Hepatitis E virus infection in pregnant women, Argentina.

BACKGROUND: Hepatitis E virus (HEV) infection is an important cause of acute hepatitis worldwide. In pregnant women, HEV can cause more severe symptoms, with high rates of fatal hepatic failure in endemic countries. However, HEV prevalence and circulation among pregnant women from South America is almost unknown. We aimed to investigate HEV infection in pregnant women for the first time in Argentina. METHODS: IgG and IgM anti-HEV antibodies and RNA-HEV were investigated (by ELISA assays and RT-Nested-PCR, respectively) in 202 serum samples from pregnant women collected in the central region of Argentina between 2015 and 2017. A control group of 155 non-pregnant women was included (year 2018). RESULTS: The IgG anti-HEV positivity rate was 8.4% (17/202), higher than the 2.6% (4/155) obtained for the non-pregnant women control group, and showing association between pregnancy and HEV infection (p = 0.023, OR = 3.5, CI95% = 1.1-10.5). Women younger than 25 years old presented higher levels of antibodies, and there were no differences in the prevalences between trimesters of pregnancy. Two samples were reactive for IgM anti-HEV, showing recent infections, although no symptoms were registered in these patients. All samples were negative for RNA-HEV amplification. CONCLUSIONS: HEV produces infections in pregnant women from Argentina, alerting health teams to consider it as a possible cause of liver disease.

Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: decreased expression of this receptor in nonclassical monocytes.

In this article, we present a flow cytometry assay by which human blood monocyte subpopulations-classical (CD14(++) CD16(-)), intermediate (CD14(++) CD16(+)), and nonclassical (CD14(+) CD16(++)) monocytes-can be determined. Monocytic cells were selected from CD45(+) leukocyte subsets by differential staining of the low-density lipoprotein receptor-related protein 1 (LRP1), which allows reducing the spill-over of natural killer cells and granulocytes into the CD16(+) monocyte gate. Percentages of monocyte subpopulations established by this procedure were significantly comparable with those obtained by a well-standardized flow cytometry assay based on the HLA-DR monocyte-gating strategy. We also demonstrated that LRP1 is differentially expressed at cell surface of monocyte subpopulations, being significantly lower in nonclassical monocytes than in classical and intermediate monocytes. Cell surface expression of LRP1 accounts for only 20% of the total cellular content in each monocyte subpopulation. Finally, we established the within-individual biological variation (bCV%) of circulating monocyte subpopulations in healthy donors, obtaining values of 21%, 20%, and 17% for nonclassical, intermediate, and classical monocytes, respectively. Similar values of bCV% for LRP1 measured in each monocyte subpopulation were also obtained, suggesting that its variability is mainly influenced by the intrinsic biological variation of circulating monocytes. Thus, we conclude that LRP1 can be used as a third pan-monocytic marker together with CD14 and CD16 to properly identify monocyte subpopulations. The combined determination of monocyte subpopulations and LRP1 monocytic expression may be relevant for clinical studies of inflammatory processes, with special interest in atherosclerosis and cardiovascular disease.

[Associated factors and clinical implications of post transplant renal anemia]. / Factores asociados y consecuencias clínicas de la anemia post trasplante renal.

A considerable percentage of patients exhibit anemia post kidney transplant. Its origin is multifactorial and the main causes involved depend on the post transplant period considered. We studied in a group of 134 consecutive patients the associated factors and the clinical implications of "late anemia" (6 months post transplant). Multiple regression analysis showed that post transplant oliguria and acute rejection episodes were significantly associated with anemia. Graft survival at 36 months was significantly reduced in the anemic group (83 % versus 96%, p < 0.01). No differences in patients survival or rate of cardiovascular events were observed. We concluded that anemia at 6 months post transplant is independently and significantly associated with events that reduced functioning renal mass and kidney survival.

Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis.

Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development. Low-density lipoprotein Receptor-related Protein 1 (LRP1) is expressed in monocytes, mainly in classical and intermediate subsets. Although LRP1 is highly expressed in macrophages and vascular smooth muscle cells (VSMCs) in atherosclerotic plaque formation, its expression in circulating monocytes has not been studied in SCA. The aim of this study was to characterize the LRP1 expression level in circulating monocytes of individuals with SCA and compared with individuals with low (LR) and intermediate (IR) risk of cardiovascular diseases, both without evidence of atherosclerotic lesions in carotid and coronary arteries. LRP1 and additional markers (CD11b, CD11c, and CD36) at cell surface of monocytes were analyzed by flow cytometry assays, whereas LRP1 and pro-inflammatory factors gene expressions were measured in isolated monocytes by quantitative RT-PCRs. Both LRP1 protein and LRP1 mRNA were significantly reduced in monocytes in SCA and IR respect to LR. Conversely, CD36, CD11b, and CD11c monocytic markers showed no significant changes between the different study groups. Finally, increased gene expressions of TNF-α and IL-1ß were detected in monocytes of SCA, which were associated with decreased LRP1 expression at the cell surface in total monocytes. In summary, we propose that the decreased LRP1 expression at cell surface in total monocytes with pro-inflammatory profile is associated with the development of atherosclerosis in asymptomatic individuals.

