RESUMO
The presence of vascular mesangial channels has been reported in idiopathic nodular glomerulosclerosis and diabetic glomerulopathy. However, only limited information on the morphology and immunohistochemical phenotype of these channels is available. This study aims to describe the light and electron microscopic features of these channels and delineate their immunohistochemical phenotype. Thirty-eight cases of human nodular diabetic glomerulopathy with mesangial channels identified by light microscopy were prospectively selected (2010-2012). The cases were stained with CD31/periodic acid-Schiff combined stain. Selected cases were immunostained for CD34, podoplanin, ERG, and Ki-67. Frequent, small and peripheral vascular mesangial channels were seen in all cases, whereas larger and more centrally located vascular channels were also observed. Communication between peripheral capillary loops and peripheral vascular mesangial channels was seen as was communication between peripheral and central vascular mesangial channels. The vascular mesangial channel lining cells showed a typical endothelial phenotype with strong expression of CD31, CD34, and ERG by immunohistochemistry. The lymphatic channel marker podoplanin was negative in all channels, and the proliferation marker Ki-67 showed no evidence of increased proliferation. By electron microscopy, mesangial channels show angulated, irregular borders with lining cells compatible with endothelium and surrounded by mesangial matrix. No basement membranes were identified surrounding the mesangial channels. These findings support the existence of vascular mesangial channels in nodular diabetic glomerulopathy and suggest neovascularization and altered blood flow within these glomeruli.
Assuntos
Nefropatias Diabéticas/patologia , Mesângio Glomerular/ultraestrutura , Diabetes Mellitus , Humanos , Imuno-Histoquímica , Microscopia Eletrônica de TransmissãoRESUMO
In patients with diabetic nephropathy (DN), the spectrum of immunoglobulin A (IgA)-dominant/codominant glomerular deposition (IgAGD) has not been addressed in the literature. The aim of our study is to detail the clinicopathological and outcome findings in patients with DN and IgAGD. Our database was retrospectively searched over a 10-year period for patients with DN and IgAGD. A total of 132 patients were included in the study, 55 with outcome data. All cases were reviewed by light microscopy, immunofluorescence, and electron microscopy. Mean age was 59 ± 13 years, with a 2:1 male-to-female ratio. Indications for biopsy were often multiple, with proteinuria/nephrotic syndrome and acute renal failure being the most common. All patients showed IgAGD and mesangial deposits by electron microscopy. Seventy-three (55.3%) patients had no proliferative glomerular changes and no clinical history of infection and were most consistent with IgA nephropathy on DN, whereas 19 (14.4%) showed proliferative glomerular changes, had a history of infection, and were most consistent with IgA-dominant infection-associated glomerulonephritis. Forty (30.3%) patients showed a mixture of these findings and did not fit into either category. Patients with a mean of 42 (2-120 range) months of follow-up showed an overall poor prognosis, with 59% of all respondents proceeding to renal replacement therapy or death (RRT/D) over an average of 23 (range, 4-54) months. Progression to RRT/D was most frequent in those most consistent with IgA-dominant infection-associated glomerulonephritis (71%), and by multivariate analysis, only advanced Tervaert morphologic classification (classes III and IV) was associated with progression to RRT/D.
Assuntos
Nefropatias Diabéticas/patologia , Glomerulonefrite por IGA/patologia , Imunoglobulina A/metabolismo , Glomérulos Renais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Nefropatias Diabéticas/metabolismo , Progressão da Doença , Feminino , Glomerulonefrite por IGA/metabolismo , Humanos , Glomérulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
The diagnostic classification of glomerulonephritis is determined by the interplay of changes seen using light, immunofluorescence, and electron microscopy of the renal biopsy. Routine direct immunofluorescence on fresh tissue is currently considered the gold standard for the detection and characterization of immune deposits. We recently found a peculiar form of glomerular immune complex deposition in which masked deposits required an antigen-retrieval step to be visualized. Over a 2-year period, 14 cases were characterized by numerous, large subepithelial deposits visualized by electron microscopy and C3-predominant staining by routine immunofluorescence on fresh tissue with weak to negative immunoglobulin staining. Repeat immunofluorescence after digestion of the formalin-fixed paraffin-embedded tissue with pronase elicited strong IgG-κ staining restricted within the deposits. The patients were often young with a mean age of 26 years and commonly had clinical evidence of vague autoimmune phenomenon. The clinicopathologic findings in this unusual form of glomerulopathy do not fit neatly into any currently existing diagnostic category. We have termed this unique form of glomerulopathy membranous-like glomerulopathy with masked IgG-κ deposits.
