Correlation between amyloid deposits affecting renal compartments and glomerular filtration rate during renal biopsy in a renal amyloidosis case series.

Amyloidosis comprises a group of disorders that accumulate modified autologous proteins in organs, mainly the kidneys. Few studies have addressed the amyloid compartmental distribution and associated clinical outcomes. The aim of this study was to present a case series of renal amyloidosis correlating histopathological data with glomerular filtration rate (GFR) during kidney biopsy. We studied 53 cases reviewed by nephropathologists from 2000 to 2018 in a single kidney biopsy center in Brazil. GFR was estimated using the CKD-EPI formula. Cases were divided into Group A ≥60 and Group B <60 mL·min-1·(1.73 m2)-1 using the estimated GFR during kidney biopsy. Semiquantitative histopathological study was performed, including extension and distribution of amyloid deposits by compartments (glomeruli, tubulointerstitial tissue, and vessels). Statistical analyses were made to understand associations with lower GFR. No difference was seen for age, gender, proteinuria, hematuria, subtype of amyloid protein, arteriosclerosis, interstitial fibrosis/infiltrate, or glomerular and interstitial amyloid deposits. After a previous P value <0.1 in the descriptive analysis, the following variables were selected: globally sclerotic glomeruli, high blood pressure, and the extension of vascular amyloid deposition. A binary logistic regression model with GFR as the dependent variable showed history of hypertension and vascular amyloid to be robust and independent predictors of Group B <60 mL·min-1·(1.73 m2)-1. Beyond the histopathologic diagnosis of amyloidosis, a semiquantitative approach on renal biopsy could provide new insights. Vascular amyloid is an independent predictor of renal dysfunction in cases of renal amyloidosis.

Correlation between amyloid deposits affecting renal compartments and glomerular filtration rate during renal biopsy in a renal amyloidosis case series

Amyloidosis comprises a group of disorders that accumulate modified autologous proteins in organs, mainly the kidneys. Few studies have addressed the amyloid compartmental distribution and associated clinical outcomes. The aim of this study was to present a case series of renal amyloidosis correlating histopathological data with glomerular filtration rate (GFR) during kidney biopsy. We studied 53 cases reviewed by nephropathologists from 2000 to 2018 in a single kidney biopsy center in Brazil. GFR was estimated using the CKD-EPI formula. Cases were divided into Group A ≥60 and Group B <60 mL·min−1·(1.73 m2)−1 using the estimated GFR during kidney biopsy. Semiquantitative histopathological study was performed, including extension and distribution of amyloid deposits by compartments (glomeruli, tubulointerstitial tissue, and vessels). Statistical analyses were made to understand associations with lower GFR. No difference was seen for age, gender, proteinuria, hematuria, subtype of amyloid protein, arteriosclerosis, interstitial fibrosis/infiltrate, or glomerular and interstitial amyloid deposits. After a previous P value <0.1 in the descriptive analysis, the following variables were selected: globally sclerotic glomeruli, high blood pressure, and the extension of vascular amyloid deposition. A binary logistic regression model with GFR as the dependent variable showed history of hypertension and vascular amyloid to be robust and independent predictors of Group B <60 mL·min−1·(1.73 m2)−1. Beyond the histopathologic diagnosis of amyloidosis, a semiquantitative approach on renal biopsy could provide new insights. Vascular amyloid is an independent predictor of renal dysfunction in cases of renal amyloidosis.

IgA nephropathy in Brazil: apropos of 600 cases.

