Preliminary Study for New Markers of Early Tubuloglomerular Injury and Renal Inflammation in Patients with Visceral Leishmaniasis Receiving Liposomal Amphotericin B Treatment.

Visceral leishmaniasis is treated with liposomal amphotericin B (L-AMB), which is associated with nephrotoxicity. Thus, we aimed to investigate nephrotoxicity through novel renal biomarkers in patients with visceral leishmaniasis during L-AMB use. Ours was a prospective study with 17 patients with visceral leishmaniasis treated with L-AMB during their hospital stay. Laboratory tests, renal parameters, urinary biomarkers (urinary kidney injury molecule 1, urinary monocyte chemoattractant protein 1 [uMCP-1], sodium-potassium-2 chloride cotransporter, sodium-hydrogen exchanger 3), and serum inflammatory biomarkers (MCP-1, interferon-γ, and IL-6) were evaluated in two periods: before and during L-AMB use. Glomerular filtration rate, creatinine, proteinuria, and albuminuria were similar before and during L-AMB use. IL-6 levels, aquaporin 2, and sodium-hydrogen exchanger 3 expression decreased, whereas uMCP-1 and urinary kidney injury molecule 1 levels increased during L-AMB treatment. In patients who developed acute kidney injury, uMCP-1 showed higher levels. L-AMB aggravated tubuloglomerular lesions, inflammation, and renal tubular disorders. Thus, patients treated with L-AMB need to be monitored for inflammatory and electrolyte disturbances to prevent acute kidney injury, longer length of hospital stay, higher public costs, and mortality.

Novel biomarkers in the prognosis of patients with atherosclerotic coronary artery disease.

Biomarkers have a variety of clinical applications in multiple stages of diagnosis and therapy. Troponin T and brain natriuretic peptide are the best-known in the cardiovascular field, but experimental studies have identified new biomarkers with potential clinical value. In this article, novel biomarkers of kidney injury are investigated in the context of their relationship with atherosclerotic coronary disease. This review was carried out through a search in the PubMed database using as keywords each biomarker to be studied with the descriptor (DECS/MeSH) "Myocardial Infarction", and the keywords "coronary" and "cardiovascular", using the Boolean operator "AND". After the selection, 24 articles published between 2003 and 2017 were identified for the review. Eight biomarkers were investigated: neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor 23 (FGF23), tissue inhibitor of metalloproteinase-2 (TIMP-2), syndecan-1, interleukin-6 (IL-6), galectin-3, and the vascular cell adhesion molecules ICAM-1 and VCAM-1. Most identified articles were experimental studies, studies on human subjects having few participants. There are several promising biomarkers in the setting of coronary disease. The main evidence available in the literature suggests that elevated NGAL levels are associated with better prognosis after cardiac arrest and with comorbid kidney injury; elevated FGF23 is associated with coronary artery disease severity; TIMP-2 protects against coronary artery disease; increased expression of syndecan-1 is observed in myocardial infarction (MI) and protects against an exacerbated inflammatory response; IL-6 is associated with atherosclerotic disease and major cardiovascular outcomes; galectin-3 correlates with adverse clinical events post-MI; and elevated ICAM-1/VCAM-1 levels are associated with risk of coronary disease. Further studies are required to better investigate the role of each of these biomarkers in both stable coronary disease and acute coronary syndrome.

Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review.

Bothrops are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on Bothrops venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar "acute kidney injury" or "kidney disease" and "Bothrops"; on Lilacs and SciELO "kidney disease" or "acute kidney injury" and "Bothrops". Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following Bothrops syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of Bothrops venom-related acute kidney injury.

Kidney involvement in malaria: an update.

Malaria is an infectious disease of great importance for Public Health, as it is the most prevalent endemic disease in the world, affecting millions of people living in tropical areas of the globe. Kidney involvement is relatively frequent in infections by P. falciparum and P. malariae, but has also been described in the infection by P. vivax. Kidney complications in malaria mainly occur due to hemodynamic dysfunction and immune response. Liver complications leading to hepatomegaly, jaundice and hepatic dysfunction can also contribute to the occurrence of acute kidney injury. Histologic studies in malaria also evidence glomerulonephritis, acute tubular necrosis and acute interstitial nephritis. It is also possible to find chronic kidney disease associated with malaria, mainly in those patients suffering from repeated episodes of infection. Plasmodium antigens have already been detected in the glomeruli, suggesting a direct effect of the parasite in the kidney, which can trigger an inflammatory process leading to different types of glomerulonephritis. Clinical manifestations of kidney involvement in malaria include proteinuria, microalbuminuria and urinary casts, reported in 20 to 50% of cases. Nephrotic syndrome has also been described in the infection by P. falciparum, but it is rare. This paper highlights the main aspects of kidney involvement in malaria and important findings of the most recent research addressing this issue.

