Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

Biomarkers of acute kidney injury in pediatric cardiac surgery.

Acute kidney injury (AKI) is characterized by a sudden decrease in kidney function. Children with congenital heart disease are a special group at risk of developing AKI. We performed a systematic review of the literature to search for studies reporting the usefulness of novel urine, serum, and plasma biomarkers in the diagnosis and progression of AKI and their association with clinical outcomes in children undergoing pediatric cardiac surgery. In thirty studies, we analyzed the capacity to predict AKI and poor outcomes of five biomarkers: Cystatin C, Neutrophil gelatinase-associated lipocalin, Interleukin-18, Kidney injury molecule-1, and Liver fatty acid-binding protein. In conclusion, we suggest the need for further meta-analyses with the availability of additional studies.

Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury.

OBJECTIVE: Liver transplant (LT) is a definitive therapeutic option for patients with chronic liver disease. However, acute kidney injury after LT (post-LT AKI) is a frequent complication that may lead to graft dysfunction and decrease life expectancy. Delay in AKI detection by traditional biomarkers boosted research with new biomarkers for post-LT AKI as neutrophil gelatinase-associated lipocalin (NGAL) and syndecan-1. We aim to evaluate associations of intraoperative systemic NGAL and syndecan-1 levels with post-LT AKI. METHODS: This is a prospective study conducted in 46 patients selected for LT. Patients were evaluated preoperatively and blood samples were collected intraoperatively: T1 (after induction of anesthesia), T2 (anhepatic phase) and T3 (2 h after reperfusion of the graft). RESULTS: The mean age was 54 ± 12 years and 60% were male. Post-LT AKI was observed in 24 (52%) patients of which 12% needed dialysis. Serum NGAL and syndecan-1 increased along surgical phases. Mostly, increment values of serum NGAL of T2 to T3 and syndecan-1 at T3 were importantly associated with post-LT AKI. Into a multivariate model with model for end-stage liver disease score, age, gender, warm ischemia, cold ischemia and surgery time, syndecan-1 levels at T3 remains capable to predict post-LT AKI. Serum NGAL had significance only with increment values calculated by the ratio of 'T3/T2'. Finally, serum syndecan-1 at T3 had a better diagnostic performance in receiver operating characteristic curve analysis. CONCLUSION: Serum syndecan-1 levels in 2 h after reperfusion were most useful in early post-LT AKI diagnosis and may be used to construct new risk groups in this context.

Urinary Syndecan-1 and acute kidney injury after pediatric cardiac surgery.

INTRODUCTION: Acute kidney injury (AKI) is a common occurrence after pediatric cardiac surgery. Plasma syndecan-1 is a biomarker of endothelial glycocalyx damage and it is associated with AKI. Syndecan-1 is also expressed in renal tubular cells but there is no study evaluating urinary syndecan-1 in predicting AKI. METHODS: Prospective cohort study with 86 patients ≤18 years submitted to cardiac surgery at one reference institution. Postoperative urinary syndecan-1 was collected within the first 2 h after cardiac surgery. Severe AKI - defined according to KDIGO as stage 2 or 3 - doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization was the main outcome. Analyses were adjusted for clinical cofounders. RESULTS: Postoperative urinary syndecan-1 levels were higher in patients with severe AKI and even after adjustment for several clinical variables; the fourth quartile was significantly associated with severe AKI. The AUC-ROC for postoperative urinary syndecan-1 showed good discriminatory capacity (AUC-ROC = 0.793). The addition of urinary syndecan-1 improved the discrimination capacity of a clinical model (0.78 to 0.84). It also improved risk prediction, as measured by net reclassification improvement (NRI). CONCLUSION: Urinary syndecan-1 predicts severe AKI after pediatric cardiac surgery. Moreover, it appears to add capacity to predict severe AKI into a clinical model.

Kinetic estimated glomerular filtration rate in critically ill patients: beyond the acute kidney injury severity classification system.

