RESUMEN
Due to its structure, the glomerular capillary has a filtration function since it is interposed between the blood stream and the urinary space exposed to circulating plasma proteins, which are likely to form a deposit. The role of renal biopsy is to diagnose glomerulonephritis and systemic autoimmune diseases, on the basis of two samples: one for light microscopy and the other for immunofluorescence (IF). Electron microscopy has specific indications. IF is necessary to identify immune deposits. Renal biopsy has made possible the identification and characterization of lesions such as those related to the new viral diseases that emerged over the last decade: cryoglobulinemia and hepatitis C virus (HCV), the BK virus, the positivity of the C4d marker in humoural rejection of transplants, glomerular lesions due to monoclonal immunoglobulin. Besides, the recent molecular biology techniques as applied in renal transplantation are likely to improve the matching donors/recipients, and to treat graft rejections as revealed by gene expression in the renal tissue.
Asunto(s)
Enfermedades Renales/patología , Riñón/patología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/patología , Biopsia/métodos , Técnica del Anticuerpo Fluorescente , Glomerulonefritis/diagnóstico , Glomerulonefritis/patología , Humanos , Riñón/citología , Enfermedades Renales/diagnóstico , Glomérulos Renales/citología , Glomérulos Renales/patología , Trasplante de Riñón/métodos , Biología Molecular/métodosRESUMEN
Renal biopsy plays a central role in the investigational approach of the nephrologist. The technique has significantly improved over the past two decades as a result of the introduction of ultrasonography and automated-gun biopsy devices. Percutaneous renal biopsy has become a relatively safe procedure with life-threatening complications occurring in less than 0.1% of biopsies in recent reports. However, percutaneous kidney biopsy is not without risk. Overt complications occurring in up to 13% of the cases, and 6 to 7% of complications were considered major, needing for an intervention such as transfusion of blood product or invasive procedure (radiographic or surgical). Major complications were apparent in more than 90% of patients by 24 hours. In situations in which the potential benefit of obtaining renal histology outweighs the risks of the procedure, transjugular kidney biopsy or surgical biopsy offers an attractive alternative. At present, we have no definite predictive indicators of postbiopsy bleeding complication, with the exception of age, gender, advanced renal insufficiency and the baseline partial thromboplastin time. Bleeding time is not significantly predictive and has been reported to have substantial limitations as a screening test. The use of the PFA-100 may replace the bleeding time and is now considered as a more valuable screening test for prebiopsy identification and management of patients with impaired haemostasis. Four groups of patients benefit from the findings of renal biopsy: those with a nephrotic syndrome, those with a renal disease in a context of systemic disorder, those with acute renal failure and those with a renal transplant. Some patients with non-nephrotic proteinuria, hematuria and chronic renal failure may also benefit from the procedure.
Asunto(s)
Biopsia/métodos , Riñón/patología , Anticoagulantes/uso terapéutico , Automatización , Biopsia/efectos adversos , Tiempo de Sangría , Transfusión Sanguínea , Humanos , Riñón/citología , Enfermedades Renales/clasificación , Enfermedades Renales/diagnóstico , Enfermedades Renales/patología , Nefrología/métodos , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/patología , Circulación Renal , Medición de RiesgoRESUMEN
Although parietal podocytes along the Bowman's capsule have been described by electron microscopy in the normal human kidney, their molecular composition remains unknown. Ten human normal kidneys that were removed for cancer were assessed for the presence and the extent of parietal podocytes along the Bowman's capsule. The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested. In addition, six normal fetal kidneys were studied to track the ontogeny of parietal podocytes. The podocyte protein labeling detected parietal podocytes in all of the kidneys, was found in 76.6% on average of Bowman's capsule sections, and was prominent at the vascular pole. WT1 and p57 were expressed in some parietal cells, whereas PAX2 was present in all or most of them, so some parietal cells coexpressed WT1 and PAX2. Furthermore, parietal podocytes coexpressed WT1 and podocyte proteins. Cytokeratin-positive cells covered a variable part of the capsule and did not express podocyte proteins. Tuft-capsular podocyte bridges were present in 15.5 +/- 3.7% of the glomerular sections. Parietal podocytes often covered the juxtaglomerular arterioles and were present within the extraglomerular mesangium. Parietal podocytes were present in fetal kidneys. Parietal podocytes that express the same epitopes as visceral podocytes do exist along Bowman's capsule in the normal adult kidney. They are a constitutive cell type of the Bowman's capsule. Therefore, their role in physiology and pathology should be investigated.