IgA nephropathy (IgAN) is th e commonest primary glomerular disease worldwide. Studies on its prevalence in Brazil are however scarce. Databases and clinical records from 10 reference centres were retrospectively reviewed. Clinical and laboratory features at the moment of the biopsy were retrieved (age, gender, presence of hematuria, serum creatinine [mg/dL], proteinuria [g/24 h]). Renal biopsy findings were classified according to Haas single grade classification scheme and the Oxford Classification of IgAN. 600 cases of IgAN were identified, of which 568 (94.7 %) were on native kidneys. Male to female ratio was 1.24:1. Patients averaged 32.76 ± 15.12 years old (range 4-89, median 32). Proteinuria and hematuria were observed, respectively in 56.63 and 72.29 % of patients. The association of both these findings occurred in 37.95 % of the cases. Serum creatinine averaged 1.65 ± 0.67 mg/dL (median 1.5 mg/dL) at diagnosis. Segmental sclerosis and mesangial hypercellularity were the main glomerular findings (47.6 and 46.2 %) The commonest combination by Oxford Classification of IgAN, was M0 E0 S0 T0 (22.4 %). Chronic tubulo-interstitial lesions with an extension wider than 25 % of the renal cortex could be identified in 32.2 % of the cases. Tubular atrophy and interstitial fibrosis were more strongly associated with higher 24-h proteinuria and serum creatinine levels. Segmental sclerosis (S1) showed a stronger tendency of association with the presence of tubulo-interstitial lesions (T1 and T2) than other glomerular variables. To the best of our knowledge this is the largest series of IgAN in Brazil. It depicts the main biopsy findings and their possible clinical correlates. Our set of data is comparable to previous reports.

Estudio histológico del tracto digestivo del neón cardenal paracheirodon axelrodi (Characidae) / Histological study of digestive tract of the neón cardenal paracheirodon axelrodi (Characidae)

Paracheirodon axelrodi es el pez ornamental que más se exporta en Colombia. Sin embargo, se desconocen varios aspectos de su biología básica. Se estudió la histología del tracto digestivo. Se sacrificaron 15 ejemplares (MS 222, 0,5 g/L), fijados en formaldehído al 4 por ciento y decalcificados con ácido nítrico 7 por ciento. Se siguió el procedimiento para H&E. El tracto digestivo de P. axelrodi presentó cuatro capas constitutivas: mucosa, submucosa, muscular y serosa. La mucosa de la boca presentó un epitelio escamoso estratificado no queratinizado con células caliciformes y sin botones gustativos, una submucosa de tejido conectivo laxo y una capa de músculo estriado esquelético. Los dientes son cónicos y abundantes. La capa serosa a lo largo del tracto digestivo es delgada compuesta de tejido conectivo laxo. La capa mucosa, submucosa y muscular del esófago posee la misma conformación tisular de la boca, sin embargo, la capa muscular presenta dos orientaciones. La mucosa del estómago está compuesta por epitelio cilíndrico simple con glándulas gástricas, submucosa de tejido conectivo laxo y una capa de músculo liso en dos orientaciones. Las capas del intestino exhi-bieron una composición tisular similar a la del estómago, sin glándulas gástricas. La mucosa presentó células caliciformes especialmente hacia la región posterior y un aumento en la longitud de los pliegues intestinales. La conformación tisular y morfológica del tracto digestivo de P. axelrodi lo ubica como un pez de hábitos alimenticios carnívoros pero de pequeñas presas.

Cardinal neon, Paracheirodon axelrodi is the most exported ornamental fish in Colombia. However, many aspects of its biology are unknown. A histological study of the digestive tract was carried out and 15 specimens were sacrificed with MS 222, 0.5 g/L, fixed in 4 percent formaldehyde and decalcified with 7 percent nitric acid. H&E technique was followed. P. axelrodi digestive tract showed four constitutive layers: mucosae, submucosae, muscular, and serosa. Mouth mucosae presents a stratified nonkeratinized squamous epithelium with many goblet cells, and no taste buds, submucosae with areolar connective tissue, and skeletal muscular layer. Teeth were conical and abundant. Along the whole intestinal tract the serous was a very thin connective tissue layer. Esophagus mucosae, submucosae, and muscular layer were similar to those of the mouth. However, muscular layer presented two layers in different orientations. Stomach mucosae were made of simple cylindrical epithelium with gastric glands. Submucosa did present areolar connective tissue, and muscular layer exhibited smooth muscle in two different orientations. The intestinal layers were similar to those of the stomach, but without gastric glands. Mucosae presented goblet cells especially at the posterior region. Intestinal folds were also observed. Tisular and morphological structure of P. axelrodi digestive tract suggests a small prey carnivorous fish.