BACKGROUND: Although significant advances have been achieved in acute kidney injury (AKI) research following its classification, potential pitfalls can be identified in clinical practice. The nonsteady-state (kinetic) estimated glomerular filtration rate (KeGFR) could add clinical and prognostic information in critically ill patients beyond the current AKI classification system. METHODS: This was a retrospective analysis using data from the Multiparameter Intelligent Monitoring in Intensive Care II project. The KeGFR was calculated during the first 7 days of intensive care unit (ICU) stay in 13,284 patients and was correlated with outcomes. RESULTS: In general, there was not a good agreement between AKI severity and the worst achieved KeGFR. The stepwise reduction in the worst achieved KeGFR conferred an incremental risk of death, rising from 7.0% (KeGFR > 70 ml/min/1.73 m2) to 27.8% (KeGFR < 30 ml/min/1.73 m2). This stepwise increment in mortality remained in each AKI severity stage. For example, patients with AKI stage 3 who maintained KeGFR had a mortality rate of 16.5%, close to those patients with KeGFR < 30 ml/min/1.73 m2 but no AKI; otherwise, mortality increased to 40% when both AKI stage 3 and KeGFR < 30 ml/min/1.73 m2 were present. In relation to another outcome-renal replacement therapy (RRT)-patients with the worst achieved KeGFR < 30 ml/min/1.73 m2 and KDIGO stage 1/2 had a rate of RRT of less than 10%. However, this rate was 44% when both AKI stage 3 and a worst KeGFR < 30 ml/min/1.73 m2 were observed. This interaction between AKI and KeGFR was also present when looking at long-term survival. CONCLUSION: Both the AKI classification system and KeGFR are complementary to each other. Assessing both AKI stage and KeGFR can help to identify patients at different risk levels in clinical practice.

Nephroprotective effects of (-)-α-bisabolol against ischemic-reperfusion acute kidney injury.

BACKGROUND: Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-α-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity. STUDY DESIGN: This study intends to evaluate the nephroprotective activity of (-)-α-bisabolol (Bis) in both in vivo and in vitro models of kidney I/R. METHODS: Male Wistar rats were submitted to right nephrectomy, followed by ischemia by clamping of the renal artery in the left kidney for 60min. and 48h of reperfusion. The animals were treated orally with Bis (100mg/kg) or vehicle for 24h after reperfusion, and placed in metabolic cages, to evaluate water consumption, diuresis, urinary osmolality, classic biochemical markers and urinary KIM-1 (kidney injury molecule-1). Additionally, the left kidney was collected for histological evaluation and determination of glutathione (GSH) and Thiobarbituric Acid Reactive Substances (TBARS) levels. Tubular epithelial cells LLC-MK2 were used to assess Bis effect on in vitro I/R, by MTT assay. It was performed the cellular respiration tests by flow cytometry: evaluation of the production of cytoplasmic reactive oxygen species by DCFH-DA assay and mitochondrial transmembrane potential analysis with the dye rhodamine 123. RESULTS: I/R caused alterations in diuresis, water intake, urinary osmolality, plasmatic creatinine, urea and uric acid, creatinine clearance, proteinuria and microalbuminuria. Treatment with Bis ameliorated all of these parameters. Also, KIM-1 level enhanced by I/R was also diminished in groups treated with Bis. The histological examination showed that Bis attenuated the morphological changes caused by I/R, markedly vascular congestion and intratubular deposits of proteinaceous material. Additionally, Bis was able to reduce the changes observed in TBARS and GSH levels in kidney tissue. In in vitro assay, Bis was capable to partially protect the cell lineage against cell damage induced by I/R. CONCLUSION: (-)-α-Bisabolol has a nephroprotective effect in kidney I/R, with antioxidant effect. Moreover, this result seems to be associated to a direct protective effect on tubular epithelia.

Syndecan-1 improves severe acute kidney injury prediction after pediatric cardiac surgery.

OBJECTIVE: Acute kidney injury is a common occurrence after pediatric cardiac surgery and is associated with adverse patient outcomes. Syndecan-1 is a biomarker of endothelial glycocalyx damage, and its early increment after surgery can be associated with acute kidney injury. METHODS: We performed a prospective cohort study with 289 patients aged less than 18 years who underwent cardiac surgery at 1 reference institution. Postoperative plasma syndecan-1 was collected within the first 2 hours after cardiac surgery. Severe acute kidney injury, defined according to Kidney Disease: Improving Global Outcomes stage 2 or 3, doubling of serum creatinine from the preoperative value, or need for dialysis during hospitalization, was the main outcome. Analyses were adjusted for clinical variables and "renal angina index" components (early decrease in estimated creatinine clearance from baseline and increase in percent of intensive care unit fluid overload on the first postoperative day). RESULTS: Plasma syndecan-1 levels measured early in the postoperative period were independently associated with severe acute kidney injury. The accuracy of postoperative syndecan-1 for the diagnosis of severe acute kidney injury was moderate (area under the curve receiver operating characteristic, 0.77; 95% confidence interval, 0.68-0.85). The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.80 to 0.86 (P = .004) and improved risk prediction, as measured by net reclassification improvement and integrated discrimination improvement. Postoperative sundecan-1 levels also were independently associated with longer length of intensive care unit and hospital stay. CONCLUSIONS: Postoperative plasma syndecan-1 is associated with subsequent severe acute kidney injury and poor outcomes among children undergoing cardiac surgery. It may be useful to identify patients who are at increased risk for acute kidney injury after cardiac surgery.

