IgA Deficiency Is Not Systematically Ruled Out in Patients Undergoing Celiac Disease Testing.

BACKGROUND: Guidelines for celiac disease (CD) testing recommend total serum IgA determination alongside anti-transglutaminase IgA antibodies. It is not well known if lack of serum IgA determination is a common finding in clinical practice. AIM: To determine the prevalence of lack of serum IgA determination among patients screened for celiac disease. MATERIALS AND METHODS: We identified all subjects who underwent serum anti-transglutaminase IgA and/or other CD-related antibodies determination at a single teaching hospital in Buenos Aires from October 2019 to February 2020. Medical records were reviewed to select adult patients who were tested for celiac disease. The primary outcome was the proportion of patients with inadequate testing for celiac disease due to lack of serum IgA determination. We retrieved the following variables from each patient's record: age, gender, body mass index, symptoms present at screening, first-grade family history of CD, history of type-1 diabetes mellitus, autoimmune hypothyroidism, Down's syndrome. RESULTS: Overall, 1122 patients were included for analysis. Lack of serum IgA determination prevalence was 20.49%. Among patients who did have serum IgA determination, the prevalence of IgA deficiency was 5.16%. The following variables were independently associated with a significantly increased odds of serum IgA determination: diarrhea [OR 1.55 (1.01-2.34)] and abdominal pain [OR 2.28 (1.44-3.63)]; higher body mass index [OR 0.91 (0.85-0.98)], osteoporosis [OR 0.49 (0.28-0.89)], hypothyroidism [OR 0.18 (0.07-0.45)], arthralgia/arthritis [OR 0.47 (0.27-0.85)], or testing by endocrinologist [OR 0.46 (0.23-0.91)] and gynecologist [OR 0.14 (0.06-0.31)] were inversely associated. CONCLUSION: IgA deficiency is not systematically ruled out in a relatively high proportion of patients undergoing serological screening of celiac disease.

Parenteral succinate reduces levels of reactive oxygen species without changing serum caspase-3 levels in septic rats.

INTRODUCTION: Sepsis is a syndrome of physiological, pathological, and biochemical disorders with several processes co-occurring; reactive oxygen species (ROS) production and apoptosis are 2 of them. Succinate is a Krebs cycle intermediate that is oxydized in complex II of the mitochondria. This study aims to investigate the influence of succinate infusion on these processes. MATERIAL AND METHODS: Sepsis was induced with caecal ligation and puncture in 200 gr Sprague Dawley rats. Four groups were formed with 10 animals (1 - control, 2 - succinate, 3 - sepsis, and 4 - sepsis + succinate). 5 mmol kg-1 of intraperitoneal succinate were administered twice in groups 2 and 4. ROS and caspase-3 levels were measured. RESULTS: Overall, ROS levels (P = 0.017), but not caspase-3 levels (P = 0.89) differed significantly between the groups. The succinate administration reduced serum ROS levels (group 4 vs. 3) in a statistically significant way [0.0623 units (95% CI: 0.0547-0.0699) vs. 0.0835 (0.06-0.106), P = 0.017)], but it did not reduce serum caspase-3 levels (P = 0.39). There was no correlation between serum ROS levels and serum caspase-3 levels. CONCLUSIONS: In this model, ROS levels were reduced with succinate infusion, but caspase-3 levels were not. In addition, ROS levels and apoptosis levels are not correlated, which suggests that those processes occur at different times.

Early decrease in the podocalyxin to synaptopodin ratio in urinary Fabry podocytes.

