Chronic interstitial nephritis of nontraditional causes in Salvadoran agricultural communities.

In El Salvador, a form of chronic kidney disease (CKD) of nontraditional causes (CKDnt) affecting farmers is being reported. Its behavior has been epidemic and is responsible for tens of thousands of deaths. This article summarizes the results obtained from a series of studies conducted to identify the epidemiology and clinical behavior of this disease, proposing a case definition and an etiopathogenic hypothesis. Methods included a survey of CKD in agricultural communities studying 2,388 people ≥ 18 years and 1,755 < 18, a descriptive clinical study followed by histopathological assessment conducted in 46 possible cases of CKDnt ≥ 18 years, and a national survey to study the prevalence of CKD and associated risk factors in 4,817 participants ≥ 20 years followed by a nested case-control study. In the agricultural communities, the prevalence of CKD in adults was 18% (men: 23.9%, women: 13.9%), 26.8% in agricultural workers (non-agricultural 13.8%), CKDnt accounted for 51.9% of cases. CKD in the population < 18 years was 3.9% (mean estimated glomerular filtration rate > 160 mL/1.73m2). The national CKD prevalence was 12.6% (urban: 11.3%; rural: 14.4%; males: 17.8%, females 8.5%), and CKDnt was only 3.8%; with associations between CKD and exposure to agrochemicals. The clinical study revealed the presence of markers of kidney damage (A3 albuminuria: 80.4%; ß2-microglobulin: 78.2%), urine electrolyte anomalies (100% hypermagnesuria, 45.7% hypernatriuria, 43.5% osmotic polyuria), abnormal osteotendinous reflexes (45.7%), sensorineural hearing loss (56.5%), and damage of the tibial arteries by Doppler imaging (66.7%). Biopsies revealed a chronic tubulointerstitial nephropathy. The etiopathogenesis of CKDnt is possibly multifactorial, including environmental contamination by agrochemicals, heat stress, and dehydration.

Chronic kidney disease mortality trends in selected Central America countries, 1997-2013: clues to an epidemic of chronic interstitial nephritis of agricultural communities.

BACKGROUND: In Central America, chronic interstitial nephritis of agricultural communities (CINAC) has reached epidemic proportions. Clusters of cases have been described in several farming communities. Its aetiology remains uncertain and a controversy exists on its key triggers, among them the heat stress-dehydration mechanism and the toxic exposure to agrochemicals. METHODS: This study analysed the mortality pattern and trend of chronic kidney disease code N18 (CKD-N18) according to the International Statistical Classification of Diseases and Related Health Problems-10th Revision, the proxy and the underlying cause of death, in four selected Central American countries from 1997 to 2013. In addition, we used exponential regression to retrospectively model the likely onset and prior trajectory of the epidemic. RESULTS: Between 1997 and 2013, CKD-N18 mortality accounting 47 885 deaths (31% were female), 19 533 of which occurred below 60 years of age (26% female). The excess of mortality starts as early as 10-14 years of age for both boys and girls. El Salvador and Nicaragua, with mortality rates between 9-fold and 12-fold higher than reference countries, were the most affected. Statistical modelling suggests that the epidemic commenced around the mid-1970s, coinciding with important changes in modes of agricultural production. CONCLUSIONS: This study provides the most comprehensive mortality analysis of this epidemic published to date and confirms an excess of CKD-N18 mortality and its relation with the epidemic of CINAC. The overall trends and the mortality pattern among women, children and adolescents suggest that the heat stress-dehydration hypothesis cannot fully explain this epidemic and that other environmental factors, more likely agricultural practices and agrochemicals, may be causally involved.

Biopsy-proven renal involvement and prognosis in 13 hispanic patients with primary Sjögren syndrome. / Afección renal confirmada mediante biopsia y pronóstico en 13 pacientes hispanos con síndrome de Sjögren primario.

