Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

Karyomegalic interstitial nephritis (KIN), first described in 1974, is a rare form of chronic tubulointerstitial nephritis. It is defined by the presence of markedly enlarged, hyperchromatic nuclei with prominent nucleoli, mainly involving tubular epithelial cells of the kidney, accompanied by marked interstitial fibrosis. The disease presents as asymptomatic proteinuria, gradually progresses to chronic kidney disease and eventually leads to end-stage renal disease by 30-40 years. The etiology of the disease remains unclear; however, genetic risk factors and possible association with HLA (B27/35) is proposed by some. It has also been linked to FAN1 (FANCD2/FANC1- associated nuclease 1) mutation. Case Report We present two cases of KIN with associated focal segmental glomerulosclerosis. Both patients presented with nephrotic range proteinuria. The biopsies demonstrated marked enlargement of tubular nuclei (3-5x larger than the uninvolved tubular nuclei, a metric used by some authors in previous studies) in some tubules, meeting the diagnostic criteria of KIN.. Interestingly, case one had a prior biopsy that showed minimal change disease. In the biopsies done at our institution, H&E sections showed patchy tubular attenuation with readily recognizable tubular cell mitotic figures, indicating concurrent acute tubular injury. Electron microscopy showed diffuse podocyte foot process effacement, along with microvillous transformation, podocyte hypertrophy, and cytoplasmic vacuoles, suggesting podocyte injury. This cytoplasmic vacuolization was also observed in the tubular epithelial cells. In both cases, the injury factor appeared to target both podocytes and tubular cells.

Histopathological kidney alterations in rats naturally infected with Leptospira / Alteraciones histopatológicas en ratas naturalmente infectadas con Leptospira

Introduction: Histopathological changes by Leptospira in naturally infected rodent reservoirs have been poorly described. Objective: The aim of the current study is to describe renal histopathology associated with leptospirosis infection of naturally infected rodents captured in the urban area of the city of Medellin, Colombia. Materials and methods: We performed hematoxilin-eosin (H-E) on kidney samples collected from 254 captured rodents. The positive samples were processed by Warthin Starry (W-S) staining and PCR- LipL 32. Results: Fifty one rodent kidneys showed H-E histopathological changes that consisted of inflammatory infiltrate with lympho-plasmocitary cells and histiocytes. We performed W-S staining and PCR- LipL 32 to 67 kidney samples, including the 51 that had shown detectable changes by H-E and 16 (8%) of 203 rodents with negative results. Eight of the samples that tested positive for H-E (15.7%) were also positive for W-S staining. All negative for H-E were also negative for W-S staining. Of the W-S positive samples also tested for culture only three tested positive for both. Additionally, 47 (92.1%) samples positive for H-E were positive for PCR; while eleven of the 16 (68.8%) negative for H-E were positive for PCR. The samples positive for PCR were subsequently tested for culture and 11 (23.4%) were positive. Seven samples were positive for PCR and W-S and three were positive for PCR, W-S and culture. All of the PCR- LipL 32 fragments were sequenced and showed specific amplicons for L. interrogans . Conclusions: The Leptospira infection was confirmed in all of the animals tested. The only histological kidney lesion attributable to leptospiral infection in the reservoir was interstitial nephritis.