BACKGROUND: In Fabry nephropathy, podocyturia is an early event that may lead to glomerulosclerosis and chronic kidney disease. The glycocalyx is a potential podocyte damaged compartment in glomerulopathies. We investigated glycocalyx podocalyxin in urinary detached podocytes compared with cytoplasmic synaptopodin. METHODS: This was a cross-sectional study including 68 individuals: Controls (n = 20) and Fabry patients (n = 48), 15 untreated and 33 treated. Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), lyso-triasocylsphingosine (lyso-Gb3) levels and enzyme replacement therapy (ERT). Podocyturia was assessed by immunofluorescence and podocyte subpopulations were analyzed. RESULTS: Fabry patients displayed higher podocyturia than controls. Fabry treated subjects (n = 33) presented significantly higher UPCR compared with untreated ones (n = 15); podocyturia, eGFR and lyso-Gb3 levels were not different. All control podocytes colocalized synaptopodin and podocalyxin; 13 Fabry patients (27%) colocalized these proteins, while 35 (73%) were only synaptopodin positive. No podocalyxin-positive/synaptopodin-negative cells were encountered. In Fabry patients, podocyturia was significantly higher and proteinuria lower in those that colocalized. CONCLUSION: Fabry patients present higher podocyturia and a presumably more damaged glycocalyx assessed by podocalyxin. Treated patients had significant higher proteinuria suggesting ERT is initiated late, at advanced stages. The degree of podocalyxin-negative podocytes was similar in both groups, but colocalization was associated with lower proteinuria. Podocyturia assessed by podocalyxin alone may be underestimated. The implications of podocyte glycocalyx damage deserve further investigations.

Parenteral Succinate Reduces Systemic ROS Production in Septic Rats, but It Does Not Reduce Creatinine Levels.

In sepsis, reactive oxygen species (ROS) production is increased. This process takes place mainly within the electron transport chain. ROS production is part of the pathophysiology of multiple organ failure in sepsis. Succinate yields Dihydroflavine-Adenine Dinucleotide (FADH2), which enters the chain through complex II, avoiding complex I, through which electrons are lost. The aim of this work is to determine if parenteral succinate reduces systemic ROS production and improves kidney function. Rats with cecal ligation and puncture were used as model of sepsis, and 4 groups were made: Control group; Succinate group, which only received parenteral succinate; Sepsis group; and Sepsis which received parenteral succinate. Systemic ROS are measured 24 hours after the procedure. Rats subjected to cecal puncture treated with succinate had less systemic ROS than Septic untreated rats (p = 0.007), while there were no differences in creatinine levels (p = 0.07). There was no correlation between creatinine and systemic ROS levels (p = 0.3). We concluded that parenteral succinate reduces ROS levels, but it does not reduce creatinine levels. Since there is no correlation between both levels, the processes would not be related.

In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia.

BACKGROUND: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. METHODS: The groups were as follows: controls (G1), n = 20 and IgAN group (G2), n = 39, subdivided into M1E0S0T0 (G2A), n = 21 and M1E0S1T0 (G2B), n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr) and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. RESULTS: Groups were not different in age and gender; urinary protein-creatinine (uP/C) ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. CONCLUSIONS: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1) at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may participate in podocyte detachment.

Expression of uPAR in Urinary Podocytes of Patients with Fabry Disease.

Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-ß (n = 21). Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein : creatinine ratio, and urinary uPAR+ podocyte : creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein : creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein : creatinine ratio (ρ = 0.5; p = 0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes. Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.

Biomarcadores en la lesión renal aguda: ¿ paradigma o evidencia ? / Biomarkers in acute kidney injury: Evidence or paradigm?

La lesión renal aguda en los pacientes críticos representa un factor de riesgo independiente de la morbilidad y la mortalidad a corto y a largo plazo, con un tremendo impacto económico en cuanto a los costes en salud pública. Por el momento, el diagnóstico de la lesión renal aguda sigue basándose en la presencia de oliguria o en un aumento gradual de la creatinina sérica, hecho que retrasa el diagnóstico, en detrimento de la llamada «ventana terapéutica». La aparición de nuevos biomarcadores de lesión renal aguda podría mejorar esta situación y contribuir a la detección de la «lesión renal aguda subclínica», lo que permitiría el uso precoz de múltiples estrategias de tratamiento con el objetivo de preservar la funcionalidad renal. No obstante, los nuevos biomarcadores presentan características que podrían vulnerar su capacidad de acción, centrada concretamente en aportar un valor añadido al abordaje precoz de la enfermedad, dada la falta de tratamientos específicos validados para la lesión renal aguda. Esta revisión tiene como objetivo analizar los puntos fuertes y débiles de esta nueva herramienta para el diagnóstico temprano de la lesión renal aguda (AU)

Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called ‘therapeutic window’. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of ‘subclinical acute kidney injury’, which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury (AU)

Heterogeneidad en los fenotipos inflamatorios de los pacientes con EPOC: rol del recuento celular diferencial en esputo / Heterogeneity of Inflammatory Phenotypes In Copd Patients: Role of Differential Cell Counting in Sputum