BACKGROUND: The aim of this study was to describe a case series of 13 Hispanic patients with primary Sjögren syndrome (pSS) and biopsy-proven renal involvement. METHODS: We describe the clinical, serological and histological characteristics as well as the prognosis in a group of patients with pSS and biopsy-proven renal involvement, treated in 2 referral nephrology units in Mexico City. RESULTS: Thirteen patients with pSS underwent kidney biopsy (KB) over a period of 27 years. The median duration from pSS diagnosis to KB was 13.9 months. Seven patients (54%) had glomerulonephritis and 6 patients (46%) had tubulointerstitial nephritis. All patients were treated with corticosteroids and/or immunosuppressants. Eight patients (62%) remained stable or their renal function improved after a median follow-up of 12 months. CONCLUSIONS: This case series reflects the broad spectrum of renal involvement in pSS. We observed that in our Hispanic population, glomerular involvement was the most frequent abnormality, mainly membranous glomerulopathy, followed by tubulointerstitial disease. Tubular atrophy and interstitial fibrosis were also common biopsy findings. Treatment with corticosteroids or other immunosuppressive agents appear to slow renal disease progression.

Granulomatous intersticial nephritis secondary to sarcoidosis / Nefrite intersticial granulomatose secundária a sarcoidose

ABSTRACT Introduction: Granulomatous interstitial nephritis is a rare condition, in which renal involvement is uncommon. Its etiology is variable, and may be medicinal, infectious or inflammatory origin. Case report: This is a 65-year-old male patient with renal lesions of unknown etiology, associated with hypercalcaemia. During the investigation, cardiac insufficiency with diastolic dysfunction and interstitial lung involvement on chest tomography were evidenced. Renal function (glomerular filtration rate) has partially improved with clinical measures. Renal biopsy was performed, which showed moderate interstitial lesion with tuberculoid granulomas without caseous necrosis. Conclusion: The objective of the article was to describe a case of NIG and to alert to the importance of its clinical investigation. In this case, renal biopsy, associated with systemic clinical manifestations, contributed to the diagnosis of sarcoidosis.

RESUMO Introdução: a nefrite intersticial granulomatosa é uma condição rara, na qual o envolvimento renal é incomum. Sua etiologia é variável e pode ter origem medicinal, infecciosa ou inflamatória. Relato de caso: trata-se de um paciente do sexo masculino, com 65 anos de idade, com lesões renais de etiologia desconhecida, associadas à hipercalcemia. Durante a investigação, evidenciaram-se insuficiência cardíaca com disfunção diastólica e envolvimento pulmonar intersticial à tomografia torácica. A função renal (taxa de filtração glomerular) melhorou parcialmente com medidas clínicas. Foi realizada biópsia renal, que apresentou lesão intersticial moderada com granulomas tuberculoides sem necrose caseosa. Conclusão: o objetivo do artigo foi descrever um caso de GIN e alertar para a importância de sua investigação clínica. Neste caso, a biópsia renal, associada a manifestações clínicas sistêmicas, contribuiu para o diagnóstico de sarcoidose.

Granulomatous intersticial nephritis secondary to sarcoidosis.

INTRODUCTION: Granulomatous interstitial nephritis is a rare condition, in which renal involvement is uncommon. Its etiology is variable, and may be medicinal, infectious or inflammatory origin. CASE REPORT: This is a 65-year-old male patient with renal lesions of unknown etiology, associated with hypercalcaemia. During the investigation, cardiac insufficiency with diastolic dysfunction and interstitial lung involvement on chest tomography were evidenced. Renal function (glomerular filtration rate) has partially improved with clinical measures. Renal biopsy was performed, which showed moderate interstitial lesion with tuberculoid granulomas without caseous necrosis. CONCLUSION: The objective of the article was to describe a case of NIG and to alert to the importance of its clinical investigation. In this case, renal biopsy, associated with systemic clinical manifestations, contributed to the diagnosis of sarcoidosis.

Mesoamerican nephropathy: a neglected tropical disease with an infectious etiology?

