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Urban sewage is a source of major contamination in aquatic systems and contributes to environmental and human health disturbances. This study investigates the effects of sewage-polluted waters from Iguaçu River on the health of juvenile Oreochromis niloticus. Two hundred four specimens were exposed to riverine water in four groups: no diluted, 25 and 50 % diluted water and a control group without tested water for 72 days. Biological samples were obtained for histopathological, neurotoxicity, antioxidant defenses, genotoxicity, metallothionines expression and polycyclic aromatic hydrocarbons (PAHs) metabolites. The results showed histopathological alterations in liver and gills, genotoxic alteration in erythrocytes, reduction of acetylcholinesterase activity in brain and muscle, activation of antioxidant defenses in the liver, recruitment of metals by metallothionein and the detection of PAHs metabolites in bile. These results demonstrate that juveniles of O. niloticus are susceptible to Iguaçu River exposure water and they can be used as indicator of water quality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In air-breathing fish a reduction of gill surface area reduces the danger of losing oxygen taken up in the air-breathing organ (ABO) to hypoxic water, but it also reduces the surface area available for ion exchange, so that ion regulation may at least in part be transferred to other organs, like the kidney or the gut. In the air-breathing Arapaima gigas, gill lamellae regress as development proceeds, and starting as a water-breathing embryo Arapaima turns into an obligate air-breathing fish with proceeding development, suggesting that ion regulation is shifted away from the gills as the fish grows. In Arapaima the kidney projects medially into the ABO and thus, probably a unique situation among fishes, is in close contact to the gas of the ABO. We therefore hypothesized that the kidney would be predestined to adopt an increased importance for ion homeostasis, because the elevated ATP turnover connected to ion transport can easily be met by aerobic metabolism based on the excellent oxygen supply directly from the ABO. We also hypothesized that in gill tissue the reduced ion regulatory activity should result in a reduced metabolic activity. High metabolic activity and exposure to high oxygen tensions are connected to the production of reactive oxygen species (ROS), therefore the tissues exposed to these conditions should have a high ROS defense capacity. Using in vitro studies, we assessed metabolic activity and ROS production of gill, kidney and ABO tissue, and determined the activity of ROS degrading enzymes in small (~ 5g, 2-3 weeks old) and larger (~ 670 g, 3-4 months old) A. gigas. Comparing the three tissues revealed that kidney tissue oxygen uptake by far exceeded the uptake measured in gill tissue or ABO. ROS production was particularly high in gill tissue, and all three tissues had a high capacity to degrade ROS. Gill tissue was characterized by high activities of enzymes involved in the glutathione pathway to degrade ROS. By contrast, the tissues of the ABO and in particular the kidney were characterized by high catalase activities, revealing different, tissue-specific strategies in ROS defense in this species. Overall the differences in the activity of cells taken from small and larger fish were not as pronounced as expected, while at the tissue level the metabolic activity of kidney cells by far exceeded the activity of ABO and gill cells., Competing Interests: The authors have declared that no competing interests exist.

Enamel renal syndrome (ERS) is a rare autosomal recessive disorder not fully characterized. Here we investigated ERS characteristics in 11 patients from 5 Brazilian families through clinical examination, imaging, renal ultrasonography, laboratory tests and DNA sequencing. The patients' age ranged from 6 to 25 years-old, and the presence of hypoplastic amelogenesis imperfecta, microdontia, intra-pulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicles, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis were common findings to all patients. Only 4 patients showed abnormal laboratory tests (vitamin D, parathyroid hormone, phosphate, calcium). Intellectual disability and renal cysts were present in 2 patients each. Biallelic loss of function mutation in FAM20A gene, characterized by one base pair deletion in exon 11, resulting in a frameshift replacing a glutamine at codon 483 for a lysine and terminating at position 24 [NG_029809.1: c.1447delG; p.(Glu483Lysfs*24)], was detected in all patients, strongly suggesting a founder effect. Our results reinforce the distinct orofacial features of ERS, which are the clue for kidney examination and genetic testing. Early diagnosis is essential to minimize the deleterious effects related to ERS. Here we report the largest series of patients with ERS in a same population, and describe, for the first time, a founder mutation for FAM20A., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Bacterial diseases are one of the major problems in freshwater fish culture and have been linked to significant losses and high mortality rate. In this study, Nile tilapia Oreochromis niloticus was infected by Providencia rettgeri to evaluate the oxidative stress and antioxidant responses in the fish tissues. Juvenile Nile tilapia was divided into two groups, as follow: control (uninfected) and experimentally infected with 100 μL of P. rettgeri suspension containing 2.4 × 10 7 viable cells/fish, and the liver and kidney tissues were collected on days 7 and 14 post-infection (PI). Liver and kidney ROS and lipid peroxidation levels were high in infected fish on day 14 PI compared to control group, while superoxide dismutase activity was lower in liver (days 7 and 14 PI) and kidney (day 14 PI) compared to their respective control groups. Liver and kidney antioxidant capacity against peroxyl radicals, non-proteic, and proteic thiols levels was lower in infected tilapia on day 14 PI compared to control group. Based on these results, P. rettgeri infection may elicit oxidative damage via increased ROS production, decreased ROS elimination and inhibits enzymatic and non-enzymatic antioxidant defense systems; which may contribute directly to disease pathophysiology of infected animals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