Acute kidney injury complicating bee stings - a review.

Bee stings can cause severe reactions and have caused many victims in the last years. Allergic reactions can be triggered by a single sting and the greater the number of stings, the worse the prognosis. The poisoning effects can be systemic and can eventually cause death. The poison components are melitin, apamin, peptide 401, phospholipase A2, hyaluronidase, histamine, dopamine, and norepinephrine, with melitin being the main lethal component. Acute kidney injury (AKI) can be observed in patients suffering from bee stings and this is due to multiple factors, such as intravascular hemolysis, rhabdomyolysis, hypotension and direct toxicity of the venom components to the renal tubules. Arterial hypotension plays an important role in this type of AKI, leading to ischemic renal lesion. The most commonly identified biopsy finding in these cases is acute tubular necrosis, which can occur due to both, ischemic injury and the nephrotoxicity of venom components. Hemolysis and rhabdomyolysis reported in many cases in the literature, were demonstrated by elevated serum levels of indirect bilirubin and creatine kinase. The severity of AKI seems to be associated with the number of stings, since creatinine levels were higher, in most cases, when there were more than 1,000 stings. The aim of this study is to present an updated review of AKI associated with bee stings, including the currently advised clinical approach.

Increasing violent deaths and organ transplantation in Brazil: is there a parallel?

Mortality from violent causes has significantly increased in Brazil, as well as the number of deceased-donor organ transplantation. Although the increase in the number of transplants correlates with higher organ availability, through the increase in potential donors, this is not the unique aspect to be considered. The effective and articulated action of transplantation network seems to be decisive to this outcome.

Resumo A mortalidade por causas violentas tem aumentado de modo significativo no Brasil, bem como o número de transplantes de órgãos com doador falecido. Apesar de o aumento do número de transplantes correlacionar-se com o aumento na disponibilidade de órgãos, por meio do aumento no número de potenciais doadores, este não é o único aspecto a ser considerado. A ação efetiva e articulada das centrais de transplante parece ser decisiva para estes resultados.

Chronic kidney disease related to renal tuberculosis: a case report.

Genitourinary tuberculosis (TB) is the third most common form of extrapulmonary TB. A 34-year-old man with severe kidney function loss secondary to renal TB initially presented with urinary symptoms, including dysuria and polacyuria. The diagnosis was based on clinical history and laboratory tests; the urinalysis revealed acid-fast bacilli. The patient's condition stabilized after beginning TB-specific treatment, but the right kidney function loss persisted. Renal TB can lead to irreversible loss of renal function. As such, renal function should be considered in all patients from TB-endemic areas who present with urinary symptoms and whose urine cultures are negative for common pathogens.

Risk factors for intensive care unit admission in patients with severe leptospirosis: a comparative study according to patients' severity.