Metabolic acidosis aggravates experimental acute kidney injury.

AIMS: Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury. MAIN METHODS: Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9). KEY FINDINGS: Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury. SIGNIFICANCE: Acute ischemic kidney injury is exacerbated by acidic conditions.

Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam.

BACKGROUND AND OBJECTIVES: Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is limited to patients undergoing cardiac surgery. There are no data about its association with oliguria and AKI in critically ill patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We obtained data from the Multiparameter Intelligent Monitoring in Intensive Care II database (2001-2008). Patient selection criteria included adult patients in their first intensive care unit (ICU) admission, need for mechanical ventilation, and treatment with propofol or midazolam. Propensity score analysis (1:1) was used and renal-related outcomes (AKI, oliguria, cumulative fluid balance, and need for RRT) were evaluated during the first 7 days of ICU stay. RESULTS: There were 1396 propofol/midazolam-matched patients. AKI in the first 7-day ICU time period was statistically lower in propofol-treated patients compared with midazolam-treated patients (55.0% versus 67.3%, P<0.001). Propofol was associated with lower AKI incidence using both urine output (45.0% versus 55.7%, P<0.001) and serum creatinine criteria (28.8% versus 37.2%, P=0.001). Patients receiving propofol had oliguria (<400 ml/d) less frequently (12.4% versus 19.6%, P=0.001) and had diuretics prescribed less often (8.5% versus 14.3%, P=0.001). In addition, during the first 7 days of ICU stay, patients receiving propofol less frequently achieved cumulative fluid balance >5% of body weight (50.1% versus 58.3%, P=0.01). The need for RRT in the first 7 days of ICU stay was also less frequent in propofol-treated patients (3.4% versus 5.9%, P=0.03). ICU mortality was lower in propofol-treated patients (14.6% versus 29.7%, P<0.001). CONCLUSIONS: In this large, propensity-matched ICU population, patients treated with propofol had a lower risk of AKI, fluid-related complications, and need for RRT.

Red propolis ameliorates ischemic-reperfusion acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated. METHODS: Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis. RESULTS: I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue. CONCLUSION: Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation.

Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model.

The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.

Metabolic acidosis components in advanced chronic kidney disease: association with serum albumin and parathyroid hormone.

OBJECTIVE: To investigate the associations between the 2 main components of metabolic acidosis (unmeasured anions [UA] and hyperchloremia) with serum albumin and intact parathormone (iPTH) in patients with advanced chronic kidney disease. DESIGN AND METHODS: Cross-sectional study with advanced chronic kidney disease patients (estimated glomerular filtration rate <30 mL/minute/1.73 m(2)) not receiving phosphate binders, alkali therapy, or vitamin D analogs. Arterial blood sample was collected for biochemical and blood gas analysis. UA and strong ion difference (SID) were calculated according to quantitative acid-base analysis. Reduced SID was used as a measure of hyperchloremia. MAIN OUTCOME MEASURES: Serum albumin and parathormone (iPTH). RESULTS: A total of 383 patients were included with a mean age of 64.7 ± 16.3 year and a mean estimated glomerular filtration rate of 19.9 ± 12.1 mL/minute/1.73 m(2). Among patients with metabolic acidosis, 45.7% had metabolic acidosis exclusively because of UA and 53.7% had a hyperchloremic component (either mixed metabolic acidosis or pure hyperchloremic metabolic acidosis). Considering the main acid-base status determinants, only UA had a significant correlation with serum albumin (r = -0.278, P < .001). There was no correlation between serum albumin and SID (r = 0.083, P = .156). This is in opposition to serum iPTH, where there was no correlation with UA (r = 0.082, P = .114), but an inverse correlation between iPTH and SID was observed (r = -0.228, P < .001). Multiple linear regressions with all acid-base determinants confirmed these findings. CONCLUSIONS: Our data brings further knowledge on the associations between metabolic acidosis with bone disorders and nutritional status, suggesting that the two main metabolic acidosis components (UA and hyperchloremia) have different effects on serum parathormone and serum albumin.

