Nefropatía por tóxicos: la cocaína y su potente daño renal / Toxic nephropathy: cocaine and its potent kidney damage

Resumen El consumo de sustancias ilícitas en menores de 16 años y en adultos jóvenes se incrementa cada día en Colombia, por lo cual se presentan complicaciones asociadas que sería inusual encontrar en este grupo poblacional. El presente reporte de caso muestra cómo el uso de cocaína llevó a un paciente joven a desarrollar daño renal agudo con requerimiento de terapia de reemplazo renal, lo que en los hallazgos histológicos puede corresponder a una glomerulonefritis rápidamente progresiva o a una enfermedad tubulointersticial tipo necrosis tubular aguda o nefritis intersticial aguda.

Abstract In Colombia, the consumption of illicit substances increases daily. The increase and related consumption in the population involves both young people under 16 and young adults. Therefore, there are complications associated with the consumption of these substances that otherwise, would be unusual to find in this population group. In this case report, we will review how the use of cocaine led a young patient to the development acute kidney injury requiring renal replacement therapy, which in the histological findings may correspond to rapidly progressive glomerulonephritis, or tubulointerstitial disease either acute renal tubular necrosis or acute interstitial nephritis.

Injuria renal aguda secundaria a crisis hipercalcémica: a propósito de un caso / Acute renal injury secondary to hypercalcemic crisis: a case report / Lesão ou injúria renal aguda secundária a crise hipercalcêmica: relatório de caso clínico

La injuria renal aguda es una entidad clínica compleja, caracterizada por la disminución abrupta de la función renal. La hipercalcemia como etiología de la misma es poco frecuente. Los mecanismos involucrados en su desarrollo son múltiples y poco estudiados. Se presenta el caso de un paciente varón de 59 años que desarrolló un cuadro severo de falla renal aguda como complicación de crisis hipercalcémica por un adenoma de paratiroides. Se observó alteración en los marcadores de daño y función renal. La bioquímica urinaria mostró una necrosis tubular aguda. Los niveles de calcio, parathormona y calciuria se asociaron a endocrinopatía. La ecografía, el centellograma y la biopsia paratiroidea mostraron la presencia de un adenoma. Se presentaron otras complicaciones sistémicas concomitantes como pancreatitis y complicaciones cardíacas. El tratamiento paliativo fue la hemodiálisis y el definitivo la paratiroidectomía. El síndrome de hueso hambriento se presentó como una complicación postquirúrgica. Tras el alta, la recuperación de la función renal nunca fue total. El daño renal agudo asociado a disfunción sistémica por hipercalcemia puede llevar a una recuperación parcial de la función renal. Se debe considerar el desarrollo de enfermedad renal crónica posterior a la falla renal aguda por hipercalcemia como complicación de la misma.

Acute renal injury is a complex clinical entity, characterized by the abrupt worsening in renal function. Hypercalcemia as its etiology is rare. The mechanisms involved in its development are multiple and rarely studied. The case of a 59-year-old male patient who developed a severe acute renal failure as a complication of an hypercalcemic crisis due to a parathyroid adenoma is presented here. Alterations in markers of damage and renal function were observed. Urinary biochemistry showed acute tubular necrosis. Calcium, parathormone and urine calcium levels were associated with endocrinopathy. The ultrasound, the scintigraphy and the parathyroid biopsy showed the presence of an adenoma. There were other concomitant systemic complications such as pancreatitis and cardiac complications. Hemodialysis was the palliative treatment, while the definitive treatment was parathyroidectomy. The hungry bone syndrome occurred as a postoperative complication. After discharge, recovery of renal function was never complete. Acute renal damage associated with systemic dysfunction due to hypercalcemia can lead to a partial recovery of renal function. The development of chronic kidney disease after acute renal failure due to hypercalcemia should be considered one of its complications.

