The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

Membranous nephropathy.

Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

In situ assessment of Mindin as a biomarker of podocyte lesions in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.

Chikungunya virus as a trigger for different renal disorders: an exploratory study.

INTRODUCTION: Chikungunya virus was detected in cases of acute chikungunya fever in renal tissue. However, chikungunya virus-related kidney injury still lacks characterization, and it is unknown whether the kidneys are reservoirs for the virus. We sought to detect histopathological changes and viral antigens in renal tissue, and to evaluate kidney injury markers in different phases of chikungunya fever. METHODS: Two groups were evaluated in this exploratory study: patients with biopsy-proven kidney injury established after chikungunya fever, and patients with post-chikungunya fever chronic joint manifestations without known kidney injury, in whom we actively searched for kidney injury markers. RESULTS: In the first group, 15 patients had kidney injury 0.5-24 months after chikungunya fever. The most frequent histopathological diagnoses were glomerular lesions. No viral antigens were detected in renal tissue. High-risk genotypes were detected in patients with atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis. In the second group, 114 patients had post-chikungunya fever joint manifestations on average for 35.6 months. Mean creatinine and proteinuria were 0.9 mg/dl and 71.5 mg/day, respectively. One patient had isolated hematuria. There was no indication for renal biopsy in this group. CONCLUSIONS: Several histopathological features were found after chikungunya fever, without virus detection in renal tissue. These findings suggest that chikungunya virus may trigger kidney lesions with varying degrees of severity at different stages of infection. However, the probability that this virus replicates in the renal tissue seems unlikely.

The Colombian Strain of Trypanosoma cruzi Induces a Proinflammatory Profile, Neuronal Death, and Collagen Deposition in the Intestine of C57BL/6 Mice Both during the Acute and Early Chronic Phase.

The objective of this study was to evaluate the histopathological changes caused by infection with the Colombian strain of Trypanosoma cruzi (T. cruzi) in the acute and chronic experimental phases. C57Bl/6 mice were infected with 1000 trypomastigote forms of the Colombian strain of T. cruzi. After 30 days (acute phase) and 90 days (early chronic phase) of infection, the animals were euthanized, and the colon was collected and divided into two parts: proximal and distal. The distal portion was used for histopathological analysis, whereas the proximal portion was used for quantification of pro- and anti-inflammatory cytokines. In addition, the weight of the animals and parasitemia were assessed. The infection induced gradual weight loss in the animals. In addition, the infection induced an increase in interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α) in the intestine in the acute phase, in which this increase continued until the early chronic phase. The same was observed in relation to the presence of intestinal inflammatory infiltrates. In relation to interleukin (IL)-10, there was an increase only in the early chronic phase. The Colombian strain infection was also able to induce neuronal loss in the myenteric plexus and deposition of the collagen fibers during the acute phase. The Colombian strain of T. cruzi is capable of causing histopathological changes in the intestine of infected mice, especially in inducing neuronal destructions. Thus, this strain can also be used to study the intestinal form of Chagas disease in experimental models.

Biomarkers and Their Possible Functions in the Intestinal Microenvironment of Chagasic Megacolon: An Overview of the (Neuro)inflammatory Process.

The association between inflammatory processes and intestinal neuronal destruction during the progression of Chagasic megacolon is well established. However, many other components play essential roles, both in the long-term progression and control of the clinical status of patients infected with Trypanosoma cruzi. Components such as neuronal subpopulations, enteric glial cells, mast cells and their proteases, and homeostasis-related proteins from several organic systems (serotonin and galectins) are differentially involved in the progression of Chagasic megacolon. This review is aimed at revealing the characteristics of the intestinal microenvironment found in Chagasic megacolon by using different types of already used biomarkers. Information regarding these components may provide new therapeutic alternatives and improve the understanding of the association between T. cruzi infection and immune, endocrine, and neurological system changes.

Renal Manifestations of Fabry Disease: A Narrative Review.

PURPOSE OF REVIEW: In this narrative review, we describe general aspects, histological alterations, treatment, and implications of Fabry disease (FD) nephropathy. This information should be used to guide physicians and patients in a shared decision-making process. SOURCE OF INFORMATION: Original peer-reviewed articles, review articles, and opinion pieces were identified from PubMed and Google Scholar databases. Only sources in English were accessed. METHODS: We performed a focused narrative review assessing the main aspects of FD nephropathy. The literature was critically analyzed from a theoretical and contextual perspective, and thematic analysis was performed. KEY FINDINGS: FD nephropathy is related to the progressive accumulation of GL3, which occurs in all types of renal cells. It is more prominent in podocytes, which seem to play an important role in the pathogenesis of this nephropathy. A precise detection of renal disorders is of fundamental importance because the specific treatment of FD is usually delayed, making reversibility unlikely and leading to a worse prognosis. LIMITATIONS: As no formal tool was applied to assess the quality of the included studies, selection bias may have occurred. Nonetheless, we have attempted to provide a comprehensive review on the topic using current studies from experts in FD and extensive review of the literature.