BACKGROUND: The aim of this study is to investigate predictive factors for intensive care unit (ICU) admission among patients with severe leptospirosis. METHODS: This is a retrospective study with all patients with severe leptospirosis admitted to a tertiary hospital. Patients were divided in ICU and ward groups. Demographical, clinical and laboratory data of the groups were compared as well as acute kidney injury (AKI) severity, according to the RIFLE criteria (R = Risk, I = Injury, F = Failure, L = Loss, E = End-stage kidney disease). RESULTS: A total of 206 patients were included, 83 admitted to ICU and 123 to ward. Mean age was 36 ± 15.8 years, with 85.9% males. Patients in ICU group were older (38.8 ± 15.7 vs. 34.16 ± 15.9 years, p = 0.037), had a shorter hospital stay (4.13 ± 3.1 vs. 9.5 ± 5.2 days, p = 0.0001), lower levels of hematocrit (29.6 ± 6.4 vs. 33.1 ± 8.6%, p = 0.003), hemoglobin (10.2 ± 2.4 vs. 11.6 ± 1.9 g/dL, p < 0.0001), and platelets (94,427 ± 86,743 vs. 128,896 ± 137,017/mm(3), p = 0.035), as well as higher levels of bilirubin (15.0 ± 12.2 vs. 8.6 ± 9.5 mg/dL, p = 0.001). ICU group also had a higher frequency of severe AKI (RIFLE-"Failure": 73.2% vs. 54.2%, p < 0.0001) and a higher prevalence of dialysis requirement (57.3% vs. 27.6%, p < 0.0001). Mortality was higher among ICU patients (23.5% vs. 5.7%, p < 0.0001). Independent predictors for ICU admission were tachypnea (p = 0.027, OR = 13, CI = 1.3-132), hypotension (p = 0.009, OR = 5.27, CI = 1.5-18) and AKI (p = 0.029, OR = 14, CI = 1.3-150). Ceftriaxone use was a protective factor (p = 0.001, OR = 0.13, CI = 0.04-0.4). CONCLUSIONS: Independent risk factors for ICU admission in leptospirosis include tachypnea, hypotension and AKI. Ceftriaxone was a protective factor for ICU admission, suggesting that its use may prevent severe forms of the disease.

Factors associated with maternal death in an intensive care unit. / Fatores associados à morte materna em unidade de terapia intensiva.

OBJECTIVE:: To identify factors associated with maternal death in patients admitted to an intensive care unit. METHODS:: A cross-sectional study was conducted in a maternal intensive care unit. All medical records of patients admitted from January 2012 to December 2014 were reviewed. Pregnant and puerperal women were included; those with diagnoses of hydatidiform mole, ectopic pregnancy, or anembryonic pregnancy were excluded, as were patients admitted for non-obstetrical reasons. Death and hospital discharge were the outcomes subjected to comparative analysis. RESULTS:: A total of 373 patients aged 13 to 45 years were included. The causes for admission to the intensive care unit were hypertensive disorders of pregnancy, followed by heart disease, respiratory failure, and sepsis; complications included acute kidney injury (24.1%), hypotension (15.5%), bleeding (10.2%), and sepsis (6.7%). A total of 28 patients died (7.5%). Causes of death were hemorrhagic shock, multiple organ failure, respiratory failure, and sepsis. The independent risk factors associated with death were acute kidney injury (odds ratio [OR] = 6.77), hypotension (OR = 15.08), and respiratory failure (OR = 3.65). CONCLUSION:: The frequency of deaths was low. Acute kidney injury, hypotension, and respiratory insufficiency were independent risk factors for maternal death.

Dengue Fever Among Renal Transplant Recipients: A Series of 10 Cases in a Tropical Country.

This is a case series of 10 consecutive renal allograft recipients, followed at a tertiary hospital in northeast Brazil, with a confirmed diagnosis of dengue. Five of the patients needed hospitalization. Half of them were males and age ranged from 19 to 60 years with a median of 38.2 years. They had been transplanted for a mean of 5 days to 166 months. Four patients developed dengue hemorrhagic fever (DHF). All patients had myalgia and headache. All of them, except one, had fever. Positive dengue serology (IgM) was found in all patients. No patient died. Dengue is an important infectious disease that can affect renal transplant recipients, mainly in endemic areas. Its presentation seems to be similar to that seen in immunocompetent patients.

Monocyte chemoatractant protein-1: a potential biomarker of renal lesion and its relation with oxidative status in sickle cell disease.

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.

Renal function in hepatosplenic schistosomiasis--an assessment of renal tubular disorders.

