Luis Alberto Batista Peres

Acute nephrotoxicity of cisplatin: molecular mechanisms

The nephrotoxic drugs have been responsible for about 20% of AKI episodes in inpatients and outpatients. The cisplatin nephrotoxicity is a major limiting factors in 20% of patients who have received the drug, triggering injuries in renal tubular epithelial cells. Cisplatin toxicity is determined by the target tissue and cells accumulation besides the interaction with various subcellular structures and macromolecules. Cisplatin accumulates and interferes with the functioning of different organelles such as mitochondria, lysosomes, endoplasmic reticulum, nuclei and cell membranes, causing inflammation and cell death. This review aims to define the pathophysiology and biochemistry of the cisplatin nephrotoxicity, reviewing the main molecular mechanisms that lead to tubular cisplatin toxicity.

Estudo epidemiológico da doença renal crônica terminal no Oeste do Paraná: uma experiência de 878 casos atendidos em 25 anos

INTRODUCAO: A incidencia e prevalencia dos pacientes em fase final da doenca renal cronica (DRC) continuam a crescer em todo o mundo. O transplante renal continua tendo preferencia na terapia renal substitutiva, mas, dada a limitada oferta de doadores de orgaos, terapias dialiticas sao as modalidades mais realizadas. OBJETIVOS: Avaliar um registro de pacientes admitidos para terapia renal substitutiva no periodo de 1984 a 2009, em um unico Centro. METODOS: Este e um estudo epidemiologico retrospectivo. Foram analisadas as caracteristicas demograficas e clinicas, incidencia, principal doenca renal de base, modalidades dialiticas, mortalidade e causas de obitos. Para comparar as variaveis, foram utilizados o teste do qui-quadrado, teste t de Student, ANOVA e teste de Tukey. Curvas de Kaplan-Meier foram utilizadas para estimar a sobrevida dos pacientes. Um valor de p < 0,05 foi considerado estatisticamente significativo. RESULTADOS: No periodo compreendido, 878 pacientes foram admitidos em dialise. A media de idade dos pacientes foi 47,0 ± 16,2 anos, 549 (62,5%) eram do sexo masculino e 712 (81,1%) eram brancos. As principais causas da DRC foram a hipertensao, encontrada em 351 (40,0%) pacientes; nefropatia diabetica, em 174 (19,8%); e glomerulonefrite cronica, em 180 (20,5%) pacientes. A principal modalidade dialitica foi a hemodialise. A taxa de mortalidade em um ano foi de 10,4%. As causas mais comuns de morte foram as cardiovasculares, em 126 (34,6%) pacientes. CONCLUSOES: Neste estudo esta coorte de pacientes apresentou baixa mortalidade. A doenca cardiovascular permanece a principal causa de obito na populacao com doenca renal cronica em estagio terminal. Triagem para doenca cardiovascular e altamente recomendada para esses pacientes.

Biomarkers of acute kidney injury

Creatinine remains the standard for laboratory diagnosis of AKI. Efforts to prevent nephrotoxicity have been harmed by the delay in the diagnosis of AKI criteria by using only the creatinine as a marker, therefore there is great interest in identifying early reliable biomarkers. Moreover, early treatment of ARF can be correlated with a better prognosis and identification of biomarkers for early diagnosis would improve the efficacy of a therapeutic strategy. Thus, it becomes imperative to find biomarkers that can stratify correctly the extent of renal damage that each patient has suffered and the risk of developing chronic kidney disease (CKD). Here, we review the main features of emerging biomarkers in nephrology.

Evaluation of the cisplatin nephrotoxicity using the urinary neutrophil gelatinase-associated lipocalin (NGAL) in patients with head and neck cancer

INTRODUCTION Acute kidney injury (AKI) in patients receiving cisplatin is common, therefore the evaluation of renal function in patients on use of nephrotoxic drugs is fundamental. OBJECTIVE To evaluate the incidence of AKI and the role of lipocalin associated to neutrophil gelatinase (NGAL) in the monitoring of renal function in patients with head and neck cancer (HNC) who received cisplatin. METHODS We prospectively studied 50 patients with HNC treated with three sessions of cisplatin. Blood and urine were collected 24 hours before cisplatin, 24 hours after infusion, 48 hours after each application and 35 days after the end of treatment (urine NGAL, C-reactive protein, creatinine, glomerular filtration rate, plasma lactate dehydrogenase and magnesium). RESULTS AKI was observed in 78% of patients. There was increase in creatinine, and decrease in GFR after each cycle of cisplatin, and increased urine NGAL. Positive association was observed between the levels of NGAL, creatinine and C-reactive protein. It was observed an increase in creatinine, NGAL, C-reactive protein and decreased GFR in AKI patients compared to patients without AKI. CONCLUSION AKI was noted in 78% of patients with HNC treated with cisplatin and showed the correlation of NGAL with creatinine and GFR in demonstrating renal injury. NGAL levels may be elevated compared to baseline levels, even before the use of cisplatin.