What Is Known and Objective: Sofosbuvir(SOF)-based regimens have been administrated with excellent efficacy in chronic hepatitis C. Few uncontrolled ("real-life") studies consider the assessment of renal function when evaluating their post-treatment outcomes. This study aims to evaluate renal biomarkers in a "real-life" experience with chronic hepatitis C patients treated with SOF therapy in a long-term follow-up., Methods: Serum and urinary biomarkers were analysed before, at the end of therapy (EoT), after 12 weeks (sustained virological response-SVR) and one year (1y) post-treatment. Patients were categorized according to baseline glomerular filtration rate (GFR-cut-off 45 mL/min/1.73 m 2 )., Results: Ninety-four patients with a mean age of 59.9 ± 8.5 years were included; 98.9% of patients reached SVR. Significant improvement in renal biomarkers was observed in patients with GFR ≥45 mL/min/1.73 m 2 , as indicated by a progressive increase in mean GFR values until 1y. No evidence of tubular dysfunction was identified. Patients with baseline GFR <45 mL/min/1.73 m 2 did not experience alterations in renal biomarkers; however, a mean change of +10.7 in GFR values was observed. We noticed significant upper stage transition in the CKD classification, and 58.7% of patients achieved G1 stage at 1y (P < .0001)., What Is New and Conclusion: In a "real-life experience" of a Brazilian centre, SOF therapy appears to guarantee renal safety for patients with chronic hepatitis C followed until one year after treatment., (© 2018 John Wiley & Sons Ltd.)

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released during early phases of a postischemic kidney in response to kidney injury, inflammation, and oxidative stress. It can be detected in urine after 2 hours of an ischemic event. The aim was to measure and to correlate the level of urine NGAL (uNGAL) with urea, creatinine, and glomerular filtration rate (GFR) of endurance cycling athletes (n = 19) and physically active individuals (control, n = 17)., Methods: Quantification of urea and creatinine were performed by dry chemical method, and GFR was calculated using the modification of diet in renal disease formula, according to Brazilian Society of Nephrology. uNGAL analyses were performed by enzyme linked immunoabsorbent assay. Analyses were performed 48 hours after exercises., Results: uNGAL (in ng/mL) levels, expressed as median, minimum, and maximum, in cyclist group, 387.7 (109.7-1691.0), was significantly higher than that observed in control (physically active) group, 141.5 (4.8-657.0), (P < .05). No significant correlations were observed between uNGAL and creatinine, urea, or GFR (P > .05)., Conclusions: Results have pointed to increased uNGAL levels in endurance cycling athletes. Increase of uNGAL in absence of clinical signs or alterations in creatinine, urea, or GFR might suggest that there is metabolic adaptation to endurance exercise, or possibly predisposition to acute kidney injury over time.

Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na + , K + -ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na + , K + -ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To determine the correlation between protein-to-creatinine ratio and 24-h urinary protein, proteinuria was measured in 45 patients attending a public HIV clinic in Porto Alegre, Brazil, using 24-h urinary protein excretion (24hUP) and urinary protein-to-creatinine ratio. Spearman's correlation test was done to evaluate the association between spot protein-to-creatinine ratio and 24hUP. The limits of agreement between the two methods were analysed by the Bland-Altman method. For protein excretion <1 g/day, limits (95%) of agreement of protein-to-creatinine ratio and 24hUP were +0.112 and -0.097 g/day. A strong correlation (r = 0.957) was found between protein-to-creatinine ratio and 24hUP excretion. The conclusion is that the protein-to-creatinine ratio in spot urine specimens is an accurate, convenient and reliable screening method to estimate the urinary protein excretion in HIV patients to detect abnormal urinary protein loss. Further studies are required to evaluate renal disease in HIV patients with chronic renal disease and higher urinary protein excretion., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aim: The focus in renal transplantation is to increase long-term allograft survival. One of the limiting factors is calcineurin inhibitor (CNI)-induced fibrosis. This study attempted to examine the histological aspect of interstitial fibrosis and the modulation of the transforming growth factor-β (TGF-β) canonical signalling pathway following early withdrawal of CNI from sirolimus-based immunosuppressive therapy., Methods: Forty-five kidney transplant recipients with low-medium immunologic risk were randomized and underwent protocol biopsies obtained at the time of transplantation and at 3 and 12 months thereafter. The recipients were taking tacrolimus, sirolimus and prednisone. After the 3rd month, patients were randomized into two groups: sirolimus (SRL) (removed CNI and increased sirolimus) and tacrolimus (TAC) (maintained CNI). Renal biopsies were analyzed according to Banff's 2007 criteria. The sum of Banff's ct and ci constituted the chronicity index. Fibrosis was evaluated by the histomorphometrical analysis of the total collagen and myofibroblast deposition. Immunohistochemical characterization and quantification of TGF-β, TGF-β receptor 1 (TGF-β-R1), receptor 2 (TGF-β-R2) and phospho-Smad2/3 (p-Smad2/3) were performed., Results: Maintenance of CNI was associated with the increase of the surface density of collagen and α-smooth muscle actin (α-SMA), (P = 0.001). Furthermore, increased TGF-β (P = 0.02), TGF-β-R1 (P = 0.02), p-Smad2/3 (P = 0.03) and stabilized TGF-β-R2. On the other hand, the removal of CNI with increase in the dose of sirolimus limited the enhancement of the chronicity index at 12 m (SRL, 2.18 vs TAC, 3.12, P = 0.0007), diminished the deposition of fibrosis and promoted the stabilization of TGF-β, TGF-β-R2, p-Smad2/3 and myofibroblasts as well as the reduction of TGF-β-R1 (P = 0.01)., Conclusion: The early withdrawal of CNI limited the fibrosis progression through the stabilization of chronicity index and of the canonical TGF-β signalling pathway., (© 2014 Asian Pacific Society of Nephrology.)

