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Acute kidney injury (AKI) is a frequent and potentially fatal complication of snakebites. In the setting of snakebites, endothelial biomarkers may be used to predict disease severity and can play a major role in AKI pathophysiology. The aim of this study was to investigate the potential role of endothelial biomarkers in predicting AKI in Bothrops envenoming. Therefore, blood and urine samples were collected from 26 patients admitted to the emergency department after Bothrops envenoming at 3 different post-bite points in time: on admission (up to 8 h post-bite), 12-16 h, and 24-28 h post-bite, to investigate the time course of endothelial biomarkers in AKI following Bothrops snakebites. The diagnostic performance of injury biomarkers in Bothrops envenomation was evaluated. AKI was diagnosed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. There was an association between endothelial injury and increased risk for AKI in bothropic envenoming. Angiopoietin- 1 (Ang-1) and Vascular cell adhesion protein-1 (VCAM-1) were useful biomarkers to predict mild AKI [AUC-ROC: Ang-1 0.82, VCAM-1 0.76] within the interval of 8-16 h post Bothrops snakebites. The use of endothelial biomarkers VCAM-1 e Ang-1 within 12-16 h post-bite may be useful in the early stage of mild AKI related to Bothrops envenoming and might have an effect on the early intervention for renal protection in less severe Bothrops-related AKI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the usefulness of early acute kidney injury (AKI) biomarkers in clinical management of visceral leishmaniasis., Methods: Prospective study with 50 hospitalised VL patients. AKI biomarkers, that is, serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL, uNGAL, respectively), urinary kidney injury molecule-1 (uKIM-1) and urinary monocyte chemotactic protein-1 (uMCP-1), were quantified by immunoassay (ELISA). Also, interferon-gamma (INF-y) and C-reactive protein (CRP) were evaluated as inflammatory biomarkers possibly related to VL severity., Results: VL patients had hyponatremia, hypoalbuminemia, hypergammaglobulinemia, haematologic and hepatic disorders. AKI was found in 46%, and one death (2%) occurred. The AKI group had significant longer hospital stay, lower levels of IFN-y and higher levels of CRP, more clinical renal abnormalities and higher levels of sNGAL, uNGAL, uKIM-1 and uMCP-1. Overall, sNGAL, uKIM-1 and uMCP-1 showed correlations with important clinical renal abnormalities, such as proteinuria, albuminuria, serum creatinine and glomerular filtration rate using adjusted correlations with CRP and IFN-y. Only sNGAL showed an early association with AKI development (OR = 2.78, 95% CI = 1.429-5.428, per each increase of 50 ng/ml), even after adjusting for clinical signals of VL severity and for immune biomarkers. Moreover, sNGAL showed a better performance in predicting AKI development (AUC-ROC = 0.81, 95% CI = 0.69-0.93; cut-off = 154 ng/ml, sensitivity = 82.6%, specificity = 74.1%, P < 0.001)., Conclusions: Visceral leishmaniasis-associated nephropathy showed important proximal tubular injury and glomerular inflammation. Serum NGAL showed an early association with VL-associated nephropathy and may be used to improve clinical management strategies and decrease morbimortality in VL patients., (© 2018 John Wiley & Sons Ltd.)