El tabaquismo es la principal causa de la EPOC, sin embargo, factores como la edad de diagnóstico, la historia previa de asma, exacerbaciones, predisposición genética y otros influirían en el desarrollo de la enfermedad. Esto estaría relacionado con los fenotipos de pacientes con EPOC, los cuales tendrían diferentes respuestas a los corticoides inhalados (CI). Recientemente, ha sido propuesto que los eosinófilos serían potenciales biomarcadores predictores de buena respuesta a los CI. Con la hipótesis de que la presencia de eosinófilos en esputo podría constituir una estrategia para diferenciar fenotipos de pacientes con EPOC, evaluamos los perfiles celulares infamatorios en muestras de esputo inducido en pacientes con EPOC no exacerbados. Para esto, se reclutaron 20 pacientes con EPOC moderado a severo que concurren al gimnasio de rehabilitación respiratoria, los cuales fueron agrupados en eosinofílicos (n: 8, cuando presentaron más de 3% de eosinófilos en la muestra de esputo inducido) o no eosinofílicos (n: 9). Se descartaron 3 muestras por contaminación con células epiteliales. Si bien no se observaron diferencias significativas en los test de función pulmonar o de marcha de 6 minutos, los pacientes con eosinoflia presentaron ligeramente mayor reversibilidad luego del broncodilatador. Además, tuvieron mayor eosinofilia periférica, mayores valores de FeNO y mejor calidad de vida (medida por cuestionarios) que los pacientes no eosinofílicos. El esputo inducido es una técnica no invasiva, económica, que representaría una herramienta útil para conocer los diferentes fenotipos inflamatorios en pacientes con EPOC.

Smoking is the major cause of COPD; however factors such as age, previous history of asthma, exacerbations, and genetic predisposition could infuence the development of the disease. This could be related with the phenotypes of COPD patients, who would have different responses to inhaled corticosteroids (ICs). Recently, it has been suggested that eosinophils are potential biomarkers that contribute to predict good response to ICs. To test the hypothesis that the presence of eosinophils in sputum could be useful to characterize different phenotypes of COPD patients, we assessed the infammatory cell profles in induced sputum samples from not exacerbated COPD patients. 20 patients with moderate to severe COPD, attending a pulmonary rehabilitation gym, were grouped into eosinophilic (8 patients who presented more than 3% eosinophils in the induced sputum sample) or neutrophilic (9 patients who had more than 60% neutrophils). Only 3 patients were excluded due to contamination of the sputum with epithelial cells. Although there were no-signifcant differences in the pulmonary function tests or the 6-minute walk, the patients with eosinophilia showed higher responsiveness to bronchodilator therapy. Besides this group presented an increase of peripheral eosinophils, higher FeNO and better quality of life (measured by questionnaires) compared with the neutrophilic patients. Induced sputum is an economic non-invasive technique and would be a useful tool to know different infammatory phenotypes in COPD patients.

Biomarkers in acute kidney injury: Evidence or paradigm? / Biomarcadores en la lesión renal aguda: ¿ paradigma o evidencia?

Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

Podocyturia is significantly elevated in untreated vs treated Fabry adult patients.

BACKGROUND: Proteinuria suggests kidney involvement in Fabry disease. We assessed podocyturia, an early biomarker, in controls and patients with and without enzyme therapy, correlating podocyturia with proteinuria and renal function. METHODS: Cross-sectional study (n = 67): controls (Group 1, n = 30) vs. Fabry disease (Group 2, n = 37) subdivided into untreated (2A, n = 19) and treated (2B, n = 18). Variables evaluated: age, gender, creatinine, CKD-EPI, proteinuria, podocyte count/10 20× microscopy power fields, podocytes/100 ml urine, podocytes/g creatininuria (results expressed as median and range). RESULTS: Group 1 vs. 2 did not differ concerning age, gender and CKD-EPI, but differed regarding proteinuria and podocyturia. Group 2A vs. 2B: age: 29 (18-74) vs. 43 (18-65) years (p = ns); gender: males n = 3 (16 %) vs. n = 9 (50 %). Proteinuria was significantly higher in Fabry treated patients, while CKD-EPI and podocyturia were significantly elevated in untreated individuals. Significant correlations: group 2A: age-proteinuria, ρ = 0.62 (p = 0.0044); age-CKD-EPI, ρ = -0.84 (p < 0.0001); podocyturia-podocytes/100 ml urine, ρ = 0.99 (p = 0.0001); podocyturia-podocytes/g creatininuria ρ = 0.86 (p = 0.0003), podocytes/100 ml urine-podocytes/g urinary creatinine, ρ = 0.84 (p = 0.0004); proteinuria-CKD-EPI, ρ = -0.68 (p = 0.0013). Group 2B: podocyturia-podocytes/100 ml urine, ρ = 0.88 (p < 0.0001); podocyturia-podocytes/g creatininuria, ρ = 0.84 (p < 0.0001); podocytes/100 ml urine-podocytes/g creatininuria, ρ = 0.94 (p < 0.0001); CKD-EPI-proteinuria, ρ = -0.66 (p = 0.0028). CONCLUSIONS: Patients with Fabry disease display heavy podocyturia; those untreated present significantly higher podocyturia, lower proteinuria and better renal function than those who are treated, suggesting that therapy may be started at advanced stages. Podocyturia may antedate proteinuria, and enzyme therapy may protect against podocyte loss.