Background: The aim of this study was to evaluate the monocyte chemoatractant protein-1 (MCP-1) as a novel biomarker of renal lesion in sickle cell disease (SCD) and correlate it with oxidative stress., Methods: This is a prospective study with SCD patients followed at a tertiary center in Brazil. Urine samples were collected to dosage of protein, MCP-1, malondialdehyde (MDA) and urinary creatinine. Patients taking hydroxyurea (SSHU) were compared to those not taking the drug (SS). Patients' data were also compared to a control group of 15 healthy blood donors., Results: MCP-1 dosage was increased in SCD patients (Control: 42.12±27.6; SSHU: 168.2±90.1 and SS: 231.4±123.7 p<0.0001). SS patients presented higher levels of MCP-1 in comparison to SSHU group (SSHU: 168.2±90.10 and SS: 231.4±123.7; p=0.023). The same results were observed for MDA (Control: 2:29±1:13; SSHU: 5.60±2.39 and SS: 7.23±2.64, p<0.0001) and NO (control: 2.25±1.9; SSHU: 56.54±9.1 and SS: 39.1±9.02, p<0.0001). A positive correlation was obtained between MCP-1 and MDA (r=0.34, p=0.01); albuminuria (r=0.5, p=0.03); NO (r=0.39, p=0.005)., Conclusion: The outcomes of the study suggest that MCP-1 is a predictive biomarker of renal lesion that can also reflect damage caused by oxidative stress present in SCD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is a leading cause of hospitalization throughout the world, and the mortality rate remains elevated. HF is frequently complicated by acute kidney injury (AKI), worsening the patient's prognosis. There have been no studies evaluating the role that endothelial glycocalyx damage plays in HF patients and its association with AKI and mortality., Methods and Results: We measured several endothelial biomarkers in 201 consecutive patients with acute decompensated HF (ADHF) during emergency department (ED) admission. In-hospital mortality, AKI development and 6-month mortality rates were assessed. ADHF patients with worsening renal function had higher levels of syndecan-1 but not those patients with stable chronic kidney disease. Syndecan-1 levels during ED admission were predictive for AKI during the hospital stay (AUC 0.741, P<0.001) and had an even better discriminatory capacity in more severe AKI (AUC 0.812, P<0.001). Additionally, after adjusting for several confounding factors, including biomarkers of endothelial function and endothelial cell activation, syndecan-1 remained associated with in-hospital mortality rates. On a Cox multivariate analysis regression, syndecan-1 was associated with 6-month mortality rates., Conclusions: The concentration of syndecan-1, a marker of glycocalyx damage measured during ED admission, is valuable in assessing the risk of developing AKI and in-hospital mortality. Its association with mortality is strong after 6-month follow-up.

Silver (Ag), cadmium (Cd), copper (Cu), lead (Pb) and zinc (Zn) concentrations were analyzed in tissues of juvenile green sea turtles (Chelonia mydas) found stranded along the southern Atlantic coast in Brazil. Green sea turtles were collected (n=29), measured (curved carapace length: CCL) and had their muscle, liver, and kidney dissected for metal concentration measurements. Sex was identified in 18 individuals (10 females and 8 males) through gonad histology. No gender differences in CCL and tissue metal concentrations were observed. In the muscle, there was a negative correlation between CCL and Cd and Cu concentrations. Metal concentrations were lower in the muscle than in the liver and kidney. Zn concentration in the muscle was the highest of all metals analyzed (16.6 mg/kg). The kidney showed the highest concentrations of Pb, Cd and Zn (5.4, 28.3 and 54.3 mg/kg, respectively), while the liver had the highest values of Ag and Cu (0.8 and 100.9 mg/kg, respectively). Tissue Ag, Zn and Cd concentrations were similar to those found in green sea turtles from other regions while Cu and Pb values were elevated, likely due to the metal-rich water and sediment reported in the collection area. In the liver and kidney, concentrations of non-essential (Ag, Cd and Pb) and essential (Cu or Zn) metals were positively correlated, likely due to an induced metallothionein synthesis to protect tissue against the toxic effect of metals. This is the first study to report and correlate the concentrations of essential and non-essential metals in tissues of green sea turtles in the Brazilian southern Atlantic coast, an important feeding and developing area for this turtle species., (© 2013 Elsevier B.V. All rights reserved.)

Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityus serrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64 Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1 μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60 min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1 μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: In this study we applied the pediatric version of the RIFLE criteria (pRIFLE) to an at-risk hospital population, analyzed the incidence and association of acute kidney injury (AKI) with mortality and length of stay in both the intensive care unit (ICU) and the hospital, and evaluated the applicability of pRIFLE as a prognostic tool in the ICU., Methods: This study was a prospective single-center cohort study in which 126 patients were enrolled. The affected group included patients who were diagnosed with AKI. Subgroups of the diagnosed patients were established according to their maximum pRIFLE strata, which were defined as the worst pRIFLE score attained during the study period., Results: Fifty-eight (46 %) of our patients developed AKI. The lengths of stay in the ICU and in the hospital were longer in the affected group than in the unaffected group. The advanced strata of pRIFLEmax were associated with longer stays in the ICU and hospital and higher median Pediatric Index of Mortality II scores. The hospital mortality rate of AKI patients was 12-fold higher than that of the patients without AKI (36 vs. 3 %)., Conclusion: The incidence of AKI in this population was both significant and directly associated with hospital mortality and the length of stay in the ICU and hospital. The pRIFLE classification facilitated the definition of AKI, indicating that it a significant prognostic predictor.

Total mercury (THg) and selenium (Se) concentrations were determined in hepatic, renal, and muscle tissues of seven specimens of Commerson's dolphins incidentally captured in artisanal fisheries of Tierra del Fuego, Argentina, by instrumental neutron activation analysis. Liver yielded the mean highest concentration of THg 9.40 (9.92) μg g(-1) dry weight (DW) (standard deviation of the average in parenthesis); kidney and muscle showed similar values, ranging from 2.34 to 3.63 μg g(-1) DW. Selenium concentrations were similar in hepatic and renal tissues, with values from 13.62 to 14.56 μg g(-1) DW; the lowest concentration was observed in muscle, 4.13 (2.05) μg g(-1) DW. Among the specimens analyzed, the maximum concentrations of THg and Se were observed in the single adult female studied. An increasing age trend is observed for THg concentrations in tissues analyzed. The molar ratio of Se/Hg in the hepatic, renal, and muscle tissues were 8.7 (9.6), 13.2 (9.5), and 9.0 (11.4), respectively, suggesting Se protection against Hg toxicity. Silver concentrations in the three tissues were included, and the Se/(Hg + 0.5×Ag) molar ratio showed values closer to 1. Both Hg and Se concentrations in liver and kidney were comparable to those found in other small odontocetes from Argentine and Brazilian waters. This study constitutes the first joint description reported of Hg and Se concentrations in liver, kidney, and muscle of the Commerson's dolphin species.

Background: The transcription factor FOXP3 is increased in acute renal rejection, but its influence on graft outcomes is unclear. This study correlated FOXP3 with dendritic cells and graft outcomes., Methods: We assessed 96 kidney transplants undergoing allograft biopsy for cause. FOXP3 mRNA was analyzed by real-time polymerase chain reaction (PCR) and FOXP3 protein and DCsCD83(+) by immunohistochemistry. Graft function and survival were assessed at 5 years post-transplantation, as well as by independent predictors of graft loss., Results: Intragraft FOXP3 gene and protein expression were significantly correlated (r = 0.541, p < 0.001). Both FOXP3 mRNA and protein were increased in patients with acute rejection (AR). High expression of FOXP3 mRNA or protein in biopsies did not correlate with clinical variables, but there was a trend to higher positive variation in the glomerular filtration rate (GFR) from biopsy to last follow-up. Patients with FOXP3-mRNA(high) had more DCsCD83(+) in biopsy, but these cells did not associate with AR. Five-year graft survival was not influenced by either FOXP3 mRNA or protein expressions., Conclusions: FOXP3 mRNA and protein had a good correlation in archival renal graft tissue. Increased FOXP3 expression was found in AR and FOXP3 associated with high numbers of DCs. However, both FOXP3 mRNA and protein was not associated with better allograft outcomes.