A Lesão renal aguda é uma entidade clínica complexa, caracterizada pela diminuição abrupta da função renal. A hipercalcemia como etiologia da mesma não é muito frequente. Os mecanismos que participam no seu desenvolvimento são múltiplos e pouco estudados. Apresenta-se o caso de um paciente, homem, de 59 anos, que desenvolveu um quadro severo de insuficiência renal aguda como complicação de crise hipercalcêmica por um adenoma da paratireóide. Foi observada alteração nos marcadores de dano e função renal. A bioquímica urinária mostrou uma necrose tubular aguda. Os níveis de cálcio, paratormona e calciúria foram associados a endocrinopatia. A ultra-sonografia, a cintilografia, e a biópsia da paratireóide mostraram a presença de um adenoma. Apresentaram-se outras complicações sistêmicas concomitantes como pancreatite e cardíacas. O tratamento paliativo foi hemodiálise e o definitivo, a paratireoidectomia. A síndrome do osso faminto apresentou-se como uma complicação pós-operatória. Após a alta, a recuperação da função renal nunca foi total. O dano renal agudo associado à disfunção sistêmica por hipercalcemia pode levar para uma recuperação parcial da função renal. Deve ser considerado o desenvolvimento da doença renal crônica posterior à insuficiência renal aguda por hipercalcemia como complicação da mesma.

Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients / 대한소화기학회지

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC). METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups. RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI. CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.

Clinical Significance of Urinary Neutrophil Gelatinase-associated Lipocalin Levels in Defining the Various Etiologies of Acute Kidney Injury in Liver Cirrhosis Patients / 대한소화기학회지

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC).METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups.RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI.CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.

Trabajos originales en Colombia de lesión renal aguda: ¿Qué hay disponible a nivel nacional? / Original works on acute kidney injury: what is currently available in Colombia?

Introducción: la lesión renal aguda (LRA) es una entidad sindromática con múltiples etiologías cuyas estrategias de prevención y tratamiento se deben basar en los datos epidemiológicos locales. En América Latina los trabajos originales son escasos y no hay certeza del estado de la investigación sobre LRA en Colombia. Objetivo: conocer la literatura colombiana disponible sobre LRA. Metodología: se realizó la búsqueda en Embase, Medline-Cochrane Library y Lilacs por medio electrónico y físico en los índices de las revistas más representativas a nivel nacional desde 1970. Se excluyeron las relacionadas con enfermedad renal crónica, trasplante renal y enfermedad glomerular primaria. Resultados: Se identificaron 46 trabajos de investigación colombiana en LRA de los cuales 16 (34,7%) son originales, 11 (23,9%) reportes y series de casos, 10 (21,7%) revisiones de tema, 7 (15,2%) póster de congreso y 2 (4,3%) guías y consensos. De los trabajos originales, 11 (68,7%) pertenecen a pacientes en unidades de cuidado intensivo (UCI). La revista nacional con más publicaciones en el tema es Acta Colombiana de Cuidado Crítico. Conclusiones: la literatura colombiana en LRA es heterogénea, la mayoría de los trabajos originales se enfocan en el paciente crítico hospitalizado en UCI. Son escasas las publicaciones sobre epidemiología de la enfermedad y no existen datos unificados a nivel nacional.

Introduction: acute kidney injury (AKI) is a clinical syndrome encompassing various etiologies. Strategies for prevention and management of affected patients should be based on local epidemiologic data. Original works on this topic in Latin America are scarce and current status of research on AKI in Colombia is unknown. Objective: to determine the available AKI literature in Colombia. Methodology: a review of the literature from Embase, Medline-Cochrane Library and Lilacs online databases and the most representative printed local journal articles on the topic from 1970 to date. Articles related to chronic kidney disease, kidney transplantation and primary glomerular disease were excluded. Results: we identified 46 Colombian research articles on AKI of which 16 (34.7%) were original works, 11 (23.9%) were reports and case series, 10 (.21.7%) were topic reviews, 7 (15.2%) were poster presentations and 2 (4.3%) were guides and consensus protocols. Of the original works, 11 (68.7%) were on intensive care unit (ICU) patients. The highest number of articles published in Colombia on AKI was found in the Colombian Journal of Critical Care. Conclusions: Colombian AKI literature is heterogeneous and most of the original works focus on critically ill patients hospitalized at the ICU. There are few publications on the epidemiology of AKI and there is no unified data at the national level

Renal damage associated with heavy metals: review work / Daño renal asociado a metales pesados: trabajo de revisión

Abstract Catheter-associated infection is an entity with multiple complications, a condition that alters the quality of life of all patients Chronic kidney disease (CKD) represents an important health problem in the entire global population, where knowledge of the environmental factors associated with this disease is currently essential for its prevention. Several heavy metals are recognized, including Cadmium (Cd), Lead (Pb), Arsenic (As) and Mercury (Hg), which are clearly associated with renal damage and progression of CKD. Studies in animals and humans primarily demonstrate a clear association between exposure to these metals and the presence of chronic renal damage, where the pathophysiology of each of these metals is important in understanding the mechanism of renal damage. The present review aims to analyze the pathophysiology and clinical manifestations of the nephrotoxicity associated with these metals, as well as the different studies in both humans and animals that have been performed.