An outbreak of unexplained and severe kidney disease, "Mesoamerican Nephropathy," in mostly young, male sugar cane workers emerged in Central America in the late 1990's. As a result, an estimated 20,000 individuals have died, to date. Unfortunately, and with great consequence to human life, the etiology of the outbreak has yet to be identified. The sugarcane fields in Chichigalpa, Chinandega, Nicaragua, have been involved in the outbreak, and during our initial investigation, we interviewed case patients who experienced fever, nausea and vomiting, arthralgia, myalgia, headache, neck and back pain, weakness, and paresthesia at the onset of acute kidney disease. We also observed a heavy infestation of rodents, particularly of Sigmodon species, in the sugarcane fields. We hypothesize that infectious pathogens are being shed through the urine and feces of these rodents, and workers are exposed to these pathogens during the process of cultivating and harvesting sugarcane. In this paper, we will discuss the epidemic in the Chichigalpa area, potential pathogens responsible for Mesoamerican Nephropathy, and steps needed in order to diagnose, treat, and prevent future cases from occurring.

NF-κB activation mediates crystal translocation and interstitial inflammation in adenine overload nephropathy.

Adenine overload promotes intratubular crystal precipitation and interstitial nephritis. We showed recently that these abnormalities are strongly attenuated in mice knockout for Toll-like receptors-2, -4, MyD88, ASC, or caspase-1. We now investigated whether NF-κB activation also plays a pathogenic role in this model. Adult male Munich-Wistar rats were distributed among three groups: C (n = 17), receiving standard chow; ADE (n = 17), given adenine in the chow at 0.7% for 1 wk and 0.5% for 2 wk; and ADE + pyrrolidine dithiocarbamate (PDTC; n = 14), receiving adenine as above and the NF-κB inhibitor PDTC (120 mg·kg⁻¹·day⁻¹ in the drinking water). After 3 wk, widespread crystal deposition was seen in tubular lumina and in the renal interstitium, along with granuloma formation, collagen accumulation, intense tubulointerstitial proliferation, and increased interstitial expression of inflammatory mediators. Part of the crystals were segregated from tubular lumina by a newly formed cell layer and, at more advanced stages, appeared to be extruded to the interstitium. p65 nuclear translocation and IKK-α increased abundance indicated activation of the NF-κB system. PDTC treatment prevented p65 migration and normalized IKK-α, limited crystal shift to the interstitium, and strongly attenuated interstitial fibrosis/inflammation. These findings indicate that the complex inflammatory phenomena associated with this model depend, at least in part, on NF-κB activation, and suggest that the NF-κB system may become a therapeutic target in the treatment of chronic kidney disease.

Renal manifestations in HIV-infected Jamaican children / Manifestaciones renales en niños jamaicanos infectados por el VIH

BACKGROUND: Documentation regarding the renal complications of paediatric HIV infection from developing countries is scarce. In the era prior to highly active antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD) and death within a few months of diagnosis. With increased public access to antiretroviral therapy since 2002 and subsequent survival, renal complications are increasingly recognized among the surviving cohort of infected children. METHODS: A cohort of 196 HIV-infected children was followed in four multicentre ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinical presentations and natural history of those patients who developed renal complications. RESULTS: Urinary tract infections were the most common diagnosis, occurring in 16.8% of patients, with a high recurrence rate and the most common organism was Escherichia coli. Four of seven patients who started indinavir developed complications of nephrolithiasis and tubulointerstitial nephropathy. Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male. Median age at diagnosis was five years; all presented with advanced HIV disease, nephrotic syndrome or nephrotic range proteinuria and three with chronic renal failure. Patients received standard medical management and were initiated on angiotensin-converting enzyme (ACE) inhibitors and HAART. While the mortality ratio was 50%, only one death was associated with HIVAN and the median survival time was 3.1 years. CONCLUSIONS: HIV-infected children present with a variety of renal complications. With improved survival since the introduction of HAART, the incidence of HIVAN is expected to increase among this maturing paediatric cohort. Early detection and treatment will optimize the outcomes for these children.