Assuntos
Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/imunologia , Imunoglobulina G/metabolismo , Cadeias kappa de Imunoglobulina/metabolismo , Adolescente , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Complexo Antígeno-Anticorpo/metabolismo , Diagnóstico Diferencial , Feminino , Glomerulonefrite Membranosa/classificação , Humanos , Imunossupressores/uso terapêutico , Masculino , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Autoantibody formation directed against phospholipase A2 receptor (PLA2R)1 is the underlying etiology in most cases of primary membranous glomerulopathy. This new understanding of the pathogenesis of primary membranous is in the process of transforming the way the disease is diagnosed. We validated an indirect immunofluorescence assay to examine PLA2R1 in renal biopsies utilizing a commercially available antibody and standard indirect immunofluorescence. Using this assay, we examined a total of 165 cases of membranous glomerulopathy including 85 primary and 80 secondary. We found tissue staining for PLA2R1 to have a sensitivity of 75% (95% CI 65-84%) and a specificity of 83% (95% CI 72-90%) for primary membranous glomerulopathy. Hepatitis C virus was the secondary etiology with the most number of cases staining positive for PLA2R1 (7/11, 64%) followed by sarcoidosis (3/4, 75%) and neoplasm (3/12, 25%). Autoimmune etiologies showed rare PLA2R1-positive staining (1/46, 2%). All cases of secondary membranous glomerulopathy with positive PLA2R1 showed IgG4-predominant staining, which is typically associated with primary membranous glomerulopathy. This IgG4 predominance raises the possibility that these cases are more pathogenically related to primary membranous glomerulopathy than secondary. We present the largest case series to date examining PLA2R1 involvement in membranous glomerulopathy utilizing a technique that is readily adoptable by most renal pathology laboratories.
Assuntos
Glomerulonefrite Membranosa/diagnóstico , Receptores da Fosfolipase A2/análise , Anticorpos , Biópsia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Sensibilidade e EspecificidadeRESUMO
Elderly patients are increasingly being considered for kidney transplantation due to a global explosion of the aging population with end-stage renal disease (ESRD). However, mounting scarcity of available organs for transplant has led to a wider disparity between organ supply and demand. Consequently, the criteria for accepting kidneys for transplantation have been extended in an attempt to allow the use of organs from elderly donors or those with significant co-morbidities, so-called "expanded criteria donor" (ECD) kidneys. Excellent outcomes have been achieved from ECD kidneys with appropriate donor and recipient profiling and selection. With increasing recovery efforts directed at older donors, the concept of age-matching is becoming more accepted as a method of optimizing utilization of organs in elderly donors and recipients. Utilization of pulsatile perfusion has further improved ECD outcomes and helped the decision-making process for the UNOS (United Network for Organ Sharing) offer. However, age-related immune dysfunction and associated co-morbidities make the elderly transplant recipients ever more susceptible to complications associated with immunosuppressive agents. Consequently, the elderly population is at a higher risk to develop infections and malignancy in the post-transplant period notwithstanding improved transplant outcomes. Appropriate immunosuppressive agents and dosages should be selected to minimize adverse events while reducing the risk of acute rejections and maximizing patient and renal allograft survival.
Assuntos
Transplante de Rim , Fatores Etários , Idoso , Envelhecimento/imunologia , Previsões , Rejeição de Enxerto/imunologia , Humanos , Terapia de Imunossupressão , Transplante de Rim/efeitos adversos , Transplante de Rim/ética , Neoplasias/etiologia , Fatores de Risco , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/tendências , Resultado do TratamentoRESUMO
Renal aging, by itself, is associated with alterations in renal morphology and a decline in renal function, which is accelerated and/or accentuated by diseases such as diabetes mellitus and hypertension. The aging-related renal insufficiency has important implications with regards to body homeostasis, drug toxicity, and renal transplantation. An understanding of renal aging and its distinction from renal insufficiency secondary to diseases is essential for individualized care of the elderly. Toward this end, investigations are underway to elucidate the molecular mechanisms of renal aging. This review summarizes the structural and functional changes of the aging kidney and highlights the advances made in our understanding of the renal aging process.