Resumen La enfermedad renal crónica (ERC) representa un importante problema de salud en todo el globo. Actualmente, es esencial para su prevención el conocimiento de los factores ambientales asociados con la enfermedad. Se reconocen diversos metales pesados, entre los que destacan el cadmio (Cd), plomo (Pb), arsénico (As) y mercurio (Hg), que están claramente asociados con la lesión renal y la progresión de la ERC. Estudios en animales y humanos demuestran, principalmente, una clara asociación entre la exposición a estos metales y la presencia de daño renal crónico, donde la fisiopatologia de cada uno de ellos es importante para entender el mecanismo de daño renal. La presente revisión tiene como objetivo analizar, tanto la fisiopatología y manifestaciones clínicas de la nefrotoxicidad asociada a dichos metales, como los diferentes estudios que se han realizado en humanos y animales.

Histological evaluation and E-cadherin and ß-catenin expression in kidney of dogs submitted to renal ischemia and reperfusion after chlorpromazine administration / Avaliação histológica e imunomarcação de E-caderina e ß-catenina em rins de cães submetidos a isquemia e referfusão renal após administração de clorpromazina

Renal ischemia can be associated with some urological procedures, such as renovascular surgery or kidney transplantation, that are often followed by acute renal failure. The aim of this study was to verify the E-cadherin and ß-catenin localization in canine kidney in different times of renal ischemia and reperfusion after chlorpromazine application. Twelve dogs were randomly distributed equally into two groups. GroupA with ischemia and reperfusion without chlorpromazine and groupB with ischemia and reperfusion treated by chlorpromazine. GroupB received intravenous chlorpromazine, 15 min before the artery obstruction, which lasted 1 hour. After this period, the clamps in the renal arteries were released and the organ remained in reperfusion for 2 hours. In each group, anti-E-cadherin and anti-ß-catenin antibodies were made in six tissue samples from renal parenchyma. E-cadherin and ß-catenin are differentially expressed in segments from cortex and medulla in dog's kidneys and the use of chlorpromazine did not alter the expression of both proteins. Occlusion of the left renal artery in dogs causes morphological alterations mainly in proximal convoluted tubules, beginning 30min after the start of ischemia and being aggravated after two hours of reperfusion. These results reveal that chlorpromazine did not change kidneys' histological aspect nor E-cadherin and ß-catenin expression.(AU)

A lesão renal isquêmica pode estar associada a procedimentos urológicos, tais como cirurgia renovascular, cirurgia renal extracorpórea ou transplante renal. Essa injúria, muitas vezes, é seguida de insuficiência renal aguda. O objetivo deste trabalho foi observar a localização da E-caderina e da ß-catenina em rim de cães, além de relacionar a expressão dessas proteínas das junções de aderência em diferentes tempos de isquemia e reperfusão com ou sem a aplicação de clorpromazina. Para tanto, foram utilizados 12 cães, distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A, com isquemia e reperfusão sem tratamento por clorpromazina, e o grupo B, com isquemia e reperfusão tratado por clorpromazina. No procedimento cirúrgico, foi realizada uma incisão paracostal esquerda para identificação e isolamento do rim esquerdo e da artéria renal esquerda. Após o isolamento da artéria, os animais de todos os grupos tiveram o vaso ocluído. Os animais do grupo B receberam clorpromazina via endovenosa, na dose de 5mg/kg, 15min antes da clampagem do vaso, que durou uma hora. Após este período, as artérias renais foram desobstruídas e os órgãos permaneceram em reperfusão por duas horas. Em cada grupo, foram extraídas seis amostras de parênquima renal, com utilização de agulha tru-cut, para marcação com anticorpos anti-E-caderina e anti-ß-catenina por meio de imunoistoquímica. E-caderina e ß-catenina são diferencialmente expressas em segmentos do córtex e da medula em rim de cães e o uso da clorpromazina não alterou a expressão das duas proteínas.(AU)

Diagnóstico de necrosis tubular aguda en pacientes egresados fallecidos / Diagnosis of acute tubular necrosis in deceased patients