OBJET DE LA REVUE: Dans cette revue narrative, nous discutons des aspects généraux, des modifications histologiques, du traitement et des implications de la néphropathie liée à la Maladie de Fabry. Des informations qui serviront à guider les médecins et les patients dans un processus commun de prise de décision. SOURCES: Les originaux d'articles évalués par les pairs, d'articles-synthèses et d'articles d'opinion ont été répertoriés dans les bases de données Pubmed et Google Scholar. Seuls les articles en anglais ont été consultés. MÉTHODOLOGIE: Nous avons procédé à une revue narrative ciblée examinant les principaux aspects de la néphropathie liés à la maladie de Fabry. La documentation a fait l'objet d'une critique rigoureuse du point de vue théorique et contextuel, et une analyse thématique a été effectuée. PRINCIPAUX RÉSULTATS: La néphropathie liée à la maladie de Fabry est associée à l'accumulation progressive de GL3, qui se produit dans tous les types de cellules rénales. Elle est plus présente dans les podocytes, qui semblent jouer un rôle important dans la pathogenèse de la néphropathie. Un dépistage précis des troubles rénaux est d'une importance capitale puisque le traitement spécifique de la maladie de Fabry est généralement retardé, ce qui rend la réversibilité peu probable et conduit à un pronostic plus défavorable. LIMITES: Des biais de sélection pourraient s'être introduits puisqu'aucun outil formel n'a été utilisé pour évaluer les études incluses. Nous avons néanmoins tenté de procéder à un examen complet du sujet grâce aux études actuelles menées par des experts de la maladie de Fabry et à une revue approfondie de la documentation.

In situ evaluation of podocytes in patients with focal segmental glomerulosclerosis and minimal change disease.

Podocyte injury in focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) results from the imbalance between adaptive responses that maintain homeostasis and cellular dysfunction that can culminate in cell death. Therefore, an in situ analysis was performed to detect morphological changes related to cell death and autophagy in renal biopsies from adult patients with podocytopathies. Forty-nine renal biopsies from patients with FSGS (n = 22) and MCD (n = 27) were selected. In situ expression of Wilms Tumor 1 protein (WT1), light chain microtubule 1-associated protein (LC3) and caspase-3 protein were evaluated by immunohistochemistry. The foot process effacement and morphological alterations related to podocyte cell death and autophagy were analyzed with transmission electronic microscopy. Reduction in the density of WT1-labeled podocytes was observed for FSGS and MCD cases as compared to controls. Foot process width (FPW) in control group was lower than in cases of podocytopathies. In FSGS group, FPW was significantly higher than in MCD group and correlated with proteinuria. A density of LC3-labeled podocytes and the number of autophagosomes in podocytes/ pedicels were higher in the MCD group than in the FSGS group. The number of autophagosomes correlated positively with the estimated glomerular filtration rate in cases of MCD. The density of caspase-3-labeled podocytes in FSGS and MCD was higher than control group, and a higher number of podocytes with an evidence of necrosis was detected in FSGS cases than in MCD and control cases. Podocytes from patients diagnosed with FSGS showed more morphological and functional alterations resulting from a larger number of lesions and reduced cell adaptation.

Renal expression of cytokines and chemokines in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, thus considered an inflammatory disease. However, further studies are required to assess the renal damage caused by the action of these molecules. Therefore, the objective of this study was to analyze the expression of cytokines and chemokines in renal biopsies from patients with DN and to correlate it with interstitial inflammation and decreased renal function. METHODS: Forty-four native renal biopsies from patients with DN and 23 control cases were selected. In situ expression of eotaxin, MIP-1α (macrophage inflammatory protein-1α), IL-8 (interleukin-8), IL-4, IL-10, TNF-α (tumor necrosis factor-α), TNFR1 (tumor necrosis factor receptor-1), IL-1ß, and IL-6 were evaluated by immunohistochemistry. RESULTS: The DN group showed a significant increase in IL-6 (p < 0.0001), IL-1ß (p < 0.0001), IL-4 (p < 0.0001) and eotaxin (p = 0.0012) expression, and a decrease in TNFR1 (p = 0.0107) and IL-8 (p = 0.0262) expression compared to the control group. However, there were no significant differences in IL-10 (p = 0.4951), TNF-α (p = 0.7534), and MIP-1α (p = 0.3816) expression among groups. Regarding interstitial inflammation, there was a significant increase in IL-6 in scores 0 and 1 compared to score 2 (p = 0.0035), in IL-10 in score 2 compared to score 0 (p = 0.0479), and in eotaxin in score 2 compared to scores 0 and 1 (p < 0.0001), whereas IL-8 (p = 0.0513) and MIP-1α (p = 0.1801) showed no significant differences. There was a tendency for negative correlation between eotaxin and estimated glomerular filtration rate (eGFR) (p = 0.0566). CONCLUSIONS: Our results indicated an increased in situ production of cytokines and chemokines in DN, including IL-6, IL-1ß, IL-4, and eotaxin. It was observed that, possibly, eotaxin may have an important role in the progression of interstitial inflammation in DN and in eGFR decrease of these patients.

Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

AIM: To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function. METHODS: Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA. RESULTS: TNFR1 and leptin were higher in the T2DM group with RA than in the T2DM group without RA and control group. All patients with T2DM showed increased resistin, IL-8, and MIP-1α compared to the control group. Adiponectin were higher and IL-4 decreased in the T2DM group with RA compared to the control group. eGFR positively correlated with IL-4 and negatively with TNFR1, TNFR2, and leptin in patients with T2DM. In the T2DM group with RA, eGFR was negatively correlated with TNFR1 and resistin. TNFR1 was positively correlated with resistin and leptin, as well as resistin with IL-8 and leptin. CONCLUSION: Increased levels of TNFR1, adipokines, chemokines and decrease of IL-4 play important role in the inflammatory process developed in T2DM and decreased renal function. We also suggest that TNFR1 is a strong predictor of renal dysfunction in patients with T2DM.

Cardiac Chagas Disease: MMPs, TIMPs, Galectins, and TGF-ß as Tissue Remodelling Players.

A century after the discovery of Chagas disease, studies are still needed to establish the complex pathophysiology of this disease. However, it is known that several proteins and molecules are related to the establishment of this disease, its evolution, and the appearance of its different clinical forms. Metalloproteinases and their tissue inhibitors, galectins, and TGF-ß are involved in the process of infection and consequently the development of myocarditis, tissue remodeling, and fibrosis upon infection with Trypanosoma cruzi. Thus, considering that the heart is one of the main target organs in Chagas disease, knowledge regarding the mechanisms of action of these molecules is essential to understand how they interact and trigger local and systemic reactions and, consequently, determine whether they contribute to the development of Chagas' heart disease. In this sense, it is believed that the inflammatory microenvironment caused by the infection alters the expression of these proteins favoring progression of the host-parasite cycle and thereby stimulating cardiac tissue remodeling mechanisms and fibrosis. The aim of this review was to gather information on metalloproteinases and their tissue inhibitors, galectins, and TGF-ß and discuss how these molecules and their different interrelationships contribute to the development of Chagas' heart disease.

Evaluation of the Diagnostic Potential of uPAR as a Biomarker in Renal Biopsies of Patients with FSGS.

Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are primary glomerulopathies leading to proteinuria, known as podocytopathies, which share syndromic and morphological similarities. Morphological similarity occurs in cases of FSGS in which the sclerotic lesion was not sampled in renal biopsy, due to the focal nature of the disease. Differentiating these entities is very important, especially in cases of suspected FSGS but with sclerotic lesion not sampled, as they are diseases that apparently have different pathogenic mechanisms and prognosis. The difference in uPAR expression in situ among these two entities may be related to a distinct molecular mechanism involved in pathogenesis. Thus, finding biomarkers involved in the pathogenesis and that can also help in differential diagnosis is very relevant. The aim of this work was to evaluate the potential of urokinase-type plasminogen activator receptor (uPAR) as a biomarker in renal biopsies of patients with podocytopathies (n = 38). Immunohistochemistry showed that FSGS (n = 22) had increased uPAR expression in podocytes compared with both the MCD group (n = 16; p = 0.0368) and control group (n = 21; p = 0.0076). ROC curve (p = 0.008) showed that this biomarker has 80.95% of specificity in biopsies of patients with FSGS. Therefore, uPAR presented a high specificity in cases of podocytopathies associated with sclerosis and it can be considered a potential biomarker for FSGS.

Melatonin treatment in fetal and neonatal diseases.