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.

Lesão renal aguda em pacientes com doença pulmonar: interação rim-pulmão / Acute kidney injury in critically ill patients with lung disease: kidney-lung crosstalk

OBJETIVO: Investigar os fatores associados à lesão renal aguda e o prognóstico em pacientes com doença pulmonar. MÉTODOS: Foi realizado estudo prospectivo com cem pacientes consecutivos admitidos em uma unidade de terapia intensiva respiratória em Fortaleza (CE). Foram investigados fatores de risco para lesão renal aguda e mortalidade em um grupo de pacientes com doenças pulmonares. RESULTADOS: A média de idade foi de 57 anos, sendo 50% do gênero masculino. A incidência de lesão renal aguda foi maior nos pacientes com PaO2/FiO2<200 mmHg (54% versus 23,7%; p=0,02). O óbito ocorreu em 40 casos. A mortalidade no grupo com lesão renal aguda foi maior (62,8% versus 27,6%; p=0,01). A relação PaO2/FiO2<200 mmHg foi fator independente associado à lesão renal aguda (p=0,01); PEEP na admissão (OR: 3,6; IC95%: 1,3-9,6; p=0,009) e necessidade de hemodiálise (OR: 7,9; IC95%: 2,2-28,3; p=0,001) foram fatores de risco independentes para óbito. CONCLUSÃO: Houve maior mortalidade no grupo com lesão renal aguda. Mortalidade aumentada foi associada com ventilação mecânica, PEEP alta, ureia e necessidade de diálise. Estudos futuros devem ser realizados para melhor estabelecer as inter-relações entre lesão renal e pulmonar e seu impacto no prognóstico.

OBJECTIVE: To examine the factors associated with acute kidney injury and outcome in patients with lung disease. METHODS: A prospective study was conducted with 100 consecutive patients admitted to a respiratory intensive care unit in Fortaleza (CE), Brazil. The risk factors for acute kidney injury and mortality were investigated in a group of patients with lung diseases. RESULTS: The mean age of the study population was 57 years, and 50% were male. The incidence of acute kidney injury was higher in patients with PaO2/FiO2<200 mmHg (54% versus 23.7%; p=0.02). Death was observed in 40 cases and the rate of mortality of the acute kidney injury group was higher (62.8% versus 27.6%; p=0.01). The independent factor that was found to be associated with acute kidney injury was PaO2/FiO2<200 mmHg (p=0.01), and the independent risk factors for death were PEEP at admission (OR: 3.6; 95%CI: 1.3-9.6; p=0.009) and need for hemodialysis (OR: 7.9; 95%CI: 2.2-28.3; p=0.001). CONCLUSION: There was a higher mortality rate in the acute kidney injury group. Increased mortality was associated with mechanical ventilation, high PEEP, urea and need for dialysis. Further studies must be performed to better establish the relationship between kidney and lung injury and its impact on patient outcome.

Cuidado ao paciente com Doença Renal Crônica no nível primário: pensando a integralidade e o matriciamento / Care for patients with Chronic Kidney Disease at the primary healthcare level: considerations about comprehensiveness and establishing a matrix

A Doença Renal Crônica é um problema de saúde pública crescente no mundo. A detecção e o tratamento precoces reduziriam as altas taxas de morbimortalidade e os custos associados. Este trabalho buscou identificar o panorama do acesso ao cuidado a partir da conduta dos médicos da Atenção Primária à Saúde na linha de cuidado da doença. Aplicaram-se questionários para 62 médicos de família dos Centros de Saúde da Família do município de Fortaleza. Os achados apontam que a Taxa de Filtração Glomerular foi mensurada por apenas 8.1% dos médicos para pacientes diabéticos e 4.8% para pacientes hipertensos. Mais da metade dos médicos (51.2%) referenciariam o paciente apresentando redução leve/moderada da Taxa de Filtração Glomerular ao nível secundário. Por outro lado, 25.8% dos médicos não referenciariam o paciente com Doença Renal Crônica avançada ao especialista. A lacuna entre esses dois níveis da atenção implica em barreira de acesso ao usuário, podendo comprometer avanços no plano da integralidade. A criação de novos dispositivos no processo de trabalho torna-se urgente e o apoio matricial apresenta-se como proposta viável para a articulação das ações entre os níveis da atenção no cuidado do portador da Doença Renal Crônica ou seus fatores de risco.