Kidney ultrastructural lesions in dogs experimentally infected with Dirofilaria immitis (Leidy, 1856).

Kidneys of 16 beagles with experimentally induced heartworm (Dirofilaria immitis) infections and 4 heartworm-nai;ve dogs were studied by light and electron microscopy. The infections were induced either by subcutaneous injection of infective larvae or by the transplantation of adult parasites, and infection periods varied from 111 to 818 days and 365 to 923 days, respectively. One control group of heartworm-naïve dogs and four groups of heartworm-infected dogs, which were divided according to the type and the length of infection, were used. In the infected dogs, thickening of the glomerular basement membrane (GBM), the presence of dense deposits in the GBM, and foot process effacement were the most frequent lesions observed. In some dogs, electron dense deposits were seen in the GBM and the mesangium and/or enlargement of the mesangial matrix could be characterized. The longer the infection period, the thicker the GBM and the more common the occurrence of foot process effacement. In general, these alterations were more evident in animals that had been infected for more than 1 year, had high microfilaremia, and had 14 or more parasites in the main pulmonary artery and its branches. The presence of dense deposits suggests that the pathogenesis of kidney disease in dirofilariasis is associated with deposits of immune complexes in the membrane. The finding of ultrastructural changes in dogs with early prepatent infections suggests that immature heartworms, as well as microfilariae and possibly adult worms, contribute to the glomerulonephropathy.

Effect of dietary linoleic acid on the progression of chronic renal failure in rats.

The role of linoleic acid in chronic renal failure (CRF) is controversial. In the present study 21 male Wistar rats submitted to 5/6 renal mass reduction (R) and 16 normal controls (C) were fed a supplement (S) or normal (N) linoleic acid diet for 60 days starting 10 days after CRF. As expected, serum creatinine, cholesterol and triglycerides (mean +/- SEM) were higher in the CRF groups compared to the C groups (P<0.05). The RS group presented lower cholesterol (84 +/- 4 vs 126 +/- 13 mg%) and triglyceride (88 +/- 9 vs 132 +/- 19 mg%) levels compared to the RN group. Proteinuria and kidney weight did not differ between CRF groups. Glomerular area increased 78% in RS and 100% in RN compared to control rats. Glomerular sclerosis index tended to be lower in RS (27%) compared to RN (38%), tubulointerstitial damage was similar between CRF groups (RS = 1.91 +/- 0.2 and RN = 2.14 +/- 0.3), and mesangial fractional volume increased to the same extent in both CRF groups. The data suggest that a linoleic acid-enriched diet did not protect against the progression of CRF after 60 days.

Effect of dietary linoleic acid on the progression of chronic renal failure in rats

The role of linoleic acid in chronic renal failure (CRF) is controversial. In the present study 21 male Wistar rats submitted to 5/6 renal mass reduction (R) and 16 normal controls (C) were fed a supplement (S) or normal (N) linoleic acid diet for 60 days starting 10 days after CRF. As expected, serum creatinine, cholesterol and triglycerides (mean SEM) were higher in the CRF groups compared to the C groups (P<0.05). The RS group presented lower cholesterol (84 4 vs 126 13 mg percent) and triglyceride (88 9 vs 132 19 mg percent) levels compared to the RN group. Proteinuria and kidney weight did not differ between CRF groups. Glomerular area increased 78 percent in RS and 100 percent in RN compared to control rats. Glomerular sclerosis index tended to be lower in RS (27 percent) compared to RN (38 percent), tubulointerstitial damage was similar between CRF groups (RS = 1.91 0.2 and RN = 2.14 0.3), and mesangial fractional volume increased to the same extent in both CRF groups. The data suggest that a linoleic acid-enriched diet did not protect against the progression of CRF after 60 days

Cytochemical localisation of calcium ATPase activity during the erythrocytic cell cycle of Plasmodium falciparum.