Post-kidney donation glomerular filtration rate measurement and estimation.

BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73m2) and 13.8% (60ml/min/1.73m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.

Post-kidney donation glomerular filtration rate measurement and estimation. / Medición y estimación del filtrado glomerular posdonación renal.

BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73 m2) and 13.8% (60ml/min/1.73 m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73 m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.

[Usefulness of equations based on serum cystatin C concentration in the study of renal function]. / Utilidad de las ecuaciones basadas en la concentracion serica de cistatina C en el estudio de la funcion renal.

Serum creatinine is an insensitive marker to identify early changes in glomerular filtration rate (GFR), for this reason alternative methods to estimate renal function result of great clinical importance. Forty-one patients were studied using creatinine clearance modified with cimetidina (Clcrc) as surrogate of GFR, cystatin C-based equations (i.e. Larsson and Hoek formulas), Cockroft-Gault and MDRD abbreviated equations. In the whole group, as well as in those patients with serum creatinine < or =1.2 mg/dl--but reduced renal function: Clcrc 62.01 +/- 17.33 ml/ min/1.73 m(2)-, Larsson and Hoek equations showed higher correlations and lower bias than creatinine-based formulas. Abbreviated MDRD equation showed good performance just in those patients with evident alteration of renal function (serum creatinine > 1.2 mg/dl). We concluded that in patients with different stages of renal function, cystatin C-based equations detect reduction of renal function earlier than the serum creatinine-based formulas.

Association between cardiovascular disease risk scores and subclinical atherosclerosis prevalence in non-elderly adult patients from Argentina.

The goal of our study was to use statistical analysis to try to associate cardiovascular disease (CVD) risk scores and the observed prevalence of subclinical atherosclerosis (SA) in a non-elderly adult local population. An observational cross-sectional study was carried out (143 male and 131 female) on non-elderly adults (20-59 years). CVD risk scores included Framingham Risk Scores for 10-year hard (FRS 10 H), 30-year lipid hard or CVD (FRS 30 L H or FRS 30 L CVD), 30 year-body mass index hard or CVD (FRS 30 BMI H or FRS 30 BMI CVD) and Pooled Cohort Risk Equations for either 10 years (PCE 10) or lifetime (PCE LT). The Carotid Ultrasound (CU) study was performed and the Coronary Artery Calcium (CAC) score were obtained to assess SA. The Receiving Operating Characteristic (ROC) curve analysis followed by Youden's index was used to evaluate and adjust the stratification of CVD risk scores. SA was detected in 32.4% of individuals. The risk scores that showed the biggest areas under the ROC curve were FRS 30 L (H and CVD). When the cut-off values for these CVD risk scores were adjusted, the FRS 30 L H increased the negative predictive value for the low risk group from 87.7 to 97.0% and the FRS 30 L CVD increased the positive predictive values for the high risk group from 69.7 to 85.7%. The CVD risk stratification of non-elderly adults using FRS 30 L H and FRS 30 L CVD may be a useful tool for selecting candidate patients for diagnostic imaging studies that assess their SA prevalence.

Transient neonatal hyperthyrotropinemia is a risk factor for developing persistent hyperthyrotropinemia in childhood with repercussion on developmental status.