This literature review aims to address the main scientific findings on oxidative stress activity in different gestational disorders, as well as the function and application of melatonin in the treatment of fetal and neonatal changes. Oxidative stress has been associated with the etiopathogenesis of recurrent miscarriages, preeclampsia, intrauterine growth restriction, and stillbirth. Both, the exacerbated consumption of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase, and the increased synthesis of reactive oxygen species, such as superoxide, peroxynitrite, and hydrogen peroxide, induce phospholipid peroxidation and endothelial dysfunction, impaired invasion and death of trophoblast cells, impaired decidualization, and remodeling of maternal spiral arteries. It has been postulated that melatonin induces specific biochemical responses that regulate cell proliferation in fetuses, and that its antioxidant action promotes bioavailability of nitric oxide and, thus, placental perfusion and also fetal nutrition and oxygenation. Therefore, the therapeutic action of melatonin has been the subject of major studies that aim to minimize or prevent different injuries affecting this pediatric age group, such as intrauterine growth restriction, encephalopathy, chronic lung diseases, retinopathy of prematurity Conclusion: the results antioxidant and indicate that melatonin is an important therapy for the clinical treatment of these diseases.

Angiogenic and antiangiogenic factors in preeclampsia.

BACKGROUND: Pre-eclampsia is a multifactorial hypertensive disorder that is triggered by placental insufficiency and that accounts for up to 15% of maternal deaths. In normal pregnancies, this process depends on the balance between the expression of angiogenic factors and antiangiogenic factors, which are responsible for remodeling the spiral arteries, as well as for neoangiogenesis and fetal development. PURPOSE: The aim of this review is to discuss the main scientific findings regarding the role of angiogenic and antiangiogenic factors in the etiopathogenesis of preeclampsia. METHODS: An extensive research was conducted in the Pubmed database in search of scientific manuscripts discussing potential associations between angiogenic and antiangiogenic factors and preeclampsia. Ninety-one papers were included in this review. RESULTS: There is an increased expression of soluble fms-like tyrosine kinase receptor and soluble endoglin in pre-eclampsia, as well as reduced placental expression of vascular endothelial growth factor and placental growth factor. Systemic hypertension, proteinuria and kidney injury - such as enlargement and glomerular fibrin deposit, capillary occlusion due to edema, and hypertrophy of endocapillary cells - are some of these changes. The complex etiopathogenesis of preeclampsia instigates research of different biomarkers that allow for the early diagnosis of this entity, such as vascular endothelial growth factor, placental growth factor, soluble fms-like tyrosine kinase receptor, soluble endoglin, placental glycoprotein pregnancy-associated plasma protein-A and protein 13. CONCLUSION: Even though it is possible to establish an efficient and effective diagnostic tool, three key principles must be observed in the management of preeclampsia: prevention, early screening and treatment.

Ultrastructural deposits appearing as "zebra bodies" in renal biopsy: Fabry disease?- comparative case reports.

BACKGROUND: Fabry Disease (FD) is a genetic disorder caused by alpha-galactosidase A deficiency. Certain drugs, such as hydroxychloroquine, can produce renal deposits that mimic morphological findings seen in FD, characterizing a type of drug-induced renal phospholipidosis. CASE PRESENTATION: Case 1: A 28-year-old female patient with systemic lupus erythematosus who had been using hydroxychloroquine for 14 months presented subnephrotic proteinuria. Renal biopsy showed deposits compatible with FD. Neither activity analysis of alpha-galactosidase A nor genetic analysis were available and were not performed. These deposits were not detected in a subsequent renal biopsy three years after withdrawal of the medication, characterizing a possible hydroxychloroquine-induced renal phospholipidosis. Case 2: A 29-year-old male patient presented with acroparesthesia, angiokeratomas, cornea verticillata and subnephrotic proteinuria. Deposits compatible with FD were detected upon renal biopsy. The evaluation of alpha-galactosidase A showed no activity in both blood and leukocytes. Genetic analysis identified an M284 T mutation in exon 6, and such mutation was also found in other family members. CONCLUSION: Clinical investigation is necessary in suspected cases of Fabry Disease upon renal biopsy in order to confirm diagnosis. Drug-induced renal phospholipidosis should be considered in differential diagnosis in cases with intracellular osmiophilic, lamellar inclusions in electron microscopy.

An overview of maternal and fetal short and long-term impact of physical activity during pregnancy.

PURPOSE: To explore information available in the literature about the possible benefits resulting from physical activity (PA) in non-risky pregnant women, repercussion on maternal organism, fetal development, and on long-term offspring health. METHODS: Critical narrative review using online databases. RESULTS: Through critical discussion of studies focused on PA practiced during pregnancy, it was observed that some of the outcomes investigated on both mother and offspring showed conflicting findings. Considering the impact of maternal PA in certain offspring characteristics, due to the fact that their findings come from studies with small samples, they do not allow the stablishment of scientific evidence. However, a feature that shows broad consensus among studies is the view of PA during pregnancy as a safe intervention for mother and fetus. In situations where studies employing PA of moderate-intensity have not enough power to ensure a positive influence on certain clinical outcomes, what is observed is the lack of their influence, not negative impacts. Regarding epigenetic modulations measured late in the offspring, it has been attributed to PA a positive modulatory role on metabolic, hemodynamic and even on behavioral characteristics. However, possible mechanisms involved in these epigenetic changes have not been sufficiently explored. CONCLUSION: Maternal PA appears to be safe for both mother and fetus, and additional studies are needed to confirm the real influence of this practice in the offspring, as well as the perpetuation and transfer of these features between generations.

Influence of the Expression of Inflammatory Markers on Kidney after Fetal Programming in an Experimental Model of Renal Failure.

Objective. To evaluate the expression of inflammatory markers in experimental renal failure after fetal programming. Methods. The offspring aged two and five months were divided into four groups: CC (control dams, control offspring); DC (diabetic dams, control offspring); CFA (control dams, folic acid offspring, 250 mg/Kg); and DFA (diabetic dams, folic acid offspring). Gene expression of inflammatory markers MCP-1, IL-1, NOS3, TGF-ß, TNF-α, and VEGF was evaluated by RT-PCR. Results. MCP-1 was increased in the CFA and DFA groups at two and five months of age, as well as in DC5 when compared to CC5. There was a higher expression of IL-1 in the CFA2, DFA2, and DC2 groups. There was a decrease in NOS3 and an increase in TNF-α in DFA5 in relation to CFA5. The gene expression of TGF-ß increased in cases that had received folic acid at two and five months, and VEGF decreased in the CFA5 and DFA5 groups. DC5 showed increased VEGF expression in comparison with CC5. Conclusions. Gestational diabetes mellitus and folic acid both change the expression of inflammatory markers, thus demonstrating that the exposure to harmful agents in adulthood has a more severe impact in cases which underwent fetal reprogramming.

Epithelial-mesenchymal transition in pediatric nephropathies.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells may express mesenchymal cell markers with subsequent change in their functions, and it may be part of the etiopathogenesis of kidney disease. OBJECTIVE: The aim of this study was to evaluate the immunexpression of some EMT inducers and markers in frequent nephropathies in pediatric patients. METHODS: 59 patients aged 2-18 years old were selected and divided into 6 groups of frequent nephropathies in children and adolescents, as well as one control group. Urea and creatinine data of the patients were recorded. TGF-ß3, fibronectin, α-SMA and vimentin were evaluated by immunohistochemistry. RESULTS: Glomerular TGF-ß3 was higher in the Lupus Nephritis and Acute Diffuse Glomerulonephritis (ADGN) groups than in the control group. Glomerular fibronectin was higher in the Podocytopathy, Lupus Nephritis, ADGN and Membranous Glomerulopathy patients than in control subjects. The expression of α-SMA was higher in the tubulointerstitial compartment of ADGN and Membranous Glomerulopathy groups than in the control group. Glomerular α-SMA was higher in ADGN patients than in control and Berger's Disease groups. Glomerular vimentin was higher in individuals with ADGN than in those with Podocytopathy, Lupus Nephritis, Berger's Disease and Thin Basement Membrane Disease/Alport Syndrome. There was a positive correlation between fibronectin in the tubulointerstitial compartment and creatinine levels, between α-SMA and vimentin in both tubulointerstitial and glomerular compartments, and between urea and creatinine levels of patients, regardless of their nephropathy (p<0.05 for all results). CONCLUSION: These markers may possibly be used as indicators of renal functional impairment in various nephropathies in pediatric patients.

Diagnosis of congenital and infantile nephrotic syndromes in renal biopsies in Minas Gerais, Brazil: Six case reports.

Congenital or infantile nephrotic syndromes (CNS/INS) correspond to a heterogeneous group of rare diseases in which glomerular renal dysfunction and proteinuria are prominent. The aim of this study is to present six cases of possible CNS/INS with diagnoses based on clinical findings and especially histological, ultrastructural, and immunohistochemical characteristics of renal biopsies. Four cases are presented with diffuse mesangial sclerosis, one of them possibly part of Denys-Drash syndrome and two cases with CNS probably of the Finnish type in patients between 3 months old and 13 years old. The study focuses on the late evolution of Denys-Drash syndrome to end-stage renal disease in a 13-year-old patient and the diagnosis of diffuse mesangial sclerosis in an 8-year-old patient. Thus, it contributes to a better epidemiological characterization of these syndromes, demonstrating cases of CNS/INS in infrequent age groups.