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

AIM: To assess residual diuresis and diverse variables according to body mass index (BMI). METHODS: Cross-sectional study (n = 57), with 3 groups. Group A: BMI < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro-BNP, Troponin T, leptin and insulin levels are expressed as median and ranges (r). RESULTS: Albumin (g/dL): GA vs GC, 3.70 (r2.20-4.90) vs 3.85 (r3.40-4.90), P = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840). Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, 3.81 (r0.78-69.60) vs GC, 32.80 (r0.78-124.50), P < 0.001. Insulin (µU/mL): GA vs GB, 7 (r2-44) vs 11.50 (r4-38), P = 0.02; GA vs GC, 7 (r2-44) vs 19.5 (r5-155), P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations: GC, Insulin-UF: ρ = 0.53; P = 0.03; TroponinT-diuresis: ρ = -0.48, P < 0.05; Pro-BNP-diuresis: ρ = -0.39, P < 0.01; Troponin T-ProBNP: ρ = 0.77, P < 0.0001; albumin-Troponin T: ρ = -0.66, P < 0.0001; albumin-ProBNP: ρ = -0.44, P < 0.05. CONCLUSION: High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.

Proteinuria, (99m) Tc-DTPA Scintigraphy, Creatinine-, Cystatin- and Combined-Based Equations in the Assessment of Chronic Kidney Disease.

Background. Precise estimation of the glomerular filtration rate (GFR) and the identification of markers of progression are important. We compared creatinine, cystatin, and combined CKD-EPI equations with (99m)Tc-DTPA scintigraphy to measure GFR and proteinuria as markers of progression. Methods. Cross-sectional, observational study including 300 subjects. CKD was classified by (99m)Tc-DTPA scintigraphy. Determinations. Creatinine, 24-hour creatinine clearance, cystatin, Hoek formula, and creatinine, cystatin, and combined CKD-EPI equations. Results. In the global assessment, creatinine CKD-EPI and combined CKD-EPI equations yielded the highest correlations with (99m)Tc-DTPA: ρ = 0.839, P < 0.0001 and ρ = 0.831, P < 0.0001. Intergroup analysis versus (99m)Tc-DTPA: control G, creatinine clearance ρ = 0.414, P = 0.013; G3, combined CKD-EPI ρ = 0.5317, P < 0.0001; G4, Hoek ρ = 0.618, P < 0.0001, combined CKD-EPI ρ = 0.4638, P < 0.0001; and G5, creatinine clearance ρ = 0.5414, P < 0.0001, combined CKD-EPI ρ = 0.5288, P < 0.0001. In the global assessment, proteinuria displayed the highest significant correlations with cystatin ( ρ = 0.5433, P < 0.0001) and cystatin-based equations (Hoek: ρ = -0.5309, P < 0.0001). When GFR < 60 mL/min: in stage 3, proteinuria-cystatin ( ρ = 0.4341, P < 0.0001); proteinuria-Hoek ( ρ = -0.4105, P < 0.0001); in stage 4, proteinuria-cystatin ( ρ = 0.4877, P < 0.0001); proteinuria-Hoek ( ρ = -0.4877, P = 0.0026). Conclusions. At every stage of GFR < 60 mL/min, cystatin-based equations displayed better correlations with (99m)Tc-DTPA. Proteinuria and cystatin-based equations showed strong associations and high degrees of correlation.