Background: This study was conducted to investigate changes in the clinical pattern of leptospirosis over time, analyzing its clinical and laboratory presentations in a metropolitan city of Brazil., Method: This was a retrospective study including all patients with leptospirosis admitted to tertiary care hospitals in Fortaleza in the northeast of Brazil, between 1985 and 2015. Patients were divided into three groups according to the year of hospital admission: group I for the years 1985-1995, group II for 1996-2005, and group III for 2006-2015. Demographic, clinical, and laboratory data were compared between the groups., Results: A total of 507 patients were included. Their mean age was 37.3±15.9years and 82.4% were male. The mean time between symptom onset and admission was 7±4 days. There was a linear decrease in the levels of serum urea (190.1±92.7, 135±79.5, and 95.6±73.3mg/dl, respectively, p <0.0001) and creatinine (5.8±2.9, 3.8±2.6, and 3.0±2.5mg/dl, respectively, p <0.0001) in each decade, while levels of hemoglobin (10.31±1.9, 10.8±2.0, and 11.5±2.1g/dl, respectively, p <0.0001) and platelets (57.900±52.650, 80.130±68.836, and 107.101±99.699×10 9 /l, respectively, p<0.0001) increased. There was a tendency towards a linear decrease in mortality (22%, 14%, and 11.6%, respectively, p=0.060)., Conclusions: Leptospirosis showed significant changes over time in this region. The main changes point to a decrease in disease severity and complications, such as acute kidney injury. Mortality has decreased, being close to 11%., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite well-documented risks, injectable supplements containing high doses of vitamins are commonly used., Objectives: To describe acute kidney injury (AKI) as a complication of vitamin intoxication., Methods: Our series consisted of 16 patients with kidney complications resulting from the use of veterinary intramuscular injection supplements of vitamin A, D and E. The patients were admitted to two referral hospitals in Fortaleza (Brazil) between January 2010 and January 2015., Results: Patients' mean age was 28.3±8.9 years (19-53 years), and 11 (68.7%) were male. Main signs and symptoms upon admission were nausea (68.7%), vomiting (62.5%), weight loss (43.7%), epigastric pain (31.2%) and headache (31.2%). At hospital admission the mean laboratory values were: hemoglobin 10±2.0g/dL (6.1-14.2), leukocytes 10,542±4871/mm 3 (4100-15,100), creatinine 3.9±5.2mg/dL (0.7-22) and urea 91±88mg/dL (22-306), respectively. Serum calcium was 12±2.2mg/dL (8.8-15.5), 24-h urine calcium was 575±329mg (10.7-1058), serum PTH was 55±141pg/mL (2-406), and serum vitamin D concentration was 135±75ng/mL (22-265). Using KDIGO criteria, AKI was diagnosed in 13 patients (81.2%), classified as stage 1 (n=3), stage 2 (n=3) or stage 3 (n=7). No deaths occurred in the study period., Conclusions: Excessive use of veterinary vitamin supplements containing high doses of vitamin A, D and E was associated with AKI. Hypercalcaemia, which was a common finding, appears to be a contributing factor to the development of this type of AKI., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The aim of this study is to investigate renal involvement in schistosomiasis. This is a retrospective cohort of 60 consecutive patients with schistosomiasis admitted to a university hospital in Maceió, Brazil. The patients were divided into 2 groups: patients with and without acute kidney injury (AKI) according to the RIFLE criteria. We compared the groups for differences in clinical manifestations and laboratory tests. Patients' mean age was 58 ± 16 yr, and 56.7% were female. The average length of hospital stay was 16.4 ± 12.1 days. Patients with hypertension and diabetes were 35% and 21.7% respectively. The main clinical symptoms and signs presented were ascites (86.7%), splenomegaly (80%), and hepatomegaly (63.3%). Current or previous history of upper gastrointestinal bleeding was found in 45% of patients, esophageal varices on endoscopy were present in 92%, and periportal fibrosis on ultrasound examination in 81% of patients. AKI incidence was 43.3% during hospital stay. Mean age and length of hospitalization were higher in the AKI group. Diuretic use, such as furosemide and spironolactone, ascites, and AST levels were also associated with AKI. Death occurred in 5 cases (8.5%), 4 of them in the AKI group. The classifications Child-Pugh score (CHILD) and Model for End-Stage Liver Disease (MELD), used to assess the severity and prognosis of chronic liver disease, presented higher scores among patients with AKI (CHILD: 9.5 ± 1.5 vs. 8.4 ± 1.7, P = 0.02; MELD: 19 ± 5.8 vs. 13 ± 3.9, P < 0.001). Renal dysfunction is an important feature of schistosomiasis, which is associated with significant morbidity and possible increased mortality. Further studies are necessary to establish the mechanisms through which schistosomiasis can lead to renal dysfunction.