Using a cytochemical technique, we evaluated the levels of Ca(2+)-ATPase activity in the plasmatic and in the parasitophorous vacuole membrane through the different developmental stages of the Plasmodium falciparum parasitised erythrocyte. We found that the activity is detectable and remains unaltered in the plasma membrane throughout the 48 h cell cycle. However, in the parasitophorous membrane, although the activity was very similar to that measured in the plasma membrane of the young stages (younger than 20-h-old parasites), it diminished gradually with maturation and in schizonts it was almost undetectable. These data suggest that the plasma membrane Ca(2+)-ATPase is important in the maintenance of a low erythrocyte cytoplasmic Ca(2+) concentration, and that in addition it could be a way to supply the vital cation to the parasite at the beginning of the infection, when other transport mechanisms have not yet developed.

Cytoadherence of the malaria-infected erythrocyte membrane to C32 melanoma cells after merozoites are released from parasitized infected cells.

Infections with the human malaria parasite Plasmodium falciparum are characterized by cytoadherence of infected erythrocytes to the venular endothelium of several organs. Video microscopy studies have shown that at the end of the asexual life of P. falciparum, the residual body containing haemozoin is released to the extracellular environment along with merozoites, leaving behind an infected erythrocyte "ghost". It is possible that these infected erythrocyte "ghosts" could remain sequestered within the blood vessels of patients infected with P. falciparum even after merozoites have been released from infected erythrocytes. In this study an in vitro cytoadherence assay was developed to show that infected erythrocyte "ghosts" can interact with C32 melanoma cells. Adherent infected erythrocyte "ghosts" contain some of the subcellular compartments of the malaria-infected red blood cell such as the tubo-vesicular membrane network and remnants of the parasitophorous vacuolar membrane, but lack haemozoin.

Early gestational hemolytic uremic syndrome: case report and review of literature.

Hemolytic uremic syndrome (HUS) is a rare condition which most frequently follows gastrointestinal or respiratory infection episodes in young children, but it can also occur in other settings such as the postpartum period and during use of drugs such as oral contraconceptives, immunosuppressors, and antineoplastics. In early pregnancy, however, its frequency is thought to be very low. The authors report a case of a 30-year-old woman who developed HUS early in her first pregnancy. She had persistent aqueous diarrhea from the beginning of the pregnancy. At the 21st week she developed hypertension which in 2 weeks was followed by seizures, oliguria, and acute pulmonary edema despite intensive medical efforts to control her blood pressure. Surgical intervention for fetal delivery was performed. The patient was initially kept on continuous hemodialysis (CVVHD) followed by an alternate-day conventional hemodialysis schedule. A peripheral blood analysis showed a microangiopathic hemolytic anemia with thrombocytopenia; blood coagulation tests were completely normal. A brain CT scan and an abdominal MRI showed no major abnormalities. HUS was confirmed by a percutaneal kidney biopsy, performed at the 21st day of anuria. Techniques for identification of verotoxin-producing E. coli were not available. Renal function did not recover and the patient has been undergoing regular maintenance hemodialysis for a year.

Antibodies against granule proteins activate neutrophils in vitro.

Polymorphonuclear leukocyte (PMN) respiratory burst was stimulated by heterologous antibodies against PMN granule proteins but not by control antibodies. Fluorescence-activated cell sorter (FACS) analysis of activated PMN demonstrated the presence of two primary granule proteins, proteinase 3 (PR-3) and cationic protein 57 (CAP-57) at the membrane surface. The presence of myeloperoxidase (MPO) at the cell surface of primed and unprimed PMN was confirmed by immunoelectron microscopy. Priming doses of recombinant tumor necrosis alpha (rTNF alpha) enhanced the rate of superoxide (O2-) production by these antibodies and increased the amount of surface protein accessible to these antibodies. Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificities for PMN granule proteins are present in patients with Wegener's granulomatosis, polyarteritis nodosa, and idiopathic and crescentic glomerulonephritis. The demonstration that antibodies against granule proteins activate PMN supports the hypothesis that the vasculitis seen in these diseases is due in part to PMN mediated oxidative injury following PMN stimulation by ANCA.