Asunto(s)
Biomarcadores/metabolismo , Cápsula Glomerular/patología , Células Epiteliales/patología , Glomérulos Renales/patología , Podocitos/patología , Adulto , Anciano , Cápsula Glomerular/metabolismo , Células Epiteliales/metabolismo , Femenino , Feto , Humanos , Glomérulos Renales/metabolismo , Persona de Mediana Edad , Podocitos/metabolismo , EmbarazoRESUMEN
BACKGROUND: A recently proposed reclassification of lupus nephritis divides class IV (diffuse proliferative) lupus nephritis into those cases with predominantly segmental proliferative lesions (class IV-S) and those with predominantly global proliferative lesions (class IV-G). This report explores the validity of this distinction and possible differences in pathogenesis between the 2 types of lesions. METHODS: Patients from a previously reported series of severe lupus nephritis, with initial biopsies (Bx1) and control biopsies (Bx2) at 6 months after induction therapy were reclassified according to the newly proposed classification. From the original series of 65 patients, 15 patients were reclassified as having class IV-S lesions and 31 patients class IV-G lesions. Clinical data at both biopsies and follow-up were available on all patients selected. RESULTS: Patients with IV-G lesions had worse proteinuria, lower serum hemoglobins, lower CH50s, and likely higher SCrs (P = .06) and lower C3s (P = .08) than class IV-S patients. Serum CH50 and C3 correlated negatively with severity of class IV-G lesions, but not at all with class IV-S lesions. Patients with class IV-G lesions had greater overall immune deposits and subendothelial deposits on IF and greater hyaline deposits on light microscopy. By contrast, class IV-S showed predominant mesangial deposits and a much higher rate of glomerular fibrinoid necroses (13.3 +/- 15.3% vs. 5.6 +/- 8.0% of viable glomeruli, P = .03). Other distinctions included the fact that membranoproliferative features were found only in class IV-G lesions, and glomerular monocyte/macrophages were much more frequent in this group than in class IV-S lesions (1.77 +/- 0.92 vs. 0.86 +/- 0.77, P = .008). Finally, class IV-G frequently involved all viable glomeruli (74.2% of cases), whereas segmental proliferative lesions never did (P < .0001). Survivals from doubling of SCr at 10 years did not differ between the 2 types at Bx1: 72.5% segmental versus 60.4% global, P= .53. However, among those with persistent lesions at Bx 2 (11 IV-S and 9 IV-G), there was a dramatic difference in 10-year survivals between IV-S lesions (63.6%) and IV-G lesions (0%), P = .08. CONCLUSION: There are definite clinical and morphologic differences between class IV-S and IV-G lesions. Data suggest that class IV-G lesions behave as an immune complex disease, having positive correlations with extent of immune deposits and negative correlations with serum complement levels, the model traditionally assumed for lupus nephritis as a whole. However, in class IV-S lesions, the presence of proportionally greater glomerular fibrinoid necroses and lack of correlation with extent of immune deposits suggest that these lesions may have a different pathogenesis.