What Is Known and Objective: Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI)., Methods: A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not., Results: Two hundred and eighty-seven patients were included, with an average age of 36·8±15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32±14 years vs. 39±16 years, P=0·0002) and had a shorter hospital stay (8·4±5·0 vs. 11±7·7 days, P<0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5±3·0 vs. 7·7±4·7, P=0·33). Systolic blood pressure was lower in the penicillin group (111±21 vs. 119±22 mmHg, P=0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (P<0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P=0·60)., Conclusion: Treatment of leptospirosis with antibiotics, including the penicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis., (© 2011 Blackwell Publishing Ltd.)

The objective of the present study was to evaluate the characteristics of acute kidney injury (AKI) in AIDS patients and the value of RIFLE classification for predicting outcome. The study was conducted on AIDS patients admitted to an infectious diseases hospital inBrazil. The patients with AKI were classified according to the RIFLE classification: R (risk), I (injury), F (failure), L (loss), and E (end-stage renal disease). Univariate and multivariate analyses were used to evaluate the factors associated with AKI. A total of 532 patients with a mean age of 35 ± 8.5 years were included in this study. AKI was observed in 37% of the cases. Patients were classified as "R" (18%), "I" (7.7%) and "F" (11%). Independent risk factors for AKI were thrombocytopenia (OR = 2.9, 95%CI = 1.5-5.6, P < 0.001) and elevation of aspartate aminotransferase (AST) (OR = 3.5, 95%CI = 1.8-6.6, P < 0.001). General mortality was 25.7% and was higher among patients with AKI (40.2 vs17%, P < 0.001). AKI was associated with death and mortality increased according to RIFLE classification - "R" (OR 2.4), "I" (OR 3.0) and "F" (OR 5.1), P < 0.001. AKI is a frequent complication in AIDS patients, which is associated with increased mortality. RIFLE classification is an important indicator of poor outcome for AIDS patients.

Leptospirosis is recognized as a globally re-emerging zoonosis. Interstitial nephritis is the principal feature of the disease. Leptospirosis-induced acute kidney injury typically is nonoliguric and includes hypokalemia. Tubular function alterations precede a decrease in the glomerular filtration rate, which could explain the high frequency of hypokalemia. Studies in human beings and animals have shown increased urinary fractional excretion of potassium and sodium, as well as an increased potassium/sodium ratio, suggesting increased distal potassium secretion caused by increased distal sodium delivery consequent to functional impairment of proximal sodium reabsorption. Confirming these findings, Western blot studies have shown lower renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2, together with higher renal expression of the Na-K-2Cl cotransporter NKCC2, in infected animals. The severe form (Weil's disease) manifests as diffuse alveolar hemorrhage, pulmonary edema, acute respiratory distress syndrome, or a combination of these features, accompanied by acute kidney injury and can be highly lethal. Antibiotic treatment is efficient in the early and late/severe phases. For critically ill leptospirosis patients, the following are recommended: daily hemodialysis, low daily net fluid intake (because of the risk for pulmonary hemorrhage), and lung-protective strategies (low tidal volumes and high positive end-expiratory pressures after recruitment maneuvers).

A prospective study was designed to evaluate disorders of hemostasis and levels of anticardiolipin antibodies (ACL) in 30 patients with severe leptospirosis and acute renal failure (ARF) (ARF was defined as serum creatinine > or =1.5 mg/dL). The patients had been admitted to the Walter Cantídio University Hospital, São José Infectious Diseases Hospital and General Hospital of Fortaleza, Ceará, from August 1999 to July 2001. They all were male, with a mean age of 32 +/- 14 years and with clinical and laboratory diagnoses of ARF leptospirosis. The time elapsed between onset of symptoms and the first hemorrhagic manifestation was 9 +/- 4 days. Bleeding was observed in 86% of the patients. Laboratory tests showed significantly high levels of urea (181 +/-95 mg/dl), fibrinogen, (515 +/- 220 mg/dl), prothrombin time (13.3 +/- 0.9 seconds) and low platelet counts (69 +/- 65 x 10(3)/mm3) on admission. There was no elevation in activated partial thromboplastin time or thrombin time. Levels of IgM and IgG ACL concentrations were significantly increased (p < 0.05) in leptospirosis patients when compared to control patients (28.5 +/- 32.4 vs. 11.5 +/- 7.9MPL U/ml and 36.7 +/- 36.1 vs. 6.5 +/- 2.5 GPL U/ml), respectively. Vasculitis, thrombocytopenia and uremia should be considered important factors for the pathogenesis of hemorrhagic disturbances and the main cause of death in severe leptospirosis.

