Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.

Time to Positivity of Bacteria Cultures in Peritoneal Dialysis Fluid: Evaluation of Different Laboratory Techniques.

Patients with chronic kidney disease on peritoneal dialysis (PD) are susceptible to infections, with peritonitis being the primary cause of dropout. Peritoneal fluid culture is one of the essential elements for proper diagnosis and peritonitis treatment. The aim of this study was to compare the time required to obtain a positive culture using different laboratory methods. An in vitro cross-sectional study was conducted comparing different techniques for preparation and culture of bacteria in peritoneal fluid. The research was carried out with 21 sterile dialysis bags and 21 PD bags containing peritoneal fluid drained from patients without peritonitis. Fluids from the 42 PD bags were contaminated by injecting a coagulase-negative Staphylococcus suspension and then prepared for culture using 4 distinct techniques: A - direct culture; B - post-centrifugation culture; C - direct culture after 4 h sedimentation; and D - culture after 4 h sedimentation and centrifugation. This was followed by seeding. In the 21 contaminated sterile bags, mean times to obtain a positive culture with techniques D (19.6 h ± 2.6) and C (19.1 h ± 2.3) were longer than with technique A (15.8 h ± 3.0; p < 0.01), but not statistically different from group B (19.0 h ± 3.2). The same occurred in the 21 bags drained from patients, with mean times for techniques D (14.0 h ± 1.9) and C (14.5 h ± 1.7) being longer than technique A (12.22 h ± 1.94; p < 0.05) but not statistically different from technique B (13.2 h ± 1.3). The sedimentation and centrifugation steps seem to be unnecessary and may delay antibiotic sensitivity test results by approximately 8 hours.

Depression, quality of life, and body composition in patients with end-stage renal disease: a cohort study.

OBJECTIVE:: To prospectively evaluate depressive symptoms, nutritional status, and quality of life (QoL) and search for possible associations in patients with end-stage renal disease undergoing hemodialysis. METHODS:: A cohort study of 104 adult patients with end-stage renal disease undergoing hemodialysis was conducted. Anthropometric, clinical, and biochemical variables were evaluated after a midweek hemodialysis session. The participants' body composition was assessed by direct segmental multi-frequency bioimpedance analysis. The WHOQOL-Bref questionnaire was used to evaluate QoL. Participants were separated into two groups - depressive symptoms and no depressive symptoms - at inclusion and evaluated annually for 2 years thereafter using the Beck Depression Inventory. Survival analysis used the Kaplan-Meier method and Cox regression analysis for the goodness of fit of associated factors. All-cause mortality was the outcome of interest. RESULTS:: Participants' mean age was 55.3±15.6 years, 60% were male, and the median time on hemodialysis was 17.5 (8.0-36.8) months. Thirty-two patients had depressive symptoms and a significantly lower QoL compared with the 72 patients in the no depressive symptoms group. The fitted outcome model showed that lean body mass had a protective effect against all-cause mortality (hazard ratio [HR] = 0.89; 95%CI 0.80-0.99; p = 0.038). CONCLUSION:: Depressive symptoms were highly prevalent in the cohort, and correlated with the physical and psychological components of the QoL life questionnaire, as well as with C-reactive protein and phosphorus levels. Lean body mass was protective for the assessed outcome.

Pacientes em hemodiálise: estado inflamatório emassa magra corporal / Hemodialysis patients: inflammatory status and lean body mass

Objetivos: Investigar a relação do estado inflamatório com a massa magra corporal de pacientes em hemodiálise.Métodos: Um estudo transversal observacional incluiu pacientes em hemodiálise há pelo menos três meses. A análise da composição corporal foi realizada por bioimpedância segmentar multi-frequência (InBody 520®). O estado nutricional associado à inflamação foi avaliado usando o instrumento que computa o Escore Desnutrição-Inflamação.Resultados: A amostra incluiu 59 indivíduos, sendo 30 mulheres. A idade média foi de 58,7±14,4 anos, a mediana do tempo em hemodiálise foi de 24 (9-49) meses, a média do peso seco estimado foi 67,0±14,7 kg e a média de massa magra foi 29,7±5,5 kg. A mediana do nível sérico de proteína C-reativa ultrassensível foi 8,6 (3,9-18,0) mg/L e acima do limite normal (≤ 5,0 mg/L), sugerindo a presença de inflamação.O escore desnutrição-inflamação teve mediana de 4 (2-6). Houve correlação significativa entre o escore desnutrição-inflamação e a idade(rs=0,350, p menor do que 0,01) e com o tempo em diálise: (rs=0,320, p menor do que 0,05). Inflamação avaliada pelo nível de proteína C-reativa ultrassensível foi significativamente associada à massa magra (rs=-0,283, p menor do que 0,05).Conclusões: O aumento do tempo em hemodiálise e a idade aumentada estiveram associados com pior estado nutricional. Nesta população, aparentemente quanto menor a massa magra corporal maior o nível de proteína C-reativa ultrassensível, sugerindo uma possível associação entre a inflamação e a massa magra corporal nestes pacientes...