Chronic kidney disease is a public health problem throughout the world. Early detection and treatment can reduce morbidity, mortality and associated expenditures. The objective of this research is to examine primary healthcare from a physician's perspective, evaluating the patient's access to other levels of healthcare. Questionnaires were given to 62 family physicians working in primary healthcare units in the city of Fortaleza. Glomerular filtration rate was measured by only 8.1% of the physicians when evaluating patients with diabetes and 4.8% when evaluating hypertensive patients. The majority of physicians (51.2%) refer patients with slight/moderate Glomerular filtration rate reduction to a nephrologist. On the other hand, 25.8% do not refer patients with advanced chronic kidney disease reduction to a specialist. The gap between these levels of healthcare creates a barrier to user access, prejudicing comprehensive healthcare. The creation of new work processes is urgently required and the matrix process is a viable option to connect these healthcare levels for the care of patients with chronic kidney disease or its main risk factors (diabetes and arterial hypertension).

Predicting hospital mortality in critically ill cancer patients according to acute kidney injury severity.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication in hospitalized patients, especially in those in intensive care units (ICU). The RIFLE classification might be a valid prognostic factor for critically ill cancer patients. The present study aims to evaluate the discriminatory capacity of RIFLE versus other general prognostic scores in predicting hospital mortality in critically ill cancer patients. METHODS: This is a single-center study conducted in a cancer-specialized ICU in Brazil. All of the 288 patients hospitalized from May 2006 to June 2008 were included. RIFLE classification, APACHE II, SOFA, and SAPS II scores were calculated and the area under receiver operating characteristic (AROC) curves and logistic multiple regression were performed using hospital mortality as the outcome. RESULTS: AKI, defined by RIFLE criteria, was observed in 156 (54.2%) patients. The distribution of patients with any degree of AKI was: risk, n = 96 (33.3%); injury, n = 30 (10.4%), and failure, n = 30 (10.4%). Mortality was 13.6% for non-AKI patients, 49% for RIFLE 'R' patients, 62.3% for RIFLE 'I' patients, and 86.8% for RIFLE 'F' patients (p = 0.0006). Logistic regression analysis showed that RIFLE criteria, APACHE II, SOFA, and SAPS II were independent factors for mortality in this population. The discrimination of RIFLE was good (AROC 0.801, 95% CI 0.748-0.854) but inferior compared to those of APACHE II (AROC 0.940, 95% CI 0.915-0.966), SOFA (AROC 0.910, 95% CI 0.876-0.943), and SAPS II (AROC 0.869, 95% CI 0.827-0.912). CONCLUSION: AKI is a frequent complication in ICU patients with cancer. RIFLE was inferior to commonly used prognostic scores for predicting mortality in this cohort of patients.

Histological features of acute tubular necrosis in native kidneys and long-term renal function.

There are few studies on the relationship between the morphology of acute tubular necrosis (ATN) in native kidneys and late functional recovery. Eighteen patients with acute renal failure (ARF) who had undergone renal biopsy were studied. All had the histological diagnosis of ATN and were followed for at least six months. Clinical characteristics of ARF were analyzed, and histological features were semi-quantitatively evaluated (tubular atrophy, interstitial inflammatory infiltrate, interstitial fibrosis, and ATN). According to the maximal GFR achieved during the follow-up, patients were divided into two groups: complete recovery (GFR >or= 90 mL/min/1.73 m(2)) and partial recovery (GFR < 90 mL/min/1.73 m(2)). Only 39% of the patients achieved complete recovery. Patients with partial recovery achieved their maximal GFR (63 +/- 9 mL/min/1.73 m(2)) 37 +/- 14 months after ARF, a period of time similar to those patients with complete recovery (i.e., 54 +/- 22 months). Patients with partial recovery had more severe ARF: oliguria was more frequent (90 versus 17%, p < 0.01), and they had higher peak creatinine (13.85 +/- 1.12 versus 8.95 +/- 1.30 mg/dL, p = 0.01), and longer hospitalization (45 +/- 7 versus 20 +/- 4 days, p = 0.03). No single histological parameter was associated with partial recovery, but the sum of all was when expressed as an injury index [4.00 (2.73-5.45) versus 2.00 (1.25-3.31), p < 0.05]. In conclusion, among patients with atypical ATN course, those with more severe ARF and tubule-interstitial lesions are more prone to partial recovery.