ANTECEDENTES: La documentación en relación con las complicaciones renales de la infección pediátrica por VIH en países en vías de desarrollo, es escasa. En la era de la terapia antiretroviral pre-altamente activa (TARAA), los niños infectados por VIH en Jamaica que desarrollaron nefropatía asociada con VIH evolucionaron hacia la enfermedad renal en fase terminal (ERFT) y la muerte dentro de pocos meses de hecho el diagnóstico. Con el aumento del acceso público a la terapia antiretroviral a partir de 2002 y la subsiguiente supervivencia, cada vez más las complicaciones renales se observan entre la cohorte sobreviviente de niños infectados. MÉTODOS: A una cohorte de 196 niños infectados con VIH, se le practicó un seguimiento en cuatro clínicas ambulatorios multicentros, desde septiembre 1 de 2002 hasta agosto 31 de 2005, como parte del Programa VIH/SIDA Prenatal y Pediátrico de Kingston, Jamaica. El trabajo describe las presentaciones clínicas y la historia natural de los pacientes que desarrollaron complicaciones renales. RESULTADOS: Las infecciones de las vías urinarias fueron el diagnóstico más común en 16.8% de los pacientes, acompañadas de una alta tasa de recurrencia, y el organismo más común fue el Escherichia coli. Cuatro de siete pacientes que comenzaron tratamiento con indinair, desarrollaron complicaciones de nefrolitiasis y nefropatía tubulointersticial. Seis pacientes (3%), cinco de ellos varones, satisfacían los criterios de NAVIH. La edad promedio al momento del diagnóstico fue de cinco años. Todos representaron con la enfermedad de VIH avanzada, síndrome nefrótico o proteniuria de rango nefrótico, y tres con fallo renal crónico. Los pacientes recibieron tratamiento médico estándar y se iniciaron en el uso de inhibidores de enzimas convertidoras de angiotensina (IECAs) y el TARAA. Si bien la proporción de la mortalidad fue 50%, sólo una muerte estuvo asociada con NAVIH y el tiempo medio de supervivencia fue 3.1 años. CONCLUSIONES: Los niños infectados con VIH se presentaron con una variedad de complicaciones renales. Con el mejoramiento de la supervivencia a partir de la introducción del TARAA, se espera que la incidencia de NAVIH aumente entre la cohorte pediátrica en maduración. La detección precoz y el tratamiento temprano optimizarán los resultados obtenidos con estos niños.

The kidney in leptospirosis.

Leptospirosis is a worldwide zoonosis. Typically, patients are young men, although children can be affected. In children, this disease causes mainly alterations of sensorium. Acute renal failure and jaundice (Weil's syndrome) are less common in children than in adults. The main renal histological findings are acute interstitial nephritis and acute tubular necrosis. Acute renal failure is characterized by hypokalemia and nonoliguria. Many factors are involved in its physiopathology: hypotension, hypovolemia, rhabdomyolysis, hyperbilirubinemia, and, primarily, the direct action of leptospiral proteins. Antibiotic administration (especially early administration) reduces length of hospitalization and leptospiruria. For children, even late antibiotic treatment has been shown to reduce the extent of acute renal failure and thrombocytopenia. Although the best method of dialysis is not yet established, early and intensive dialysis can decrease mortality. Mortality in patients with acute renal failure is approximately 15-20% in association with the presence of oliguria, higher levels of creatinine, and older age. Functional recovery is fast and complete; however, abnormal urinary concentration can persist.

An experimental study of tissue reaction to polymethyl methacrylate (PMMA) microspheres (Artecoll) and dimethylsiloxane (DMS) in the mouse.

Various methods are available for the treatment of scars, wrinkles, and other cutaneous defects, and the material used must be as biocompatible as possible. This study analyzes the biological behavior of polymethyl methacrylate/bovine collagen (Artecoll) and of polydimethylsiloxane (DMS), using a histopathological study in mice. A prospective study was performed using 40 mice for each substance: polymethyl methacrylate/bovine collagen or polydimethylsiloxane was injected into the right ear, the left ear being used as a control. Histopathological analyses of the right ear, liver, and kidney were performed at intervals during the study and revealed the development of an intense granulomatous reaction of the foreign body type in the right ear, periportal and intralobular infiltrates in the liver, and interstitial nephritis and chronic pyelonephritis in the kidney for polymethyl methacrylate/bovine collagen. A variable reaction with less intense fibrosis and a reduced foreign body reaction were seen in the mice injected with polydimethylsiloxane.

Renal manifestations in HIV-infected Jamaican children.