Introducción: el diagnóstico histopatológico de necrosis tubular aguda, generalmente de causa isquémica o nefrotóxica, se encuentra muy relacionado con el desarrollo de insuficiencia renal aguda. Objetivo: analizar la presencia de diagnóstico histopatológico de necrosis tubular aguda en los egresados fallecidos autopsiados y explorar la relación con posibles factores favorecedores. Métodos: estudio retrospectivo, observacional de las autopsias en el Hospital Militar Central Dr. Luis Díaz Soto, en el período 1962 al 2015. Se estableció en ellas el diagnóstico histopatológico de necrosis tubular aguda y se analizó el comportamiento de variables demográficas, clínicas y anatomopatológicas. Resultados: se registraron 843 341 egresados, de ellos 25 213 fallecidos (índice de mortalidad 3,0), se realizaron 18 630 autopsias (índice autopsia 75,3 por ciento), en estas se estableció diagnóstico de necrosis tubular aguda en 6.264 (33,6 por ciento). Predominaron los pacientes masculinos y los mayores de 45 años de edad. El shock (22,3 por ciento), la bronconeumonía (16,3 por ciento), la aterosclerosis coronaria(18,5 por ciento) y el edema pulmonar (11,3 por ciento) constituyeron las principales causas directas de muerte. La aterosclerosis coronaria (18,5 por ciento) fue la principal causa básica de muerte. Conclusiones: se registró un incremento sostenido de egresos, de fallecidos y de autopsias practicadas, así como del diagnóstico histopatológico de necrosis tubular aguda. Predominaron los pacientes del sexo masculino y aquellos mayores de 45 años de edad. Las principales causas directas de muerte en estos fueron el shock, la bronconeumonía y el edema pulmonar. La aterosclerosis fue la principal causa básica de muerte(AU)

Introduction: The histopathological diagnosis of acute tubular necrosis, usually of ischemic or nephrotoxic cause, is closely related to the development of acute renal failure. Objective: To analyze the presence of histopathological diganosis of acute tubular necrosis in deceased autopsied and to explore the relationship with possible favoring factors. Method: Retrospective, observational study, with descriptive statistical study of the autopsies at the Central Military Hospital Dr. Luis Díaz Soto in the period from 1962 to 2015. The histopathological diagnosis of acute tubular necrosis was done and demographic, clinical and anatomopathological variables were analyzed. Results: 843 341 discharged from hospital were recorded, of which 25 213 died (mortality rate 3.0), 18 630 autopsies were performed (autopsy rate 75.3 percent). In these cases a diagnosis of acute tubular necrosis was done in 6 264 (33.6 percent). Male patients and those over 45 years of age predominated. Shock (22.3 percent), bronchopneumonia (16.3 percent), coronary atherosclerosis (18.5 percent) and pulmonary edema (11.3 percent) were the main direct causes of death. Coronary atherosclerosis (18.5 percent) was the main underlying cause of death. Conclusions: There was a sustained increase in discharged patients, deaths and autopsies, as well as the histopathological diagnosis of acute tubular necrosis. Male patients predominated and those older than 45 years of age. The main direct causes of death in these were shock, bronchopneumonia and pulmonary edema. Atherosclerosis was the leading cause of death(AU)

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Marcadores biológicos para necrose tubular aguda em pacientes com doença glomerular / Biological markers for acute tubular necrosis in patients with glomerular disease

INTRODUCTION: Acute kidney injury (AKI) is a common complication in patients with nephrotic syndrome (NS), and it is reported in 34% of adults with idiopathic nephrotic syndrome. Emergence of AKI in the course of nephrotic syndrome requires a prompt differential diagnosis between acute tubular necrosis (ATN) and proliferative glomerular lesions leading to rapidly progressive glomerulonephritis. Although clinical and conventional laboratory clues can be decisive in many cases, sometimes such distinctions rely on renal biopsy, which is an invasive procedure and is not available in many centers. Several new biomarkers have emerged, increasing the perspective on early diagnosis and the prognostic prediction of AKI. OBJECTIVES: In this work, we studied the use of tests based on the urinary concentrations of kidney injury molecule-1 (KIM-1)...