BACKGROUND: Renal involvement in Schistosoma mansoni infection is not well studied. The aim of this study is to investigate the occurrence of renal abnormalities in patients with hepatosplenic schistosomiasis (HSS), especially renal tubular disorders. METHODS: This is a cross-sectional study with 20 consecutive patients with HSS followed in a medical center in Maceió, Alagoas, Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2) after a 12-h period of water and food deprivation. The biomarker monocyte chemoattractant protein 1 (MCP-1) was quantified in urine. Fractional excretion of sodium (FENa+), transtubular potassium gradient (TTKG) and solute-free water reabsorption (TcH2O) were calculated. The HSS group was compared to a group of 17 healthy volunteers. RESULTS: Patients' mean age and gender were similar to controls. Urinary acidification deficit was found in 45% of HSS patients. Urinary osmolality was significantly lower in HSS patients (588 ± 112 vs. 764 ± 165 mOsm/kg, p = 0,001) after a 12-h period of water deprivation. TcH2O was lower in HSS patients (0.72 ± 0.5 vs. 1.1 ± 0.3, p = 0.04). Urinary concentration deficit was found in 85% of HSS patients. The values of MCP-1 were higher in HSS group than in control group (122 ± 134 vs. 40 ± 28 pg/mg-Cr, p = 0.01) and positively correlated with the values of microalbuminuria and proteinuria. CONCLUSIONS: HSS is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating ability and incomplete distal acidification defect, demonstrating the occurrence of tubular dysfunction. There was also an increase in urinary MCP-1, which appears to be a more sensitive marker of renal damage than urinary albumin excretion rate.

Urinary monocyte chemotactic protein-1 (MCP-1) in leprosy patients: increased risk for kidney damage.

BACKGROUND: We aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease. METHODS: This is a cross-sectional study of 44 patients with diagnosis of leprosy and no previous treatment. Skin smear was assessed through a bacteriological index - from 0 to 6+. Glomerular filtration rate (GFR), protein excretion rate, microalbuminuria, urinary oxidative stress, malondialdehyde (MDA) and urinary MCP-1 were measured. Also, high- sensitivity C-reactive protein (hs-CRP) was measured in the blood. Fifteen healthy subjects composed a control group. RESULTS: Age and gender were similar between leprosy patients and control groups. No patient had a GFR < 60 mL/min/1.73 m2 or albumin excretion rate greater than 30 mg/g-Cr. Leprosy patients had higher urinary protein excretion (97.6 ± 69.2 vs. 6.5 ± 4.3 mg/g-Cr, p < 0.001), urinary MCP-1 (101.0 ± 79.8 vs. 34.5 ± 14.9 mg/g-Cr, p = 0.006) and urinary MDA levels (1.77 ± 1.31 vs. 1.27 ± 0.66 mmol/g-Cr, p = 0.0372) than healthy controls. There was a positive correlation between urinary MCP-1 and bacteriological index in skin smears (r = 0.322, p = 0.035), urinary protein excretion (r = 0.547, p < 0.001), albumin excretion rate (r = 0.414, p = 0.006) and urinary MDA (r = 0.453, p = 0.002). After adjusting for hs-CRP, urinary MCP-1 remained correlated with albumin excretion rate (rpartial = 0.483, p = 0.007) and MDA levels (rpartial = 0.555, p = 0.001). CONCLUSION: Leprosy patients with no clinical kidney disease have increased urinary MCP-1 mainly in lepromatous polar form. Inflammatory (MCP-1) and oxidative stress markers suggest leprosy patients are at high risk of developing kidney disease.

Acute kidney injury in a tropical country: a cohort study of 253 patients in an infectious diseases intensive care unit.

INTRODUCTION: Acute kidney injury (AKI) is a frequent and potentially fatal complication in infectious diseases. The aim of this study was to investigate the clinical aspects of AKI associated with infectious diseases and the factors associated with mortality. METHODS: This retrospective study was conducted in patients with AKI who were admitted to the intensive care unit (ICU) of a tertiary infectious diseases hospital from January 2003 to January 2012. The major underlying diseases and clinical and laboratory findings were evaluated. RESULTS: A total of 253 cases were included. The mean age was 46±16 years, and 72% of the patients were male. The main diseases were human immunodeficiency virus (HIV) infection, HIV/acquired immunodeficiency syndrome (AIDS) (30%), tuberculosis (12%), leptospirosis (11%) and dengue (4%). Dialysis was performed in 70 cases (27.6%). The patients were classified as risk (4.4%), injury (63.6%) or failure (32%). The time between AKI diagnosis and dialysis was 3.6±4.7 days. Oliguria was observed in 112 cases (45.7%). The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were higher in patients with HIV/AIDS (57±20, p-value=0.01) and dengue (68±11, p-value=0.01). Death occurred in 159 cases (62.8%). Mortality was higher in patients with HIV/AIDS (76.6%, p-value=0.02). A multivariate analysis identified the following independent risk factors for death: oliguria, metabolic acidosis, sepsis, hypovolemia, the need for vasoactive drugs, the need for mechanical ventilation and the APACHE II score. CONCLUSIONS: AKI is a common complication in infectious diseases, with high mortality. Mortality was higher in patients with HIV/AIDS, most likely due to the severity of immunosuppression and opportunistic diseases.

