpful in the diagnosis and management of congestive heart failure patients, the relationship among brain natriuretic peptides (BNP), renal function, and the severity of heart failure is less clear. It is obvious that the metabolism and elimination of BNP and N-terminal prohormone brain natriuretic peptide (NT-proBNP) are different with BNP clearance less dependent upon renal function. This paper reviews current data about the diagnostic and predictive role of natriuretic peptides to detect cardiac events in patients with chronic kidney disease. Although BNP and Nt-proBNP can be used to diagnose acute heart failure and may help predict risk and future cardiac events in patients with chronic kidney disease (CKD), a strategy that incorporates their use in daily clinical practice is still lacking.

Background: Uremic syndrome is the consequence of the retention of solutes usually cleared by the healthy kidneys. p-Cresol can be considered a prototypic protein-bound uremic toxin. It is conceivable, analogous with drugs, that the non-protein-bound fraction of p-cresol exerts toxicity. This aspect had never been evaluated, nor have the factors influencing the free fraction of p-cresol.Methods: In a transsectional study we evaluated the relationship between prehemodialysis free p-cresol and the ratio of free to total p-cresol (F:T) to clinical and biological factors in 44 chronic renal failure patients. The evolution of free p-cresol was assessed prospectively in 12 patients showing a change in serum albumin of at least 5 g/L over time. Hospitalization days attributable to infection and the free p-cresol concentrations were noted over a 1-year period. The impact of free p-cresol in vitro on leukocyte functional capacity was evaluated by chemiluminescence.Results: We observed a correlation between total and free p-cresol (r = 0.84; P Conclusions: Hypoalbuminemia and total p-cresol increase the free fraction of p-cresol. Patients hospitalized for infections have higher free p-cresol. In vitro, high free p-cresol has a negative impact on leukocyte chemiluminescence production. These data demonstrate the toxicity of free p-cresol.

Enterococcus cecorum was isolated as the etiologic agent of a continuous ambulatory peritoneal dialysis peritonitis episode in an alcoholic patient. To date, this is only the third infection due to this bacterium, found in the intestinal tract of many domestic animals, that has been reported in humans.

Introduction Acute renal failure after cardiac surgery increases in-hospital mortality. We evaluated the effect of intra- and postoperative tight control of blood glucose levels on renal function after cardiac surgery based on the Risk, Injury, Failure, Loss, and End-stage kidney failure (RIFLE) criteria, and on the need for acute postoperative dialysis. Methods We retrospectively analyzed two groups of consecutive patients undergoing cardiac surgery with cardiopulmonary bypass between August 2004 and June 2006. In the first group, no tight glycemic control was implemented (Control, n = 305). Insulin therapy was initiated at blood glucose levels > 150 mg/dL. In the group with tight glycemic control (Insulin, n = 745), intra- and postoperative blood glucose levels were targeted between 80 to 110 mg/dL, using the Aalst Glycemia Insulin Protocol. Postoperative renal impairment or failure was evaluated with the RIFLE score, based on serum creatinine, glomerular filtration rate and/or urinary output. We used the Cleveland Clinic Severity Score to compare the predicted vs observed incidence of acute postoperative dialysis between groups. Results Mean blood glucose levels in the Insulin group were lower compared to the Control group from rewarming on cardiopulmonary bypass onwards until ICU discharge (p < 0.0001). Median ICU stay was 2 days in both groups. In non-diabetics, strict perioperative blood glucose control was associated with a reduced incidence of renal impairment (p = 0.01) and failure (p = 0.02) scoring according to RIFLE criteria, as well as a reduced incidence of acute postoperative dialysis (from 3.9% in Control to 0.7% in Insulin; p < 0.01). The 30-day mortality was lower in the Insulin than in the Control group (1.2% vs 3.6%; p = 0.02), representing a 70% decrease in non-diabetics (p < 0.05) and 56.1% in diabetics (not significant). The observed overall incidence of acute postoperative dialysis was adequately predicted by the Cleveland Clinic Severity Score in the Control group (p = 0.6), but was lower than predicted in the Insulin group (1.2% vs 3%, p = 0.03). Conclusions In non-diabetic patients, tight perioperative blood glucose control is associated with a significant reduction in postoperative renal impairment and failure after cardiac surgery according to the RIFLE criteria. In non-diabetics, tight blood glucose control was associated with a decreased need for postoperative dialysis, as well as 30-day mortality, despite of a relatively short ICU stay.