Introducción. Los hallazgos histopatológicos ocasionados por Leptospira spp. han sido poco estudiados en poblaciones de roedores naturalmente infectados. Objetivo. Describir la histopatología renal asociada con las infecciones naturalmente adquiridas en un grupo de roedores capturados en el área urbana de Medellín, Colombia. Materiales y métodos. Se llevaron a cabo coloraciones de hematoxilina y eosina de los riñones de 254 roedores recolectados en el área de estudio. Las muestras positivas se procesaron con la coloración de Warthin-Starry y mediante reacción en cadena de la polimerasa (PCR)-LipL32. Results. Se observaron cambios histopatológicos con hematoxilina y eosina en 51 riñones de roedores, que consistieron en infiltrado inflamatorio con linfoplasmocitos e histiocitos. Se utilizó coloración de Warthin-Starry y PCR-LipL32 en 67 muestras de riñón que incluyeron las 51 muestras que tuvieron cambios detectables por hematoxilina y eosina y 16 de 203 (8 %) muestras con resultados negativos. Ocho de las muestras positivas por hematoxilina y eosina (15,7 %) también fueron positivas por la coloración de Warthin-Starry. Las muestras negativas por hematoxilina y eosina (8 %) también fueron negativas con la coloración de Warthin-Starry. Tres de las ocho muestras positivas por esta última, también lo fueron por cultivo. Además, 47 (92,1 %) muestras positivas por hematoxilina y eosina fueron positivas por PCR. Del grupo de 16 negativos por hematoxilina y eosina, 11 (68,8 %) fueron positivos por PCR. De las muestras positivas por PCR, 11 también lo fueron por cultivo (23,4 %). Siete muestras fueron positivas por PCR y Warthin-Starry y tres lo fueron por PCR, Warthin-Starry y cultivo. Todos los fragmentos de la PCR-LipL32 fueron secuenciados y mostraron secuencias específicas de L. interrogans . Conclusiones. Se confirmó la infección por Leptospira y la única lesión presente en el reservorio atribuible fue la nefritis intersticial.

Prediction of tubulo-interstitial injury by Doppler ultrasound in glomerular diseases: value of resistive and atrophic indices.

BACKGROUND: Doppler ultrasound is increasingly used in Nephrology for diagnosis of renovascular hypertension and evaluation of allograft dysfunction. However, its utility in glomerular disease remains controversial. OBJECTIVES: Using Doppler Ultrasound, we prospectively tested the role of resistive and atrophic indices in predicting tubulointerstitial lesions in patients with glomerular disease as demonstrated by renal biopsy. METHODS: Seventy one patients with primary or secondary glomerular diseases were examined by Doppler ultrasonography immediately before renalbiopsy. The resistive and atrophic indices (RI & AI) were calculated and compared with histologic changes in biopsy specimen. RESULTS: Receiver Operator Characteristics analysis showed RI of 0.60 as an optimal value for discriminating tubulointerstitial changes with sensitivity of 82.7% and specificity of 92%. An AI of 0.65 was shown to be optimal for discriminating tubulointerstitial injury with sensitivity of 69.2% and specificity of 85%. The combination of the two indices had not been found to be superior to either index alone. There was a significant correlation between atrophic and resistive indices. (r=0.358, p< 0.01). It was observed that older age, smoking, elevated AI and RI, low GFR, high serum cholesterol and Hypertension were found to be significantly associated with the presence of tubulointerstitial injury in the univariate analysis whereas only elevated AI and RI were found to predict tubulointerstitial injury in multivariate analysis. CONCLUSION: Measurement of RI by Doppler ultrasound can be considered as a supplementary diagnostic tool in glomerular diseases to predict the severity of tubulointerstitial injury.

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.

Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin

Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, im, twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, im, twice a day for 9 days, and 14 with 0.15 M NaCl , im, twice a day for 9 days and PDTC, 50 mg kg-1 day-1, ip, twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm². Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

Nefritis tubulo intersticial asociada a parvovirus b19 / Tubulointerstitial nephritis associated with parvovirus beta19 infection