INTRODUÇÃO: A lesão renal aguda (LRA) é uma complicação frequente em pacientes com glomerulopatias, acomentendo até 34% dos adultos com síndrome nefrótica (SNO) idiopática. O diagnóstico diferencial de necrose tubular aguda (NTA) de glomeulonefrite proliferativa ou crescêntica em pacientes com SNO e LRA é fundamental, visto que a NTA pode mimetizar quadro de glomerulonefrite rapidamente progressiva. Dados clínicos e laboratoriais podem ser úteis no diagnóstico diferencial da LRA na SNO, entretanto a distinção entre NTA e glomerulonefrite proliferativa ou crescêntica é feito pela biópsia renal, procedimento invasivo e que não está disponível amplamente. Novos biomarcadores para diagnóstico precoce e preditores diagnósticos na LRA têm sido identificados. OBJETIVOS: Neste trabalho nós avaliamos o uso de testes baseados nas concentrações urinárias de kidney injury molecule-1 (KIM-1)...

Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis / 소아과

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature.

Acute tubular necrosis as a part of vancomycin induced drug rash with eosinophilia and systemic symptoms syndrome with coincident postinfectious glomerulonephritis / 소아과

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal condition characterized by skin rash, fever, eosinophilia, and multiorgan involvement. Various drugs may be associated with this syndrome including carbamazepine, allopurinol, and sulfasalazine. Renal involvement in DRESS syndrome most commonly presents as acute kidney injury due to interstitial nephritis. An 11-year-old boy was referred to the Children's Hospital of Pusan National University because of persistent fever, rash, abdominal distension, generalized edema, lymphadenopathy, and eosinophilia. He previously received vancomycin and ceftriaxone for 10 days at another hospital. He developed acute kidney injury with nephrotic range proteinuria and hypocomplementemia. A subsequent renal biopsy indicated the presence of acute tubular necrosis (ATN) and late exudative phase of postinfectious glomerulonephritis (PIGN). Systemic symptoms and renal function improved with corticosteroid therapy after the discontinuation of vancomycin. Here, we describe a biopsy-proven case of severe ATN that manifested as a part of vancomycin-induced DRESS syndrome with coincident PIGN. It is important for clinicians to be aware of this syndrome due to its severity and potentially fatal nature.

Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 +/- 18.5 years and the mean peak creatinine level was 8.2 +/- 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.

Marcadores de necrose tubular aguda e lesão inflamatória glomerular no sedimento urinária de pacientes com síndrome / Acute tubular necrosis markers and inflammatory glomerular injury urinary sediment syndrome patients

Necrose tubular aguda (NTA) é a causa mais frequente de lesão renal aguda (LRA) em pacientes hospitalizados. Em pacientes com síndrome nefrótica (SNO), a NTA mimetiza, por vezes, quadro de glomerulonefrite rapidamente progressiva e requer instituição precoce de imunossupressores. A análise do sedimento urinário é uma ferramenta não invasiva, de baixo custo e ampla disponibilidade. O achado de células epiteliais no sedimento urinário de pacientes com LRA foi associado ao diagnóstico de NTA. Entretanto, estudos em pacientes com SNO associada são escassos. Técnicas de diagnóstico utilizando sedimento urinário corado normalmente não são utilizadas nesses casos. Além do mais, o sedimento urinário é uma importante fonte de proteínas; estudos proteômicos do sedimento urinário revelaram importantes frações de proteínas não encontradas em sobrenadante, que pode ser usado como potencial biomarcador de LRA. Nosso objetivo é identificar alterações citológicas e protéicas no sedimento urinário que permitam o diagnóstico diferencial entre NTA ou lesão inflamatória-proliferativa glomerular (INF) em pacientes com SNO. Trata-se de um estudo de corte transversal, onde foram incluídos 32 pacientes: 5 pacientes normais (grupo controle), 10 com NTA, 9 sem NTA e 8 com glomerulonefrites exsudativas. As células do sedimento urinário foram contadas, citocentrifugadas, coradas em hematoxilina/eosina ou Papanicolaou e contadas diferencialmente como pequenas (<30μm de diâmetro), médias (30-48μm)...