Asunto(s)
Glomérulos Renales/patología , Nefritis Lúpica/clasificación , Nefritis Lúpica/patología , Adulto , Complejo Antígeno-Anticuerpo/metabolismo , Biopsia , Creatinina/sangre , Femenino , Humanos , Nefritis Lúpica/mortalidad , Macrófagos/patología , Masculino , Persona de Mediana Edad , Monocitos/patología , Necrosis , Recurrencia , Análisis de SupervivenciaRESUMEN
Transdifferentiation is characterized by a loss of normal epitopes by differentiated cells, accompanied by the acquisition of new epitopes and new functions. Podocytes are differentiated epithelial cells that cover and adhere to the outer surface of the glomerular basement membrane (GBM). The podocyte/GBM complex contributes to the selective filter function of the glomerular tuft. We have shown that, in various human glomerulonephritides, "dysregulated" podocytes acquire the potential to proliferate and multiply, undergo profound morphologic changes, detach from the GBM, and show phenotypic changes indicative of transdifferentiation. In the course of these events they lose their original epitopes and acquire macrophagic markers.
Asunto(s)
Diferenciación Celular , Células Epiteliales/fisiología , Glomerulonefritis/fisiopatología , Membrana Basal , Adhesión Celular , Humanos , FenotipoRESUMEN
BACKGROUND: The role of podocytes in human crescentic glomerulonephritis (GN) has been underestimated. This may be due to the confounding fact that "dysregulated" podocytes are able to proliferate, lose their markers, and acquire new epitopes. Moreover, in experimental anti-glomerular basement membrane (GBM) crescentic GN, podocytes participate in the crescent formation. The aim of this study was to investigate the involvement of podocytes in human immune crescentic GN. METHODS: Renal biopsies from 12 patients with anti-GBM disease and 14 with class IV lupus GN were studied by immunohistochemistry for the following markers: (1) synaptopodin, GLEPP1, podocalyxin, podocin, alpha-actinin-4, and vimentin for podocyte identification; (2) PCNA, Ki-67, and p57 for cell cycle assessment; (3) cytokeratins for identifying epithelial cells but not normal podocytes; (4) CD68 for tagging a macrophagic epitope; (5) alpha-smooth-muscle actin (alpha-SMA), a phenotypic marker of myofibroblasts. RESULTS: "True" (capsular) crescents lining Bowman's capsule and (tuft) "pseudocrescents" covering the glomerular tuft with a persistent patent urinary space were present in the 2 types of crescentic GN in similar percentages. Several features indicated that podocytes were involved in the formation of the both crescent types. Identifiable podocytes expressed proliferation markers. Podocyte cytoplasmic expansions and racket-like podocytes bridged between the tuft and Bowman's capsule. True and pseudocrescents contained labeled podocytes. In addition, podocytes located outside of the crescents had often lost their markers (dedifferentiation) and acquired new epitopes (cytokeratins and CD68). CONCLUSION: In human immune crescentic GN, podocytes undergo proliferation and dysregulation that are indicative of a podocytopathy. Podocytes contribute to crescent formation.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Podocitos/inmunología , Podocitos/patología , Actinas/metabolismo , Adulto , Anciano , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Biopsia , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Humanos , Queratinas/metabolismo , Antígeno Ki-67/metabolismo , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Podocitos/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Vimentina/metabolismoRESUMEN
Transplantation for patients possessing allo-antibodies against HLA antigens can be delayed for years, and, once the graft has been transplanted, its survival is significantly reduced. We and others have shown that administration of intravenous immunoglobulins (IVIgs) can induce a profound and sustained decrease in the titres of the anti-HLA antibodies, thus greatly enhancing the chances of those patients to obtain a transplant. In a number of cases, pre-treatment sera contained anti-donor antibodies that disappeared after IVIg administration. A similar approach, combining plasmapheresis and low-dose IVIgs, has shown similar results and has been successfully applied to ABO-incompatible transplantations. Patient and graft survival are excellent, despite a rather high rate of rejections, most notably humoral ones. These protocols thus demonstrate that the presence of anti-donor antibody, once an absolute contra-indication to transplantation, can, nowadays, be considered as an immunological hurdle that can be managed through appropriate immunological manipulation.
Asunto(s)
Antígenos HLA/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Isoanticuerpos/análisis , Trasplante de Órganos , Inmunología del Trasplante , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunización , Isoanticuerpos/inmunologíaRESUMEN
BACKGROUND: Among the cellular changes occurring in renal fibrosis, epithelial-mesenchymal cell transdifferentiation or transition (EMT) is a phenomenon characterized in epithelial cells by loss of epithelial markers and acquisition of mesenchymal phenotype and of fibrosing properties. METHODS: To test the hypothesis that EMT is involved in human pauci-immune crescentic glomerulonephritis (PICGN), we studied 17 renal biopsies from 11 PICGN patients for: (i) proliferating cell nuclear antigen (PCNA) and cell cycle inhibitors (cyclin-dependent kinase inhibitors) p27 and p57; (ii) cell lineage phenotype markers: podocalyxin, synaptopodin and GLEPP-1 for podocytes; CD68 for macrophagic epitope; CD3 for T lymphocytes; alpha-smooth muscle actin (alpha-SMA) for myofibroblasts; vimentin for mesenchymal cells; and cytokeratins (CKs) for parietal epithelial cells (PECs); (iii) glomerular fibrosis by labelling collagens I, III and IV, and heat-shock protein 47 (HSP47), a marker of collagen-synthesizing cells; and (iv) co-localization of alpha-SMA, CK and HSP47 using confocal laser microscopy. RESULTS: The crescent cells proliferated greatly. They did not express p27 and p57. Different cell lineage markers could be identified in crescents: the major component was made of 'dysregulated' PECs negative for CK, followed by PECs positive for CK, macrophagic cells and myofibroblasts. Furthermore, some cells co-expressed CK and alpha-SMA. This latter co-expression suggests a transitional phase in the dynamic phenomenon of EMT. Therefore, proliferative and dysregulated glomerular epithelial cells could be a possible cellular source of myofibroblasts via EMT. In addition, HSP47 labelled many crescent cells and frequently co-localized in CK-positive epithelial cells and in alpha-SMA-positive myofibroblasts, indicating that these cells were involved in glomerular accumulation of collagens. CONCLUSION: EMT is a transient cellular phenomenon present in glomeruli in human PICGN contributing to the formation of myofibroblasts from epithelial cells and to glomerular fibrosis.
Asunto(s)
Fibroblastos/patología , Glomerulonefritis/patología , Glomerulonefritis/fisiopatología , Riñón/patología , Adulto , Anciano , Diferenciación Celular/fisiología , Epitelio/patología , Femenino , Fibrosis/patología , Fibrosis/fisiopatología , Humanos , Masculino , Mesodermo/patología , Persona de Mediana EdadRESUMEN
BACKGROUND: In the past it was widely assumed that hyaline afferent arteriolosclerosis was responsible for ischemic glomerulosclerosis in the aging and hypertensive kidney. However, glomerular lesions of focal segmental glomerulosclerosis are now recognized in essential hypertension. Experimentally, such lesions are associated with loss of autoregulation of blood flow and glomerular hyperperfusion, as well as initial glomerular hypertrophy. These observations challenge the notion of ischemia as a unitary explanation for glomerulosclerosis. METHODS: A morphometric study was performed on normal portions of eight kidneys removed for tumors in aging, normotensive patients. Measurements were made of 126 pairs of afferent arterioles and their associated glomeruli. In addition, the amount of extracellular matrix (ECM) in the immediate periglomerular region was quantitated. RESULTS: Afferent arterioles were divided into three types according to the presence or absence of hyaline deposits and whether these did or did not obstruct the lumen. Arterioles with nonobstructive hyaline deposits had lumens over twice as large as those without deposits (482 +/- 240 micro2 vs. 204 +/- 160 micro2, P=0.0000). Their associated glomeruli had significantly greater total capillary area, particularly the hilar capillaries (1276 +/- 797 micro2 vs. 667 +/- 492 micro2, P=0.002), but with larger individual capillaries elsewhere as well (P=0.03). Arterioles with obstructive deposits differed from those with nonobstructive deposits by their smaller lumens (P=0.001) and walls (P=0.004), with a higher proportion of ECM in the periglomerular region (P=0.001), all consistent with a later stage of lesion. Glomeruli were divided into four basic types: normal, hypertrophic, glomeruli with features of focal segmental glomerulosclerosis (FSGS-type), and ischemic. Compared to normal glomeruli, hypertrophic glomeruli were larger, with greater total capillary area (P=0.0005), particularly the hilar capillaries (P=0.0000), and larger capillaries in the remainder of the tuft (P=0.003), but showed no evident lesions. FSGS-type glomeruli were also larger, with larger hilar capillaries (P=0.0005), but showed an increase in ECM due to sclerotic lesions (P=0.004). The remaining capillaries showed an inverse relation with the amount of mesangial matrix, showing a spectrum of sizes from enlarged to shrunken. As anticipated, ischemic glomeruli were significantly smaller than normal ones in every parameter measured. There was a strong association between hypertrophic/FSGS-type glomeruli and hyaline arteriolosclerosis, found in 90.3% of such glomeruli, versus 29.1% for the remaining glomeruli (P=0.0001). The great majority of hyaline deposits were of the nonobstructive variety (86.2%), but some were obstructive (13.8%), particularly in FSGS-type glomeruli, consistent with a more advanced lesion. CONCLUSIONS: We believe we have demonstrated in the aging kidney of humans the morphologic correlates of loss of autoregulation, occurring on a focal basis, with afferent arteriolar dilatation and increase in glomerular capillary size and subsequent focal segmental glomerulosclerosis. Hyaline arteriolosclerosis of the nonobstructive sort is strongly associated with these changes and may play a role in their pathogenesis.
Asunto(s)
Envejecimiento/fisiología , Arteriosclerosis/fisiopatología , Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Glomérulos Renales/irrigación sanguínea , Glomérulos Renales/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Arteriolas/metabolismo , Arteriolas/patología , Arteriolas/fisiopatología , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Capilares/metabolismo , Capilares/patología , Capilares/fisiopatología , Matriz Extracelular/metabolismo , Glomeruloesclerosis Focal y Segmentaria/patología , Homeostasis/fisiología , Humanos , Hialina/metabolismo , Glomérulos Renales/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To correlate the susceptibility of low-(LDL) and very-low-density lipoprotein to oxidation in vitro and the concentrations of serum antibodies against malondialdehyde-modified LDL and plasma vitamin E with the anthropometric and laboratory characteristics of obesity. RESEARCH METHODS AND PROCEDURES: A total of 75 nondiabetic, normotensive obese patients were assigned to one of four groups according to their body mass index (BMI): moderately obese (30 Asunto(s)
Peroxidación de Lípido
, Obesidad/sangre
, Vitamina E/sangre
, Adulto
, Consumo de Bebidas Alcohólicas
, Anticuerpos/sangre
, Constitución Corporal
, Índice de Masa Corporal
, Colesterol/sangre
, Cobre/química
, Femenino
, Humanos
, Lipoproteínas LDL/sangre
, Lipoproteínas LDL/inmunología
, Lipoproteínas VLDL/sangre
, Masculino
, Malondialdehído/farmacología
, Persona de Mediana Edad
, Obesidad Mórbida/sangre
, Fumar
, Triglicéridos/sangre
RESUMEN
BACKGROUND: Lipids are involved in the onset and/or the progression of renal diseases. ApoE null mice are hyperlipidaemic and thus represent an experimental model for the study of the effect of severe hypercholesterolaemia on renal lesion development. METHODS: ApoE null mice were studied at 6 weeks of age fed a normal chow, after 20 weeks on a normal chow (mild hypercholesterolaemia), or a 0.15% cholesterol Western diet (WD; severe hypercholesterolaemia). Age- and diet-matched C57/B6 mice were used as controls. Glomerular structure was assessed by histology, electron microscopy and computerized morphometry. Glomerular macrophage recruitment and alpha-smooth-muscle actin, PCNA, VCAM-1 and MHC class II (I-A(b)) expressions were assessed by immunohistochemistry. RESULTS: ApoE null mice fed the WD developed mesangial expansion characterized by an increase in mesangial area (P<0.05 vs C57BL/6 mice at 20 weeks). In apoE null mice, this was accompanied by a glomerular inflammatory process as demonstrated by (i) the presence of foam cells, (ii) macrophage recruitment, (iii) a higher expression of the I-A(b) activation marker and (iv) endothelial-cell activation (VCAM-1 expression in 100% of glomeruli and electron microscopy showing cytoplasmic foldings protruding in the capillary lumina). This might explain why we also observed blood monocytes adhering to glomerular endothelial cells. CONCLUSIONS: In apoE null mice, severe hyperlipidaemia leads to glomerular injury characterized by glomerular endothelial cell activation and macrophage recruitment.
Asunto(s)
Apolipoproteínas E/deficiencia , Endotelio Vascular/fisiopatología , Mesangio Glomerular/patología , Hiperlipidemias/fisiopatología , Glomérulos Renales/fisiopatología , Macrófagos/fisiología , Animales , Apolipoproteínas E/genética , Células Espumosas/patología , Hiperlipidemias/patología , Riñón/patología , Glomérulos Renales/patología , Ratones , Ratones Noqueados/genéticaRESUMEN
Transplantation of patients possessing antibodies against allo-HLA antigens can be delayed for years. We have shown that administration of intravenous immunoglobulins (IVIg) can induce a profound and sustained decrease in the titers of anti-HLA antibodies. We report here the first series of patients desensitized, then transplanted using IVIg therapy. Fifteen patients have been included and treated with IVIg, given as 3 monthly courses of 2g/kg body weight. Thirteen of those 15 patients (87%) were effectively desensitized and underwent immediate transplantation. Eleven were transplanted with a cadaveric donor, and two with a living donor against which the pretreatment cross-match was positive. One graft was lost from thrombosis and one from rejection. All other patients had uneventful courses, without any episodes of rejection, with a follow-up of more than 1 year. Thus, IVIg therapy allows safe and prompt kidney transplantation of immunized patients.
Asunto(s)
Rechazo de Injerto/prevención & control , Inmunoglobulinas Intravenosas/farmacología , Trasplante de Riñón , Adolescente , Adulto , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Persona de Mediana Edad , Proyectos Piloto , Resultado del TratamientoRESUMEN
BACKGROUND: Renal relapse in lupus nephritis has been shown to have ominous prognostic significance with the majority of patients progressing to doubling of serum creatinine (CRX2). However, not all patients do so. This report explores the roles of response of inflammation to therapy and of glomerular scarring and interstitial fibrosis and their potential reversal to outcome of renal relapse. METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy, as well as subsequent biopsies for clinical indications, were studied. The relationships of morphologic factors to renal relapse and its outcome as well as to CRX2 and end-stage renal disease (ESRD) were analyzed. Cox proportional hazards modeling was used to assess association of morphologic variables with outcomes. RESULTS: Renal interstitial fibrosis and glomerular segmental scarring were partially reversible in 17 and 11 patients, respectively. This decline was associated with an excellent prognosis, with only one patient in each group (5.9% and 9.1% respectively) progressing to CRX2. All 18 patients who progressed to CRX2 either failed to respond to therapy (7 patients) as defined by normalization of serum creatinine (SCr) and reduction of proteinuria to < or =1 g/day, or relapsed after initial response (11 patients), as defined by recent rise of SCr > 50% and/or proteinuria > 3.5 g/day. However, relapse also occurred in 11 of 47 other patients without progression to CRX2. These patients showed a greater initial response of inflammation and deposits to therapy and fibrous lesions partially reversed in the period prior to relapse, so that active lesions were superimposed on a lower level of chronic lesions. By contrast, chronic lesions mounted steadily in those who progressed to CRX2. Cox proportional hazards modeling indicated a strong association of inflammatory variables with renal relapse, CRX2 and ESRD. However, the extent of immunoglobulin deposits was not significantly associated with any outcome. Finally, we found that failure of disease to remit also is associated with a high rate of CRX2 (64.8% vs. 13.0%, P = 0.00034). CONCLUSIONS: Interstitial fibrosis and glomerular scarring in systemic lupus erythematosus are partially reversible, and this reversal is attended by an excellent outcome. The outcome of renal relapse is determined by the initial response of inflammatory and chronicity elements to therapy, those with prior partial reversal of interstitial and glomerular scarring having a good outcome, and those in whom fibrotic lesions have continued to increase and have a poor outcome. Inflammatory variables appear to be more important in determining outcome than immunoglobulin deposits.
Asunto(s)
Riñón/patología , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Enfermedad Crónica , Creatinina/sangre , Progresión de la Enfermedad , Fibrosis , Humanos , Hialina/metabolismo , Fallo Renal Crónico/etiología , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Glomérulos Renales/fisiopatología , Nefritis Lúpica/complicaciones , Pronóstico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.
Asunto(s)
Síndrome Antifosfolípido/etiología , Enfermedades Renales/etiología , Lupus Eritematoso Sistémico/complicaciones , Adolescente , Adulto , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Creatinina/sangre , Femenino , Enfermedades de los Genitales Femeninos/etiología , Humanos , Hipertensión/etiología , Glomérulos Renales , Inhibidor de Coagulación del Lupus/análisis , Nefritis Lúpica/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Trombosis/etiologíaRESUMEN
This study examined six cases of idiopathic nephrotic syndrome with primary lesions of focal segmental glomerulosclerosis (FSGS) that relapsed after renal transplantation. The glomerular lesions comprised the cellular, the collapsing, and the scar variants of FSGS and showed shedding of large round cells into Bowman's space and within the tubular lumens. Immunohistochemistry and confocal laser microscopy carried out on kidneys with FSGS relapse disclosed several phenomena. (1) Some podocytes that expressed podocalyxin, synaptopodin, and glomerular epithelial protein-1 were detached from the tuft and were free in the urinary space. (2) In the cellular variant, most podocytes had lost podocyte-specific epitopes (podocalyxin, synaptopodin, glomerular epithelial protein-1, Wilm's tumor protein-1, complement receptor-1, and vimentin). In the scar variant, these podocyte markers were absent from cobblestone-like epithelial cells and from pseudotubules. (3) Podocytes had acquired expression of various cytokeratins (CK; identified by the AE1/AE3, C2562, CK22, and AEL-KS2 monoclonal antibodies) that were not found in the podocytes of control glomeruli. Parietal epithelial cells expressed AE1/AE3 CK that were faintly, if ever, found on the parietal epithelial cells of normal glomeruli. (4) Numerous cells located at the periphery of the tuft or free in Bowman's space and within tubular lumens expressed macrophagic epitopes (identified by PGM1 [CD68], HAM56, and 25F9 monoclonal antibodies). These macrophage-like cells expressed the activation epitopes HLA-DR and CD16. (5) A number of these cells coexpressed podocalyxin + AE1/AE3 CK, podocalyxin + CD68, and CD68 + AE1/AE3. These findings suggest that in primary FSGS relapsing on transplanted kidneys, some "dysregulated" podocytes, occasionally some parietal epithelial cells, and possibly some tubular epithelial cells undergo a process of transdifferentiation. This process of transdifferentiation was especially striking in podocytes that acquired macrophagic and CK epitopes that are absent from normal adult and fetal podocytes.