Nefrolitíase em pacientes pediátricos: investigação metabólica e anatômica

Metabolic disorders are frequently observed in pediatric patients with renal lithiasis. OBJECTIVES: Study the metabolic and anatomical alterations and perform the chemical analysis of stones found in children with nephrolithiasis in our region. METHODS: A retrospective study on 158 children with evidence of recent renal stone formation was performed. One hundred and nine children concluded the metabolic study. Laboratory investigation consisted in two samples of 24-hour urine for calcium, uric acid, citrate, oxalate, sodium and creatinine; qualitative cystinuria, urinary pH following 12-hour fasting and water restriction, urine culture and chemical analysis when the stones were available. Renal imaging techniques included, at least, renal ultrasound and excretory urogram. RESULTS: A cause for nephrolithiasis was identified in 96.3% of children. The main metabolic alteration was hypercalciuria (73.4%). Chemical analysis of stones showed calcium oxalate in 90.9% of the cases. Anatomical alterations were found in 18.0% of the investigated cases and the most frequently found alteration was pyelo-ureteral duplication (28.6%). CONCLUSIONS: Hypercalciuria was the most frequently found disorder and pyelo-ureteral duplication was the most common anatomical alteration; moreover, calcium oxalate was the most frequent chemical constituent. The present study showed the characteristics of pediatric patients with nephrolithiasis in our region.

Metabolic investigation of patients with urolithiasis in a specific region

OBJECTIVE To assess the prevalence of the main metabolic alterations found in patients with recent diagnosis of urolithiasis in the West region of Parana state, Brazil. MATERIALS AND METHODS We made a retrospective study on 425 patients with evidence of recent formation of renal stones. Laboratory assessment consisted in 3 samples of 24-hour urine with dosing of calcium, uric acid, citrate, oxalate, sodium and creatinine. A urine culture was also made and qualitative cystinuria and urinary pH following 12-hour fasting and water restriction were evaluated. RESULTS In 96.5% of patients a cause was detected for the urolithiasis. Metabolic alterations most frequently found were: hypercalciuria (38.3%), hypocitraturia (29.6%) and hyperexcretion of uric acid (21.6%). Low urinary volume (17.9%), urinary tract infection (12.9%), hyperparathyroidism (3.3%), renal tubular acidosis (1.2%), cystinuria (0.9%) and anatomical alterations (12.7%) were also observed. CONCLUSIONS Hypercalciuria, hypocitraturia and hyperuricuria are the most frequent metabolic disorders in the population under study and these data are in accordance to the literature.

Alterações anatômicas em pacientes com nefrolitíase

INTRODUCTION: Nephrolithiasis is a multifactorial disease related to genetic disorders and environmental factors. Kidney stones are more common in adults and are associated with several metabolic and anatomical disorders. The major anatomical abnormalities, such as obstruction of the ureteropelvic junction, horseshoe kidney, complete or incomplete duplicated ureter, bifid pelvis, and medullary sponge kidney, are known to be responsible for stone formation. The objective of this study is to evaluate anatomical alterations in patients with nephrolithiasis in our region. METHODS: Retrospective study on 1,378 patients with evidence of recent formation of kidney stones. Laboratory investigation and chemical analysis were performed when stones were available. Renal imaging techniques comprised at least renal ultrasound and excretory urography. RESULTS: Of the 1,378 patients with nephrolithiasis cared for, only 367 (26.5%) (mean age, 36.8 ± 4.3 years) underwent anatomical investigation, of whom 198 (54.5%) were females. At least one anatomical alteration was found in 132 (36%) patients, the most common being renal cyst, completely or incompletely duplicated ureter, and obstruction of the ureteropelvic junction. CONCLUSIONS: Anatomical alterations were found in 36% of the investigated patients. Renal cyst, ureteral duplication, and obstruction of the ureteropelvic junction were the most frequently found anatomical alterations in the group.