Evaluation of renal function in patients with psoriasis using immunobiologicals.

The aim of this study was to evaluate renal function in patients with psoriasis using immunobiologicals. A prospective study was conducted with 15 patients with confirmed diagnosis of psoriasis who were starting to use immunobiologicals. The mean age was 41 ± 11 years, with 60% females. The mean time of disease was 11 ± 6.6 years. Significant changes in creatinine and creatinine clearance were not observed in the course of the study. There was an increase in transaminases and a decrease in magnesium levels.

Renal tuberculosis in the modern era.

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. The disease remains as an important public health problem in developing countries. Extrapulmonary TB became more common with the advent of infection with human immunodeficiency virus and by the increase in the number of organ transplantation, which also leads to immunosuppression of thousand of persons. Urogenital TB represents 27% of extrapulmonary cases. Renal involvement in TB can be part of a disseminated infection or a localized genitourinary disease. Renal involvement by TB infection is underdiagnosed in most health care centers. Most patients with renal TB have sterile pyuria, which can be accompanied by microscopic hematuria. The diagnosis of urinary tract TB is based on the finding of pyuria in the absence of common bacterial infection. The first choice drugs include isoniazide, rifampicin, pirazinamide, ethambutol, and streptomycin. Awareness of renal TB is urgently needed by physicians for suspecting this disease in patients with unexplained urinary tract abnormalities, mainly in those with any immunosuppression and those coming from TB-endemic areas.

New insights on pathophysiology, clinical manifestations, diagnosis, and treatment of sickle cell nephropathy.

Sickle cell nephropathy is one of the main chronic complications of sickle cell disease (SCD), the most common of the hematological hereditary disorders. Several studies have been performed since the first description of SCD 100 years ago to investigate the mechanisms of kidney involvement in this disease. It has been demonstrated that both glomerular and tubular compartments can be damaged as a direct consequence of SCD, including renal function loss, concentration and acidification deficits, and glomerulopathies. This article highlights the aspects of sickle cell nephropathy pathophysiology and clinical manifestations and describes the most recent advances in the diagnosis and treatment of this disorder.

Blood pressure measurement in different outpatient clinics.

The objective of this study is to investigate how blood pressure is measured in different outpatient clinics. This is a retrospective study performed with 1,000 patients, randomly selected among patients followed in different outpatient clinics in Fortaleza, Brazil. Among the 1,000 patients, 962 had available records. The older the patient, the greater the possibility of having had blood pressure measured. In subsequent visits, blood pressure was measured more often than in the first visits. Blood pressure was measured more often among patients with chronic disease. The specialty with the highest proportion of blood pressure measurement was cardiology (85%). At the surgery, dermatology and traumatology clinics, blood pressure was measured in less than 5% of visits, and at the ophthalmology, sexually transmitted diseases, psychiatry, proctology and otolaryngology clinics, blood pressure was not measured in any visit. Cardiology, endocrinology, nephrology, geriatrics and internal medicine were the specialties where blood pressure was more frequently measured. It is important to measure blood pressure in any medical specialty in order to give early diagnosis of hypertension and provide adequate blood pressure control.

Paraneoplastic syndromes and the kidney.

A paraneoplastic syndrome is defined as a group of symptoms that develop when substances released by some cancer cells disrupt the normal function of the surrounding cells and tissue. Paraneoplastic renal syndromes are diseases that indirectly compromise tubular and glomerular function by electrolyte imbalance, hormone-producing tumors or deposition of antigen-antibody complexes in the glomeruli. In order to describe the most common paraneoplastic syndromes, which may compromise the renal function, an extensive review was performed of papers, including case reports, guidelines, meta-analysis and other scientific publications. Renal function can be affected by many paraneoplactic syndromes: hypercalcemia in malignancies, syndrome of inappropriate secretion of antidiuretic hormone, tumor lysis syndrome, renin-producing tumors and paraneoplastic glomerulopathies. An early diagnosis and effective treatment might improve quality of life and alter prognosis of these patients.