Paciente de 9 años, previamente sana, que ingresa en anasarca con síndrome nefrótico clínico y humoral, asociado a hipertensión arterial y microhematuria, con función renal normal y se comporta como corticorresistente. Se realiza 1° biopsia renal que informa glomerulonefritis proliferativa mesangial difusa con esclerosis focal y segmentaria. En tratamiento con ciclofosfamida y corticoides, presenta síndrome febril prolongado con anemia secundaria a crisis aplásica de la serie roja, asociada con una infección aguda por parvovirus B19, e insuficiencia renal aguda secundaria a nefritis tubulointersticial severa. La PCR para parvovirus B19 DNA fue positiva en tejido renal y médula ósea. La paciente evoluciona a insuficiencia renal crónica terminal. No se puede descartar que desde su inicio, el síndrome nefrótico estuviera asociado al daño glomerular por la infección viral, que comenzó como síndrome nefrótico con componentes nefríticos y que evoluciona inesperadamente a una nefritis tubulointersticial. Este sería el primer caso en el que se documenta como causa de insuficiencia renal crónica terminal, un daño tubulointersticial secundario a parvovirus B19.

Nefritis intersticial aguda y lamotrigina / Acute interstitial nephritis associated to lamotrigine use: report of one case

Acute interstitial nephritis is a mononuclear and sterile inflammation of the renal interstice caused by drugs, infections or immune phenomena. The clinical presentation is characterized by the triad of rash, fever and eosinophilia. We report a 32 years old man, in treatment with lamotrigine for depression, admitted to the hospital due to fever, abdominal pain, jaundice, cutaneus rash and malaise. Due to an oliguric renal failure of acute onset, a renal biopsy was done. The pathological study showed a granulomatous acute interstitial nephritis. He was started on hemodialysis and treated with cessation of the drug and corticosteroids, with complete recovery of the renal function (Rev Méd Chile 2004; 132: 742-6).

Idiopathic necrotising granulomatous interstitial nephritis.

We report a case of idiopathic necrotising granulomatous interstitial nephritis seen as an incidental autopsy finding in a 65 years female. The unusual features were the presence of necroses, with a florid, bizarre giant cell reaction. There were varying degrees of tubular damage, with relative sparing of glomeruli. There was no history of drug ingestion; Mycobacteria, fungi or crystals were not identified.

Crescentic glomerulonephritis: a clinicopathologic analysis of 17 cases with emphasis on glomerular and interstitial neutrophil infiltration

In order to determine the extent to which specific forms of glomerulonephritis (GN) contribute to the pool of crescentic GN, renal tissues from 17 crescentic GN patients were examined with special attention to glomerular and interstitial neutrophil infiltration. Renal tissues from five normal kidneys served as normal controls. Renal biopsy tissues from five patients with postinfectious GN in which crescent formation was not observed were also examined as disease controls. The patients were put into both three groups according to immunofluorescence findings and two groups according to the active or inactive phase of the crescents: group 1 with anti-glomerular basement membrane crescentic GN, one case; group 2 with immune complex crescentic GN, ten cases; and group 3 with pauci-immune crescentic GN, six cases. Four of the nine individuals tested were positive for anti-neutrophil cytoplasmic antibody (44.4%). Glomerular and interstitial neutrophil infiltrations were prominent in both the active and inactive phase groups, compared to normal controls (p<.05). Glomerular neutrophil infiltration was significantly prominent in the active phase group, compared to the inactive phase group (p<.001). In both the active and inactive phase groups, interstitial neutrophil infiltration was prominent, compared to disease control groups (p<.05). These results support the concept of the participation of periglomerular leukocytes in the renal tissue damage of crescentic GN, although the role of neutrophils was not examined.

Amiloidosis renal: estudio clínico y patológico / Renal amyloidosis: study pathologic and clinic

