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BACKGROUND: Preliminary evidence suggests patients on hemodialysis have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing the vaccination strategy in this population requires a thorough understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV-2 vaccines. METHODS: This prospective multicenter study of 543 patients on hemodialysis and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti–SARS-CoV-2 spike antibodies and T cell responses by IFN-γ secretion of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses. RESULTS: Compared with healthy volunteers, patients on hemodialysis had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P

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 Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

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.

End-stage renal disease-stage 5 chronic kidney disease (CKD)-of the native kidneys, related to biopsy-proven Arndt-Gottron scleromyxoedema, developed in a male patient. From 1998 until 2001, the patient was treated by haemodialysis. In June 2001, cadaveric kidney transplantation was performed. In January 2004, a kidney biopsy was performed because of deteriorating renal function revealing relapse of scleromyxoedema with typical concentric narrowing of the arterioles due to accumulation of mucopolysaccharides with severe glomerular ischaemia. Arndt-Gottron scleromyxoedema is an as yet unsuspected cause of stage 5 CKD of the native kidneys. Moreover, the disease can relapse in the transplanted kidney, again leading to intractable transplant stage 5 CKD.

When the calibration of a routine measurement procedure is traced back to metrological higher order, a significant discrepancy can occur between the analytical conditions of the routine measurement and the analytical conditions that were used in the clinical studies upon which the decision-making criteria are based. This can lead to serious interpretation errors with possible dramatic consequences for patients. The calibration of the creatinine Jaffe method is an excellent example of the importance of medical traceability. The compensated Jaffe method correlated accurately with the reference method and the compensated Jaffe creatinine clearance (CrCl), Cockroft and Gault and MDRD with the 51Cr EDTA clearance. The Schwartz estimate based upon the compensated Jaffe and enzymatic method overestimated, while uncompensated Jaffe slightly underestimated glomerular filtration rate (GFR). The situation in children is complex since serum creatinine concentrations are much lower in infants, rendering tubular secretion relatively more important. Low-molecular weight proteins have been suggested to replace serum creatinine as a marker for GFR. β-trace protein, cystatin C, and β2-microglobulin showed good correlation with GFR. However, care should be taken in patients presenting with some malignant tumors, since significant increases of cystatin C in patients with metastatic melanoma or colorectal cancer has been reported.

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.

Background Use of vitamin K antagonists for the prevention of stroke and systemic embolism in dialysis patients with nonvalvular atrial fibrillation is controversial. However, no good alternatives presently are available. The anti−factor Xa antagonist rivaroxaban is contraindicated for lack of pharmacokinetic, pharmacodynamic, and clinical data. This study aims to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban in maintenance hemodialysis patients. Study Design Pharmacokinetic and pharmacodynamic study. Setting & Participants 18 maintenance hemodialysis patients without residual kidney function at 2 centers. Drug Administration, Outcomes, & Measurements (1) A single dose of 10mg of rivaroxaban was administered at the end of each of 3 consecutive dialysis sessions and area under the curve (AUC) and the effect on coagulation parameters were measured for 44 hours thereafter. (2) A single dose of 10mg of rivaroxaban was given 6 to 8 hours before a dialysis session and the effect of dialysis on rivaroxaban concentrations was evaluated. (3) To assess potential accumulation, 10mg of rivaroxaban was given once daily and AUC was measured during 24 hours on days 1 and 7. Results Mean AUC 0-44 of rivaroxaban plasma concentrations after a single dose of 10mg was 2,072μg/L/h, mean maximum concentration was 172.6μg/L, and mean terminal elimination half-life was 8.6 hours. Dialysis had no appreciable effect on rivaroxaban plasma concentrations. Mean trough concentration after multiple daily doses of 10mg was 20.2μg/L. Limitations Higher rivaroxaban doses and patients with substantial residual kidney function were not studied. Conclusions A 10-mg dose of rivaroxaban in hemodialysis patients without residual kidney function results in drug exposure similar as published for 20mg in healthy volunteers. Rivaroxaban is not eliminated by dialysis. There is no accumulation after multiple daily dosing. The efficacy and safety of rivaroxaban in hemodialysis patients should be the subject of a large randomized trial.