In a previous study oxidative damage markers - lipid peroxidation and protein oxidation - were determined in organs of wild Caiman yacare captured in winter-2001 and summer-2002 at various developmental stages. An increase in oxidative damage occurred in the hatchling-juvenile transition (but not in the juvenile-adult transition) and winter-summer transition (in juveniles), suggesting that oxidative stress is associated with development and season. Herein the effect of development and season on glutathione (GSH) metabolism and the effect of development on the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase) and glucose 6-phosphate dehydrogenase were analyzed. The ratio GSSG:GSH-eq increased in lung, liver, kidney and brain by 1.8- to 4-fold in the embryo/hatchling to juvenile transition. No changes occurred in juvenile-adult transition. GSSG:GSH-eq across seasons was significantly elevated in summer. Total-glutathione content was mostly stable in various organs; in liver it increased in the embryo-juvenile transition. Enzyme activities were only determined in summer-animals (embryos, hatchlings and juveniles). For most antioxidant enzymes, activities increased from embryo/hatchling to juvenile in liver and Kidney. In lung, there was an inverse trend for enzyme activities and total glutathione content. Thus, increased metabolic rates during early caiman growth - in embryo-juvenile transition - appears to be related to redox imbalance as suggested by increased GSSG:GSH-eq and activation of antioxidant defenses. Differences in oxidative stress across seasons were related with summer-winter nocturnal temperatures. These results, as a whole, were interpreted in the context of ecological biochemistry., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Total mercury concentrations were determined in muscle, liver and kidney of Cichlia ocellaris and Colossoma macropomum sampled at Tapajos and Carnapijo Rivers in Amazon ecosystem during the flood period of 2009. In background area the highest levels of mercury were observed in liver of piscivorous (0.3 ± 0.03 ug/g dry wt) and non piscivorous fish (0.20 ± 0.1 ug/g dry wt), but in contaminated area the highest level of mercury in piscivorous fish was detected in liver (0.45 ± 0.27 ug/g dry wt) and in muscle (0.26 ± 0.05 ug/g dry wt) of non piscivorous fish. These results suggested that the presence of anthropogenic source plays a key role in the pattern of mercury distribution in fish tissues., (© Springer Science+Business Media, LLC 2011)

An oil tanker loaded with methanol and bunker oil has exploded in November 2004 in Paranaguá Bay, in front of Paranaguá Harbor, southern Brazil. In order to investigate the chronic effects of an oil spill on a resident estuarine fish, the Brazilian silverside Atherinella brasiliensis was sampled 1, 4, and 7 months after the spill, from 2 sites inside Paranaguá Bay, and also from a reference site inside nearby Guaratuba Bay, non-affected by the spill. Increases in plasma osmolality (reaching ~525 mOsm/kg H₂O, or ~70% above values in reference fish) and chloride (reaching 214 mM in site C, or ~51% above values in reference fish) were detected 4 months after the spill, in parallel with branchial carbonic anhydrase inhibition (to 56% of the activity measured in reference fish) in silversides obtained from the contaminated sites. Plasma cortisol concentration increased progressively in samples from fish obtained 4 (462 ng/mL) and 7 (564-650 ng/mL) months after the spill, when compared to values in reference fish (192 ng/mL). Osmoregulation of a resident estuarine fish is still affected by an oil spill, months after the accident. It is, thus, a sensitive tool for the evaluation of the chronic effects of oil spills inside tropical estuarine systems, and A. brasiliensis is proposed as an adequate sentinel species for monitoring protocols., (Copyright © 2010. Published by Elsevier B.V.)

Accidental and intentional poisonings or drug overdoses constitute a significant cause of aggregate morbidity and mortality, and health care expenditures. The nephrologist is frequently called to the emergency room and ICU as a consultant to help with the indication of measures to enhance renal depuration of toxic agents. This study reviews the use of dialysis in acute poisonings due to medications or pesticides, whose specialized toxicological support was provided via telephone by the poison control center of the state of Rio Grande do Sul (CIT-RS from Portuguese). The correlation between need for dialysis and death was assessed in a retrospective cohort (1998-2000). Of the 36,055 cases registered, 337 were identified as severe, and 245 met the inclusion criteria required. Mean age was 30 ± 18 years, and 53% of the patients were women. The most commonly involved medications were anticonvulsants and antidepressants, and the pesticides were organophosphates, bipyridyl compounds, and glyphosate. Techniques to enhance elimination included urinary alkalinization (n = 37) and dialysis. In severe poisonings, dialysis was performed in 4.5% of the cases (n = 11), 3.67 procedures/year (1/22.7 reports of severe cases). In the group undergoing dialysis, 91% involved a suicide attempt (mainly phenobarbital and paraquat). Two cases required hemoperfusion (chloramphenicol and paraquat). Death among non-dialyzed severely ill patients occurred in 25.6%, versus 36.3% of dialyzed patients (RR = 0.89; 95% CI = 0.54-1.35). The findings can be explained by the statistic power associated with the number of procedures performed. The nephrologist should be aware of situations requiring the use of dialysis, even if not necessarily aimed at renal replacement, but at enhancing depuration of a toxic agent.

Introduction: The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up., Methods: Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function., Results: Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 ± 8.5 months. The mean Cr at biopsy time was 1.44 ± 0.33 mg/dL, and after the follow-up it was 1.29 ± 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively., Conclusion: Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: In Brazil, arterial hypertension (AH) constitutes one of the main risk factors for chronic kidney disease (CKD). The monitoring of glomerular filtration (GF) is recommended for the assessment of kidney function in hypertensive individuals, as GF decrease precedes symptom onset., Objective: To assess GF and its associated factors in hypertensive individuals., Methods: A cross-sectional study was carried out from January to June 2008 in 297 individuals with arterial hypertension (AH) with or without diabetes mellitus (DM), treated at a primary care facility in the city of São Luís, Maranhão. Patients older than 20 years and of both sexes were included in the study. Sociodemographic and nutritional status data, GF rate and microalbuminuria levels in 24-hour urine were assessed, as well as blood pressure, glucose and serum creatinine levels and a lipidogram., Results: Mean age was 60.6 x 11.5 years, with a predominance of the female sex (75.1%), overweight/obesity (65.0%) and large waist circumference (60.6%). The prevalence of GF < 60 ml/min was 24.6% in the AH group without DM and 18.3% in the AH group with DM, with no significant difference. For the AH group without DM, there was an association only between reduced GF and age > 65 years, which remained after adjustment. For the AH group with DM, there was an association between reduced GF and age > 65 years, smoking habit and obesity. However, after the adjustment, age and smoking habit remained as associated factors., Conclusion: In these patients, the prevalence of GF < 60 ml/min was high and after the adjustment, only age > 65 years and smoking habit were shown to be factors associated to GF. This reinforces the need to systematically evaluate GF in hypertensive individuals, aiming at the secondary prevention of chronic kidney disease.