OBJECTIVE: Transient neonatal hyperthyrotropinemia (TNH) is defined as a neonatal abnormality of thyroid function, which reverts to normal at re-examination after 2 weeks of life. The thyroid function of these infants has not been sufficiently studied in terms of the risk of developing persistent hyperthyrotropinemia (PH) in later childhood and its impact on growth and development. DESIGN: A prospective cohort study included all babies born in our hospital between 2001 and 2006 and screened for hypothyroidism, whose thyroid function was re-examined 6 years later. Exclusion criteria included the following conditions: preterm birth, birth weight <2500 g, Down's syndrome, descendants of mothers with immune thyroid disease, congenital malformations, cardiac, renal, hepatic, and metabolic diseases, and steroid or dopamine medication. The variables included are TSH and thyroxine at neonatal screening and 6 years later. Main outcomes are the risk of developing PH in childhood, linear growth, and development using Parents' Evaluation of Developmental Status (PEDS). RESULTS: Out of 5040 normal-term newborns, 301 (6.0%, 95% CI 5.3-6.6%) have TSH ≥10 mU/l (TNH). Six years later, we re-examined 65 randomly selected children with TNH and 185 controls. In the TNH cohort, we found six out of 65 children (9.2%, 95% CI 1.4-17.0%) with PH (TSH ≥6.4 mU/l), and three out of 185 (1.6%, 95% CI 0.3-4.7%) among controls, relative risk 5.7 (95% CI 1.5-22.1), P=0.0114. TSH and developmental delay were found to be significantly higher in the TNH cohort (4.7±1.3 mU/l vs 2.1±0.5 mU/l, P<0.0001 and 15/65 (23%, 95% CI 12-34.1) vs 21/185 (11.3%, 95% CI 6.5-16.2) P=0.0348). CONCLUSIONS: Newborns with TNH have a higher risk of developing PH in childhood, with repercussion on developmental status.

High prevalence of secondary hyperparathyroidism in chronic kidney disease patients on dialysis in Argentina.

BACKGROUND: There are few data in Argentina on the prevalence and management of bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD). OBJECTIVES AND METHODS: A survey was carried out in dialysis units in 2010 to measure the prevalence of and types of treatments for BMM disorders in Argentina. The data obtained was then compared to the published results from other large population studies. We recorded characteristics of dialysis centres and participating patients, the frequency of measurements and individual results for BMM biochemical markers, as well as the type of management used to control hyperphosphataemia and secondary hyperparathyroidism. RESULTS: 1210 patients from 25 dialysis centres in Argentina participated in the study (representing 4.7% of the country's prevalent dialysis population in 2010). The mean patient age was 55.3±17.6 years, 60.8% were male, 3.3% were on peritoneal dialysis and 29.1% suffered diabetes. In all centres, phosphataemia and calcaemia were measured on a monthly basis, 60% of centres measured intact parathyroid hormone (iPTH) every 6 months, 36% every 3 to 4 months, and 4% annually. As recommended by K/DOQI, 51.6% of patients had adequate levels of calcium (8.4-9.5 mg/dl), 51.6% had adequate phosphorus (3.5-5.5 mg/dl) and 21.1% displayed acceptable iPTH levels (150-300 pg/ml). 24% had iPTH <150 pg/ml and 54.5% >300 pg/ml. iPTH ≥600 pg/ml was present in 28.3%, and 13.3% had values ≥1000 pg/ml. These figures differed from those published by the DOPPS II study, in which 51.1% of patients had iPTH <150 pg/ml, and only 26.7% had iPTH ≥300 pg/ml. Calcium-based phosphate binders were used in 83.6% of the patients, 5.6% used sevelamer and 4.0% used aluminium-containing compounds. To achieve control of hyperparathyroidism, oral or intravenous calcitriol was predominantly used (50.5%) with a small percentage of patients receiving paricalcitol or doxercalciferol. CONCLUSIONS: The present study shows a high prevalence of secondary hyperparathyroidism, which differs from that published by other large population studies. There was a high proportion of patients with BMM markers outside the ranges suggested by K/DOQI. Mainly phosphate binders based on calcium and calcitriol continue to be used for the management of hyperphosphatemia and hyperparathyroidism respectively.

CKD-EPI instead of MDRD for candidates to kidney donation.

BACKGROUND: The determination of the glomerular filtration rate (GFR) is critical for the selection of a potential kidney donor. The complex and impractical techniques for the measurement of GFR have led to the development of equations to estimate GFR. Modification of diet in renal disease (MDRD) formula is the most widely used but its performance is poor because it systematically underestimates GFR above 60 mL/min. A new formula called the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) seems to overcome this limitation but needs to be tested in healthy potential kidney donors. METHODS: From 2007 to 2011, a cross-sectional study was performed on 85 adults who were candidates for living-related kidney donation. GFR was measured by nonradiolabeled iothalamate clearance determined by high-performance liquid chromatography, and renal function was estimated by using CKD-EPI and MDRD equations. The overall performance of the equations was analyzed, and the estimation for GFR above 90 mL/min was studied by means of receiver operating characteristic curves. RESULTS: The mean (SD) (range) of the measured GFR was 116 (24) (64-160) mL/min per 1.73 m(2), estimated GFR with CKD-EPI was 108 (22) (64-153) mL/min per 1.73 m(2), and MDRD was 99 (28) (46-157) mL/min per 1.73 m(2). CKD-EPI presented lower bias (3.3 vs. 10.2 mL/min/1.73 m(2)), higher precision [interquartile range (minimum value-maximum value), 25 (53-140) vs. 32 (43-161) ml/min] and higher accuracy (100% vs. 89%) compared with MDRD. CONCLUSION: The CKD-EPI equation showed a higher performance than the MDRD equation in the GFR estimation of healthy population. CKD-EPI is applicable instead of MDRD, to subjects or candidates for kidney donation to avoid wrong GFR underestimates, which may lead to an inappropriate exclusion of candidates.