Se realizó un estudio retrospectivo de corte transversal en 28 pacientes con amiloidosis renal primaria y secundaria, evaluados en el Hospital Arzobispo Loayza entre enero de 1985 y febrero de 1994. La edad promedio fue 38.6 ñ 13.9 años; 26 pacientes (92.8 por ciento) fueron de sexo femenino y 2 de sexo masculino; el tiempo de enfermedad promedio fue de 7.2 ñ 8.15 años. La presentación clínica fue: edema en el 100 por ciento, hipertensión arterial 7.1 por ciento, proteinuria 100 por ciento e insuficiencia renal 71.4 por ciento. Las causas de amiloidosis secundaria fueron: tuberculosis pulmonar en 20 pacientes (71.4 por ciento), bronquiectasias en 3 (10.7 por ciento ); otras causas fueron osteomielitis en 2 pacientes (7.1 por ciento) y linfoma no-Hodking en 1 (3.5 por ciento). En 2 pacientes no se encontró enfermedad asociada. En los pacientes con tuberculosis pulmonar se encontró que el 100 por ciento presentaba lesiones fibrocavitarias, 75 por ciento BK en esputo positivo y 85 por ciento había recibido tratamiento en forma incompleta. Los hallazgos anatomopatológicos fueron: infiltrado amiloide a nivel glomerular en el 100 por ciento, sin relación con el grado de proteinuria ni con el nivel de función renal; la nefritis intersticial crónica se encontró en 10 pacientes evidenciándose relación entre ésta y el deterioro de la función renal (p<0.01). La intensidad de la atrofia tubular guarda relación con la severidad. Los resultados de este estudio permiten establecer que la amiloidosis renal es secundaria a cuadros inflamatorios crónicos en particular a la tuberculosis, siendo la presentación clínica más frecuente el síndrome nefrótico. La nefritis intesticial crónica y atrofia tubular guardan una mejor relación con el deterioro de la función que el compromiso amiloideo a nivel glomerular.

Megalocytic interstitial nephintis [case report]

Megalocytic interstitial nephritis [M.I.N] is extremely rare disease affecting primarily the renal cortex. It is characterised by discrete or confluent yellow foci composed of macrophages lacking Michaelis-gutmann bodies which are seen in Malakoplakia. To our knowledge this is the first case of M.I.N. in bahrain

Patologia da leptospirose: ensaio de corrrelaçäo anatomo-clínica / Pathology of leptospirosis: assay with anatomoclinical correlation

Correlacionan-se as principais manifestaçöes clínicas encontradas na forma úctero-hemorrágica da leptospirose com seus achados anatomopatológicos em autópsias e biópsias, consubstanciados em vasta experiência nas três últimas décadas na cidade do Rio de Janeiro. O mecanismo patogênico básico das lesöes é analisado como decorrente de dano celular direto pela estrutura da leptospira e de seus produtos de degradaçäo, por via de alteraçöes vasculares propiciadoras de hipoxia tecidual. O quadro clínico e laboratorial de icterícia com insuficiência renal correlaciona-se com aspectos histopatológicos de hepatite colestática centrolobular e de necrose tubular aguda com nefrite intesticial. As mialgias, presentes na quase totalidade dos casos, säo justificadas pelo quadro histológico de miosite alterativa com lesöes multifocais em aproximadamente 80 por cento dos 88 espécimes estudados em material de biópsias musculares. As manifestaçöes cardiovasculares, pulmonares, digestivas e neuropsiquiátricas derivam de miocardite, pneumonite e de lesöes associadas a fenômenos congestivos e hemorrágicos

Características do infiltrado inflamatório renal na nefropatia de refluxo / Characteristics of the renal inflamatory infiltrates in reflux nephropathy

Este trabalho objetivou caracterizar, in situ, o infiltrado inflamatório da nefropatia de refluxo. Para tal, estudamos rins de ratos infectados experimentalmente com Escherichia coli e espécimes renais humanos obtidos por biópsia renal ou nefrectomia. A caracterizaçäo das células mononucleares foi feita pela técnica de imunoperoxidase em quatro etapas, utilizando-se anticorpos monoclonais na primeira etapa. Observamos que a nefrite tubulointersticial era constituída de 72,1% de linfocitos T, dos quais 79,7 - 88,2% eram células T auxiliares e 11, 7-20,3% linfócitos T citotóxicos supressores. O restante do infiltrado inflamatório (27,9%) constituiu-se de monócitos-macrófagos (18%) e linfócitos B e/ou células "nulas" (10%)