AIMS: To investigate the relationship of the inflammatory status with the lean body mass in hemodialysis patients.METHODS: A cross-sectional observational study included patients on hemodialysis for at least three months. The body composition analysis was performed by segmental multi-frequency bioimpedance (InBody 520�). The nutritional status associated with inflammation was evaluated using the instrument that computes the Malnutrition-Inflammation Score.RESULTS: The sample included 59 subjects, 30 were female. The mean age was 58.7 � 14.4 years, the median time on dialysis was 24 (9-49) months, the mean estimated dry weight was 67.0 � 14.7 kg and mean lean body mass was 29.7 � 5.5 kg. The median serum level of ultrasensitive C-reactive protein was 8.6 (3.9 to 18.0) mg / L and above the normal limit (equal or less than 5.0 mg / L), suggesting the presence of inflammation. The malnutrition-inflammation score had a median of 4 (2-6). There was a significant correlation between the score malnutrition-inflammation and age (rs = 0.350, p less than 0.01) and with time on dialysis: (rs = 0.320, p less than 0.05). Inflammation assessed by the level of ultrasensitive C-reactive protein was significantly associated with lean body mass (rs = - 0.283, p less than 0.05).CONCLUSIONS: The increased time on dialysis and increased age were associated with poorer nutritional status. In this population, apparently the lower lean body mass the higher level of ultrasensitive C-reactive protein, suggesting a possible association between inflammation and lean body mass in these patients...

Hand hygiene in peritoneal dialysis patients: a comparison of two techniques.

INTRODUCTION AND OBJECTIVES: Hand hygiene is essential for preventing peritoneal dialysis (PD)-related infections. The present study compared the effectiveness of two hygiene techniques in reducing the number of colony-forming units (CFUs) on the hands of patients undergoing PD. METHODS: In this controlled clinical trial, 22 participants enrolled in the same PD program underwent a two-hand evaluation for microbiologic flora. Participants participated in two treatments: a) simple hand hygiene plus antiseptic hand hygiene, in which the patients washed their hands with water and glycerin soap for 1 minute and then rubbed and dried their hands with 70% ethyl alcohol gel; and b) antiseptic hand hygiene, in which the patients rubbed their hands with 70% ethyl alcohol gel until fully dry. To sample distal finger surfaces, we asked the participants to touch sheep blood agar plates directly. RESULTS: The CFU count for both hands was significantly higher in the regular hygiene group than in the gel-only group [69.0 (16.0 - 101.0) CFU vs 9.0 (2.2 - 55.5) CFU, p < 0.010]. Growth of coagulase-negative Staphylococcus colonies was significantly higher in right-hand cultures from the regular hygiene group than in those from the gel-only group [69.5 (26.25 - 101.0) CFU vs 9.5 (1.0 - 41.7) CFU; p < 0.050]. CONCLUSIONS: Among patients undergoing PD, using 70% ethyl alcohol gel to cleanse the hands may be more effective than following the regular hygiene recommendations in reducing bacterial populations.

Nutritional status evaluated by multi-frequency bioimpedance is not associated with quality of life or depressive symptoms in hemodialysis patients.