Factores asociados y consecuencias clínicas de la anemia post trasplante renal / Associated factors and clinical implications of post transplant renal anemia

Un porcentaje considerable de pacientes presentan anemia post trasplante renal. Su origen es multifactorial y sus principales etiologías dependen de la etapa post trasplante que se considere. Estudiamos en un grupo de 134 pacientes los factores asociados con anemia tardía (6 meses post trasplante) y sus implicaciones clínicas a mediano plazo. En el análisis de regresión múltiple, la duración de la oliguria post trasplante y el número de episodios de rechazo fueron las variables significativamente asociadas con esta complicación. La supervivencia del órgano mostró una diferencia significativa a los 36 meses entre los grupos (83% en los anémicos versus 96% de los no anémicos p < 0.01). No observamos diferencias en mortalidad o eventos cardiovasculares. Concluimos que la presencia de anemia al sexto mes post trasplante renal está independiente y significativamente asociada con factores que condicionan la masa renal funcionante que explicarían además la menor supervivencia del injerto renal observada en estos pacientes.

A considerable percentage of patients exhibit anemia post kidney transplant. Its origin is multifactorial and the main causes involved depend on the post transplant period considered. We studied in a group of 134 consecutive patients the associated factors and the clinical implications of "late anemia" (6 months post transplant). Multiple regression analysis showed that post transplant oliguria and acute rejection episodes were significantly associated with anemia. Graft survival at 36 months was significantly reduced in the anemic group (83 % versus 96%, p < 0.01). No differences in patients survival or rate of cardiovascular events were observed. We concluded that anemia at 6 months post transplant is independently and significantly associated with events that reduced functioning renal mass and kidney survival.

Utilidad de las ecuaciones basadas en la concentración sérica de cistatina C en el estudio de la función renal / Usefulness of equations based on serum cystatin C concentration in the study of renal function

La creatinina sérica es un marcador poco sensible para identificar reducciones leves del índice de filtración glomerular (IFG); por ello resulta de gran importancia clínica disponer de métodos alternativos para estimar la función renal. Con este objetivo estudiamos la función renal de 41 pacientes -grupo completo y divididos según la creatinina sérica (menor o igual 1.2 mg/dl o mayores)- usando el clearance de creatinina modificado con cimetidina (Clcrc) como aproximación al IFG, las ecuaciones de Larsson y Hoek que incluyen el uso de cistatina C sérica y las tradicionales fórmulas de Cockroft-Gault y MDRD abreviada. En el grupo completo de pacientes y especialmente en aquellos con creatinina sérica menor o igual 1.2 mg/dl - con reducción de la función renal: Clcrc: 62.01 mas o menos 17.33 ml/min/1.73 m2-, las ecuaciones de Larsson y Hoek mostraron mejores correlaciones y menores diferencias promedio respecto a las fórmulas basadas en la creatinina sérica. La ecuación MDRD abreviada mostró buen rendimiento sólo en el grupo con evidente alteración de la función renal (creatinina sérica > 1.2 mg/dl). Concluimos que en pacientes con diferentes estadios de función renal, las fórmulas que emplean la cistatina C sérica detectan la reducción del IFG más precozmente respecto a aquellas basadas en la creatinina sérica.

Serum creatinine is an insensitive marker to identify early changes in glomerular filtration rate (GFR), for this reason alternative methods to estimate renal function result of great clinical importance. Forty-one patients were studied using creatinine clearance modified with cimetidina (Clcrc) as surrogate of GFR, cystatin C-based equations (i.e. Larsson and Hoek formulas), Cockroft-Gault and MDRD abbreviated equations. In the whole group, as well as in those patients with serum creatinine less than or equal to 1.2 mg/dl -but reduced renal function: Clcrc 62.01 more or less 17.33 ml/min/1.73 m2-, Larsson and Hoek equations showed higher correlations and lower bias than creatinine-based formulas. Abbreviated MDRD equation showed good performance just in those patients with evident alteration of renal function (serum creatinine > 1.2 mg/dl). We concluded that in patients with different stages of renal function, cystatin C-based equations detect reduction of renal function earlier than the serum creatinine-based formulas.