Comparación ensayos de parathormona de segunda y tercera generación y su utilidad en hemodializados crónicos / Comparison of third and second generation parathyroid hormone assays and their use in chronic hemodialysis patiens

Introducción: El objetivo del trabajo es comparar ensayos de PTH de 2da y 3ra generación en pacientes con función renal normal y en hemodializados crónicos y sus implicancias en el tratamiento de esta última población. Métodos: Se estudiaron 60 pacientes hemodializados crónicos y 40 con función renal normal a quienes se les midió PTH por ambos ensayos. Resultados: En la población con función renal normal la mediana de PTH fue de 51.8 y de 45.6 pg/ml con el ensayo de 2da y 3ra generación respectivamente. En hemodializados crónicos la mediana de PTH fue de 193.9 y de 137.1 pg/ml con los ensayos de 2da y 3ra generación respectivamente. La diferencia entre los ensayos fue de 11.3% y 29.3% en la población con función renal y hemodializados respectivamente. El ensayo de 3ra generación produjo un corrimiento en la cantidad de pacientes que caen en los distintos rangos de PTH según las guías KDIGO, para un valor menor de 2 veces el límite superior de referencia: cambia de 20 a 25 pacientes, entre 2 y 9 veces: cambia de 31 a 32 pacientes y mayor de 9 veces: cambia de 9 a 3 pacientes. Conclusiones: Al aumentar la concentración de PTH aumentan las diferencias entre ambos ensayos, por lo que no se pueden utilizar indistintamente en una población de hemodializados crónicos.Con los ensayos de 3ra generación 11 pacientes (18.3%) modificaron su clasificación de acuerdo a las guías KDIGO lo que implicaría un cambio en el tratamiento.

Introduction: This work's objective is to compare third and second generation assays in patients with normal kidney function and in chronic hemodialysis patients, and the implications on the latter. Methods: 60 chronic hemodialysis patients and 40 patients with normal kidney function were studied and their PTH levels were measured for both assays. Results: In patients population with normal kidney function the average on PTH was 51.8 and 45.6 pg/ml with second and third generation assays respectively. In chronic hemodialysis patients the average PTH was 193.9 and 137.1 pg/ml with second and third generation assays respectively. The difference between assays was 11.3% and 29.3% in patients with normal kidney function and in hemodialysis patients respectively. Third generation assay caused a variation in the amount of patients that fall over several PTH ranges according to KDIGO guidelines, for a lesser value of 2 times the reference upper limit: it changes from 20 to 25 patients, between 2 and 9 times: it changes from 31 to 32 patients, and more than 9 times: it changes from 9 to 3 patients. Conclusions: When PTH concentration increases the difference between both assays also increases, for this reason we cannot use them indiscriminately in a chronic hemodialysis patient population. With third generation assays 11 patients (18.3%) changed their classification according to KDIGO guidelines, which will result in a change of treatment.

Pro-calcitonin and inflammation in chronic hemodialysis.

UNLABELLED: Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients. In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. VARIABLES: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/ dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: p = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

Pro-calcitonin and inflammation in chronic hemodialysis / Pro-calcitonina e inflamación en hemodiálisis crónica

Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients.In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. Variables: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: ρ = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