Rosiglitazona, agonista do PPAR-y "Peroxisome Proliferator-Activated Receptor-y" reverte a nefrotoxicidade induzida pelo tenofovir-DF / The peroxisome proliferator-activated receptor-y agonist rosiglitazone reverses tenofovir-induced nephrotoxicity

Introdução: A nefrotoxicidade dos antiretrovirais constituem atualmente fator importante na morbidade e mortalidade de pacientes com HIV. O tenofovir DF (TDF) se enquadra em um dos antiretrovirais mais lesivos ao rim. Conhecer seu mecanismo de nefrotoxicidade e estudar medidas protetoras podem melhorar seu uso clínico. Material e Métodos: Ratos foram tratados durante 30 dias com uma de duas doses de TDF (50 ou 300mg/Kg de dieta), sendo que um grupo teve adicionado em sua dieta maleato de rosiglitazona (RSG) na dose de 92mg/Kg de dieta nos últimos 15 dias. Após esse período, os ratos foram colocados em gaiola metabólica e sacrificados. Foram estudados parâmetros bioquímicos, fluxo sanguíneo renal e os rins extraídos para expressão semiquantitativa dos transportadores epiteliais tubulares. Resultados: Os animais que receberam TDF em dose alta apresentaram insuficiência renal severa acompanhada de redução da expressão da oxido-nítrico sintase endotelial e vasoconstricção renal intensa. Todos esses parâmetros foram parcialmente revertidos pela administração de RSG. Baixas doses de TDF não causou alteração significativa do ritmo de filtração glomerular, porém induziu fosfatúria, acidose tubular proximal, poliúria e redução da capacidade de concentração urinária. Essas alterações foram associadas a redução da expressão de alguns transportadores epiteliais (cotransportador sódio-fosforo, contratransportador sódio-hidrogênio tipo 3 e aquaporina tipo 2). Não foi caracterizado síndrome de Fanconi, pois não houve proteinúria ou glicosúria. O tratamento com RSG reverteu todos os parâmetros de nefrotoxicidade estudados, normalizando as alterações bioquímicas urinárias e a expressão dos transportadores de membrana. Conclusões: Os achados desses experimentos tem potencial aplicação clínica em pacientes com nefrotoxicidade induzida pelo TDF, especialmente naqueles com hipofosfatemia e/ou redução do ritmo de filtração glomerular.

Objective: To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)- induced nephrotoxicity and the protective effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-y agonist. Methods: Rats were treated for 30 days with one of two TDF doses (50 or 300 mg/kg of food), to which RSG (92 mg/kg of food) was added for the last 15 days. Biochemical parameters were measured, and renal tissue was extracted for immunoblotting. Results: Mean daily ingestion was comparable among all the treated groups. Highdose TDF induced severe renal failure accompanied by reduced expression of endothelial nitric-oxide synthase and intense renal vasoconstriction. All of these features were ameliorated by RSG administration. Low-dose TDF did not alter the glomerular filtration rate but induced significant phosphaturia, proximal tubular acidosis and polyuria, as well as reducing urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. No Fanconi's syndrome was identified (proteinuria was normal and there was no glycosuria). Treatment with RSG reversed TDF-induced tubular nephrotoxicity, normalizing urinary biochemical parameters and membrane transporter protein expression. Conclusion: These findings have potential clinical applications in patients presenting with TFV-induced nephrotoxicity, especially in those presenting with hypophosphatemia or a reduction in glomerular filtration rate.

Malignant hypertension with intestinal ischemia secondary to juxtaglomerular cell tumor.

Malignant hypertension is a well-defined condition associated with high blood pressure and acute target-organ damage. Although 95% of cases are secondary to essential hypertension, its etiological profile is broad. Juxtaglomerular cell tumor is a rare condition, with only approximately 65 cases reported to date. We describe a patient with malignant hypertension with acute renal failure and intestinal ischemia secondary to a juxtaglomerular cell tumor. We believe this is the first case of juxtaglomerular cell tumor causing malignant hypertension. The diagnostic approach and treatment are discussed.