Nefrite intersticial aguda apos tratamento com rifampicina. / Acute interstitial nephritis after treatment with refampicin

E relatado um caso de nefrite intersticial aguda, nao oligurica, em um paciente com mal de Hansen, em uso de rifampicina.O unico sinal de hipersensibilidade a droga correspondeu a eosinofilia no sangue periferico. A biopsia renal mostrou acentuado edema intersticial, infiltrado mononuclear e eosinofilico, alem de dano tubular focal, com ausencia de lesao glomerular ou vascular. Apos a suspensao da droga houve recuperacao da funcao renal.Os achados sugerem um mecanismo de hipersensibilidade como causa da lesao renal provavelmente induzida pela rifampicina

Correlacao anatomo-clinica em glomerulopatias. Estudo retrospectivo de 65 casos em adultos. / Anatomo-clinical correlation in glomerulopathies. Retrospective study of 65 cases in adults

O presente trabalho compreende estudo anatomo-clinico retrospectivo de 65 casos de glomerulopatias em adultos. Os casos foram classificados em tres sindromes clinicas: nefritica, nefrotica, nao nefritica - nao nefrotica. A intensidade das lesoes histologicas renais foi avaliada no material de biopsia e/ou autopsia atraves de metodo semiquantitativo (0 a 4 +) obtendo-se indices de lesao glomerular, tubular, intersticio-vascular e renal total. Para cada paciente, foram estabelecidas correlacoes entre estes indices com a apresentacao clinica, niveis pressoricos, funcao renal (creatinina serica) e evolucao. No conjunto, observou-se que lesoes historicas mais graves associam-se a agravamento da funcao renal e piora da evolucao dos pacientes.A analise estatistica de regressao linear simples demonstrou correlacao significante entre os diferentes indice de lesao com os niveis de creatinina serica, porem o indice de lesao intersticio-vascular foi o que melhor se correlacionou com a funcao renal (r2 = 0,53)

[Retrospective study in hepatic biopsies, of hepatitis B surface antigen by the orcein method and indirect immunofluorescence methods]. / Estudo retrospectivo em biopsias hepáticas, do antígeno de superfície do vírus da hepatite B, pelos métodos de orceína e de immunofluorescência indireta.

A retrospective study of the HBsAg was done in 56 liver biopsies of children less than 12 year-old and 78 biopsies of adults. The study was performed by orcein stain and indirect immunofluorescent method. In 23 of the adults patients, the serological detection of HBsAg and antibodies (HbsAb) was determined by reverse passive haemagglutination technique. The adults patients' histological dianosis were variable and included acute or chronic hepatitis (20.5%) and cirrhosis (24.4%). Orcein was positive in 7 and IFI in 6 cases; 5 biopsies were positive by both methods. The highest incidence of HBsAg was seen in active cirrhosis (75%), including two cases of alcoholic cirrhosis. In the 23 serologically studied patients, 15 cases were HBsAg negative and 3 were HBsAg positive both in the liver and serum; only 2 cases showed discrepancy between these results. Three patients were HBsAb positive and HBsAg negative both in the liver and serum. All children biopsies were HBsAg negative. Among these patients, 26.8% had acute or chronic hepatitis and 10.7% cirrhosis. Serological and tissue techniques for HBsAg and HbsAb detection have different sensitivity. This should be kept in mind when studying the incidence of hepatitis B virus related to liver diseases.

[Multiple neuropaty caused by giant cell arteritis. Clinico-pathological report of a case]. / Neuropatia múltipla for arterite de células gigantes. Registro clínico-patológico de um caso.

The case of a 67 years old woman with giant cell arteritis and neuritis multiplex is reported. The diagnosis was based on the microscopic appearances of temporal artery biopsy specimens. The authors described the involvement of peripheral nerves in this disease and made differential diagnosis with polyarteritis nodosa. There was also hemorragic infarction of the brain without giant-cells in brain vessels. It is concluded that this diagnosis should be considered in any elderly patient with peripheral neuropathy.