Acute tubular necrosis (ATN) is the most frequent cause of acute kidney injury (AKI) in hospitalized patients. In patients with nephrotic syndrome (NS), acute tubular necrosis mimic, sometimes, rapidly progressive glomerulonephritis and requires premature institution of immunosuppressive treatment. The analysis of urinary sediment is a noninvasive tool, low cost and wide availability. The found of epithelial cells in the urinary sediment of patients with AKI was associated to ATN diagnosis. However, studies in patients with AKI in the set of NS are scarce. Diagnostics techniques using stained urinary sediment are not ordinarily used in these cases. Furthermore, urinary sediment is an important source of proteins; proteomic studies revealed important fractions of proteins not found in urinary supernatant that could be used as potential biomarkers for AKI. Our goal is identify cytological alterations and protein in urinary sediment which allow the differential diagnosis between ATN and inflammatory-proliferative glomerular lesion (INF) in patients with NS. This is a cross sectional study, in which 32 patients were included: 5 normal patients (control group), 10 with ATN, 9 without ATN and 8 with exudative glomerulonephritis. The cells of urinary sediment were counted, cytocentrifuged, stained of hematoxylin/eosin or Papanicolaou and differentially counted as small (<30μm of diameter), medium (30-48μm)...

Aggravation of gentamicin induced nephrotoxicity by ciprofloxacin

To evaluate histopathological changes of gentamicin induced nephrotoxicity in rabbits receiving the combination of ciprofloxacin and gentamicin compared with rabbits receiving gentamicin alone. Laboratory based Randomized controlled trial. Study was conducted in the department of Histopathology with the collaboration of the department of Pharmacology, Army Medical College Rawalpindi and National University of Sciences and Technology [NUST] Islamabad. Eighteen rabbits were used in this study. They were divided randomly into three groups. Each group contained six rabbits. Group 1 [control] was injected subcutaneously with 0.9% NaCl. The second group of animals was injected with gentamicin. The third group of animals was injected with the same dose of gentamicin and additionally ciprofloxacin. The findings were entered and analyzed with the help of histopathological [HP] score calculated by summing up the histological parameters through Microsoft excel and Graph pad Instat 3. Necrosis, congestion and inflammatory infiltrate were graded as absent, mild, moderate and severe. The score assigned was from 0 to 4 accordingly. Highest tubular necrosis grade [grade 3] and maximum inflammatory changes [moderate grade] were observed in 50% of rabbits of group 3, receiving combination of gentamicin and ciprofloxacin. p-values were significant <0.01. Combined administration of ciprofloxacin along with gentamicin in rabbits enhances adverse histopathological effects of gentamicin induced nephrotoxicity

Effects of diclofenac sodium on renal parenchyma and prevention by vitamin-E in adult albino rats

To determine the preventive role of Vitamin E on renal parenchyma after given of Diclofenac Sodium in albino rats. Experimental Study This study was conducted in the Department of Anatomy Baqai Medical University and Muhammad Medical College, Mirpurkhas from June 2011 to November 2011, For this experimental study, 30 albino rats were taken. They were divided into three groups ; A, B and C. The animals in group-A given normal saline 10 ml/kg per day. Group-B received diclofenac sodium 2 mg/kg per day and group-C receives diclofenac sodium 2mg/kg/day dissolved in distilled water with vitamin-E 2 mg/kg/day dissolved in olive oil administered half an hour before the diclofenac sodium by feeding tube per day for 2 weeks. On day 15 all animals were sacrificed with deep ether anesthesia. Their kidneys were removed, fixed in 10% formalin. Representative blocks were taken and embedded in liquid paraffin. For routine histological examination 5 micro m thick section cut by microtome and stained with H and E, PAS and silver methenamine. Renal histology was done under light microscope to see the proximal and distal tubular diameter and count. No significant [P>0.05] changes were observed in the histopathology of kidney tissues of the groups A and C rats. The group B significantly [P<0.001] affected the histopathology of kidney. It may be concluded that diclofenac sodium produces changes in kidney, which may be attributed to ischaemia induced by inhibition of prostaglandin synthesis resulting in tubular necrosis in albino rats simultaneous administration of vitamin-E partially protect the morphological and histological changes induced by diclofenac sodium

Bone marrow cells contribute to tubular epithelium regeneration following acute kidney injury induced by mercuric chloride.