BACKGROUND: Documentation regarding the renal complications of paediatric HIV infection from developing countries is scarce. In the era prior to highly active antiretroviral therapy (HAART), HIV-infected children in Jamaica who developed HIV-associated nephropathy (HIVAN) progressed to end stage renal disease (ESRD) and death within a few months of diagnosis. With increased public access to antiretroviral therapy since 2002 and subsequent survival, renal complications are increasingly recognized among the surviving cohort of infected children. METHODS: A cohort of 196 HIV-infected children was followed in four multicentre ambulatory clinics from September 1, 2002 to August 31, 2005 as part of the Kingston Paediatric and Perinatal HIV/AIDS Programme, Jamaica. We describe the clinical presentations and natural history of those patients who developed renal complications. RESULTS: Urinary tract infections were the most common diagnosis, occurring in 16.8% of patients, with a high recurrence rate and the most common organism was Escherichia coli. Four of seven patients who started indinavir developed complications of nephrolithiasis and tubulointerstitial nephropathy. Six patients (3%) fulfilled the criteria for HIVAN, five of whom were male. Median age at diagnosis was five years; all presented with advanced HIV disease, nephrotic syndrome or nephrotic range proteinuria and three with chronic renal failure. Patients received standard medical management and were initiated on angiotensin-converting enzyme (ACE) inhibitors and HAART While the mortality ratio was 50%, only one death was associated with HIVAN and the median survival time was 3.1 years. CONCLUSIONS: HIV-infected children present with a variety of renal complications. With improved survival since the introduction of HAART, the incidence of HIVAN is expected to increase among this maturing paediatric cohort. Early detection and treatment will optimize the outcomes for these children.

Aplicação dos modelos experimentais de camundongos transgênicos e ratos no estudo da interação leptospira-hospedeiro / Application of experimental models of transgenic mice and rats in the study of Leptospira-host interaction

A leptospirose é uma zoonose de importância global. Em nosso meio, a doença associa-se às condições de saneamento precário e pobreza. Sua patogenia permanece pouco compreendida sendo ainda necessário o desenvolvimento de modelos experimentais que esclareçam os mecanismos de disseminação e colonização da leptospira nos tecidos do hospedeiro, bem como a avaliação de determinantes da susceptibilidade e resistência do hospedeiro à doença. Diversos modelos experimentais já foram utilizados no estudo da leptospirose e, especificamente, dois deles foram pouco explorados, incluindo o modelo do rato (Rattus norvegicus), principal hospedeiro de leptospiras patogênicas e protótipo de resistência à doença aguda letal, e o modelo murino, que oferece a vantagem de amplas possibilidades para estudos genéticos e imunológicos. Foi estabelecido o modelo de colonização, avaliação das lesões associadas a este processo e tempo de persistência das leptospiras nos rins. O modelo de ratos foi utilizado para o estudo da cinética de disseminação de leptospiras do primeiro até o nono dia da infecção experimental. Além disso, foram realizados estudos comparativos das lesões renais observadas em ratos de laboratório com aquelãs presentes em ratos da mesma espécie capturados em Salvador, com e sem evidência microbiológica de infecção. Foi avaliado ainda o papel de citocinas através da infecção experimental de camundongos selvagens e com deficiências genéticas específicas. Os animais transgênicos usados foram da linhagem C57BL6, deficientes para os genes do receptor Rp55 do fator de necrose tumoral alfa (TNFRKO) ou do interferon gama (IFNKO), e BALB/c deficientes para o gene da interleucina 4. Os resultados comprovam a reprodutibilidade da infecção renal persistente e resistência de ratos à doença aguda letal. A disseminação é ampla nos tecidos até o quinto dia da infecção sendo seguida por persistência seletiva nos rins, semelhante ao que é descrito em outros modelos de animais susceptíveis à leptospirose. Uma neftite intersticial discreta é o único achado que pode ser atribuível à infecção por leptospiras, visto que é a única reprodutível experimentalmente. A deficiência específica dos genes estudados tem pouco efeito sobre o curso da infecção experimental em camundongos. A maior gravidade da nefrite intersticial nos animais C57BL6 TNFRKO sugere que esta é uma lesão residual provavelmente secundária ao menor controle da disseminação precoce de leptospiras na ausência desta via da imunidade inata. A linhagem C57BL6 apresenta alterações inflamatórias renais com maior freqüência do que a BALB/c. Isto indica que camundongos C57BL6 devem ser priorizados em estudos genéticos na leptospirose experimental por permitir um segundo desfecho a ser avaliado, além da sobrevida.