Assuntos
Envelhecimento/fisiologia , Rim/fisiopatologia , Insuficiência Renal/etiologia , Idoso , Envelhecimento/patologia , Humanos , Rim/patologia , Transplante de Rim , Estresse Oxidativo , Insuficiência Renal/terapiaRESUMO
Kidneys are significantly affected by profound anatomic and functional changes with senescence. These changes lead to decline in glomerular filtration rate, decreased urinary concentrating and diluting ability, diminished urinary acidification, and impaired potassium clearance, to list a few. Such changes make the elderly prone to drug toxicity and serious fluid and electrolyte imbalance. While the entire mystery of aging is far from being clear, the role of oxidative stress, telomere length, Klotho gene expression, and the renin angiotensin system seem to be the key mechanisms involved in aging. Aging, being a complex process, involves an array of intertwined molecular pathways. Simultaneous study of multiple molecular pathways in parallel could provide invaluable information in understanding the clinical course of kidney aging and elucidating mechanisms that play key roles in the aging process. A better understanding of these mechanisms may help to preserve renal function, improve morbidity and mortality, and hopefully reduce healthcare costs for the aging population.
Assuntos
Envelhecimento/fisiologia , Rim/anatomia & histologia , Rim/fisiopatologia , Equilíbrio Ácido-Base/fisiologia , Glucuronidase/fisiologia , Humanos , Proteínas Klotho , Estresse Oxidativo , Telômero/fisiologia , Equilíbrio Hidroeletrolítico/fisiologiaAssuntos
Envelhecimento/fisiologia , Rim/fisiologia , Animais , Arteriosclerose/patologia , Arteriosclerose/fisiopatologia , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Rim/patologia , Glomérulos Renais/anatomia & histologia , Glomérulos Renais/fisiologia , Túbulos Renais/fisiologia , Nefroesclerose/patologia , Nefroesclerose/fisiopatologia , EscleroseRESUMO
It is almost ironic that one of the major organs that serves to maintain the "internal milieux" by secretion of various toxic agents, can itself become injured in the process. The pattern of morphologic renal injury is nonspecific and can involve any of the components of the kidney, although the injury and subsequent morphologic changes are most commonly noted in the tubules and/or interstitium. Of course, unless the drug/toxin is commonly or regularly noted to be associated with tubular and/or interstitial injury, the association of the drug with the renal changes may be missed and the correlation may not necessarily identify causation. For example, if a drug is associated with a renal injury in a given individual, it may be quite difficult to prove that the drug is the cause of the injury. This scenario is somewhat reminiscent of the test question-is it "true-true-related," or "true-true-unrelated"? Sometimes it is only by the accrual of a great many examples or correlations, and or dissection of the pathophysiology, can it be shown that the drug is directly related to the observed morphologic (and subsequent clinical) injury. Renal changes induced by chemicals can affect the tubules, interstitium or both. This review of chemically induced nephropathy in humans considers acute tubular necrosis, interstitial nephritis, and tubulointerstitial nephritis or nephropathy. Because the tubules and the interstitium are so intimately related, injury to 1 of these 2 components may eventually lead to injury of the other, resulting in tubulointerstitial disease.
Assuntos
Nefropatias/induzido quimicamente , Nefropatias/patologia , Necrose Tubular Aguda/patologia , Nefrite Intersticial/patologia , Toxinas Biológicas/farmacologia , HumanosRESUMO
Induction of chronic oxidative stress by glutathione (GSH) depletion has been shown to cause hypertension in normal rats. This was accompanied by and perhaps in part due to inactivation and sequestration of NO by reactive oxygen species (ROS), leading to diminished NO bioavailability. This study was designed to examine renal histology, nitric oxide synthase (NOS) isotype expression, and nitrotyrosine distribution in this model. Sprague-Dawley rats were subjected to oxidative stress by administration of the GSH synthase inhibitor buthionine sulfoximine (BSO; 30 mM/l in drinking water) for 2 weeks. The controls were given tap water. Blood pressure, renal histology, tissue expression of endothelial and inducible NOS (eNOS and iNOS) and nitrotyrosine, tissue GSH content, and urinary excretion of NO metabolites (NOx) were examined. The BSO-treated group showed a 3-fold decrease in tissue GSH content, a marked elevation in blood pressure, and a significant reduction in the urinary excretion of NOx. Histological examination of kidneys revealed no significant abnormalities in either group. In addition, no significant differences were observed in either intensities or localizations of eNOS and iNOS in the kidney. However, the BSO-treated group exhibited intense accumulation in the renal tissue of nitrotyrosine, which is the footprint of NO oxidation by ROS. These observations suggest that oxidative stress-induced hypertension is not caused by either structural abnormality of or depressed NOS expression by the kidney in this model. Instead, it is associated with and perhaps partially related to enhanced renal NO inactivation by ROS and diminished NO bioavailability.