Primary hypomagnesemia is a heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg2+) wasting, resulting in tetany, cardiac arrhythmias, and seizures. The kidney plays an essential role in maintaining blood Mg2+ levels, with a prominent function for the Mg2+-transporting channel transient receptor potential cation channel, subfamily M, member 6 (TRPM6) in the distal convoluted tubule (DCT). In the DCT, Mg2+ reabsorption is an active transport process primarily driven by the negative potential across the luminal membrane. Here, we studied a family with isolated autosomal dominant hypomagnesemia and used a positional cloning approach to identify an N255D mutation in KCNA1, a gene encoding the voltage-gated potassium (K+) channel Kv1.1. Kv1.1 was found to be expressed in the kidney, where it colocalized with TRPM6 along the luminal membrane of the DCT. Upon overexpression in a human kidney cell line, patch clamp analysis revealed that the KCNA1 N255D mutation resulted in a nonfunctional channel, with a dominant negative effect on wild-type Kv1.1 channel function. These data suggest that Kv1.1 is a renal K+ channel that establishes a favorable luminal membrane potential in DCT cells to control TRPM6-mediated Mg2+ reabsorption.

Aim: Few prospective studies have assessed renal dysfunction in older persons. We sought to define kidney dysfunction among a community-based cohort of elderly subjects and to determine the factors for its progression., Methods: The Epidemiologia do Idoso (EPIDOSO) Study is a prospective study of individuals > or =65 years old (mean 72.6 +/- 0.3), living in the community in the city of São Paulo. The creatinine clearance (CrCl) of 269 individuals of this cohort was estimated during 8 years of follow-up. The rate of decline in CrCl was calculated using linear regression analysis and dividing the group into tertiles of CrCl change., Results: Overall mean change in CrCl was -2.37 +/- 0.23 mL/min per year. Mean age increased with the greatest degree of decline in renal function (71.1 +/- 0.59, 72.5 +/- 0.54 and 74.3 +/- 0.58, for the first, second and third CrCl change tertiles, respectively, P < 0.01). A higher value of baseline CrCl was associated with progressive decline in CrCl (P < 0.01). Diastolic BP was greater in the second versus the first estimated glomerular filtration rate tertile (83 +/- 1 vs 80 +/- 1 mmHg, P < 0.05). High-density lipoprotein (HDL) cholesterol was inversely associated with CrCl decline (P < 0.05)., Conclusion: Progression of kidney dysfunction occurs in most community-dwelling elderly. Strategies aimed at slowing the progression should be considered for possible risk factors of older age, baseline CrCl, BP and HDL.

Methylmercury is a potent toxic present in Amazonian fish species due to gold mining activities. In the present work, we investigated the morphological effects of methylmercury in liver and kidney of Hoplias malabaricus feeding contaminated prey fish over 70 days. Two groups of nine mature fish (tested and control) were acclimatized for four weeks to laboratory conditions and then the tested group fed prey fish previously contaminated at an additional level of 0.075 microg MeHg g(-1) at 5-day intervals and over 14 successive intervals whereas control group fed uncontaminated fish. H. malabaricus specimens were then dissected for chemical and morphological analyses. The low and realistic level of MeHg in the prey fish induced a low increase of total mercury in liver (1.8-fold) and muscle (2.2-fold). The biomagnification factor (Hg in predator/Hg in prey) reached 142 in liver and 21 in muscle and was indicative of a relatively fast contamination of internal organs by dietary exposure. The liver of exposed individuals presented leukocyte infiltration, increased number of melano-macrophage centers, necrotic areas and lesions in Disse's space. Evident disorder and chaos in cytoskeleton organization suggest a strong toxic effect in hepatocytes, such as organelles positioning and movement, vesicles traffic and secretion. Head kidney showed large necrosis areas, increased number of melano-macrophages centers, phagocytic areas, intercellular space among parenquimal cells and atypical cells. Injuries and damages to tissues suggest too slow defense mechanisms to immobilize or eliminate ingested methylmercury, demonstrating that the sensitivity of fish cells to methylmercury exposure is higher than it has been previously described in the literature.

Hemoglobin (Hb) Indianapolis [beta112 (G14) Cys-->Arg] is a rare and slightly unstable beta-globin variant. All carriers described to date were clinically normal with only mild reticulocytosis. We report here a case of a Brazilian patient in whom hemolytic anemia and acute renal failure were probably caused by the presence of this variant.