Catalytic activity of oxidative phosphorylation complexes is maintained following separation by Blue Native polyacrylamide gel electrophoresis (BN-PAGE). In BN-PAGE gels, using histochemical staining methods, we have demonstrated enzymatic activity of the complexes I, II, IV, and V in heart and skeletal muscle, liver, and cultured skin fibroblasts. The combination of BN-PAGE and catalytic staining can be successfully applied for detection of complex deficiencies. Tissues from 18 patients with deficiency in the oxidative phosphorylation as detected by spectrophotometric assay were used (10 patients complex IV, three patients complex I, one patient complex II, one patient complex I+III, three patients complex I+IV). The gene defect was located in nuclear DNA in five patients and mitochondrial DNA in one patient. In samples from patients with a severe deficiency, almost complete absence of the corresponding enzyme band is observed after catalytic staining in the gel. In patients with known partial deficiency, a milder decrease of the corresponding enzyme band is demonstrated. The amount of protein in complexes I, V, and III can easily be evaluated in samples from heart and skeletal muscle after separation by BN-PAGE using silver or Coomassie staining. The protein amount in complex IV is difficult to visualize by silver staining but easier by the Coomassie technique. In samples from liver and cultured skin fibroblasts, evaluation of protein amount is more difficult due to high background staining. In these tissues, immunoblotting can be done after BN-PAGE and subsequent transfer to a nitrocellulose membrane.

The Marmara earthquake: Epidemiological analysis of the victims with nephrological problems.BackgroundCrush syndrome resulting from earthquakes is a major cause of morbidity and mortality, as seen during the catastrophic Marmara earthquake that struck Northwestern Turkey in August 1999. This report analyzes the epidemiological characteristics of the crush syndrome victims of this disaster.MethodsIn order to analyze the nephrological problems caused by this earthquake, questionnaires were prepared within the first week of the disaster and sent to 35 reference hospitals that treated the victims. Data obtained by these questionnaires are the subject of this report.ResultsOf the 5302 hospitalized patients in reference hospitals, 639 (12.0%) suffered from nephrological problems, and 477 (9.0%) needed dialysis support. Considering the patients with renal problems, there was not any significant difference in gender; however, the incidence of children younger than 10 years and the older population (older than 60 years of age) was significantly lower as compared with the resident population of the affected area (P < 0.001). Nonsurvivors were older (34.5 ± 16.1 years) than survivors (31.2 ± 14.4 years, P = 0.048), while no deaths were recorded under the age of 10. Most patients (70.1%) were admitted within the first three days after the earthquake, and the mortality rate among these victims was higher (17.7%) as compared with victims admitted thereafter (10.0%, P = 0.016). The average time period under the rubble was 11.7 ± 14.3 hours, which was not significantly different between survivors and nonsurvivors, while the victims who required dialysis support spent shorter durations under the rubble, as compared with the ones who were not dialyzed at all (10.3 ± 9.5 vs. 15.9 ± 23.1 hours, P < 0.001).ConclusionVictims of catastrophic earthquakes are characterized by a high incidence of renal problems and the need for dialysis support. The incidence of nephrological problems is lower in children, while the period of time under the rubble is not a prognostic indicator of survival.

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.

Telomeric refinement of the MCKD1 locus on chromosome 1q21. Background Autosomal-dominant medullary cystic kidney disease type 1 (MCKD1) is a tubulointerstitial nephropathy that causes renal salt wasting and end-stage renal failure in the sixth decade of life. The chromosomal locus for MCKD1 was localized to chromosome 1q21 in a Cyprotic kindred. In this report we describe further refinement of the critical genetic region by a recombination in a Belgian kindred. Methods Clinical data and blood samples of 33 individuals from a large Belgian kindred were collected and high-resolution haplotype analysis was performed. Results In the Belgian kindred linkage to the MCKD1 locus on chromosme 1q21 was found with a logarithm of odds (LOD) score significant for linkage. A recombination in individual III:7 for marker D1S2624 refines the critical genetic region to 2.1 Mb. In this kindred a wide variety of clincial symptoms and age of onset of renal failure was detected. Conclusion We confirm the MCKD1 locus on chromosome 1q21 and show further refinement of the MCKD1 locus to 2.1 Mb. This allowed us to exclude another 17 genes as positional candidate genes.

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.

Despite the abundance of reports emerging in the literature on metabolic disorders, some disorders remain undiagnosed or misdiagnosed, not only in clinical pathology but also in forensic pathology. The authors report a patient who had recurrent episodes characterized by nausea, vomiting, and signs of dehydration necessitating admission to the hospital. At each admission, he was found to have lactic acidosis. On the first admission, glycolic acid was detected in his blood and he was diagnosed as having ethylene glycol intoxication. Only at the third admission, 2 years after the first, was the possibility of an underlying metabolic disorder considered. Laboratory investigations showed a deficiency of complex I in the mitochondrial oxidative phosphorylation. Possible medicolegal implications are discussed.

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.