Hemodialysis therapy significantly impacts on patients' physical, psychological, and social performances. Such reduced quality of life depends on several factors, such as malnutrition, depression, and metabolic derangements. This study aims to evaluate the current nutritional status, quality of life and depressive symptoms, and determine the possible relationships with other risk factors for poor outcomes, in stable hemodialysis patients. This was a single-center, cross-sectional study that enrolled 59 adult patients undergoing hemodialysis. Laboratory tests that included high-sensitivity c-reactive protein (CRP), and quality of life and depressive symptom evaluation, as well as malnutrition-inflammation score, nutritional status and body composition (by direct segmental multi-frequency bioimpedance analysis) determinations were performed. Patients were classified as "underfat", "standard", "overfat", or "obese" by multi-frequency bioimpedance analysis. Seven patients were underfat, 19 standard, 19 overfat, and 14 obese. Triglyceride levels significantly differed between the underfat, standard, overfat, and obese groups (1.06 [0.98-1.98]; 1.47 [1.16-1.67]; 2.53 [1.17-3.13]; 2.12 [1.41-2.95] mmol/L, respectively; P=0.026), as did Kt/V between the underfat, overfat, and obese groups (1.49 ± 0.14; 1.23 ± 0.19; 1.19 ± 0.22; P=0.015 and P=0.006, respectively). Depressive symptoms, quality of life, and CRP and phosphate levels did not diverge among nutritional groups. Creatinine, albumin, and phosphate strongly correlated, as well as percent body fat, body mass index, and waist circumference (r=0.859 [P<0.001], and r=0.716 [P<0.001], respectively). Depressive symptoms and physical and psychological quality-of-life domains also strongly correlated (r(s) = -0.501 [P<0.001], r(s) = -0.597 [P<0.001], respectively). The majority of patients were overfat or obese and very few underfat. Inflammation was prevalent, overall. No association of nutritional status with malnutrition-inflammation, quality of life, or depressive symptoms could be established.

Erythrocytes L-arginine y+ transporter inhibition by N-ethylmaleimide in ice-bath.

Erythrocytes L: -arginine uptake is conveyed by y+ and y+L membrane transport systems. Pre-incubation with N-ethylmaleimide for 10 min at 37°C inhibits the y+ system. The aim of this study was to determine the ideal pre-incubation temperature in evaluating y+ and y+L systems. Cells were pre-incubated with or without N-ethylmaleimide for 10 min at 4°C and 37°C. L: -Arginine uptake was quantified by radioisotope and standard erythrocytes membrane flux methodology. Results demonstrate that erythrocytes L: -arginine content is depleted by pre-incubation at 37°C for 10 min, thus changing the V (max) measurement. The inhibitory effect of N-ethylmaleimide pre-incubation was temperature independent and already complete after 1 min of incubation. No significant difference in kinetic parameters was detected between cells pre-incubated at 37°C or 4°C, under zero-trans conditions. In conclusion, we suggest that measurement of erythrocytes L: -arginine uptake by y+ and y+L systems could be carried out without N-ethylmaleimide pre-incubation at 37°C.

Two variable sodium profiles and adverse effects during hemodialysis: a randomized crossover study.

Intradialytic symptomatic hypotension and muscle cramps are frequent and disturbing adverse effects involving hemodialysis patients. The use of sodium profiling has been a proposed approach to preclude such events. The aim of the study was to compare the frequency of intradialytic adverse effects and changes in anthropometric and physiological variables without profiling and with two distinct sodium profiles. A prospective study randomized 22 stable hemodialysis patients to receive either a step (11 patients) or a linear (11 patients) dialysate sodium profile for 12 consecutive sessions, following a 12-session steady sodium control period. After a wash-out period of 12 sessions, the groups were crossed over for another 12-session period. Frequency of adverse effects, interdialytic weight gain, pre- and post-dialysis blood pressure were computed. The frequency of intradialytic adverse effects was significantly different between the control and either the step or linear periods (48.5%, 33.7%, and 36.0%, respectively; P < 0.001). No significant differences in interdialytic weight gain or pre-dialysis blood pressure were detected between treatment periods. The mean post-dialysis systolic blood pressure was lower in the linear period (128 +/- 21; 127 +/- 20; 123 +/- 22 mm Hg, for the control, step and linear periods, respectively; P = 0.014). Seven patients benefited from sodium profiling, yet two became more symptomatic. Overall, both sodium profiles were associated with fewer intradialytic adverse effects. Intradialytic symptomatic hypotension occurred less often with the step profile, while a tendency to fewer cramps was associated with the linear profile. However, sodium profiling may not benefit every dialysis patient and should be individually evaluated.

Solutes transport characteristics in peritoneal dialysis: variations in glucose and insulin serum levels.