Background & objectives: Acute tubular necrosis (ATN) caused by renal ischaemia, renal hypo-perfusion, or nephrotoxic substances is the most common form of acute kidney injury (AKI). There are a few treatment options for this life-threatening disease and the mortality rate exceeds 50 per cent. In critical cases of AKI the only option is renal transplantation. In the present study we evaluated whether bone marrow cells (BMCs) are involved in regeneration of kidney tubules following acute tubular necrosis in the mouse. Methods: Six to eight week old C57BL6/J and congenic enhanced green fluorescence protein (eGFP) mice were used. The relative contributions of eGFP-expressing BMCs were compared in two different approaches to kidney regeneration in the mercuric chloride (HgCl2)-induced mouse model of AKI: induced engraftment and forced engraftment. In vitro differentiation of lineage-depleted (Lin-) BMCs into renal epithelial cells was also studied. Results: In the forced engraftment approach, BMCs were found to play a role in the regeneration of tubules of renal cortex and outer medulla regions. About 70 per cent of donor-derived cells expressed megalin. In vitro culture revealed that Lin- BMCs differentiated into megalin, E-cadherin and cytokeratin-19 (CK-19) expressing renal epithelial cells. Interpretation & conclusions: The present results demonstrate that Lin- BMCs may contribute in the regeneration of renal tubular epithelium of HgCl2-induced AKI. This study may also suggest a potential role of BMCs in treating AKI.

Lesões do sistema urinário em 1.063 cães / Lesions of the urinary system in 1.063 dogs

Com o objetivo de realizar um estudo abrangente das lesões do sistema urinário em cães e determinar a sua prevalência, epidemiologia, importância clínica e possíveis causas associadas, foram revisados os protocolos de necropsias de cães realizadas no período de janeiro de 1999 a dezembro de 2010 no LPV-UFSM. Nesse período foram necropsiados 3.189 cães e destes, cerca de 30% apresentaram lesões no sistema urinário. Na maioria dos cães (79,1%) foram observadas lesões únicas e em aproximadamente 21% havia lesões múltiplas no sistema urinário, totalizando 1.373 lesões. Destas, 1.014 (73,8%) foram observadas no rim. No trato urinário inferior (TUI) foram diagnosticadas 359 (26,2%) lesões. Um terço das lesões no sistema urinário dos cães necropsiados foram causa de morte espontânea ou razão para eutanásia (ME/EUT). As demais foram consideradas como achados incidentais. As principais lesões renais diagnosticadas, em ordem decrescente de prevalência, foram: nefrite túbulo-intersticial, infarto, nefrite granulomatosa (parasitária), glomerulonefrite, neoplasmas metastáticos/multicêntricos, pielonefrite/ pielite e hidronefrose. As principais lesões do TUI diagnosticadas, em ordem decrescente de prevalência, foram: cistite, presença de inclusões virais (morbilivírus), urolitíase, dilatação da bexiga, ruptura de bexiga (com uroperitônio) e neoplasmas metastáticos/multicêntricos. As características epidemiológicas como sexo, raça e idade dos cães afetados tiveram variações expressivas de acordo com o tipo de lesão diagnosticada. Uremia foi observada em um número significativo de casos de ME/EUT e foi principalmente secundária a lesões renais.

The aim of this study was to determine the prevalence, epidemiology, clinical significance, and possible associated causes of the urinary system lesions in dogs necropsied between January 1999 and December 2010 at the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria (LPV-UFSM). To accomplish this, the necropsy reports were analyzed retrospectively. In this time frame, 3,189 dogs were necropsied and about 30% had lesions in the urinary system. In most of the dogs (79.1%), lesions were single and in about 21% they were multiple, totalizing 1,373 lesions. Out of them, 1,014 (73.8%) were observed in the kidney and 359 (26.2%) were in the lower urinary tract (LUT). One third of the lesions in the urinary system were causes of spontaneous death or reason for euthanasia (SD/EUTH) of the affected dogs. The other two third of the lesions were considered incidental findings. The main renal lesions diagnosed, in descending order of prevalence, were: tubulointerstitial nephritis, infarct, granulomatous nephritis (parasitary), glomerulonephritis, metastatic/multicentric neoplasms, pyelonephritis/pyelitis, and hydronephrosis. The main LUT lesions, in descending order of prevalence, were: cystitis, presence of viral inclusions bodies (morbillivirus), urolithiasis, urinary bladder dilatation, urinary bladder rupture (with uroperitoneum), and metastatic/multicentric neoplasms. Epidemiological aspects such as gender, breed, and age of affected dogs had expressive variations according to the type of lesion diagnosed. Uremia was observed in a significant number of cases of SD/EUTH and was mostly due to renal lesions.

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg percent] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg percent], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

A Case of Severe Acute Kidney Injury by Near-Drowning

Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near-drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr-old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis.