Swimming exercise demonstrates advantages over running exercise in reducing proteinuria and glomerulosclerosis in spontaneously hypertensive rats.

Experimental studies in animal models have described the benefits of physical exercise (PE) to kidney diseases associated with hypertension. Land- and water-based exercises induce different responses in renal function. Our aim was to evaluate the renal alterations induced by different environments of PE in spontaneously hypertensive rats (SHRs). The SHRs were divided into sedentary (S), swimming exercise (SE), and running exercise (RE) groups, and were trained for 8 weeks under similar intensities (60 min/day). Arterial pressure (AP) and heart rate (HR) were recorded. The renal function was evaluated through urinary volume at each week of training; sodium and potassium excretions, plasma and urinary osmolarities, glomerular filtration rate (GFR), levels of proteinuria, and renal damage were determined. SE and RE rats presented reduced mean AP, systolic blood pressure, and HR in comparison with S group. SE and RE rats showed higher urine osmolarity compared with S. SE rats showed higher free water clearance (P < 0.01), lower urinary density (P < 0.0001), and increased weekly urine volume (P < 0.05) in comparison with RE and S groups. GFR was increased in both SE and RE rats. The proteinuria of SE (7.0 ± 0.8 mg/24 h) rats was decreased at the 8th week of the PE in comparison with RE (9.6 ± 0.8 mg/24 h) and S (9.8 ± 0.5 mg/24 h) groups. The glomerulosclerosis was reduced in SE rats (P < 0.02). SE produced different response in renal function in comparison with RE, in which only swimming-trained rats had better profile for proteinuria and glomerulosclerosis.

ANCA-associated pauci-immune glomerulonephritis: always pauci-immune?

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN. METHODS: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded. RESULTS: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036). CONCLUSIONS: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.

Pathogenesis and treatment of glomerulonephritis-an update.

This review updates current concepts of the genetic risk factors, etiologic events, nephtitogenic responses and treatment of the major immunologically mediated types of glomerulonephritis (GN). These include post-infectious GN, IgA nephropathy, anti-glomerular basement membrane (GBM) antibody disease, ANCA-associated vasculitis (AAV) and lupus nephritis. Although the etiology(s) of most GNs remain undefined, many are now believed to be initiated by environmental insults, particularly infectious processes, that trigger host responses in genetically susceptible individuals which lead to GN. Mechanistic concepts of these diseases have evolved from earlier views that most were consequent to glomerular trapping of preformed immune complexes to the current view that most of these diseases are auto-immune in nature mediated by both antibodies and T cells reactive with self-antigens. Therapy of GN has lagged behind advances in understanding pathogenesis. Newly appreciated roles for older mediators like complement and complement regulatory proteins offer new therapeutic targets.

Patogênese e tratamento da glomerulonefrite - uma atualização / Pathogenesis and treatment of glomerulonephritis-an update

Resumo A presente revisão traz os conceitos mais atuais acerca dos fatores de risco genéticos, eventos etiológicos, respostas nefritogênicas e tratamento dos principais tipos de glomerulonefrite (GN) imunomediada. Tais patologias incluem GN pós-infecciosa, nefropatia por IgA, doença por anticorpo antimembrana basal glomerular (anti-MBG), vasculite associada a ANCA (VAA) e nefrite lúpica. Apesar da(s) etiologia(s) da maioria dos casos de GN permanecer indefinida, acredita-se que seu início se deva, em grande parte, a insultos ambientais, particularmente na forma de processos infecciosos que deflagram respostas de hospedeiro em indivíduos geneticamente suscetíveis, levando assim a quadros de GN. A concepção mecanicista em torno dessas patologias evoluiu a partir da visão mais antiga de que a maioria seria consequência do aprisionamento glomerular de complexos imunes pré-formados para a percepção atual de que as mesmas, em sua maioria, são doenças autoimunes por natureza mediadas por anticorpos e linfócitos T reativos a auto-antígenos. O tratamento da GN não tem acompanhado os progressos na compreensão de sua patogênese. Os papéis recentemente atribuídos a mediadores mais antigos como complemento e proteínas reguladoras do complemento lançam luz sobre novos alvos terapêuticos.

Abstract This review updates current concepts of the genetic risk factors, etiologic events, nephtitogenic responses and treatment of the major immunologically mediated types of glomerulonephritis (GN). These include post-infectious GN, IgA nephropathy, anti-glomerular basement membrane (GBM) antibody disease, ANCA-associated vasculitis (AAV) and lupus nephritis. Although the etiology(s) of most GNs remain undefined, many are now believed to be initiated by environmental insults, particularly infectious processes, that trigger host responses in genetically susceptible individuals which lead to GN. Mechanistic concepts of these diseases have evolved from earlier views that most were consequent to glomerular trapping of preformed immune complexes to the current view that most of these diseases are auto-immune in nature mediated by both antibodies and T cells reactive with self-antigens. Therapy of GN has lagged behind advances in understanding pathogenesis. Newly appreciated roles for older mediators like complement and complement regulatory proteins offer new therapeutic targets.

Glomerulonefritis lúpica y otras glomerulopatías autoinmunes / Lupus glomerulonephritis and other autoimmune glomerulonephritis

La glomerulonefritis es un término empleado para expresar la proliferación e inflamación endocapilar del glomérulo renal, que clínicamente puede manifestarse de numerosas formas e incluso permanecer asintomática. En su etiología se encuentran múltiples mecanismos, como la participación de microorganismos y parásitos, aunque es destacable el mecanismo autoinmune en el que se identifican varios componentes del sistema inmune, entre ellos el sistema del complemento. Un ejemplo de este último mecanismo es la glomerulonefritis secundaria al Lupus Eritematoso Sistémico (LES), que ha sido objeto de investigación en los últimos años, y en la que se han hecho importantes avances en cuanto al descubrimiento de nuevas moléculas implicadas en el proceso etiopatogénico. Esto ha conseguido abrir una puerta a nuevas terapias que reduzcan la mortalidad y mejoren la calidad de vida. Se ha revisado la fisiopatología, clínica, diagnóstico, pronóstico y tratamientos, incluyendo los emergentes, en cuanto a glomerulonefritis haciendo hincapié en la glomerulonefritis lúpica y otras glomerulonefritis de mecanismo igualmente autoinmune.

[Epidemiology of glomerular disease in adults: a database review]. / Epidemiología de la enfermedad glomerular en adultos. Revisión de una base de datos.

INTRODUCTION: Glomerular disease is among the top ten leading causes of death in Mexico. AIM: To assess the frequency of glomerulopathy in western Mexico in a Regional Hospital belonging of the Instituto Mexicano Del Seguro Social. METHODS: Single hospital center retrospective analysis. We reviewed all native kidney biopsies between January 2003 and December 2011, in patients more than 16 years old, to establish clinical features, presentation, and histological report. RESULTS: A total of 163 reports were analyzed; patients with a mean age of 32.6 ± 13.3 years, 55% female, 24% had systemic arterial hypertension, and 10% with a family history of chronic renal failure. The most frequent types of primary glomerulonephritis were focal segmental glomerulosclerosis (FSGS) in 47% of cases, followed by membranous nephropathy in 15%. The most frequent types of secondary glomerulonephritis were lupus nephritis in 14%, followed by diabetic nephropathy in 4% and amyloidosis in 1.2%. CONCLUSION: Focal segmental glomerulosclerosis is the most frequent type of glomerulopathy in our population; we observed a minor percentage of Inmunoglobulin A (IgA) nephropathy compared with worldwide reports. This information is a contribution to the understanding of the prevalence of glomerulopathy in western Mexico.

Regression of albuminuria and hypertension and arrest of severe renal injury by a losartan-hydrochlorothiazide association in a model of very advanced nephropathy.

Treatments that effectively prevent chronic kidney disease (CKD) when initiated early often yield disappointing results when started at more advanced phases. We examined the long-term evolution of renal injury in the 5/6 nephrectomy model (Nx) and the effect of an association between an AT-1 receptor blocker, losartan (L), and hydrochlorothiazide (H), shown previously to be effective when started one month after Nx. Adult male Munich-Wistar rats underwent Nx, being divided into four groups: Nx+V, no treatment; Nx+L, receiving L monotherapy; Nx+LH, receiving the L+H association (LH), and Nx+AHHz, treated with the calcium channel blocker, amlodipine, the vascular relaxant, hydralazine, and H. This latter group served to assess the effect of lowering blood pressure (BP). Rats undergoing sham nephrectomy (S) were also studied. In a first protocol, treatments were initiated 60 days after Nx, when CKD is at a relatively early stage. In a second protocol, treatments were started 120 days after Nx, when glomerulosclerosis and interstitial fibrosis are already advanced. In both protocols, L treatment promoted only partial renoprotection, whereas LH brought BP, albuminuria, tubulointerstitial cell proliferation and plasma aldosterone below pretreatment levels, and completely detained progression of renal injury. Despite normalizing BP, the AHHz association failed to prevent renal damage, indicating that the renoprotective effect of LH was not due to a systemic hemodynamic action. These findings are inconsistent with the contention that thiazides are innocuous in advanced CKD. In Nx, LH promotes effective renoprotection even at advanced stages by mechanisms that may involve anti-inflammatory and intrarenal hemodynamic effects, but seem not to require BP normalization.

Interstitial expression of angiotensin II and AT1 receptor are increased in patients with progressive glomerulopathies.

In animal models, interstitial angiotensin II (ang II) and AT1 receptor (AT1R) are key mediators of renal inflammation and fibrosis in progressive chronic nephropathies. We hypothesized that these molecules were overexpressed in patients with progressive glomerulopathies. In this observational retrospective study, we described the expression of ang II and AT1R by immunohistochemistry in kidney biopsies of 7 patients with minimal change disease (MCD) and in 25 patients with progressive glomerulopathies (PGPs). Proteinuria, serum albumin, and serum creatinine were not statistically different between MCD and PGP patients. Total expression of ang II and AT1R was not statistically different between MCD (108.7+/-11.5 and 73.2+/-13.6 cells/mm(2), respectively) and PGN patients (100.7+/-9.0 and 157.7+/-13.8 cells/mm(2), respectively; p>0.05). Yet, interstitial expression of ang II and AT1R (91.6+/-16.0 and 45.6+/-5.4 cells/mm(2), respectively) was higher in patients with PGN than in those with MCD (22.0+/-4.1 and 17.9+/-2.9 cells/mm(2), respectively, p<0.05), as was the proportion of interstitial fibrosis (11.0+/-0.7% versus 6.1+/-1.2%, p<005). In patients with MCD, ang II and AT1R expressions predominate in the tubular compartment (52% and 36% of the positive cells, respectively). In those with PGP, the interstitial expression of ang II and AT1R predominates (58% and 45%, respectively). In conclusion, interstitial expression of ang II and AT1R is increased in patients with progressive glomerulopathies. The relationship of these results and interstitial fibrosis and disease progression in humans warrants further investigations.

Renal disorders involved in the pathophysiology of urinary excretion of a-1 microglobulin in patients with glomerulopathies.

AIMS: The protein alpha1-microglobulin (alpha1-microg) is filtered by the glomeruli and fully reabsorbed by the proximal tubules, and tubulointerstitial injury compromises its reabsorption. The aim of this study was to determine which functional, morphological and inflammatory renal disorders associated with tubulointerstitial damage interfere with urinary excretion of alpha1-microg in patients with glomerulopathies. PATIENTS AND METHODS: 38 patients (33.6 +/- 11.3 years) with primary or secondary glomerulopathies diagnosed by renal biopsies were studied. The urinary fractional excretion of alpha1-microg (FEalpha1-microg), the urinary monocyte chemoattractant protein-1/urinary creatinine (UMCP-1) index and 24-h proteinuria were determined. In the cortex of renal biopsies, the number of macrophages/104 microm2 of glomerular tuft (GT) and tubulointerstitial (TI) areas, the relative interstitial area (RCIA), and the relative interstitial fibrosis area (CIF) were measured. Results are reported as median and range and the Spearman non-parametric test was used to determine the correlations. RESULTS: FEalpha1-microg was 0.165% (0.008% - 14,790.0%) in patients with glomerulopathies and 0.065% (0.010% - 0.150%) in the control group (p < 0.05; Mann-Whitney U-Test). FEalpha1-microg was correlated with creatinine clearance (r = -0.4396; p = 0.0358), UMCP-1 index (r = 0.5978; p < 0.0001), number of macrophages/TI area (r = 0.5634; p = 0.0034) and RCIA (r = 0.7436; p < 0.0001). However, FEa1-microg was not correlated with proteinuria (r = 0.1465; p = 0.5153) or with CIF (r = 0.0039; p = 0.98). CONCLUSIONS: renal MCP-1 and the expansion and number of macrophages of the tubulointerstitial area participate in the increase of urinary excretion of alpha1-microg in patients with glomerulopathies. Although proteinuria and interstitial fibrosis have not been associated with this effect, the present study does not exclude some of these disorders in the pathophysiology of urinary excretion of alpha1-microg.

Biopsia renal en pediatría: análisis de la casuística de 28 años: Hospital de Niños de Valencia-Venezuela: [revisión] / Renal biopsy in pediatrics: casuistica analysis of 28 years: Hospital of Niños of Valencia-Venezuela: [review]

El análisis de los resultados de casuísticas de biopsias renales es importante con fines diagnósticos, terapéuticos y de pronóstico. Evaluar la serie de biopsias renales en el Hospital de Niños de Valencia, Venezuela, durante el período 1978-2007. Fueron analizadas 421 biopsias renales practicadas en 395 pacientes, de 2 meses a 20 años, 57% varones. El material fue procesado por microscopía óptica, inmunofluorescencia y microscopía electrónica en 98% de los casos. Se obtuvo muestra adecuada (más de 10 glomérulos) en 93% de los casos (n=392). Indicaciones clínicas: síndrome nefrótico 199(50%), síndrome nefrítico atípico 53(13%), otro: (hematuria/proteinuria, proteinuria, trasplante, enfermedades sistémicas 143(37%). Resultados Histopatológicos: A.-Glomerulonefrítis primaria (GNP) 302 casos (77%), B.-Nefropatías secundarias (NS) 68 casos (17%), C.-Riñones trasplantados 28 casos (7%).-Diagnósticos en GNP: 1) Lesión de cambios mínimos 140(46%), 2) Glomeruloesclerosis segmentaria y focal 79 (26%), 3) GN proliferativa y/o mesangial 67(22%), 4) GN Membranosa 16 (5%). -Diagnósticos en NS: Nefritis lúpica: 20 casos (32.25%), Nefropatía IgA: 22 casos (35.50%); Otras: 20 casos (32.25%). -Diagnósticos en riñones trasplantados: rechazo agudo 50%, necrosis tubular aguda 25%, rechazo crónico 20%, enfermedad recurrente en trasplante 5%. Complicaciones: Hematuria transitoria: 21 casos (5%), hematoma perirenal: 3(<1%), perforación intestinal: 2 (<0.5%), hemorragia importante: 2 (<0.5%), nefrectomía: 1(0.2%). La presente es una de las primeras casuísticas de biopsias renales reportadas en Latinoamérica y una de las más grandes en el mundo y, de acuerdo a nuestros resultados, es un procedimiento seguro con gran utilidad diagnóstica, pocas complicaciones, sin mortalidad.

Evaluation and analysis of the results of renal biopsy are important for diagnostic, therapeutic and prognostic matters. To evaluate a series of renal biopsies performed during the period 1978-2007 in the Hospital de Niños de Valencia, Venezuela. All patients had history of either primary or secondary nephropathies. 421 biopsies were done in 377 patients, ages 2 months-20 years; 57% boys. 26 patients were re-biopsed. Percutaneous needle biopsy (PNB) was performed in all the patients, except in one who underwent open biopsy because of a solitary kidney. Renal tissue was processed for optical, inmunofluorescence and electronic microscopy in 98% of cases. The biopsy technique, clinical syndromes at presentation, hystopathological pattern, effectiveness and complications are described. Adequate sample was obtained in 392 cases (93%) (more than 10 glomeruli) and inadequate or failed biopsy in 29(7%). Clinical syndromes at presentation were: nephrotic syndrome: 199 cases (50%), atypical acute nephritic syndrome: 53 (13%), others: hematuria and proteinuria, isolated proteinuria, kidney transplant biopsy or systemic diseases: 143(37%). The hystopathological pattern obtained was as follows. A.-Primary glomerulonephritis (PG): 302 cases, 77%, B.-Secondary nephropathies: 68 cases, 17%, C.- Kidney transplant biopsies: 28 cases, 5 %. Primary Glomerulonephritis diagnosis: minimal change disease: 140 cases, 46%, Focal Segmental Glomerulosclerosis: 79(26%), diffuse proliferative glomerulonephritis/mesangial: 67(22%), membranous glomerulonephritis: 16(5%). Secondary nephropathies: lupus nephritis: 20 cases (32.25%), IgA Nephropathy: 22 cases (35.50%), others: 20 cases (32.25%).Transplant biopsies: rejection 50%, acute tubular necrosis 25%, chronic rejection 20%, and recurrent disease 5%. Complications: transient hematuria: 21(5%), perirenal hematoma: 3(<1%), gut perforation (<0.2%), bleeding which required blood transfusion: 2(<0.5%) and nephrectomy because of incontrollable...

Administration of M. leprae Hsp65 interferes with the murine lupus progression.

The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K(409)A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F(1) mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F(1) serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K(409)A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K(409)A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process.

Should adolescents with glomerulopathies be treated as children or adults?

BACKGROUND: Glomerular diseases are an important cause of end-stage renal disease, especially among young adults. However, clinical and epidemiological surveys involving adolescent populations are scarce. AIM: To determine the pattern of glomerulopathies (GP) in adolescents submitted to renal biopsy. METHODS: A retrospective study of patients' records of the Glomerulopathy Section, UNIFESP (Brazil), was performed RESULTS: Among 72 adolescents (12-18 years) with GP, 15.6 +/- 1.5 years, 58.3% females, the most frequent clinical manifestation was nephrotic syndrome (NS, 71%) and focal segmental glomerulosclerosis (FSGS) was the main histological pattern (24%), followed by minimal change disease (MCD, 19.5%). After comparing the main causes of NS in adolescents with those of adults, we found no statistically significant differences in clinical presentation or outcome. Renal failure-free survival of 1 and 5 years for all GP corresponded to 87.9 and 73.6%, respectively (88.5 and 76.3% for NS). CONCLUSIONS: NS was the main manifestation; FSGS and MCD were the most common histological diagnoses. Our data suggest the GP and particularly the NS pattern in adolescents is similar to that of adults, pointing to the need for an adaptation in diagnostic and treatment protocols for this age group, a pattern which corresponds more closely to that of adults.

Delay in diagnosis in poststreptococcal glomerulonephritis.

OBJECTIVE: To determine the frequency and risk factors for diagnostic delays in children with poststreptococcal glomerulonephritis (PSGN). STUDY DESIGN: We reviewed the charts of 52 children with PSGN, and identified children with a delay in diagnosis of more than 24 hours. We determined risk factors for delay in diagnosis using univariate and multivariate logistic regression. RESULTS: 17 children (33%) with PSGN had a delay in diagnosis. Delay in diagnosis occurred in 14% of children with gross hematuria as a presenting complaint and in 54% of children without gross hematuria as a presenting complaint (3.8 increased relative risk, 95% CI = 1.4 to 10; P = .02). A delay in diagnosis was more common in children with a negative infection history (P = .04). In multiple logistic regression, only the absence of gross hematuria as a presenting complaint was associated with a delay in diagnosis (P = .01). All children with a delay in diagnosis had microscopic hematuria on their initial urinalysis. CONCLUSIONS: Delay in diagnosis is common in children with PSGN, especially if visible hematuria is not a presenting complaint. Physicians should consider the possibility of PSGN in children with symptoms that may be secondary to volume overload. A urinalysis is a helpful initial diagnostic test.

Prognostic factors associated with poor graft outcomes in renal recipients with post-transplant glomerulonephritis.

BACKGROUND: Little data are available concerning post-transplantation glomerulonephritis (PTx-GN) and its prognostic factors associated with graft outcomes. METHODS: We retrospectively evaluated patients with de novo and recurrent PTx-GN to identify the factors associated with their negative impact on graft and patient outcomes. PTx-GN was diagnosed in 55 patients, wherein 17 (31%) had recurrent glomerulonephritis (GN) and 16 (29%) had de novo. RESULTS: Our enrolled population consisted of 34 +/- 13.7-yr-old male patients (72%), on hemodialysis for a median of 18 months (0-204) and mainly grafted from living donors (76%). The median onset time of proteinuria and hematuria was 50 d (10-2160) and 30 d (4-1170), respectively. One-yr graft survival rates after PTx-GN diagnosis was 64%. The most frequent de novo GN was membranous GN (26%), while focal segmental glomerulosclerosis was the most frequent recurrent GN (41%), with a very early onset (median of three months). One-yr graft survival was better in the recurrent disease than in the de novo patients, 76% vs. 55% (p = 0.24). The best predictor factors that correlated with graft survival were: proteinuria <3.5 g [relative risk (RR) = 0.24, p = 0.017], serum creatinine below 2.0 mg/dL (RR = 0.06, p = 0.016) at the time of biopsy and the use of angiotensin-converting enzyme inhibitors (ACEI) (RR = 0.12, p = 0.005). The use of ACEI markedly improved one-yr graft survival rates (92% vs. 47%, p < 0.001). CONCLUSION: PTx-GN has a strong negative impact on kidney graft survival. De novo GN appears to have a poorer prognosis than the recurrent type. Patients who used ACEI showed a better survival rate in the follow-up.

Glomerulonefritis: revisión del tema / Glomerulonephritis

Las glomerulonefritis (GN) son enfermedades caracterizadas por inflamación glomerular y proliferación celular, asociada a hematuria. Los mecanismos inmunes humorales y los mediados por células, juegan un papel importante en la patogenia de la inflamación glomerular. La enfermedad glomerular tiende a producir síndromes de disfunción renal específica. Sin embargo, diferentes enfermedades glomerulares pueden producir síndromes semejantes. En este trabajo se revisa la fisiopatología, la historia natural y el tratamiento de la hematuria asintomática, la glomerulonefritis aguda y la glomerulonefritis rápidamente progresiva.

Anticuerpos anti-citoplasma de neutrófilos: aspectos bioquímicos y metodológicos, importancia en diferentes patologías / Antineutrophil cytoplasmic antibodies: biochemical and methodological aspects, their importance in diferents pathologies

Los anticuerpos anticitoplasma de neutrófilos, ANCA, se encuentran involucrados en la patogénesis de las diferentes formas de las vasculitis inmunes. Su descubrimiento y posterior estudio ha permitido su utilización como elemento de ayuda diagnóstica y de seguimiento en enfermedades tales como la granulomatosis de Wegener, panarteritis microscópica y glomerulonefritis cresenticas necrotizantes. El objetivo de esta revisión es tratar de comprender las diferentes formas de vasculitis y así orientarse con respecto al diagnóstico de las mismas. La técnica de inmunofluorescencia indirecta (IFI) que hasta el momento es la única normatizada, sigue siendo una herramienta fundamental para la detección de ANCA dada su elevada especificidad; pero no debe olvidarse que posee como interferentes a los anticuerpos antinucleares (ANA). Se desarrolló un absorvente a partir de un extracto nucleoproteico de timo vacuno que permite eliminar la interferencia que producen los ANA cuando están presente en una muestra donde se quiere determinar ANCA. De esta manera se logró optimizar la IFI-ANCA, lo cual quedó demostrado que los resultados obtenidos cuando se utilizó esta técnica en conjunto con ELISA antígeno específico, LIA blot antígeno específico y Dot blot gránulos Ó desarrollados. Resultados preexistentes en relación con los ANCA y colangenopatías como el lupus eritematoso sistémico (LES) pediátrico y la artritis reumatoidea (AR) mostraban resultados dispares entre diferentes autores, lo que generó la inquietud de estudiar la seroprevalencia en estas enfermedades y su importancia clínica. Se demostró relación entre ANCA e insuficiencia renal en LES pediátrico, no así en AR. Se generó la hipótesis que la presencia de ANCA sea un epifenómeno derivado de la respuesta inflamatoria. También se pudo demostrar la presenciade ANCA en pacientes con glomerulopatías sin evidencias clínicas ni anatomopatológicas de vasculitis como son las glomerulopatías: de la diabetes, IgA, membranoproliferativas, mesangial, membranosa, nefroesclerosis, esclerosis focal y segmentaria, todas ellas asociadas a microhematuria y/o proteinuria en diferentes grados. Finalmente la revisión de este tema y en particular el desarrollo y optimización de los métodos de detección ha permitido ampliar y profundizar el campo de estudio en relación con los ANCA arribando a las conclusiones aquí expresadas

Anticuerpos anti-citoplasma de neutrófilos: aspectos bioquímicos y metodológicos, importancia en diferentes patologías / Antineutrophil cytoplasmic antibodies: biochemical and methodological aspects, their importance in diferents pathologies

Los anticuerpos anticitoplasma de neutrófilos, ANCA, se encuentran involucrados en la patogénesis de las diferentes formas de las vasculitis inmunes. Su descubrimiento y posterior estudio ha permitido su utilización como elemento de ayuda diagnóstica y de seguimiento en enfermedades tales como la granulomatosis de Wegener, panarteritis microscópica y glomerulonefritis cresenticas necrotizantes. El objetivo de esta revisión es tratar de comprender las diferentes formas de vasculitis y así orientarse con respecto al diagnóstico de las mismas. La técnica de inmunofluorescencia indirecta (IFI) que hasta el momento es la única normatizada, sigue siendo una herramienta fundamental para la detección de ANCA dada su elevada especificidad; pero no debe olvidarse que posee como interferentes a los anticuerpos antinucleares (ANA). Se desarrolló un absorvente a partir de un extracto nucleoproteico de timo vacuno que permite eliminar la interferencia que producen los ANA cuando están presente en una muestra donde se quiere determinar ANCA. De esta manera se logró optimizar la IFI-ANCA, lo cual quedó demostrado que los resultados obtenidos cuando se utilizó esta técnica en conjunto con ELISA antígeno específico, LIA blot antígeno específico y Dot blot gránulos O desarrollados. Resultados preexistentes en relación con los ANCA y colangenopatías como el lupus eritematoso sistémico (LES) pediátrico y la artritis reumatoidea (AR) mostraban resultados dispares entre diferentes autores, lo que generó la inquietud de estudiar la seroprevalencia en estas enfermedades y su importancia clínica. Se demostró relación entre ANCA e insuficiencia renal en LES pediátrico, no así en AR. Se generó la hipótesis que la presencia de ANCA sea un epifenómeno derivado de la respuesta inflamatoria. También se pudo demostrar la presenciade ANCA en pacientes con glomerulopatías sin evidencias clínicas ni anatomopatológicas de vasculitis como son las glomerulopatías: de la diabetes, IgA, membranoproliferativas, mesangial, membranosa, nefroesclerosis, esclerosis focal y segmentaria, todas ellas asociadas a microhematuria y/o proteinuria en diferentes grados. Finalmente la revisión de este tema y en particular el desarrollo y optimización de los métodos de detección ha permitido ampliar y profundizar el campo de estudio en relación con los ANCA arribando a las conclusiones aquí expresadas (AU)