BACKGROUND: Differences in small solutes transport rate (SSTR) during peritoneal dialysis (PD) may affect water and solutes removal. Patients with high SSTR must rely on shorter dwell times and increased dialysate glucose concentrations to keep fluid balance. Glucose absorption during peritoneal dialysis (PD), besides affecting glucose and insulin metabolism, may induce weight gain. The study aimed at examining acute glucose and insulin serum level changes and other potential relationships in PD patients with diverse SSTR. METHODS: This cross-sectional study used a modified peritoneal equilibration test (PET) that enrolled 34 prevalent PD patients. Zero, 15, 30, 60, 120, 180, and 240-minute glucose and insulin serum levels were measured. Insulin resistance index was assessed by the homeostasis model assessment (HOMA-IR) formula. SSTR categories were classified by quartiles of the four-hour dialysate/serum creatinine ratio (D(4)/P(Cr)). Demographic and clinical variables were evaluated, and the body mass index (BMI) was estimated. Correlations among variables of interest and categories of SSTR were explored. RESULTS: Glucose serum levels were significantly different at 15, 30, and 60 minutes between high and low SSTR categories (p = 0.014, 0.009, and 0.022). Increased BMI (25.5 +/- 5.1) and insulin resistance [HOMA-IR = 2.60 (1.40-4.23)] were evidenced overall. Very strong to moderate correlations between insulin levels along the PET and HOMA-IR (r = 0.973, 0.834, 0.766, 0.728, 0.843, 0.857, 0.882) and BMI (r = 0.562, 0.459, 0.417, 0.370, 0.508, 0.514, 0.483) were disclosed. CONCLUSIONS; Early glucose serum levels were associated with SSTR during a PET. Overweight or obesity and insulin resistance were prevalent. An association between insulin serum levels and BMI was demonstrated.

Erythrocyte L-arginine uptake in peritoneal dialysis patients changes over time.

During long-term exposure to continuous ambulatory peritoneal dialysis (PD), the characteristics of the peritoneal membrane may be altered. The substrate for nitric oxide synthesis is L-arginine, which may enter cells via the y+ and y+L transport systems. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-NO pathway. Maximal capacity for L-arginine transport is higher in patients with a lower dialysis adequacy index. Our aim was to evaluate erythrocyte L-arginine uptake in PD patients at the start and end of a 3-year interval. Our longitudinal study evaluated 8 stable patients on PD who were not using NO donors and who had been free of peritonitis for at least 1 month. Uptake of L-arginine was measured in 2003 and again in 2006. Maximal transport capacity (Vmax, in micromoles per liter-cells per hour) and half-saturation constant (km, in micromoles per liter) were measured in erythrocytes using 14C as a marker and N-ethylmaleimide as inhibitor of the y+ system. For the years 2003 and 2006 respectively, mean +/- standard deviation for total L-arginine uptake Vmax was 749 +/- 182 micromol/L-cells/h and 1146 +/- 365 micromol/L-cells/h (p = 0.016, paired t-test),for y+L Vmax was 180 +/- 58 micromol/L-cells/h and 515 +/- 142 micromol/L-cells/h (p = 0. 002), and for y+ Vmax was 556 +/- 177 micromol/L-cells/h and 662 +/- 267 micromol/ L-cells/h (nonsignificant). The total y+L and y+km were not significantly different. The L-arginine maximal uptake capacity in erythrocytes increased after 3 years of PD treatment. These findings agree with the suggestion of an association between y+L activity and dialysis adequacy or uremia toxicity. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-NO pathway.

Erythrocyte L-arginine uptake in peritoneal dialysis patients: systems y and y+ L.