Experimental model for the study of chronic renal ischemia in rats: morphologic, histological and ultra-structural analysis.

PURPOSE: To evaluate a model of chronic renal ischemia in rats and to characterize the effects on renal tissue. METHODS: 168 Wistar rats were divided into two equal groups, control (GC) and ischemia (GI). The animals of the GI (n=84) were submitted to partial ligation of the left renal artery, and the animals of GC (n=84) stayed with the renal artery intact. In seven successive and identical periods of time, in weekly intervals, 12 animals of each group were submitted to nephrectomy, with morphometric determinations and histological and ultra-structural analysis. RESULTS: The GI presented progressive reduction in renal weight, volume and cortical thickness observed from the 7th day of the experiment, reaching maximum degree in the 49th day (p < 0.05). The proximal tubular atrophy in the GI was observed in 75/84 analysis (89,2%), with highly significant difference among the groups starting from the 7th day (p=0 .0009) and in the other periods of the experiment (p=0 .00001). The most prevalent interstitial alteration was the infiltrate, present in 98,8% of the GI, with highly significant difference among the groups in the whole experiment (p=0 .00001). Ultra-structural analysis didn't demonstrate glomerular lesions, evidencing that the glomerule preserves its intact architecture during chronic ischemia. CONCLUSION: The model showed that chronic renal ischemia in rats provokes progressive renal atrophy, with preservation of glomerular structure.

Experimental model for the study of chronic renal ischemia in rats: morphologic, histological and ultra-structural analysis

PURPOSE: To evaluate a model of chronic renal ischemia in rats and to characterize the effects on renal tissue. METHODS: 168 Wistar rats were divided into two equal groups, control (GC) and ischemia (GI). The animals of the GI (n=84) were submitted to partial ligation of the left renal artery, and the animals of GC (n=84) stayed with the renal artery intact. In seven successive and identical periods of time, in weekly intervals, 12 animals of each group were submitted to nephrectomy, with morphometric determinations and histological and ultra-structural analysis. RESULTS: The GI presented progressive reduction in renal weight, volume and cortical thickness observed from the 7th day of the experiment, reaching maximum degree in the 49th day (p < 0.05). The proximal tubular atrophy in the GI was observed in 75/84 analysis (89,2 percent), with highly significant difference among the groups starting from the 7th day (p=0 .0009) and in the other periods of the experiment (p=0 .00001). The most prevalent interstitial alteration was the infiltrate, present in 98,8 percent of the GI, with highly significant difference among the groups in the whole experiment (p=0 .00001). Ultra-structural analysis didn't demonstrate glomerular lesions, evidencing that the glomerule preserves its intact architecture during chronic ischemia. CONCLUSION: The model showed that chronic renal ischemia in rats provokes progressive renal atrophy, with preservation of glomerular structure.

OBJETIVO: Avaliar um modelo de isquemia renal crônica em ratos e caracterizar os efeitos no tecido renal. MÉTODOS: Utilizaram-se 168 ratos Wistar divididos em dois grupos iguais, controle (GC) e isquemia (GI). Os animais do GI (n=84) foram submetidos à ligadura parcial da artéria renal esquerda, e os animais do GC (n=84) permaneceram com a artéria renal intacta. Em sete períodos de tempo sucessivos e iguais, em intervalos semanais, 12 animais de cada grupo foram submetidos à nefrectomia, com determinações morfométricas e análises histológica e ultra-estrutural. RESULTADOS: O GI apresentou redução progressiva no peso, volume e espessura cortical renal a partir do 7° dia do experimento, atingindo grau máximo no 49° dia (p < 0.05). A atrofia tubular proximal no GI ocorreu em 75/84 análises (89,2 por cento), com diferença altamente significativa entre os dois grupos a partir do 7° dia (p=0.0009) e nos demais períodos do experimento (p=0.00001). A alteração intersticial mais comum no GI foi o infiltrado, presente em 98,8 por cento, com diferença altamente significativa entre os dois grupos (p=0.00001). A análise ultra-estrutural não demonstrou lesões glomerulares, evidenciando que os glomérulos preservam sua arquitetura intacta durante a isquemia crônica. CONCLUSÃO: O modelo mostrou que a isquemia renal crônica em ratos provoca atrofia renal progressiva, com preservação da estrutura glomerular.