We investigated the vascular effects of a crude aqueous extract (AEEG) of Echinodorus grandiflorus (Alismataceae) using the in vitro experimental models of the rabbit isolated aorta and perfused kidney. Echinodorus grandiflorus, a native semi-aquatic plant widely distributed in Brazil, has been extensively used in Brazilian folk medicine for the treatment of high blood pressure and inflammatory diseases. The bolus injection of AEEG (0.1-10 mg) into the rabbit renal circulation pre-contracted with norepinephrine induced marked and dose-dependent vasodilator responses (maximum of 37+/-4%; n=6; P<0.001), which was similar to that induced by injection of 10 mmol acetylcholine (41+/-3%). Moreover, AEEG elicited a significant and concentration-dependent relaxation in the endothelium-intact, but not endothelium-denuded aortic rings, reaching the maximum of 81+/-5% (n=7, P<0.001). Inhibition of the nitric oxide-cGMP pathway with L-NAME (100 microM) or Methylene Blue (20 microM) reduced maximum relaxation induced by AEEG from 81+/-5% to 46+/-3 and 45+/-3%, respectively (n=7, P<0.001). A similar reduction was obtained with the incubation of the aortic rings with the selective PAF receptor antagonist WEB 2086 (10 microM) (from 81+/-5% to 55+/-3%; n=7; P<0.01). Conversely, blockade of muscarinic receptors with atropine (10 microM) did not affect the vasodilator effects of AEEG, while inhibition of the enzyme cyclooxigenase not only did not block, but rather potentiated vasodilation induced by AEEG (n=7, P<0.001). Finally, blockade of Ca(2+)- and ATP-activated K(+) channels using the specific blockers charydbotoxin (100 nM) and glibenclamide (3 microM), respectively, did not modify aortic relaxation induced by AEEG. We conclude that water-soluble extracts from leaves of Echinodorus grandiflorus elicit an endothelium-dependent, nitric oxide and PAF receptor-mediated vasodilation in rabbit aortic rings, which does not appear to involve the generation of vasodilating prostaglandins or the activation of K(+) channels. This potent vasodilator effect of the extracts was confirmed in the isolated rabbit renal circulation.

Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa+, %TK+). The B. erythromelas venom (10 microg mL(-1)) decreased the PP (ct = 108.71+/-5.09 mmHg; BE = 65.21+/-5.6 mmHg*) and RVR (ct = 5.76+/-0.65 mmHg mL(-1) g(-1) min(-1); BE = 3.10+/-0.45 mmHg mL(-1) g(-1) min(-1)*). On the other hand, the GFR decreased at 60 min (ct60 = 0.76+/-0.07 mL g(-1) min(-1); BE60 = 0.42+/-0.12 mL g(-1) min(-1)*) and increased at 120 min (ct120 = 0.72+/-0.01 mL g(-1) min(-1); BE120 = 1.24+/-0.26 mL g(-1) min(-1)*). The UF increased significantly when compared with the control group (ct = 0.14+/-0.01 mL g(-1) min(-1); BE = 0.47+/-0.08 mL g(-1) min(-1)*). The venom reduced the %TNa(+) (ct90 = 79.18+/-0.88%; BE90 = 58.35+/-4.86%*) and %TK+ (ct90 = 67.20+/-4.04%; BE90 = 57.32+/-5.26%*) The anti-bothropic factor from D. marsupialis (10 microg mL(-1)) incubated with B. erythromelas venom (10 microg mL(-1)) blocked the effects on PP, RVR, %TNa+, and %TK+, but was not able to reverse the effects in UF and GFR promoted by venom alone. However, the highest concentration of D. marsupialis serum (30 microg mL(-1)) reversed all the renal effects induced by the venom. In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the anti-bothropic factor from D. marsupialis was able to inhibit the effects induced by the venom in isolated kidney.

This research reports the first data on mercury levels found in Giant otters (Pteronura brasiliensis) from South America. Mercury concentrations were analyzed from different organs/tissues of two animals found dead floating on the water of the Rio Negro in the Pantanal, Brazil. The mean mercury concentration ranged from 2.94 to 3.68 microg/g in hair, from 1.52 to 4.3 microg/g in liver, and from 1.11 to 4.59 microg/g in kidney and was 0.17 microg/g in muscle samples. In comparison with other research, there is no evidence of contamination in these animals and mercury concentrations in tissues appeared to be at levels below those associated with toxicity.

Effects of increasing dietary protein were studied in matrinxa, (Brycon cephalus), an omnivorous teleost from the Amazon Basin in Brazil. Four isocaloric diets were formulated to contain 20%, 27%, 34% and 41% of crude protein (CP). Plasma glucose levels were significantly increased while triacylglycerols were significantly reduced at 41% of CP. Free fatty acids were significantly reduced at each level of rising CP. Plasma amino acids and ammonium followed the dietary CP increase. Liver glycogen and amino acids were reduced; liver glucose and lactate were constant, and ammonium increased with the CP in diets. Muscle glycogen and pyruvate decreased, protein did not change, while lactate and free amino acids increased. Kidney glycogen proportionally rose with the increase of CP from 20-41%. Pyruvate and lactate augmented irregularly from 20-41% CP. A gluconeogenic profile was observed in the kidney; the liver worked as regulator of body glucose. Increase of dietary CP and decrease of carbohydrates pushed muscle and liver catabolism of fat and sugar stores to satisfy energetical demands. CP contents above 34% were not recommended for B. cephalus, if the carbohydrate does not compensate the metabolical demands.