La procalcitonina (PCT) puede ser un marcador de infección en la hemodiálisis (HD). Analizamos los niveles de PCT en sujetos sin infección aguda en HD crónica, su correlación con marcadores inflamatorios y nutricionales y, de acuerdo a ello, proponemos niveles de referencia de PCT. En un estudio observacional transversal se estudiaron 48 pacientes en HD y 36 controles. Variables: edad; sexo, tiempo en HD; diabetes; acceso vascular, PCT, proteína C-reactiva (PCR), albúmina, score de malnutrición-inflamación, hematocrito, recuento leucocitario, e índice de masa muscular (IMC). En los controles se determinaron PCT y PCR. Se comparó grupo control (G1, n = 36, 43%) vs. pacientes (G2, n = 48, 57%). G1: edad, 54.3 ± 13.7, rango (r): 30-81 años; hombres: 19 (53%); PCT mediana: 0.034 ng/ml (r: 0.020-0.080); PCR mediana: 0.8 mg/dl (r: 0.36-3.9); el nivel p95 de PCT: 0.063 ng/ml. En el G2, edad media 60.2 ± 15.2 años, hombres: 32 (66%), tiempo en HD: 27.0 2 4.4; diabéticos: 19 (32%); PCT: 0.26 ng/ml (r: 0.09-0.82); PCR: 1.1 mg/dl (r: 0.5-6.2); p95 PCT: 0.8 ng/ml. En G1 los niveles de PCT y PCR fueron significativamente más bajos que en G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; PCR: 0.8 vs 1.1 mg/dl, p = 0.0004. Correlación PCT- PCR en G2: ρ = 0.287, p = 0.048. La PCT y la PCR están elevadas en HD crónica independientemente de infección, diabetes y acceso vascular. Se propone p95 de PCT de 0.8 ng/ml como límite superior del intervalo de referencia en sujetos sin infección aguda en HD. El valor de PCT en HD está por determinarse.

Pro-calcitonin and inflammation in chronic hemodialysis / Pro-calcitonina e inflamación en hemodiálisis crónica

Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients.In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. Variables: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: ρ = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.(AU)

La procalcitonina (PCT) puede ser un marcador de infección en la hemodiálisis (HD). Analizamos los niveles de PCT en sujetos sin infección aguda en HD crónica, su correlación con marcadores inflamatorios y nutricionales y, de acuerdo a ello, proponemos niveles de referencia de PCT. En un estudio observacional transversal se estudiaron 48 pacientes en HD y 36 controles. Variables: edad; sexo, tiempo en HD; diabetes; acceso vascular, PCT, proteína C-reactiva (PCR), albúmina, score de malnutrición-inflamación, hematocrito, recuento leucocitario, e índice de masa muscular (IMC). En los controles se determinaron PCT y PCR. Se comparó grupo control (G1, n = 36, 43%) vs. pacientes (G2, n = 48, 57%). G1: edad, 54.3 ± 13.7, rango (r): 30-81 años; hombres: 19 (53%); PCT mediana: 0.034 ng/ml (r: 0.020-0.080); PCR mediana: 0.8 mg/dl (r: 0.36-3.9); el nivel p95 de PCT: 0.063 ng/ml. En el G2, edad media 60.2 ± 15.2 años, hombres: 32 (66%), tiempo en HD: 27.0 2 4.4; diabéticos: 19 (32%); PCT: 0.26 ng/ml (r: 0.09-0.82); PCR: 1.1 mg/dl (r: 0.5-6.2); p95 PCT: 0.8 ng/ml. En G1 los niveles de PCT y PCR fueron significativamente más bajos que en G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; PCR: 0.8 vs 1.1 mg/dl, p = 0.0004. Correlación PCT- PCR en G2: ρ = 0.287, p = 0.048. La PCT y la PCR están elevadas en HD crónica independientemente de infección, diabetes y acceso vascular. Se propone p95 de PCT de 0.8 ng/ml como límite superior del intervalo de referencia en sujetos sin infección aguda en HD. El valor de PCT en HD está por determinarse.(AU)

Proteinuria and its relation to diverse biomarkers and body mass index in chronic hemodialysis.