Experimental model for the study of chronic renal ischemia in rats: morphologic, histological and ultra-structural analysis / Modelo experimental para o estudo da isquemia renal crônica em ratos. Análises morfológica, histológica e ultra-estrutural

PURPOSE: To evaluate a model of chronic renal ischemia in rats and to characterize the effects on renal tissue. METHODS: 168 Wistar rats were divided into two equal groups, control (GC) and ischemia (GI). The animals of the GI (n=84) were submitted to partial ligation of the left renal artery, and the animals of GC (n=84) stayed with the renal artery intact. In seven successive and identical periods of time, in weekly intervals, 12 animals of each group were submitted to nephrectomy, with morphometric determinations and histological and ultra-structural analysis. RESULTS: The GI presented progressive reduction in renal weight, volume and cortical thickness observed from the 7th day of the experiment, reaching maximum degree in the 49th day (p < 0.05). The proximal tubular atrophy in the GI was observed in 75/84 analysis (89,2 percent), with highly significant difference among the groups starting from the 7th day (p=0 .0009) and in the other periods of the experiment (p=0 .00001). The most prevalent interstitial alteration was the infiltrate, present in 98,8 percent of the GI, with highly significant difference among the groups in the whole experiment (p=0 .00001). Ultra-structural analysis didn't demonstrate glomerular lesions, evidencing that the glomerule preserves its intact architecture during chronic ischemia. CONCLUSION: The model showed that chronic renal ischemia in rats provokes progressive renal atrophy, with preservation of glomerular structure.(AU)

OBJETIVO: Avaliar um modelo de isquemia renal crônica em ratos e caracterizar os efeitos no tecido renal. MÉTODOS: Utilizaram-se 168 ratos Wistar divididos em dois grupos iguais, controle (GC) e isquemia (GI). Os animais do GI (n=84) foram submetidos à ligadura parcial da artéria renal esquerda, e os animais do GC (n=84) permaneceram com a artéria renal intacta. Em sete períodos de tempo sucessivos e iguais, em intervalos semanais, 12 animais de cada grupo foram submetidos à nefrectomia, com determinações morfométricas e análises histológica e ultra-estrutural. RESULTADOS: O GI apresentou redução progressiva no peso, volume e espessura cortical renal a partir do 7º dia do experimento, atingindo grau máximo no 49º dia (p < 0.05). A atrofia tubular proximal no GI ocorreu em 75/84 análises (89,2 por cento), com diferença altamente significativa entre os dois grupos a partir do 7º dia (p=0.0009) e nos demais períodos do experimento (p=0.00001). A alteração intersticial mais comum no GI foi o infiltrado, presente em 98,8 por cento, com diferença altamente significativa entre os dois grupos (p=0.00001). A análise ultra-estrutural não demonstrou lesões glomerulares, evidenciando que os glomérulos preservam sua arquitetura intacta durante a isquemia crônica. CONCLUSÃO: O modelo mostrou que a isquemia renal crônica em ratos provoca atrofia renal progressiva, com preservação da estrutura glomerular.(AU)

Pathology of renal diseases in the tropics

Renal diseases unique to the tropics are those that occur in association with infectious diseases including dengue hemorrhagic fever, typhoid fever, shigellosis, leptospirosis, lepromatous leprosy, malaria, opisthorchiasis, and schistosomiasis. These renal complications can be classified on the basis of their clinical and pathologic characteristics into acute transient reversible glomerulonephritis, chronic progressive irreversible glomerulonephritis, amyloidosis, and acute renal failure (ARF) resulting from acute tubular necrosis, acute tubulointerstitial nephritis, and thrombotic microangiopathy. Certain primary glomerular diseases including immunoglobulin (Ig) M nephropathy and focal segmental and global glomerulosclerosis are prevalent in some tropical countries. Renal complications of venomous snakebites also are common in the tropics. This article discusses and summarizes important works in the literature in respect to the clinical syndromes, pathologic features, and pathogenesis of tropical renal diseases both in humans and experimental animal models.