Background: Acute renal failure (ARF) is a common complication after liver transplantation (LTx). Identification of risk factors may prevent the development and attenuate the impact of ARF on patients outcome after LTX., Methods: Retrospective analysis of variables in the pre, intra, and postoperative periods of 92 patients submitted to LTx was performed in order to identify risk factors for development of ARF after LTx. ARF was defined as serum creatinine > or = 2.0 mg/dL in the first 30 days after LTx. Univariate and multivariate analysis by logistic regression were performed., Results: ARF group comprised 56 patients (61%). Preoperative serum creatinine was higher in ARF group. During the intraoperative period, ARF group required more blood transfusions, developed more episodes of hypotension and presented longer anesthesia time. In the postoperative period, ARF group presented higher serum bilirubin and more episodes of hypotension. Dialysis was required in 10 patients (11%). The identifled risk factors for development of ARF were: preoperative serum creatinine > 1.0 mg/dL. more than five blood transfusions in the intraoperative period, hypotension during intra and postoperative periods. The identified mortality risk factors were hypotension in the postoperative period and no recovery of renal function after 30 days., Conclusions: Several factors are involved in the pathogenesis of ARF after LTx and may influence patients outcome and mortality. Pretransplant renal function and hemodynamic conditions in the operative and postoperative periods were identified as risk factors for development of ARF after LTx. Nonrenal function recovery and postoperative hypotension were identified as mortality risk factors after LTx.

Lead (Pb), cadmium (Cd) and mercury (Hg) concentrations on liver and kidney of Sotalia fluviatilis (Cetacea: Delphinidae) stranded in the coast of Ceará, Brazil, were studied from 1996 to 1999. Pb levels were usually lower than the detection limit (0.1 microg/g). Concentrations of Cd were significantly higher in kidney than liver, averaging 0.8 microg/g. Mercury accumulation took place mainly in liver with an average concentration of 4.6 microg/g. Both metals were significantly higher in larger mature individuals, but differences between sexes were not significant. The detection of Cd, Hg and Pb in tissue samples of S. fluviatilis off the coast of Ceará indicated that heavy metals are locally available in the water, and bioaccumulation may be occurring through the food web. Contamination levels were not considered critical, but could be related to Ceará's growing industrial development. The associated risks of pollution outfalls may pose a threat to marine organisms in a near future, especially for top predators such as S. fluviatilis.

Different aspects of mercury accumulation, retention, and elimination in temperate fish species have been reported, but few data are available for tropical species. In this work Hg accumulation in Trichomycterus zonatus, where experimental losses were estimated, was studied. Forty individuals (males and females) of T. zonatus were acclimatized for 30 days. In each experiment 10 aquaria were used, with 1 fish each (5 exposed to HgCl2 and the others as controls). The concentration tested was 15 microg Hg x liter-1 including 18 kBq x liter-1 203HgCl2 as tracer. Fish were dissected and measured for Hg by gamma scintillation spectrometry at regular intervals, and after 96 hr were transferred to mercury-free tap water. Approximately 40% of added mercury was lost by volatilization (20%) and adsorption (20%) in 48 hr. A faster absorption of inorganic mercury was observed initially in gills, a higher and lower retention in kidney and muscle, respectively. For T. zonatus the kidney, gills, and liver were considered the critical organs, but this order changed after 98 hr in mercury-free tap water. The distribution of inorganic mercury in T. zonatus seems quite similar to that found in temperate species, but the sensitivity of this species to Hg seems higher.

Porulaca pilosa has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and analgesia. Achyrocline satureioides has been used in folk medicine as antiinflammatory, hypoglycemic, sedative and to treat gastrointestinal disorders such as diarrhea and dysentery suggesting that it may affect salt and water reabsorption by the gastrointestinal tract. In the current study, hydroalcoholic extracts of both plants were investigated in order to examine their renal effects. The results support the claim that extracts of P. pilosa present renal effects but not the popular belief that it affects diuresis. It has also been provided that, in rats, it causes an increase in K excretion without a concomitant change in water diuresis or Na excretion. Our findings also support the popular belief that A. satureioides does not apparently have renal effects and it might change renal ion transport based on observations that it affects gastrointestinal reabsorption.

The infusion of the dried roots of Bredemeyera floribunda Willd. is used in Brazilian popular medicine as a potent diuretic, especially in the treatment of hypertension and nephrolithiasis (renal calculi). Intravenous administration of crude root-extract (20-80 mg/kg) to anesthetized rats induces clear dose-dependent and reversible hypotensive responses. At higher doses the extract leads to bradycardia and death. In doses that do not alter the arterial blood pressure, the extract elicited immediate and dose-dependent reversible increase of water, sodium, and potassium renal excretion. The results, apart from indicating that the renal effect of the extract is not due to its systemic hypotensive action, support the folk therapeutic use of the infusion of the root-extract as a diuretic.