The effectiveness of specific antibiotic treatment in severe leptospirosis is still under debate. As part of a prospective study designed to evaluate renal function recovery after leptospirosis acute renal failure (ARF) (ARF was defined as Pcr > or =1.5 mg/dL), the clinical evolutions of 16 treated patients (T) were compared to those of 18 untreated patients (nT). Treatment or non-treatment was the option of each patient's attending infectologist. The penicillin treatment was always with 6 million IU/day for 8 days. No difference was found between the two groups in terms of age, gender, number of days from onset of symptoms to hospital admission, or results of laboratory tests performed upon admission and during hospitalization, but proteinuria was higher in the treated group. There were no significant difference in the other parameters employed to evaluate patients' clinical evolution as: length of hospital stay, days of fever, days to normalization of renal function, days to total bilirubins normalized or reached 1/3 of maximum value and days to normalization of platelet counts. Dialytic treatment indication and mortality were similar between group T and nT. In conclusion, penicillin therapy did not provide better clinical outcome in patients with leptospirosis and ARF.

The risk factors for death and changes in clinical patterns in leptospirosis (Weil's disease) have not been well studied. We retrospectively studied 110 patients with Weil's disease hospitalized in Brazil between 1985 and 1996. Univariate statistical analysis showed that nonsurvivors were older than survivors, and had higher frequency of oliguria, cardiac arrhythmia, dyspnea, and pulmonary rales. Logistic regression showed that the only independent factor associated with death was oliguria (odds ratio [OR] = 8.98). The presence of arthralgia (OR = 4.71), dehydration (OR = 6.26), dyspnea (OR = 17.7), and pulmonary rales (OR = 9.91) increased after 1994. These data suggest that in Weil's disease the clinical patterns have changed and the presence of oliguria is a risk factor for death.

To assess the mechanisms related to tetanus-induced acute renal failure (ARF), 30 patients with tetanus had their renal function prospectively studied and factors possibly related to renal changes were evaluated during four weeks of hospitalization. Fifty percent of these patients had a glomerular filtration rate (GFR) < or = 50 ml/min in the first or second week of hospitalization (Group I) and 50% had a GFR > 50 ml/min throughout the entire hospitalization period (Group II). Age, gender, tetanus incubation time and tetanus onset time, hospitalization time, use of nephrotoxic drugs, need for mechanical ventilation with intermittent positive pressure, and presence of systemic infection were similar in both groups. None of the patients presented with oliguria. Autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, by increased heart rate and elevated urinary metanephrine excretion, was higher in Group I compared with Group II. Plasma renin activity, serum creatinephosphokinase levels, and myoglobinuria were not significantly different between the two groups. These results strongly suggest that tetanus-induced ARF has a high prevalence, is characterized by early onset, and is probably related to ANS overactivity.

Rhabdomyolysis is a clinical and biochemical syndrome that occurs when skeletal muscle cells disrupt and release creatine phosphokinase (CK), lactate dehydrogenase (LDH), and myoglobin into the interstitial space and plasma. The main causes of rhabdomyolysis include direct muscular injury, strenuous exercise, drugs, toxins, infections, hyperthermia, seizures, meta-bolic and/or electrolyte abnormalities, and endocrinopathies. Acute kidney injury (AKI) occurs in 33-50% of patients with rhabdomyolysis. The main pathophysiological mechanisms of renal injury are renal vasoconstriction, intraluminal cast formation, and direct myoglobin toxicity. Rhabdo-myolysis can be asymptomatic, present with mild symptoms such as elevation of muscular en-zymes, or manifest as a severe syndrome with AKI and high mortality. Serum CK five times higher than the normal value usually confirms rhabdomyolysis. Early diagnosis and saline volume expansion may reduce the risk of AKI. Further studies are necessary to establish the importance of bicarbonate and mannitol in the prevention of AKI due to rhabdomyolysis.