Late-onset cytomegalovirus-associated interstitial nephritis in a kidney transplant.

Cytomegalovirus is the most important viral infection in kidney transplants, but rarely affects the allograft after the sixth month posttransplantation. We present a patient who developed renal failure eighteen months posttransplant; a kidney biopsy showed cytomegalovirus inclusions, acute tubular necrosis and mild interstitial nephritis. After intravenous ganciclovir, renal function transiently improved. Cytomegalovirus pp65 antigen was weekly reported as negative. One month later another biopsy was performed due to renal failure. The findings were consistent with tubular atrophy and severe interstitial nephritis. No cytomegalovirus cellular inclusions were found on histology, including immunohistochemical and polymerase chain reaction studies; pp65 antigen studies were persistently negative. Despite an attempt to recover renal function with steroid therapy, the patient restarted hemodialysis 20 months posttransplantation. This report suggests that cytomegalovirus should be considered as a late cause of kidney failure even in the absence of infection-related symptoms. The irreversible allograft damage can be caused despite the successful eradication of the virus with intravenous ganciclovir.

Protective role of enalapril for chronic tubulointerstitial lesions of hyperoxaluria.

PURPOSE: Hyperoxaluria is a recognized cause of tubulointerstitial lesions and it may contribute to chronic renal failure. In previous studies we demonstrated that enalapril was effective against the progression of tubulointerstitial lesions in a 4-week hyperoxaluria rat model. We evaluated whether the action of enalapril on the tubulointerstitial lesions produced by hyperoxaluria persisted for a long period. MATERIALS AND METHODS: Two-month-old male Sprague-Dawley rats were divided into 4 groups of 12 each, including 1--control animals given tap water, 2--animals with hyperoxaluria, 3--animals with hyperoxaluria plus enalapril, 4--animals with enalapril. Hyperoxaluria in groups 2 and 3 rats was induced by administering 1% ethylene glycol, a precursor for oxalates, in the tap water continuously throughout the whole study. Meanwhile, groups 3 and 4 received 20 mg./l. enalapril in the drinking water. At the end of the study renal tubulointerstitial lesions were evaluated by immunostaining using monoclonal antibodies against macrophage infiltrates (ED1), tubulointerstitial alpha-smooth muscle actin and transforming growth factor-beta1. The lesions were quantified by semiquantitative scores. Creatinine clearance and urinary albumin excretion were also determined. RESULTS: There was no difference in urine oxalate excretion in groups 2 and 3. Group 3 rats treated with enalapril showed fewer tubulointerstitial lesions than nontreated group 2 rats, as indicated by the mean scores plus or minus standard error of mean for inflammatory infiltrate (2.16 +/- 0.2 versus 0.83 +/- 0.16), tubular atrophy (2 +/- 0.27 versus 0.66 +/- 0.14), interstitial fibrosis (2.5 +/- 0.15 versus 0.5 +/- 0.1), glomerular ED1 (1.75 +/- 0.25 versus 0.16 +/- 0.11), interstitial ED1 (2.33 +/- 0.18 versus 0.58 +/- 0.10) tubular transforming growth factor-beta1 (2.09 +/- 0.08 versus 0.91 +/- 0.14), interstitial transforming growth factor-beta 1 (2.33 +/- 0.22 versus 0.66 +/- 0.12), tubulointerstitial alpha-smooth muscle actin (2.91 +/- 0.22 versus 0.83 +/- 0.16), lower urinary albumin excretion (35.5 +/- 2.7 mg. daily versus 10.9 +/- 1) and higher creatinine clearance (2.29 +/- 0.04 ml. per minute versus 2.54 +/- 0.03, all p <0.05). CONCLUSIONS: Based on our results we believe that enalapril would provide a beneficial effect against chronic tubulointerstitial lesions caused by oxalates.