Predictors of acute kidney injury and mortality in an Intensive Care Unit

Introduction and Objectives: To compare clinical characteristics and outcomes of patients with and without acute kidney injury (AKI), to evaluate the incidence and mortality of AKI and predictors of AKI and death in patients hospitalized in an Intensive Care Unit (ICU). Methods: A retrospective study analyzed 152 patients admitted to a single ICU. We assessed age, gender, reason for hospitalization, risk factors for ARF, laboratory data, the need for renal therapy substitutive and mortality. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA) and RIFLE were recorded on the day of ICU admission. We determined the incidence of AKI, mortality and the independent predictors of AKI and death using logistic regression model. Results: Mean age was 57.1 ± 20 years, ranging between 19 to 88 years, and 60.1% were male. Non-dialysis dependent AKI occurred in 81 patients (53.2%) while the ARF requiring dialysis occurred in 19 patients (12.4%). The overall mortality rate in the ICU was 35.9%, whereas the mortality rate in patients with non-dialysis dependent AKI was 43.2% and the IRA with dialysis of 84.2%. In multivariate analysis, invasive mechanical ventilation, elevated creatinine and urea at admission were independent risk factors for AKI, whereas clinical diagnosis, invasive mechanical ventilation, increased lactate and urea and hypernatremia were independent risk factors for ICU mortality. Conclusion: The incidence and mortality of AKI in ICU were high in this study, despite the advances that have been emerging in their management.INTRODUCTION AND OBJECTIVES To compare clinical characteristics and outcomes of patients with and without acute kidney injury (AKI), to evaluate the incidence and mortality of AKI and predictors of AKI and death in patients hospitalized in an Intensive Care Unit (ICU). METHODS A retrospective study analyzed 152 patients admitted to a single ICU. We assessed age, gender, reason for hospitalization, risk factors for ARF, laboratory data, the need for renal therapy substitutive and mortality. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA) and RIFLE were recorded on the day of ICU admission. We determined the incidence of AKI, mortality and the independent predictors of AKI and death using logistic regression model. RESULTS Mean age was 57.1 ± 20 years, ranging between 19 to 88 years, and 60.1% were male. Non-dialysis dependent AKI occurred in 81 patients (53.2%) while the ARF requiring dialysis occurred in 19 patients (12.4%). The overall mortality rate in the ICU was 35.9%, whereas the mortality rate in patients with non-dialysis dependent AKI was 43.2% and the IRA with dialysis of 84.2%. In multivariate analysis, invasive mechanical ventilation, elevated creatinine and urea at admission were independent risk factors for AKI, whereas clinical diagnosis, invasive mechanical ventilation, increased lactate and urea and hypernatremia were independent risk factors for ICU mortality. CONCLUSION The incidence and mortality of AKI in ICU were high in this study, despite the advances that have been emerging in their management.

Mineral and bone disorder and vascular calcification in patients with chronic kidney disease

Vascular calcifications has been associated with bone and mineral disorders. The alterations in the serum level of calcium concentrations and phosphate are importants factors implicated in the arterial calcification in chronic kidney disease. The pathogenesis of vascular calcification is a complex mechanism and not completely clear, being able to correspond to an active process of cellular transformation and heterotopic ossification. Beyond the hypercalcemia and hyperphosphatemia, they are involved in this process changes in the metabolism of inhibitors and promoters of calcification such as fetuin A, osteopontin, osteoprotegerin, and matrix gla protein. For the diagnosis of the calcified arterial injury are available several complementary methods, a method of estimate of the cardiovascular risk based on plain radiographs of the lumbar column and another method based on simple x-rays of the pelvis and hands. Below, we will present a review approching the link between vascular calcifications and mineral disorders.

Skin lesions in chronic renal dialysis

OBJECTIVE Cutaneous and mucosal disorders are the most common problems in patients on long-term hemodialysis. The dialysis prolongs the life expectancy, giving time of these changes to manifest. The aim of this study was to evaluate the prevalence of dermatologic problems among patients with chronic renal disease (CRD) undergoing hemodialysis. METHODS One hundred forty-five patients with chronic renal disease undergoing hemodialysis were studied. All patients were thoroughly examined for skin changes, hair, nails and mucous membranes by a single examiner and laboratory tests were assessed. The data were stored in a database Microsoft Excel and analyzed using descriptive statistics. The continuous variables were compared using Students t-test and categorical variables the chi-square test or Fishers Exact test. RESULTS The study included 145 patients, mean age of 53.6 ± 14.7 years, predominantly male (64.1%) and caucasian (90.0%). The average time of dialysis was 43.3 ± 42.3 months. The main underlying diseases were: hypertension in 33.8%, diabetes mellitus in 29.6% and chronic glomerulonephritis in 13.1% of the patients. The main dermatologic manifestations observed were: xerosis in 109 (75.2%), ecchymosis in 87 (60.0%), pruritus in 78 (53.8%) and lentigo in 33 (22.8%) patients. CONCLUSION Our study showed the presence of more than one alteration per patient. Cutaneous alterations are frequent in patients on dialysis. Further studies are needed to better characterization and management of these dermatosis.