L-Arginine is the substrate for nitric oxide synthesis and may enter cells by the y+ and y+ L transport systems. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-nitric oxide pathway. In a cross-sectional study, we evaluated erythrocyte L-arginine uptake in stable peritoneal dialysis (PD) patients with various categories of peritoneal transport function. We used 14C as a marker and N-ethyl-maleimide as an inhibitor of the y+ system to measure maximal uptake capacity (Vma in ulmol/L cell/h) and the half-saturation constant (Km in micromol/L) in erythrocytes. The sample consisted of 41 patients (mean age: 50 +/- 17 years; 5 with diabetes; 18 men). Mean dialysate-toplasma creatinine (D/P(Cr)) was 0.62 +/- 0.14. Peritoneal membrane transport was classified as high, high-average, low-average, or low in 10, 11, 11, and 9 patients, respectively. Mean y+ L Vmax, was 208 +/- 111 micromol/L cell/h, 494 +/- 893 micromol/L cell/h, 222 +/- 59 micromol/L cell/h, and 193 +/- 63 umol/L cell/h [p = 0.404, analysis of variance (ANOVA)] for the high, high-average, low-average, and low transporters respectively. Similarly, mean y+ Vmax was 963 +/- 1034 micromol/L cell/h 843 +/- 366 micromol/L cell/h, 639 +/- 254 micromol/L cell/h, and 774 +/- 378 micromol/L cell/h (p = 0.647, ANOVA). As with Vmax, the y+ L Km and y+ Km values were not significantly different between the various peritoneal transport categories. A negative correlation was observed between y+ Vmax and Kt/V (r = -0.393, p = 0.011). Erythrocyte uptake of L-arginine does not vary with peritoneal membrane transport characteristics, but maximal L-arginine uptake capacity is higher in patients with a lower Kt/V.

L-arginine erythrocyte transport increases during pregnancy and immediately postpartum.

OBJECTIVE: This study was undertaken to evaluate erythrocyte membrane transport of L-arginine in pregnancy and immediately postpartum. STUDY DESIGN: The study comprised 103 women with normal pregnancy, initially evaluated at the second trimester (II), followed into the third trimester (III), and immediately postpartum (PP). Total erythrocyte L-arginine uptake was measured with (14)C-L-arginine, at 37 degrees C, for 3 minutes. The maximal transport capacity (V(max)) and half-saturation constant (K(m)) were obtained with the use of Michaelis-Menten kinetics. Results are expressed as mean+/-SD. Analysis of variance, followed by Tukey test, was used in statistical analysis (alpha< or =.05). RESULTS: V(max) (micromol/L cells per hour) progressively increased at each consecutive time period: 779+/-283, 946+/-289, and 1349+/-390, at II, III, and PP, respectively (P<.001). Similarly, K(m) (micromol/L) values increased from 56+/-20 at time II, to 62+/-18 at time III, and 69+/-24 at PP (P<.001). CONCLUSION: Total erythrocyte L-arginine uptake (V(max) and K(m)) increases progressively along normal pregnancy, with a further increase immediately postpartum.

Acute renal failure needing dialysis in the intensive care unit and prognostic scores.

BACKGROUND: Generic prognostic scores used in acute renal failure (ARF) give imprecise results; disease-specific indices applied to distinct populations or intensive care practices becomes inaccurate. The current study evaluates the adequacy of prognostic scores, in patients with severe ARF needing dialysis. METHODS: Known generic (APACHE II) and disease-specific (ATN-ISS) indices were applied to a cohort (n = 280) with ARF needing dialysis, under intensive care. Possible risk factors as causal factors, organ dysfunctions and clinical variables were examined, and a local index assembled by multivariate logistic regression analysis. Area under the receiver operating characteristics (ROC) curves evaluated the indices discriminating capacity. Goodness-of-fit testing and linear regression analysis appraised calibration. Validation was accomplished by the bootstrapping technique. The end-point was hospital mortality. RESULTS: Overall mortality was 85%. Female gender < 44 years (OR: 0.29; 95% CI: 0.10-0.84), liver/obstructive biliary disease (OR: 6.03; 95% CI: 1.65-22.08), being conscious (OR: 0.49; 95% CI: 0.21-1.14), use of vasoactive drug (OR: 3.13; 95% CI: 1.25-7.83), respiratory dysfunction (OR: 5.20; 95% CI: 1.25-7.83) or sepsis (OR: 2.62; 95% CI: 1.14-6.02) were associated with outcome. Areas under the ROC curve of 0.815, 0.652 and 0.814; Goodness-of-fit test P = 0.593, P < 0.001 and P = 0.002; and linear regression R2 = 0.973, R2 = 0.526 and R2 = 0.919 for the local index, APACHE II and ATN-ISS, respectively, indicate better performance by the local index. The local index median area under the ROC curve, by bootstrapping, was 0.820 (95% CI: 0.741-0.907). CONCLUSIONS: APACHE II score was inaccurate, and ATN-ISS poorly calibrated. When mortality or intensive care practices significantly deviate, local scores may better evaluate prognosis in severe ARF.