BACKGROUND: Certain adipokines exert direct effects on proteinuria, a cardiovascular risk factor ignored in hemodialysis. We measured different adipokines according to body mass index (BMI) in relation to proteinuria. METHODS: Patients numbered 57: group A (GA), BMI<25, n = 22; GB, BMI 25-30, n = 15; and GC, BMI > 30, n = 20. There were no statistical differences in age, sex, time on dialysis, cause of renal failure, diabetes, hypertension, C-reactive protein, or nutritional status. Measures were taken of 24-hour diuresis and proteinuria, ultrafltration, albumin, pro-brain natriuretic peptide (Pro-BNP), insulin, adiponectin, leptin, and ghrelin. RESULTS: Proteinuria was signifcantly higher in GC versus (vs) GA (1.5 g/day, range 0.30-14 vs 0.72 g/day, range 0.1-2.7; P < 0.01) and correlated signifcantly with leptin levels (ρ = 0.47, P < 0.05). In GA, elevated levels of Pro-BNP, adiponectin, and ghrelin were associated with lower degrees of proteinuria. Signifcant correlations were found between adiponectin and leptin (ρ = -0.54, P = 0.03), and adiponectin and Pro-BNP (ρ = 0.59, P = 0.02). Though not signifcant, there were more diabetics in GC (GA four, GB three, GC ten). As BMI increased in GB and GC, Pro-BNP, adiponectin, and ghrelin levels decreased signifcantly, while proteinuria, insulin, and homeostasis model assessment of insulin resistance increased. Leptin levels were signifcantly elevated in GC vs GA and GB. In GC, ghrelin correlated signifcantly with Pro-BNP (ρ = 0.51, P = 0.03), while leptin correlation with Pro-BNP was inverse and signifcant in GA (ρ = -0.74, P < 0.001) and inverse and nonsignifcant in GB and GC. CONCLUSION: In patients with BMI < 25, higher adiponectin, ghrelin, and Pro-BNP levels were associated with lower proteinuria and leptinemia. In obesity, hyperleptinemia and hyperinsulinemia associated with higher proteinuria; whether decreased adiponectin-ghrelin-ProBNP and/or elevated leptin-insulin levels aggravate proteinuria remains to be determined.

Pro-calcitonin and inflammation in chronic hemodialysis. / Pro-calcitonin and inflammation in chronic hemodialysis.

UNLABELLED: Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients. In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. VARIABLES: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43

) vs. non-infected patients (G2, n = 48, 57

) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53

); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/ dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67

), time on HD: 27.0 ± 24.4; diabetics: 19 (32

); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: p = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

Proteinuria: an ignored marker of inflammation and cardiovascular disease in chronic hemodialysis.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients, the main etiologies being diabetes and hypertension. Cardiac and inflammatory biomarkers are usually employed to assess risk or damage, or during follow-up. Proteinuria is considered a strong predictor of morbidity, a cause of inflammation, oxidative stress, hemodynamic alteration, and progression of chronic kidney disease. However, proteinuria is rarely considered in the clinical assessment of HD patients. METHODS: This was a concurrent, cohort-observational, cross-sectional study in which 52 chronic HD subjects were divided into three groups according to the degree of proteinuria: Group (G) A: <1 g/day, n = 25; GB: 1-3 g/day, n = 13; GC: >3 g/day, n = 14. Baseline hemoglobin, albuminemia, cholesterol, body mass index, Malnutrition-Inflammatory Score, pro-B-type natriuretic peptide, troponin T, C-reactive protein (CRP), and ultrafiltration rates were analyzed. RESULTS: There was no difference between groups in terms of baseline age, gender, hypertension, cause of renal failure, hemoglobin, cholesterol, albumin, CRP levels, cardiac biomarkers, adiponectin, body mass index, or Malnutrition-Inflammatory Score. Time on HD: GA, 34.56 ± 23.3 (range [r]: 6-88); GB, 25.15 ± 19.40 (r: 6-58); GC, 18.21 ± 9.58 (r: 6-74) months; P = 0.048. Proteinuria: GA, 0.33 ± 0.30 (r: 0.0-0.88); GB, 1.66 ± 0.54 (r: 1.03-2.75); GC, 7.18 ± 2.80 (r: 3.04-21.5) g/day; P < 0.001. Mean ultrafiltration rates were significantly different: GA, 2.80 ± 0.73; GB: 1.85 ± 0.96 liters/session; P = 0.003. Fourteen diabetic patients were identified (27%): GA, 3 (12%); GB, 3 (23%); GC, 8 (57%); P = 0.009. A positive and significant correlation was observed between diabetes and proteinuria >3 g/day: rho 0.438, P = 0.027. Although troponin T, pro-B-type natriuretic peptide, adiponectin, and CRP were not different among groups, the positive correlation between troponin T and CRP elevated significantly as proteinuria increased: GA, rho 377, P = 0.063; GB, rho 663, P = 0.013; GC, rho 687, P = 0.007. CONCLUSION: In chronic HD, nephrotic-range proteinuria was significantly higher in diabetic nephropathy patients versus other causes. This was associated with inflammation and cardiac stress and was independent of fluid removal. Proteinuria >3 g/day was associated with shorter time on HD. Whether severe proteinuria is associated with shorter survival in HD, independent of diabetes, is to be determined. Proteinuria should be considered in the assessment of cardiovascular and inflammatory states in HD patients.